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91.
92.
Felix Moerman Angelina Arquint Stefanie Merkli Andreas Wagner Florian Altermatt Emanuel A. Fronhofer 《Evolution; international journal of organic evolution》2020,74(3):573-586
Abiotic stress is a major force of selection that organisms are constantly facing. While the evolutionary effects of various stressors have been broadly studied, it is only more recently that the relevance of interactions between evolution and underlying ecological conditions, that is, eco-evolutionary feedbacks, have been highlighted. Here, we experimentally investigated how populations adapt to pH-stress under high population densities. Using the protist species Tetrahymena thermophila, we studied how four different genotypes evolved in response to stressfully low pH conditions and high population densities. We found that genotypes underwent evolutionary changes, some shifting up and others shifting down their intrinsic rates of increase (r0). Overall, evolution at low pH led to the convergence of r0 and intraspecific competitive ability (α) across the four genotypes. Given the strong correlation between r0 and α, we argue that this convergence was a consequence of selection for increased density-dependent fitness at low pH under the experienced high density conditions. Increased density-dependent fitness was either attained through increase in r0, or decrease of α, depending on the genetic background. In conclusion, we show that demography can influence the direction of evolution under abiotic stress. 相似文献
93.
Susanne von Bargen Rim Al Kubrusli Thomas Gaskin Stephanie Fürl Florian Hüttner Dag-Ragnar Blystad David G. Karlin Risto Jalkanen Carmen Büttner 《The Annals of applied biology》2020,176(3):210-222
Since Emaraviruses have been discovered in 2007 several new species were detected in a range of host plants. Five genome segments of a novel Emaravirus from mosaic-diseased Eurasian aspen (Populus tremula) have been completely determined. The monocistronic, segmented ssRNA genome of the virus shows a genome organisation typical for Emaraviruses encoding the viral RNA-dependent RNA polymerase (RdRP, 268.2 kDa) on RNA1 (7.1 kb), a glycoprotein precursor (GPP, 73.5 kDa) on RNA2 (2.3 kb), the viral nucleocapsid protein (N, 35.6 kDa) on RNA3 (1.6 kb), and a putative movement protein (MP, 41.0 kDa) on RNA4 (1.6 kb). The fifth identified genome segment (RNA5, 1.3 kb) encodes a protein of unknown function (P28, 28.1 kDa). We discovered that it is distantly related to proteins encoded by Emaraviruses, such as P4 of European mountain ash ringspot-associated virus. All proteins from this group contain a central hydrophobic region with a conserved secondary structure and a hydrophobic amino acid stretch, bordered by two highly conserved positions, thus clearly representing a new group of homologues of Emaraviruses. The virus identified in Eurasian aspen is closely associated with observed leaf symptoms, such as mottle, yellow blotching, variegation and chloroses along veins. All five viral RNAs were regularly detectable by RT-PCR in mosaic-diseased P. tremula in Norway, Finland and Sweden (Fennoscandia). Observed symptoms and testing of mosaic-diseased Eurasian aspen by virus-specific RT-PCR targeting RNA3 and RNA4 confirmed a wide geographic distribution of the virus in Fennoscandia. We could demonstrate that the mosaic-disease is graft-transmissible and confirmed that the virus is the causal agent by detection in symptomatic, graft-inoculated seedlings used as rootstocks as well as in the virus-infected scions used for graft-inoculation. Owing to these characteristics, the virus represents a novel species within the genus Emaravirus and was tentatively denominated aspen mosaic-associated virus. 相似文献
94.
Stanislaus J. Schymanski Carsten F. Dormann Juliano Cabral Isabelle Chuine Catherine H. Graham Florian Hartig Michael Kearney Xavier Morin Christine Römermann Boris Schröder Alexander Singer 《Journal of Biogeography》2013,40(3):612-613
In a recent article (Dormann et al., 2012, Journal of Biogeography, 39, 2119–2131), we compared different approaches to species distribution modelling and depicted modelling approaches along an axis from purely ‘correlative’ to ‘forward process‐based’ models. In their correspondence, Kriticos et al. (2013, Journal of Biogeography, doi: 10.1111/j.1365‐2699.2012.02791.x ) challenge this view, claiming that our continuum representation neglects differences among models and does not consider the ability of fitted process‐based models to combine the advantages of both process‐based and correlative modelling approaches. Here we clarify that the continuum view resulted from recognition of the manifold differences between models. We also reinforce the point that the current trend towards combining different modelling approaches may lead not only to the desired combination of the advantages but also to the accumulation of the disadvantages of those approaches. This point has not been made sufficiently clear previously. 相似文献
95.
Christoph Domschke Yingzi Ge Isa Bernhardt Sarah Schott Sophia Keim Simone Juenger Mariana Bucur Luisa Mayer Maria Blumenstein Joachim Rom Joerg Heil Christof Sohn Andreas Schneeweiss Philipp Beckhove Florian Schuetz 《Cancer immunology, immunotherapy : CII》2013,62(6):1053-1060
Background
The bone marrow (BM) of breast cancer patients harbors tumor-reactive memory T cells (TCs) with therapeutic potential. We recently described the immunologic effects of adoptive transfer of ex vivo restimulated tumor-reactive memory TCs from the BM of 12 metastasized breast cancer patients in a clinical phase-I study. In this trial, adoptive T cell transfer resulted in the occurrence of circulating tumor antigen-reactive type-1 TCs. We here describe the long-term clinical outcome and its correlation with tumor-specific cellular immune response in 16 metastasized breast cancer patients, including 12 included in the original study.Methods
Sixteen metastatic breast cancer patients with preexisting tumor-reactive BM memory TCs were included into the study. The study protocol involved one transfusion of TCs which were reactivated in vitro with autologous dendritic cells pulsed with lysates of MCF-7 breast cancer cells as source of tumor antigens. The presence of tumor-reactive memory TCs was analyzed by IFN-γ ELISpot assays.Results
Tumor-reactive memory TCs in the peripheral blood were induced de novo in 7/16 patients (44 %) after adoptive TC transfer. These patients were considered immunologic responders to the therapy. Positive adoptive immunotherapy (ADI) response was observed significantly more often in patients without bone metastases (p = 0.0051), in patients with high levels of tumor-reactive BM TCs prior to therapy (p = 0.036) and correlated significantly with the estimated numbers of transferred tumor-reactive TCs (p = 0.0021). After the treatment, we observed an overall median survival of 33.8 months in the total cohort with three patients alive at last follow-up and more than 7 years after ADI. Numbers of transferred tumor-reactive TCs correlated significantly with the overall survival of patients (p = 0.017). Patients with an immunologic response to ADI in the peripheral blood had a significantly longer median survival than nonresponders (median survival 58.6 vs. 13.6 months; p = 0.009).Conclusion
In metastasized breast cancer patients, adoptive transfer of BM TCs can induce the presence of tumor antigen-reactive type-1 TCs in the peripheral blood. Patients with immunologic response after ADI show a significantly longer overall survival. Patients with bone metastases significantly less frequently respond to the treatment and, therefore, might not be optimal candidates for ADI. Although the present study does not yet prove the therapeutic effect of ADI, these findings shed light on the relation between immune response and cancer prognosis and suggest that transfer of reactivated BM TCs might bear therapeutic potential. 相似文献96.
The cranial and hyobranchial muscles of the Triassic temnospondyl Gerrothorax have been reconstructed based on direct evidence (spatial limitations, ossified muscle insertion sites on skull, mandible, and hyobranchium) and on phylogenetic reasoning (with extant basal actinopterygians and caudates as bracketing taxa). The skeletal and soft‐anatomical data allow the reconstruction of the feeding strike of this bottom‐dwelling, aquatic temnospondyl. The orientation of the muscle scars on the postglenoid area of the mandible indicates that the depressor mandibulae was indeed used for lowering the mandible and not to raise the skull as supposed previously and implies that the skull including the mandible must have been lifted off the ground during prey capture. It can thus be assumed that Gerrothorax raised the head toward the prey with the jaws still closed. Analogous to the bracketing taxa, subsequent mouth opening was caused by action of the strong epaxial muscles (further elevation of the head) and the depressor mandibulae and rectus cervicis (lowering of the mandible). During mouth opening, the action of the rectus cervicis muscle also rotated the hyobranchial apparatus ventrally and caudally, thus expanding the buccal cavity and causing the inflow of water with the prey through the mouth opening. The strongly developed depressor mandibulae and rectus cervicis, and the well ossified, large quadrate‐articular joint suggest that this action occurred rapidly and that powerful suction was generated. Also, the jaw adductors were well developed and enabled a rapid mouth closure. In contrast to extant caudate larvae and most extant actinopterygians (teleosts), no cranial kinesis was possible in the Gerrothorax skull, and therefore suction feeding was not as elaborate as in these extant forms. This reconstruction may guide future studies of feeding in extinct aquatic tetrapods with ossified hyobranchial apparatus. J. Morphol., 2013. © 2012 Wiley Periodicals, Inc. 相似文献
97.
Daniela Niemeyer Thomas Zillinger Doreen Muth Florian Zielecki Gabor Horvath Tasnim Suliman Winfried Barchet Friedemann Weber Christian Drosten Marcel A. Müller 《Journal of virology》2013,87(22):12489-12495
Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory infection with as yet unclear epidemiology. We previously showed that MERS-CoV counteracts parts of the innate immune response in human bronchiolar cells. Here we analyzed accessory proteins 3, 4a, 4b, and 5 for their abilities to inhibit the type I interferon response. Accessory protein 4a was found to block interferon induction at the level of melanoma differentiation-associated protein 5 (MDA5) activation presumably by direct interaction with double-stranded RNA. 相似文献
98.
Florian G?rtner Thorsten Seidel Uwe Schulz Jan Gummert Hendrik Milting 《The Journal of biological chemistry》2013,288(45):32138-32148
Endothelin receptor A (ETA), a G protein-coupled receptor, mediates endothelin signaling, which is regulated by GRK2. Three Ser and seven Thr residues recently proven to be phosphoacceptor sites are located in the C-terminal extremity (CTE) of the receptor following its palmitoylation site. We created various phosphorylation-deficient ETA mutants. The phospholipase C activity of mutant receptors in HEK-293 cells was analyzed during continuous endothelin stimulation to investigate the impact of phosphorylation sites on ETA desensitization. Total deletion of phosphoacceptor sites in the CTE affected proper receptor regulation. However, proximal and distal phosphoacceptor sites both turned out to be sufficient to induce WT-like desensitization. Overexpression of the Gαq coupling-deficient mutant GRK2-D110A suppressed ETA-WT signaling but failed to decrease phospholipase C activity mediated by the phosphorylation-deficient mutant ETA-6PD. In contrast, GRK2-WT acted on both receptors, whereas the kinase-inactive mutant GRK2-D110A/K220R failed to inhibit signaling of ETA-WT and ETA-6PD. This demonstrates that ETA desensitization involves at least two autonomous GRK2-mediated components: 1) a phosphorylation-independent signal decrease mediated by blocking of Gαq and 2) a mechanism involving phosphorylation of Ser and Thr residues in the CTE of the receptor in a redundant fashion, able to incorporate either proximal or distal phosphoacceptor sites. High level transfection of GRK2 variants influenced signaling of ETA-WT and ETA-6PD and hints at an additional phosphorylation-independent regulatory mechanism. Furthermore, internalization of mRuby-tagged receptors was observed with ETA-WT and the phosphorylation-deficient mutant ETA-14PD (lacking 14 phosphoacceptor sites) and turned out to be based on a phosphorylation-independent mechanism. 相似文献
99.
Sonja Sucic Florian Koban Ali El-Kasaby Oliver Kudlacek Thomas Stockner Harald H. Sitte Michael Freissmuth 《The Journal of biological chemistry》2013,288(8):5330-5341
The serotonin transporter (SERT) maintains serotonergic neurotransmission via rapid reuptake of serotonin from the synaptic cleft. SERT relies exclusively on the coat protein complex II component SEC24C for endoplasmic reticulum (ER) export. The closely related transporters for noradrenaline and dopamine depend on SEC24D. Here, we show that discrimination between SEC24C and SEC24D is specified by the residue at position +2 downstream from the ER export motif (607RI608 in SERT). Substituting Lys610 with tyrosine, the corresponding residue found in the noradrenaline and dopamine transporters, switched the SEC24 isoform preference: SERT-K610Y relied solely on SEC24D to reach the cell surface. This analysis was extended to other SLC6 (solute carrier 6) transporter family members: siRNA-dependent depletion of SEC24C, but not of SEC24D, reduced surface levels of the glycine transporter-1a, the betaine/GABA transporter and the GABA transporter-4. Experiments with dominant negative versions of SEC24C and SEC24D recapitulated these findings. We also verified that the presence of two ER export motifs (in concatemers of SERT and GABA transporter-1) supported recruitment of both SEC24C and SEC24D. To the best of our knowledge, this is the first report to document a change in SEC24 specificity by mutation of a single residue in the client protein. Our observations allowed for deducing a rule for SLC6 family members: a hydrophobic residue (Tyr or Val) in the +2 position specifies interaction with SEC24D, and a hydrophilic residue (Lys, Asn, or Gln) recruits SEC24C. Variations in SEC24C are linked to neuropsychiatric disorders. The present findings provide a mechanistic explanation. Variations in SEC24C may translate into distinct surface levels of neurotransmitter transporters. 相似文献
100.
Birte Plitzko Gudrun Ott Debora Reichmann Colin J. Henderson C. Roland Wolf Ralf Mendel Florian Bittner Bernd Clement Antje Havemeyer 《The Journal of biological chemistry》2013,288(28):20228-20237
The mitochondrial amidoxime reducing component mARC is a recently discovered molybdenum enzyme in mammals. mARC is not active as a standalone protein, but together with the electron transport proteins NADH-cytochrome b5 reductase (CYB5R) and cytochrome b5 (CYB5), it catalyzes the reduction of N-hydroxylated compounds such as amidoximes. The mARC-containing enzyme system is therefore considered to be responsible for the activation of amidoxime prodrugs. All hitherto analyzed mammalian genomes code for two mARC genes (also referred to as MOSC1 and MOSC2), which share high sequence similarities. By RNAi experiments in two different human cell lines, we demonstrate for the first time that both mARC proteins are capable of reducing N-hydroxylated substrates in cell metabolism. The extent of involvement is highly dependent on the expression level of the particular mARC protein. Furthermore, the mitochondrial isoform of CYB5 (CYB5B) is clearly identified as an essential component of the mARC-containing N-reductase system in human cells. The participation of the microsomal isoform (CYB5A) in N-reduction could be excluded by siRNA-mediated down-regulation in HEK-293 cells and knock-out in mice. Using heme-free apo-CYB5, the contribution of mitochondrial CYB5 to N-reductive catalysis was proven to strictly depend on heme. Finally, we created recombinant CYB5B variants corresponding to four nonsynonymous single nucleotide polymorphisms (SNPs). Investigated mutations of the heme protein seemed to have no significant impact on N-reductive activity of the reconstituted enzyme system. 相似文献