@article{VollmuthSchlickerGuoetal.2022, author = {Vollmuth, Nadine and Schlicker, Lisa and Guo, Yongxia and Hovhannisyan, Pargev and Janaki-Raman, Sudha and Kurmasheva, Naziia and Schmitz, Werner and Schulze, Almut and Stelzner, Kathrin and Rajeeve, Karthika and Rudel, Thomas}, title = {c-Myc plays a key role in IFN-γ-induced persistence of Chlamydia trachomatis}, series = {eLife}, volume = {11}, journal = {eLife}, doi = {10.7554/eLife.76721}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301385}, year = {2022}, abstract = {Chlamydia trachomatis (Ctr) can persist over extended times within their host cell and thereby establish chronic infections. One of the major inducers of chlamydial persistence is interferon-gamma (IFN-γ) released by immune cells as a mechanism of immune defence. IFN-γ activates the catabolic depletion of L-tryptophan (Trp) via indoleamine-2,3-dioxygenase (IDO), resulting in persistent Ctr. Here, we show that IFN-γ induces the downregulation of c-Myc, the key regulator of host cell metabolism, in a STAT1-dependent manner. Expression of c-Myc rescued Ctr from IFN-γ-induced persistence in cell lines and human fallopian tube organoids. Trp concentrations control c-Myc levels most likely via the PI3K-GSK3β axis. Unbiased metabolic analysis revealed that Ctr infection reprograms the host cell tricarboxylic acid (TCA) cycle to support pyrimidine biosynthesis. Addition of TCA cycle intermediates or pyrimidine/purine nucleosides to infected cells rescued Ctr from IFN-γ-induced persistence. Thus, our results challenge the longstanding hypothesis of Trp depletion through IDO as the major mechanism of IFN-γ-induced metabolic immune defence and significantly extends the understanding of the role of IFN-γ as a broad modulator of host cell metabolism.}, language = {en} } @article{SchulSchmittRegnerietal.2013, author = {Schul, Daniela and Schmitt, Alexandra and Regneri, Janine and Schartl, Manfred and Wagner, Toni Ulrich}, title = {Bursted BMP Triggered Receptor Kinase Activity Drives Smad1 Mediated Long-Term Target Gene Oscillation in c2c12 Cells}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0059442}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130131}, pages = {e59442}, year = {2013}, abstract = {Bone Morphogenetic Proteins (BMPs) are important growth factors that regulate many cellular processes. During embryogenesis they act as morphogens and play a critical role during organ development. They influence cell fates via concentration-gradients in the embryos where cells transduce this extracellular information into gene expression profiles and cell fate decisions. How receiving cells decode and quantify BMP2/4 signals is hardly understood. There is little data on the quantitative relationships between signal input, transducing molecules, their states and location, and ultimately their ability to integrate graded systemic inputs and generate qualitative responses. Understanding this signaling network on a quantitative level should be considered a prerequisite for efficient pathway modulation, as the BMP pathway is a prime target for therapeutic invention. Hence, we quantified the spatial distribution of the main signal transducer of the BMP2/4 pathway in response to different types and levels of stimuli in c2c12 cells. We found that the subcellular localization of Smad1 is independent of ligand concentration. In contrast, Smad1 phosphorylation levels relate proportionally to BMP2 ligand concentrations and they are entirely located in the nucleus. Interestingly, we found that BMP2 stimulates target gene expression in non-linear, wave-like forms. Amplitudes showed a clear concentration-dependency, for sustained and transient stimulation. We found that even burst-stimulation triggers gene-expression wave-like modulations that are detectable for at least 30 h. Finally, we show here that target gene expression oscillations depend on receptor kinase activity, as the kinase drives further expression pulses without receptor reactivation and the target gene expression breaks off after inhibitor treatment in c2c12 cells.}, language = {en} } @phdthesis{BollazziSosa2008, author = {Bollazzi Sosa, Leonardo Martin}, title = {Building behaviour and the control of nest climate in Acromyrmex leaf-cutting ants}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-27610}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2008}, abstract = {This work was aimed at experimentally studying whether climatic variables act as environmental cues for workers' building behaviour in leaf-cutting ants of the genus Acromyrmex, and to what extent building responses account for the maintenance of nest climate in a proper range for the inhabiting colony. Specifically, this work presents independent analysis in different Acromyrmex species with disparate ecology and nesting habits, aimed at understanding to what extent: i) temperature and humidity act as cues for workers' building behaviour, ii) inter- and intraspecific differences in the nesting habits observed in South American Acromyrmex are based on distinct building behaviours and on the variation in regional climate across continent, iii) differences in nest architecture account for the maintenance of nest climate in a proper range for colony members and, iv) climatic variables trigger building responses aimed at controlling short-term changes in nest climate. It is first experimentally shown that soil temperature acts as a cue for workers' digging behaviour. Acromyrmex lundi workers were observed to respond to both soil temperature as well as its changes, and to decide accordingly where to start or whether to stop digging. The soil temperature range preferred by workers to dig, between 20°C and maximally 30.6°C, matches the range at which colony growth is expected to be maximized. Temperature-sensitive digging might therefore lead to the establishment of the fungus chambers in soil layers with a proper range of temperatures for colony growth. Based on that, it was hypothesized that nest depth in Acromyrmex largely depends on the depth at which this temperature range is located across the soil profile, i.e., the higher the temperature in the superficial soil layers, the deeper the nest location, since soil temperature decreases with increasing depth. A bibliographic survey on nesting habits of 21 South American Acromyrmex species confirmed that the warmer the soil temperature at 50 cm depth throughout the South American continent, the higher the number of species presenting subterranean nests, compared with those inhabiting superficial nests. Temperature-sensitive digging in Acromyrmex would therefore explain the geographical distribution of nesting habits observed for this genus in the South American continent, i.e., subterranean in the northern tropical regions, and superficial in the southern temperate ones. In addition, results showed that Acromyrmex colonies from temperate regions indeed achieve thermoregulatory benefits through the determination of nest depth based on thermoregulatory needs. In sympatrically-occurring colonies of the grass-cutting ant A. heyeri, temperature inside superficial thatched nests was higher, and more suitable for colony growth, than that inside subterranean nests. This temperature surplus was even higher in spring, at the time of production of sexual brood, than in winter or summer. It was demonstrated that such temperature surplus was brought about by the low thermal diffusivity of the nest thatch, which prevents diurnal nest overheating by the incoming solar radiation, and avoids losses of the accumulated daily heat into the cold air during night, thus leading to high average nest temperatures. Although highly advantageous for colonies in terms of nest temperature, the determination of nest depth based on thermoregulatory needs may differentially affect nest ventilation and humidity depending on how nest exposition influences the exchange of nest air with the outside air. For instance, colonies with a superficial nesting habit might benefit from improved nest ventilation, but be at risk of desiccation due to their exposition and the consequent humidity losses into the dry outside air. Results demonstrated that in two Acromyrmex species, short-term regulatory building responses triggered and spatially organized by climatic variables occur, and may counteract undesired changes in internal nest humidity. Workers of the thatching grass-cutting ant A. heyeri, for instance, closed a number of nest-thatch openings as a response to desiccation of the outside air, even at a nest temperature that otherwise triggered the response of opening them so as to reduce nest temperature. In the leaf-cutting ant A. ambiguus, the direction of the airflow inside nest tunnels was shown to act as a cue for spatially guiding the building behaviour of plugging nest entrances. However, workers only responded if the humidity content of the circulating air was low, trading therefore nest ventilation for humidity maintenance.}, subject = {Verhaltens{\"o}kologie}, language = {en} } @phdthesis{Halboth2018, author = {Halboth, Florian}, title = {Building behavior and nest climate control in leaf-cutting ants: How environmental cues affect the building responses of workers of \(Atta\) \(vollenweideri\)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161701}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {The present work investigates the influence of environmental stimuli on the building behavior of workers of the leaf-cutting ant Atta vollenweideri. It focuses on cues related to the airflow-driven ventilation of their giant underground nests, i.e., air movements and their direction, carbon dioxide concentrations and humidity levels of the nest air. First, it is shown that workers are able to use airflow and its direction as learned orientation cue by performing learning experiments with individual foragers using a classical conditioning paradigm. This ability is expected to allow workers to also navigate inside the nest tunnels using the prevailing airflow directions for orientation, for example during tasks related to nest construction and climate control. Furthermore, the influence of carbon dioxide on the digging behavior of workers is investigated. While elevated CO2 levels hardly affect the digging rate of the ants, workers prefer to excavate at locations with lower concentrations and avoid higher CO2 levels when given a choice. Under natural conditions, shifting their digging activity to soil layers containing lower carbon dioxide levels might help colonies to excavate new or to broaden existing nest openings, if the CO2 concentration in the underground rises. It is also shown that workers preferably transport excavated soil along tunnels containing high CO2 concentrations, when carbon dioxide levels in the underground are elevated as well. In addition, workers prefer to carry soil pellets along outflow tunnels instead of inflow tunnels, at least for high humidity levels of the air. The material transported along tunnels providing outflow of CO2-rich air might be used by workers for the construction of ventilation turrets on top of the nest mound, which is expected to promote the wind-induced ventilation and the removal of carbon dioxide from the underground. The climatic conditions inside the nest tunnels also influence the structural features of the turrets constructed by workers on top the nest. While airflow and humidity have no effect on turret structure, outflow of CO2-rich air from the nest causes workers to construct turrets with additional openings and increased aperture, potentially enhancing the airflow-driven gas exchanges within the nest. Finally, the effect of airflow and ventilation turrets on the gas exchanges in Atta vollenweideri nests is tested experimentally on a physical model of a small nest consisting of a single chamber and two nest tunnels. The carbon dioxide clearance rate from the underground was measured depending on both the presence of airflow in the nest and the structural features of the built turrets. Carbon dioxide is removed faster from the physical nest model when air moves through the nest, confirming the contribution of wind-induced flow inside the nest tunnels to the ventilation of Atta vollenweideri nests. In addition, turrets placed on top of one of the tunnel openings of the nest further enhance the CO2 clearance rate and the effect is positively correlated with turret aperture. Taken together, climatic variables like airflow, carbon dioxide and humidity levels strongly affect the building responses of Atta vollenweideri leaf-cutting ants. Workers use these environmental stimuli as orientation cue in the nest during tasks related to excavation, soil transport and turret construction. Although the effects of these building responses on the microclimatic conditions inside the nest remain elusive so far, the described behaviors are expected to allow ant colonies to restore and maintain a proper nest climate in the underground.}, subject = {Verhalten}, language = {en} } @article{PaulPauliEhmannetal.2015, author = {Paul, Mila M. and Pauli, Martin and Ehmann, Nadine and Hallermann, Stefan and Sauer, Markus and Kittel, Robert J. and Heckmann, Manfred}, title = {Bruchpilot and Synaptotagmin collaborate to drive rapid glutamate release and active zone differentiation}, series = {Frontiers in Cellular Neuroscience}, volume = {9}, journal = {Frontiers in Cellular Neuroscience}, number = {29}, doi = {10.3389/fncel.2015.00029}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148988}, year = {2015}, abstract = {The active zone (AZ) protein Bruchpilot (Brp) is essential for rapid glutamate release at Drosophila melanogaster neuromuscular junctions (NMJs). Quantal time course and measurements of action potential-waveform suggest that presynaptic fusion mechanisms are altered in brp null mutants (brp\(^{69}\)). This could account for their increased evoked excitatory postsynaptic current (EPSC) delay and rise time (by about 1 ms). To test the mechanism of release protraction at brp\(^{69}\) AZs, we performed knock-down of Synaptotagmin-1 (Syt) via RNAi (syt\(^{KD}\)) in wildtype (wt), brp\(^{69}\) and rab3 null mutants (rab3\(^{rup}\)), where Brp is concentrated at a small number of AZs. At wt and rab3\(^{rup}\) synapses, syt\(^{KD}\) lowered EPSC amplitude while increasing rise time and delay, consistent with the role of Syt as a release sensor. In contrast, syt\(^{KD}\) did not alter EPSC amplitude at brp\(^{69}\) synapses, but shortened delay and rise time. In fact, following syt\(^{KD}\), these kinetic properties were strikingly similar in wt and brp\(^{69}\), which supports the notion that Syt protracts release at brp\(^{69}\) synapses. To gain insight into this surprising role of Syt at brp\(^{69}\) AZs, we analyzed the structural and functional differentiation of synaptic boutons at the NMJ. At tonic type Ib motor neurons, distal boutons contain more AZs, more Brp proteins per AZ and show elevated and accelerated glutamate release compared to proximal boutons. The functional differentiation between proximal and distal boutons is Brp-dependent and reduced after syt\(^{KD}\). Notably, syt\(^{KD}\) boutons are smaller, contain fewer Brp positive AZs and these are of similar number in proximal and distal boutons. In addition, super-resolution imaging via dSTORM revealed that syt\(^{KD}\) increases the number and alters the spatial distribution of Brp molecules at AZs, while the gradient of Brp proteins per AZ is diminished. In summary, these data demonstrate that normal structural and functional differentiation of Drosophila AZs requires concerted action of Brp and Syt.}, language = {en} } @inproceedings{Mahsberg1990, author = {Mahsberg, Dieter}, title = {Brood care and family cohesion in the tropical scorpion Pandinus imperator (Koch) (Scorpiones: Scorpionidae)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45776}, year = {1990}, abstract = {Pandinus imperator is a forest dweller of tropical West Africa. In the field, lobserved aggregations of up to 15 individuals. In the laboratory, mixed age groups of related and also unrelated animals lived jointly in terraria rarely showing within-group aggression or cannibalism. Brood-caring behavior of the mother influenced growth rate and survival probability of the young. With birth, mothers became very aggressive. To study family cohesion in Pandinus, experiments with family groups were conducted. Siblings aggregated around their mother. In choice experiments with two family groups, mothers were placed in enclosures that only the young were able to enter or to leave. Second instars significantly preferred the enclosure containing their own mother. Aggression among unrelated young of the same age was not observed. Feeding experiments studied the possible advantages of long-Iasting group living with regard to enhanced success in prey capture and its effect on growth of the young. Even groups of second instars were unable to subdue large prey on their own. Sibling groups with their mother removed suffered high mortality due to starvation and cannibalism compared to groups with mothers present. Here, young grew significantly faster: they shared the prey that only the mother was able to kill and dismember. Pandinus imperator has to be considered an intermediate subsocial scorpion.}, subject = {Skorpion}, language = {en} } @phdthesis{Muellner2004, author = {M{\"u}llner, Antje}, title = {Breeding ecology and related life-history traits of the hoatzin, Opisthocomus hoazin, in a primary rainforest habitat}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-13239}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2004}, abstract = {The hoatzin (Opisthocomus hoazin) is an enigmatic bird that lives in the riparian lowlands of northern South America. Among its peculiar attributes are 1) microbial foregut fermentation, unique in birds, to convert plant cellulose in the foliage which it consumes into simple sugars, 2) an ongoing debate about the puzzling taxonomic position, although a relationship to the Cuculiformes appears likely, 3) adaptive wing claws in the young which are used for climbing, and 4) co-operative breeding behaviour. Despite the information available on digestive mode and taxonomy little has been published on its breeding biology and behaviour and until now almost all knowledge was based on a study in the savannah of Venezuela. This is the first detailed study of the hoatzin's nesting ecology in a rainforest habitat. From 1995-1998 and in 2000 I monitored a hoatzin population which consisted of approximately 700 individuals in an Amazonian rainforest in Ecuador situated in the Cuyabeno Wildlife Reserve (between 0°02' N, 76°0' W, 0°03' S, and 76°14' W). The area is composed of various black water lagoons and small rivers, flooded forests and terra firme forest. Primarily, I examined group composition and breeding pattern and success related to traits such as clutch and egg size, offspring sex ratio and the number of parents involved in a common breeding attempt. Apart from standardised observations and monitoring I took blood samples from chicks, which were later used for molecular sexing and for DNA fingerprints. Food plants were collected and determined and a rough habitat mapping was conducted. Since the impacts of boat tourism in the area became apparent I investigated the interactions of adult and young hoatzins with tourists and measured the plasma concentration of the hormone corticosterone in chicks as an indicator of stress. Each chapter has its own introduction to the specific topic and can be read independently. The main findings of this study are: The reproduction of the hoatzin was timed strictly following the bimodal rainy pattern in the area. There was only one breeding attempt per year. Only 18\% of breeding attempts ended successfully with at least one fledgling. Incubation started with the first egg laid and led to hatching asynchrony. In most cases only the A-chick survived and there is evidence for a brood reduction strategy. I observed egg size variation patterns both within the clutches and between the clutches. Approximately 80\% of breeding attempts were carried out with auxiliaries. Units with alloparentals had a higher breeding success than single pairs. The results indicate a trade-off between helping and group size. DNA band-sharing comparisons revealed the existence of joint-nests, where several females laid their eggs in one single nest. The clutches of these joint-nests suffered severe egg loss during all stages of incubation. Breeding success did not differ between single- and joint-nests. The primary offspring sex ratio was biased towards daughters. There was no differential mortality between the sexes until fledging. Individual breeding units employed an adaptive production of offspring of each sex according to their current group size. Rainforest tourism negatively influenced the survival and growth of young, not yet fledged hoatzins. In addition tourist-exposed young showed a stronger hormonal stress response than their conspecifics from undisturbed sites. In contrast, breeding adults appear to have habituated to tourist boats and exposure to observers.}, subject = {Hoatzins}, language = {en} } @article{GoetzRaulfSchartl1992, author = {G{\"o}tz, Rudolf and Raulf, Friedrich and Schartl, Manfrad}, title = {Brain-derived neurotrophic factor is more highly conserved in structure and function than nerve growth factor during vertebrate evolution}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61703}, year = {1992}, abstract = {Mammalian nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are members of a protein family with perfectly conserved domains arranged around the cysteine residues thought to stabilize an invariant three-dimensional scaffold in addition to distinct sequence motifs that convey different neuronal functions. To study their structural and functional conservation during evolution, we have compared NGF and BDNF from a lower vertebrate, the teleost fi.sh Xiphophorus, with the mammalian homlogues. Genomic clones encoding fish NGF and BDNF were isolated by cross-hybridization using probes from the cloned mammalian factors. Fish NGF and BDNF were expressed by means of recombinant vaccinia viruses, purified, and their neuronal survival specificities for different classes of neurons were found to mirror those of the mammalian factors. The half-maximal survival concentration for chick sensory neurons was 60 pg/ml for both fish and mammalian purifi.ed recombinant BDNF. However, the activity ofrecombinant fish NGF on both chick sensory and sympathetic neurons was 6 ng,lml, 75-fold lower than that of mouse NGF. The different functional conservation of NGF and BDNF is also reflected in their structures. The DNA-deduced amino acid sequences of processed mature fish NGF and BDNF showed, compared to mouse, 63\% and 90\% identity, respectively, indicating that NGF bad reached an optimized structure later than BDNF. The retrograde extrapolation of these data indicates that NGF and BDNF evolved at strikingly different rates ftom a common ancestral gene about 600 million years ago. By RNA gel blot anaJysis NGF mRNA was detected during late embryonie development; BDNF was present in adult brain.}, subject = {Physiologische Chemie}, language = {en} } @article{MuellerKoehlerHendricksetal.2021, author = {M{\"u}ller, Sophie and K{\"o}hler, Franziska and Hendricks, Anne and Kastner, Carolin and B{\"o}rner, Kevin and Diers, Johannes and Lock, Johan F. and Petritsch, Bernhard and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Brain metastases from colorectal cancer: a systematic review of the literature and meta-analysis to establish a guideline for daily treatment}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {4}, issn = {2072-6694}, doi = {10.3390/cancers13040900}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228883}, year = {2021}, abstract = {Colorectal cancer (CRC) is the third most common malignancy worldwide. Most patients with metastatic CRC develop liver or lung metastases, while a minority suffer from brain metastases. There is little information available regarding the presentation, treatment, and overall survival of brain metastases (BM) from CRC. This systematic review and meta-analysis includes data collected from three major databases (PubMed, Cochrane, and Embase) based on the key words "brain", "metastas*", "tumor", "colorectal", "cancer", and "malignancy". In total, 1318 articles were identified in the search and 86 studies matched the inclusion criteria. The incidence of BM varied between 0.1\% and 11.5\%. Most patients developed metastases at other sites prior to developing BM. Lung metastases and KRAS mutations were described as risk factors for additional BM. Patients with BM suffered from various symptoms, but up to 96.8\% of BM patients were asymptomatic at the time of BM diagnosis. Median survival time ranged from 2 to 9.6 months, and overall survival (OS) increased up to 41.1 months in patients on a multimodal therapy regimen. Several factors including age, blood levels of carcinoembryonic antigen (CEA), multiple metastases sites, number of brain lesions, and presence of the KRAS mutation were predictors of OS. For BM diagnosis, MRI was considered to be state of the art. Treatment consisted of a combination of surgery, radiation, or systemic treatment.}, language = {en} } @article{GrimmHufnagelWobseretal.2018, author = {Grimm, Johannes and Hufnagel, Anita and Wobser, Marion and Borst, Andreas and Haferkamp, Sebastian and Houben, Roland and Meierjohann, Svenja}, title = {BRAF inhibition causes resilience of melanoma cell lines by inducing the secretion of FGF1}, series = {Oncogenesis}, volume = {7}, journal = {Oncogenesis}, number = {71}, doi = {10.1038/s41389-018-0082-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177261}, year = {2018}, abstract = {Approximately half of all melanoma patients harbour activating mutations in the serine/threonine kinase BRAF. This is the basis for one of the main treatment strategies for this tumor type, the targeted therapy with BRAF and MEK inhibitors. While the initial responsiveness to these drugs is high, resistance develops after several months, frequently at sites of the previously responding tumor. This indicates that tumor response is incomplete and that a certain tumor fraction survives even in drug-sensitive patients, e.g., in a therapy-induced senescence-like state. Here, we show in several melanoma cell lines that BRAF inhibition induces a secretome with stimulating effect on fibroblasts and naive melanoma cells. Several senescence-associated factors were found to be transcribed and secreted in response to BRAF or MEK inhibition, among them members of the fibroblast growth factor family. We identified the growth factor FGF1 as mediator of resilience towards BRAF inhibition, which limits the pro-apoptotic effects of the drug and activates fibroblasts to secrete HGF. FGF1 regulation was mediated by the PI3K pathway and by FRA1, a direct target gene of the MAPK pathway. When FGFR inhibitors were applied in parallel to BRAF inhibitors, resilience was broken, thus providing a rationale for combined therapeutical application.}, language = {en} }