More Is Not Always Better-the Double-Headed Role of Fibronectin in Staphylococcus aureus Host Cell Invasion

While Staphylococcus aureus has classically been considered an extracellular pathogen, these bacteria are also capable of being taken up by host cells, including nonprofessional phagocytes such as endothelial cells, epithelial cells, or osteoblasts. The intracellular S. aureus lifestyle contributes to infection development. The predominant recognition and internalization pathway appears to be the binding of the bacteria via a fibronectin bridge to the alpha 5 beta 1-integrin on the host cell membrane, followed by phagocytosis. Although osteoblasts showed high expression of alpha 5 beta 1-integrin and fibronectin, and bacteria adhered to osteoblasts to a high proportion, here we demonstrate by internalization assays and immunofluorescence microscopy that S. aureus was less engulfed in osteoblasts than in epithelial cells. The addition of exogenous fibronectin during the infection of cells with S. aureus resulted in an increased uptake by epithelial cells but not by osteoblasts. This contrasts with the previous conception of the uptake mechanism, where high expression of integrin and fibronectin would promote the bacterial uptake into host cells. Extracellular fibronectin surrounding osteoblasts, but not epithelial cells, is organized in a fibrillary network. The inhibition of fibril formation, the short interfering RNA-mediated reduction of fibronectin expression, and the disruption of the fibronectin-fibril meshwork all resulted in a significant increase in S. aureus uptake by osteoblasts. Thus, the network of fibronectin fibrils appears to strongly reduce the uptake of S. aureus into a given host cell, indicating that the supramolecular structure of fibronectin determines the capacity of particular host cells to internalize the pathogen. IMPORTANCE Traditionally, Staphylococcus aureus has been considered an extracellular pathogen. However, among other factors, the frequent failure of antimicrobial therapy and the ability of the pathogen to cause recurrent disease have established the concept of eukaryotic invasion of the pathogen, thereby evading the host's immune system. In the current model of host cell invasion, bacteria initially bind to alpha 5 beta 1 integrin on the host cell side via a fibronectin bridge, which eventually leads to phagocytosis of S. aureus by host cells. However, in this study, we demonstrate that not the crude amount but the supramolecular structure of fibronectin molecules deposited on the eukaryotic cell surface plays an essential role in bacterial uptake by host cells. Our findings explain the large differences of S. aureus uptake efficacy in different host cell types as well as in vivo differences between courses of bacterial infections and the localization of bacteria in different clinical settings

CAMbase – A XML-based bibliographical database on Complementary and Alternative Medicine (CAM)

The term "Complementary and Alternative Medicine (CAM)" covers a variety of approaches to medical theory and practice, which are not commonly accepted by representatives of conventional medicine. In the past two decades, these approaches have been studied in various areas of medicine. Although there appears to be a growing number of scientific publications on CAM, the complete spectrum of complementary therapies still requires more information about published evidence. A majority of these research publications are still not listed in electronic bibliographical databases such as MEDLINE. However, with a growing demand by patients for such therapies, physicians increasingly need an overview of scientific publications on CAM. Bearing this in mind, CAMbase, a bibliographical database on CAM was launched in order to close this gap. It can be accessed online free of charge or additional costs. The user can peruse more than 80,000 records from over 30 journals and periodicals on CAM, which are stored in CAMbase. A special search engine performing syntactical and semantical analysis of textual phrases allows the user quickly to find relevant bibliographical information on CAM. Between August 2003 and July 2006, 43,299 search queries, an average of 38 search queries per day, were registered focussing on CAM topics such as acupuncture, cancer or general safety aspects. Analysis of the requests led to the conclusion that CAMbase is not only used by scientists and researchers but also by physicians and patients who want to find out more about CAM. Closely related to this effort is our aim to establish a modern library center on Complementary Medicine which offers the complete spectrum of a modern digital library including a document delivery-service for physicians, therapists, scientists and researchers

nor-Mevaldic acid surrogates as selective antifungal agent leads against Botrytis cinerea. Enantioselective preparation of 4-hydroxy-6-(1-phenylethoxy)tetrahydro-2H-pyran-2-one

Solvent-free desymmetrisation of meso-dialdehyde 1 with chiral 1-phenylethan-1-ol, led to preparation of 4-silyloxy-6-alkyloxytetrahydro-2H-pyran-2-one (+)-3a with a 96:4 dr Deprotected lactone (+)-19a and the related racemic lactones 16a–18a present a lactone moiety resembling the natural substrate of HMG-CoA reductase and their antifungal properties have been evaluated against the phytopathogenic fungi Botrytis cinerea and Colletotrichum gloeosporioides. These compounds were selectively active against B. cinerea, while inactive against C. gloeosporioides

Genesis of Neuronal and Glial Progenitors in the Cerebellar Cortex of Peripuberal and Adult Rabbits

Adult neurogenesis in mammals is restricted to some brain regions, in contrast with other vertebrates in which the genesis of new neurons is more widespread in different areas of the nervous system. In the mammalian cerebellum, neurogenesis is thought to be limited to the early postnatal period, coinciding with end of the granule cell genesis and disappearance of the external granule cell layer (EGL). We recently showed that in the rabbit cerebellum the EGL is replaced by a proliferative layer called ‘subpial layer’ (SPL) which persists beyond puberty on the cerebellar surface. Here we investigated what happens in the cerebellar cortex of peripuberal rabbits by using endogenous and exogenously-administered cell proliferation antigens in association with a cohort of typical markers for neurogenesis. We show that cortical cell progenitors extensively continue to be generated herein. Surprisingly, this neurogenic process continues to a lesser extent in the adult, even in the absence of a proliferative SPL. We describe two populations of newly generated cells, involving neuronal cells and multipolar, glia-like cells. The genesis of neuronal precursors is restricted to the molecular layer, giving rise to cells immunoreactive for GABA, and for the transcription factor Pax2, a marker for GABAergic cerebellar interneuronal precursors of neuroepithelial origin that ascend through the white matter during early postnatal development. The multipolar cells are Map5+, contain Olig2 and Sox2 transcription factors, and are detectable in all cerebellar layers. Some dividing Sox2+ cells are Bergmann glia cells. All the cortical newly generated cells are independent from the SPL and from granule cell genesis, the latter ending before puberty. This study reveals that adult cerebellar neurogenesis can exist in some mammals. Since rabbits have a longer lifespan than rodents, the protracted neurogenesis within its cerebellar parenchyma could be a suitable model for studying adult nervous tissue permissiveness in mammals

Autopoiesis, Biological Autonomy and the Process View of Life

In recent years, an increasing number of theoretical biologists and philosophers of biology have been opposing reductionist research agendas by appealing to the concept of biological autonomy which draws on the older concept of autopoiesis. In my paper, I shall investigate some of the ontological implications of this approach. The emphasis on autonomy and autopoiesis, together with the associated idea of organisational closure, might evoke the impression that organisms are to be categorised ontologically as substances: ontologically independent, well-individuated, discrete particulars. However, I shall argue that this is mistaken. Autopoiesis and biological autonomy, properly understood, require a rigorous commitment to a process ontological view of life

Metabolic constituents of grapevine and grape-derived products

The numerous uses of the grapevine fruit, especially for wine and beverages, have made it one of the most important plants worldwide. The phytochemistry of grapevine is rich in a wide range of compounds. Many of them are renowned for their numerous medicinal uses. The production of grapevine metabolites is highly conditioned by many factors like environment or pathogen attack. Some grapevine phytoalexins have gained a great deal of attention due to their antimicrobial activities, being also involved in the induction of resistance in grapevine against those pathogens. Meanwhile grapevine biotechnology is still evolving, thanks to the technological advance of modern science, and biotechnologists are making huge efforts to produce grapevine cultivars of desired characteristics. In this paper, important metabolites from grapevine and grape derived products like wine will be reviewed with their health promoting effects and their role against certain stress factors in grapevine physiology