Martin Luther University of Halle-Wittenberg

About: Martin Luther University of Halle-Wittenberg is a education organization based out in Halle, Germany. It is known for research contribution in the topics: Population & Liquid crystal. The organization has 20232 authors who have published 38773 publications receiving 965004 citations. The organization is also known as: MLU & University of Wittenberg.

Metamaterial-inspired silicon nanophotonics

Abstract: Applying metamaterial concepts to dielectric systems offers low losses compared with metallic structures. Here, silicon-based metamaterial and nanophotonic advances are reviewed. The prospect of creating metamaterials with optical properties greatly exceeding the parameter space accessible with natural materials has been inspiring intense research efforts in nanophotonics for more than a decade. Following an era of plasmonic metamaterials, low-loss dielectric nanostructures have recently moved into the focus of metamaterial-related research. This development was mainly triggered by the experimental observation of electric and magnetic multipolar Mie-type resonances in high-refractive-index dielectric nanoparticles. Silicon in particular has emerged as a popular material choice, due to not only its high refractive index and very low absorption losses in the telecom spectral range, but also its paramount technological relevance. This Review overviews recent progress on metamaterial-inspired silicon nanostructures, including Mie-resonant and off-resonant regimes.

A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme.

Abstract: Previous uncontrolled clinical trials have shown the in vivo retrovirus (RV)-mediated transduction of glioblastoma cells with the herpes simplex virus thymidine kinase (HSV-tk) gene and subsequent systemic treatment with ganciclovir to be feasible and well tolerated. However, because of continued tumor progression in most patients, the antitumor effect could not be determined using historical controls. Here, we describe a phase III, multicenter, randomized, open-label, parallel-group, controlled trial of the technique in the treatment of 248 patients with newly diagnosed, previously untreated glioblastoma multiforme (GBM). Patients received, in equal numbers, either standard therapy (surgical resection and radiotherapy) or standard therapy plus adjuvant gene therapy during surgery. Progression-free median survival in the gene therapy group was 180 days compared with 183 days in control subjects. Median survival was 365 versus 354 days, and 12-month survival rates were 50 versus 55% in the gene therapy and control groups, respectively. These differences were not significant. Therefore, the adjuvant treatment improved neither time to tumor progression nor overall survival time, although the feasibility and good biosafety profile of this gene therapy strategy were further supported. The failure of this specific protocol may be due mainly to the presumably poor rate of delivery of the HSV-tk gene to tumor cells. In addition, the current mode of manual injection of vector-producing cells with a nonmigratory fibroblast phenotype limits the distribution of these cells and the released replication-deficient RV vectors to the immediate vicinity of the needle track. Further evaluation of the RV-mediated gene therapy strategy must incorporate refinements such as improved delivery of vectors and transgenes to the tumor cells, noninvasive in vivo assessment of transduction rates, and improved delivery of the prodrug across the blood-brain and blood-tumor barrier to the transduced tumor cells.

Cyclic adenosine monophosphate is a key component of regulatory T cell–mediated suppression

Abstract: Naturally occurring regulatory T cells (T reg cells) are a thymus-derived subset of T cells, which are crucial for the maintenance of peripheral tolerance by controlling potentially autoreactive T cells. However, the underlying molecular mechanisms of this strictly cell contact–dependent process are still elusive. Here we show that naturally occurring T reg cells harbor high levels of cyclic adenosine monophosphate (cAMP). This second messenger is known to be a potent inhibitor of proliferation and interleukin 2 synthesis in T cells. Upon coactivation with naturally occurring T reg cells the cAMP content of responder T cells is also strongly increased. Furthermore, we demonstrate that naturally occurring T reg cells and conventional T cells communicate via cell contact–dependent gap junction formation. The suppressive activity of naturally occurring T reg cells is abolished by a cAMP antagonist as well as by a gap junction inhibitor, which blocks the cell contact–dependent transfer of cAMP to responder T cells. Accordingly, our results suggest that cAMP is crucial for naturally occurring T reg cell–mediated suppression and traverses membranes via gap junctions. Hence, naturally occurring T reg cells unexpectedly may control the immune regulatory network by a well-known mechanism based on the intercellular transport of cAMP via gap junctions.

Central role of Drosophila SU(VAR)3-9 in histone H3-K9 methylation and heterochromatic gene silencing.

Abstract: Su(var)3–9 is a dominant modifier of heterochromatin-induced gene silencing. Like its mammalian and Schizosaccharomyces pombe homologues, Su(var) 3–9 encodes a histone methyltransferase (HMTase), which selectively methylates histone H3 at lysine 9 (H3-K9). In Su(var)3–9 null mutants, H3-K9 methylation at chromocentre heterochromatin is strongly reduced, indicating that SU(VAR)3–9 is the major heterochromatin-specific HMTase in Drosophila. SU (VAR)3–9 interacts with the heterochromatin-associated HP1 protein and with another silencing factor, SU(VAR)3–7. Notably, SU(VAR)3–9–HP1 interaction is interdependent and governs distinct localization patterns of both proteins. In Su(var)3–9 null mutants, concentration of HP1 at the chromocentre is nearly lost without affecting HP1 accumulation at the fourth chromosome. By contrast, in HP1 null mutants SU(VAR)3–9 is no longer restricted at heterochromatin but broadly dispersed across the chromosomes. Despite this interdependence, Su(var)3–9 dominates the PEV modifier effects of HP1 and Su(var)3–7 and is also epistatic to the Y chromosome effect on PEV. Finally, the human SUV39H1 gene is able to partially rescue Su(var)3–9 silencing defects. Together, these data indicate a central role for the SU(VAR)3–9 HMTase in heterochromatin-induced gene silencing in Drosophila.

A bacterial effector acts as a plant transcription factor and induces a cell size regulator.

Abstract: Pathogenicity of many Gram-negative bacteria relies on the injection of effector proteins by type III secretion into eukaryotic cells, where they modulate host signaling pathways to the pathogen's benefit. One such effector protein injected by Xanthomonas into plants is AvrBs3, which localizes to the plant cell nucleus and causes hypertrophy of plant mesophyll cells. We show that AvrBs3 induces the expression of a master regulator of cell size, upa20, which encodes a transcription factor containing a basic helix-loop-helix domain. AvrBs3 binds to a conserved element in the upa20 promoter via its central repeat region and induces gene expression through its activation domain. Thus, AvrBs3 and likely other members of this family provoke developmental reprogramming of host cells by mimicking eukaryotic transcription factors.