Tyro3 family-mediated cell entry of Ebola and Marburg viruses

Filoviruses, represented by the genera Ebolavirus and Marburgvirus, cause a lethal hemorrhagic fever in humans and in nonhuman primates. Although filovirus can replicate in various tissues or cell types in these animals, the molecular mechanisms of its broad tropism remain poorly understood. Here we show the involvement of members of the Tyro3 receptor tyrosine kinase family-Axl, Dtk, and Mer-in cell entry of filoviruses. Ectopic expression of these family members in lymphoid cells, which otherwise are highly resistant to filovirus infection, enhanced infection by pseudotype viruses carrying filovirus glycoproteins on their envelopes. This enhancement was reduced by antibodies to Tyro3 family members, Gas6 ligand, or soluble ectodomains of the members. Live Ebola viruses infected both Axl- and Dtk-expressing cells more efficiently than control cells. Antibody to Axl inhibited infection of pseudotype viruses in a number of Axl-positive cell lines. These results implicate each Tyro3 family member as a cell entry factor in filovirus infection.     

Clinical outcome of henipavirus infection in hamsters is determined by the route and dose of infection

Nipah virus (NiV) and Hendra virus (HeV) are emerging zoonotic viruses and the causative agents of severe respiratory disease and encephalitis in humans. Little is known about the mechanisms that govern the development of respiratory and neurological disease. Using a hamster model of lethal NiV and HeV infection, we describe the role of the route and dose of infection on the clinical outcome and determine virus tropism and host responses following infection. Infection of hamster with a high dose of NiV or HeV resulted in acute respiratory distress. NiV initially replicated in the upper respiratory tract epithelium, whereas HeV initiated infection primarily in the interstitium. In contrast, infection with a low dose of NiV or HeV resulted in the development of neurological signs and more systemic spread of the virus through involvement of the endothelium. The development of neurological signs coincided with disruption of the blood-brain barrier (BBB) and expression of tumor necrosis alpha (TNF-α) and interleukin 1 β (IL-1β). In addition, interferon-inducible protein 10 (IP-10) was identified as playing an important role in NiV and HeV pathogenesis. These studies reveal novel information on the development and progression of NiV and HeV clinical disease, provide a mechanism for the differences in transmission observed between NiV and HeV outbreaks, and identify specific cytokines and chemokines that serve as important targets for treatment.     

Cytochrome P450s as genes for crop improvement

In the past year, several cytochrome P450 genes have been identified that will be important for generating crop protectants and natural medicinal products. Among these are the 2-hydroxyisoflavone synthase (CYP93C) and the indole-3-acetaldoxime N-hydroxylase (CYP83B1) genes, which catalyze the formation of isoflavones and glucosinolates, respectively.     

Analysis of taxonomic and geographic patterns of Turkish Veronica orientalis using nuclear and plastid DNA and morphological data

Veronica orientalis and related species form one of the taxonomically most challenging subgroups within the genus Veronica. Hybridization and polyploidization on the one hand and convergent character evolution on the other have made delimitation of species difficult. Amplified fragment length polymorphisms and plastid DNA markers were used in conjunction with 54 morphological characters to study relationships among 35 accessions of V. orientalis Mill. as well as other closely related species of Veronica occurring in Turkey and adjacent areas of Georgia and Armenia. In addition, ploidy levels were estimated for 15 accessions using flow cytometry. Diploid to hexaploid individuals were detected in V. orientalis. Analysis of DNA markers demonstrated the non-monophyly of V. orientalis, especially with regard to V. fuhsii and V. multifida from Eastern Turkey, but nuclear and plastid DNA markers are largely incongruent. Neither demonstrates a clear biogeographic pattern. The morphological analysis reveals the distinction of V. orientalis subsp. carduchorum, which is weakly retrieved in some molecular analyses and some clustering according to geography. V. multifida is not monophyletic likely due to parallel evolution of pinnatifid leaves east and west of the Anatolian diagonal.     

Characterization of a Novel Single-Chain Bispecific Antibody for Retargeting of T Cells to Tumor Cells via the TCR Co-Receptor CD8

There is currently growing interest in retargeting of effector T cells to tumor cells via bispecific antibodies (bsAbs). Usually, bsAbs are directed on the one hand to the CD3 complex of T cells and on the other hand to a molecule expressed on the surface of the target cell. A bsAb-mediated cross-linkage via CD3 leads to an activation of CD8+ T cells and consequently to killing of the target cells. In parallel, CD4+ T cells including TH₁, TH₂, TH₁₇ cells and even regulatory T cells (Tregs) will be activated as well. Cytokines produced by CD4+ T cells can contribute to severe side effects e. g. life-threatening cytokine storms and, thinking of the immunosupressive function of Tregs, can even be counterproductive. Therefore, we asked whether or not it is feasible to limit retargeting to CD8+ T cells e. g. via targeting of the co-receptor CD8 instead of CD3. In order to test for proof of concept, a novel bsAb with specificity for CD8 and a tumor-associated surface antigen was constructed. Interestingly, we found that pre-activated (but not freshly isolated) CD8+ T cells can be retargeted via CD8-engaging bsAbs leading to an efficient lysis of target cells.     

Insights into Fisheries Management Practices: Using the Theory of Planned Behavior to Explain Fish Stocking among a Sample of Swiss Anglers

Using inadequate management tools often threatens the natural environment. This study focuses on the example of Swiss recreational fishermen (hereafter called “anglers”) as recreational fisheries management stakeholders. In recreational fisheries, fish stocking conducted by anglers has been identified as one important factor associated with declining fish catches. We therefore aimed to a) gain insights into why anglers want to maintain fish stocking and b) identify entry points for interventions to promote more pro-ecological management practices. Results (N = 349) showed that the majority of anglers think very uncritically about stocking and that they frequently engage in it. We conclude that outcome expectancies and beliefs about risks, in combination with a lack of stocking success controls are the main reasons that anglers retain stocking measures. We suggest that providing anglers with direct experience and feedback about stocking success is suitable to change their intentions regarding stocking and their actual stocking behavior, and thus, to promote more pro-ecological management methods. From a more general perspective, the results of this study are likely to help improve pro-ecological ecosystem management in other domains where problems similar to those in recreational fisheries management might exist.