University of Düsseldorf

About: University of Düsseldorf is a education organization based out in Düsseldorf, Germany. It is known for research contribution in the topics: Population & Diabetes mellitus. The organization has 25225 authors who have published 49155 publications receiving 1946434 citations.

Fungal endophytes from higher plants: a prolific source of phytochemicals and other bioactive natural products

Abstract: Bioactive natural products from endophytic fungi, isolated from higher plants, are attracting considerable attention from natural product chemists and biologists alike as indicated by the steady increase of publications devoted to this topic during recent years (113 research articles on secondary metabolites from endophytic fungi in the period of 2008–2009, 69 in 2006–2007, 36 in 2004–2005, 14 in 2002–2003, and 18 in 2000–2001). This overview will highlight the chemical potential of endophytic fungi with focus on the detection of pharmaceutically valuable plant constituents, e.g. paclitaxel, camptothecin and podophyllotoxin, as products of fungal biosynthesis. In addition, it will cover new bioactive metabolites reported in recent years (2008–2009) from fungal endophytes of terrestrial and mangrove plants. The presented compounds are selected based on their antimicrobial, antiparasitic, cytotoxic as well as neuroprotective activities. Furthermore, possible factors influencing natural product production in endophytes cultivated in vitro and hence the success of bioprospecting from endophytes are likewise discussed in this review.

Decoding Human Cytomegalovirus

Abstract: The human cytomegalovirus (HCMV) genome was sequenced 20 years ago. However, like those of other complex viruses, our understanding of its protein coding potential is far from complete. We used ribosome profiling and transcript analysis to experimentally define the HCMV translation products and follow their temporal expression. We identified hundreds of previously unidentified open reading frames and confirmed a fraction by means of mass spectrometry. We found that regulated use of alternative transcript start sites plays a broad role in enabling tight temporal control of HCMV protein expression and allowing multiple distinct polypeptides to be generated from a single genomic locus. Our results reveal an unanticipated complexity to the HCMV coding capacity and illustrate the role of regulated changes in transcript start sites in generating this complexity.

Up-Regulation of Macrophage Inflammatory Protein-3α/CCL20 and CC Chemokine Receptor 6 in Psoriasis

Abstract: Autoimmunity plays a key role in the immunopathogenesis of psoriasis; however, little is known about the recruitment of pathogenic cells to skin lesions. We report here that the CC chemokine, macrophage inflammatory protein-3 alpha, recently renamed CCL20, and its receptor CCR6 are markedly up-regulated in psoriasis. CCL20-expressing keratinocytes colocalize with skin-infiltrating T cells in lesional psoriatic skin. PBMCs derived from psoriatic patients show significantly increased CCR6 mRNA levels. Moreover, skin-homing CLA+ memory T cells express high levels of surface CCR6. Furthermore, the expression of CCR6 mRNA is 100- to 1000-fold higher on sorted CLA+ memory T cells than other chemokine receptors, including CXCR1, CXCR2, CXCR3, CCR2, CCR3, and CCR5. In vitro, CCL20 attracted skin-homing CLA+ T cells of both normal and psoriatic donors; however, psoriatic lymphocytes responded to lower concentrations of chemokine and showed higher chemotactic responses. Using ELISA as well as real-time quantitative PCR, we show that cultured primary keratinocytes, dermal fibroblasts, and dermal microvascular endothelial and dendritic cells are major sources of CCL20, and that the expression of this chemokine can be induced by proinflammatory mediators such as TNF-alpha/IL-1 beta, CD40 ligand, IFN-gamma, or IL-17. Taken together, these findings strongly suggest that CCL20/CCR6 may play a role in the recruitment of T cells to lesional psoriatic skin.

Excitation of Ventral Tegmental Area Dopaminergic and Nondopaminergic Neurons by Orexins/Hypocretins

Abstract: Orexins/hypocretins are involved in mechanisms of emotional arousal and short-term regulation of feeding. The dense projection of orexin neurons from the lateral hypothalamus to mesocorticolimbic dopaminergic neurons in the ventral tegmental area (VTA) is likely to be important in both of these processes. We used single-unit extracellular and whole-cell patch-clamp recordings to examine the effects of orexins (A and B) and melanin-concentrating hormone (MCH) on neurons in this region. Orexins caused an increase in firing frequency (EC(50) 78 nm), burst firing, or no change in firing in different groups of A10 dopamine neurons. Neurons showing oscillatory firing in response to orexins had smaller afterhyperpolarizations than the other groups of dopamine neurons. Orexins (100 nm) also increased the firing frequency of nondopaminergic neurons in the VTA. In the presence of tetrodotoxin (0.5 microm), orexins depolarized both dopaminergic and nondopaminergic neurons, indicating a direct postsynaptic effect. Unlike the orexins, MCH did not affect the firing of either group of neurons. Single-cell PCR experiments showed that orexin receptors were expressed in both dopaminergic and nondopaminergic neurons and that the calcium binding protein calbindin was only expressed in neurons, which also expressed orexin receptors. In narcolepsy, in which the orexin system is disrupted, dysfunction of the orexin modulation of VTA neurons may be important in triggering attacks of cataplexy.

Nerve injury, axonal degeneration and neural regeneration: basic insights.

Abstract: Axotomy or crush of a peripheral nerve leads to degeneration of the distal nerve stump referred to as Wallerian degeneration (WD). During WD a microenvironment is created that allows successful regrowth of nerve fibres from the proximal nerve segment. Schwann cells respond to loss of axons by extrusion of their myelin sheaths, downregulation of myelin genes, dedifferentiation and proliferation. They finally aline in tubes (Bungner bands) and express surface molecules that guide regenerating fibres. Hematogenous macrophages are rapidly recruited to the distal stump and remove the vast majority of myelin debris. Molecular changes in the distal stump include upregulation of neurotrophins, neural cell adhesion molecules, cytokines and other soluble factors and their corresponding receptors. Axonal injury not only induces muscle weakness and loss of sensation but also leads to adaptive responses and neuropathic pain. Regrowth of nerve fibres occurs with high specificity with formerly motor fibres preferentially reinnervating muscle. This involves recognition molecules of the L2/HNK-1 family. Nerve regeneration occurs at a rate of 3-4 mm/day after crush and 2-3 mm/day after sectioning a nerve. Nerve regeneration can be fostered pharmacologically. Upon reestablishment of axonal contact Schwann cells remyelinate nerve sprouts and downregulate surface molecules characteristic for precursor/premyelinating or nonmyelinating Schwann cells. At present it is unclear whether axonal regeneration after nerve injury is impeded in neuropathies.