Effectiveness of EGFR/HER2-targeted drugs is influenced by the downstream interaction shifts of PTPIP51 in HER2-amplified breast cancer cells

Breast cancer is the most common female cancerous disease and the second most cause of cancer death in women. About 20-30% of these tumors exhibit an amplification of the HER2/ErbB2 receptor, which is coupled to a more aggressive and invasive growth of the cancer cells. Recently developed tyrosine kinase inhibitors and therapeutic antibodies targeting the HER2 receptor improved the overall survival time compared with sole radio- and chemotherapy. Upcoming resistances against the HER2-targeted therapy make a better understanding of the receptor associated downstream pathways an absolute need. In earlier studies, we showed the involvement of Protein Tyrosine Phosphatase Interacting Protein 51 (PTPIP51) in the mitogen-activated protein kinase (MAPK) pathway. The MAPK pathway is one of the most frequently overactivated pathways in HER2-amplified breast cancer cells. This study is aimed to elucidate the effects of four different TKIs on the interactome of PTPIP51, namely with the receptors EGFR and HER2, 14-3-3/Raf1 (MAPK pathway), its regulating enzymes, and the mitochondria-associated interaction partners in HER2 breast cancer cell lines (SK-BR3 and BT474) by using the Duolink proximity ligation assay, immunoblotting and knockdown of PTPIP51. Inhibition of both EGFR and HER2/ErbB2R shifted PTPIP51 into the MAPK pathway, but left the mitochondria-associated interactome of PTPIP51 unattended. Exclusively inhibiting HER2/ErbB2 by Mubritinib did not affect the interaction of PTPIP51 with the MAPK signaling. Selective inhibition of HER2 induced great alterations of mitochondria-associated interactions of PTPIP51, which ultimately led to the most-effective reduction of cell viability of SK-BR3 cells of all tested TKIs. The results clearly reveal the importance of knowing the exact mechanisms of the inhibitors affecting receptor tyrosine kinases in order to develop more efficient anti-HER2-targeted therapies

Theory of hydrodynamic phenomena in optical mesh lattices

Signatures of superfluid-like behavior have recently been observed experimentally in a nonlinear optical mesh lattice, where the arrival time of optical pulses propagating in a pair of coupled optical fiber loops is interpreted as a synthetic spatial dimension. Here we develop a general theory of the fluid of light in such optical mesh lattices. On the one hand, this theory provides a solid framework for an analytical and numerical interpretation of the experimental observations. On the other hand, it anticipates new physical effects stemming from the specific spatiotemporally periodic geometry of our setup. Our work opens the way towards the full exploitation of optical mesh lattices system as a promising platform for studies of hydrodynamics phenomena in fluids of light in novel configurations

Der österreichische Biofachhandel: Eine Branchen- und SWOT-Analyse zur Ermittlung strategischer Optionen mit Hilfe qualitativer Experteninterviews

Der österreichische Biofachhandel konnte 2006 eine Umsatzsteigerung von 8 % verbuchen. Durch den Erfolg der Handelsmarken des LEH (es werden immerhin 64 % der Biolebensmittel im LEH – inkl. Hofer und Lidl - abgesetzt) und die boomenden Biosupermärkte sehen sich die Händler immer mehr bedroht. Die Interessensvertretung der Biofachhändler, welche in die BIO AUSTRIA integriert ist, erkannte, dass der Trend zu Bio zwar anhalten wird, ob die Fachhändler dem zunehmenden Konkurrenzdruck standhalten werden können und ob Unterstützung zur langfristigen Sicherung des Erfolgs nützlich sein kann, sollte durch eine qualitative Befragung von 13 Akteuren aus der Biohandelsbranche (kleine, klassische Biofachhändler, mittelgroße Biofachhändler, Biosupermärkte und ein Biogroßhändler) herausgefunden werden. Die Interviews wurden im Wesentlichen mit der Branchenanalyse nach Porter und der SWOT-Analyse ausgewertet. Um die Interviews besser zu strukturieren, wurden Begriffe aus den Bereichen Marketing und Betriebswirtschaft mittels Kärtchentechnik abgefragt. Die Ergebnisse können folgendermaßen in kurzer Form zusammengefasst werden: Die kleinen und mittelgroßen Biofachhändler sehen neben dem konventionellen LEH im Besonderen die Biosupermärkte als Konkurrenz. In der Branche wird es gerne gesehen, wenn sich jemand mit einem kleinen Biofachhandelsgeschäft selbstständig macht, den großen Biosupermärkten steht man aber mit Skepsis gegenüber. Die Zuverlässigkeit der Lieferanten lässt zu wünschen übrig und die Konsumenten werden nur von den Biosupermärkten mit Marketingmedien umworben. Wenn sich die Biofachhändler auf deren Stärken konzentrieren (u. a. Spezialisierung, Frischesortiment und Beratungskompetenz), die Schwächen minimieren und zudem noch die erwarteten Trends beachten, kann der Branche eine gute Zukunftsprognose ausgestellt werden

Physiological Responses of Contrasting Maize (Zea mays L.) Hybrids to Repeated Drought

Maize is the most important crop worldwide in terms of production and yield, but every year a considerable amount of yield is lost due to drought. The foreseen increase in the number of drought spells due to climate change raises the question whether the ability to recover quickly after a water pulse may be a relevant trait for overall drought resistance. We here address the following hypotheses: (i) different maize hybrids exhibit distinct physiological adaptive responses to drought stress and (ii) these responses affect the ability to recover from the stress. (iii) The relative biomass production of maize hybrids, which show severe drought symptoms but are able to recover quickly after a water pulse, is comparable to those hybrids, which invest more energy into tolerance mechanisms. The physiological responses of eight maize hybrids to repeated drought were elucidated employing physiological parameters such as electrolyte leakage, osmolality, relative water content, growth rate and gas-exchange measurements. Only one hybrid was able to maintain biomass production under drought conditions. Amongst the others, two hybrids with similar growth inhibition but contrasting physiological responses were identified by a PCA analysis. Both strategies, i.e. stabilization of leaf water content via resistance mechanisms versus high recovery potential were equally effective in maintaining aboveground biomass production in the scenario of a long drought intermitted by a water-pulse. However, each strategy might be advantageous under different drought stress scenarios. Overall, the recovery potential is underestimated in drought resistance under natural conditions, which includes periodic cycles of drought and rewatering, and should be considered in screening trials.Regional Research AllianceUniversität Hohenheim (3153)Peer Reviewe

Determination of soluble wheat protein fractions using the Bradford assay

Background and objectives Determination of different grain protein fractions in wheat cultivars is an important task in analyzing bread baking quality. In many laboratories, the Bradford assay is used to determine protein concentrations in solutions. In any protein assay (including Bradford), the ideal protein to use as a standard is the purified protein being assayed. In the absence of such an absolute reference, protein another protein must be selected as a relative standard such as bovine serum albumin (BSA) which is widely used. The aim of this work was to find conversion factors for BSA to determine correct albumin–globulin, gliadin, and glutenin concentrations, because these purified wheat grain protein fractions are mostly not available to be used for calibration purposes. Findings In case of BSA calibration, gluten concentration was underestimated (50%–54%) compared to calibration with the respective purified wheat proteins (65%–70%) in extracts of wheat grain samples. This result is explained with the different amino acid composition of BSA and wheat protein fractions leading to a more intense signal with BSA in the Bradford assay. Calibration of the Bradford assay using BSA as well as purified wheat protein fractions allowed to calculate the conversion factors of 2.11 for BSA/albumin–globulin, 4.25 for BSA/gliadin, and 3.42 for BSA/glutenin. Application of these conversion factors proved to accurately adjust protein concentrations of wheat fractions originating from ten cultivars, determined with BSA calibration of the Bradford assay. Conclusions BSA calibration of the Bradford assay in combination with the conversion factors can be used to determine protein concentration of wheat grain fractions. Significance and novelty Findings of this study make a contribution toward the correction of a common method, to provide a basis for better comparability of research results from different laboratories

Intrastriatal injection of interleukin-1 beta triggers the formation of neuromyelitis optica-like lesions in NMO-IgG seropositive rats

BACKGROUND: Neuromyelitis optica (NMO) is a severe, disabling disease of the central nervous system (CNS) characterized by the formation of astrocyte-destructive, neutrophil-dominated inflammatory lesions in the spinal cord and optic nerves. These lesions are initiated by the binding of pathogenic aquaporin 4 (AQP4)-specific autoantibodies to astrocytes and subsequent complement-mediated lysis of these cells. Typically, these lesions form in a setting of CNS inflammation, where the blood–brain barrier is open for the entry of antibodies and complement. However, it remained unclear to which extent pro-inflammatory cytokines and chemokines contribute to the formation of NMO lesions. To specifically address this question, we injected the cytokines interleukin-1 beta, tumor necrosis factor alpha, interleukin-6, interferon gamma and the chemokine CXCL2 into the striatum of NMO-IgG seropositive rats and analyzed the tissue 24 hours later by immunohistochemistry. RESULTS: All injected cytokines and chemokines led to profound leakage of immunoglobulins into the injected hemisphere, but only interleukin-1 beta induced the formation of perivascular, neutrophil-infiltrated lesions with AQP4 loss and complement-mediated astrocyte destruction distant from the needle tract. Treatment of rat brain endothelial cells with interleukin-1 beta, but not with any other cytokine or chemokine applied at the same concentration and over the same period of time, caused profound upregulation of granulocyte-recruiting and supporting molecules. Injection of interleukin-1 beta caused higher numbers of blood vessels with perivascular, cellular C1q reactivity than any other cytokine tested. Finally, the screening of a large sample of CNS lesions from NMO and multiple sclerosis patients revealed large numbers of interleukin-1 beta-reactive macrophages/activated microglial cells in active NMO lesions but not in MS lesions with comparable lesion activity and location. CONCLUSIONS: Our data strongly suggest that interleukin-1 beta released in NMO lesions and interleukin-1 beta-induced production/accumulation of complement factors (like C1q) facilitate neutrophil entry and BBB breakdown in the vicinity of NMO lesions, and might thus be an important secondary factor for lesion formation, possibly by paving the ground for rapid lesion growth and amplified immune cell recruitment to this site

A Protein-Linger Strategy Keeps the Plant On-Hold After Rehydration of Drought-Stressed Beta vulgaris

Most crop plants are exposed to intermittent drought periods. To cope with these continuous changes, plants need strategies to prevent themselves from exhaustive adjustment maneuvers. Drought stress recovery has been shown to be an active process, possibly involved in a drought memory effect allowing plants to better cope with recurrent aridity. An integrated understanding of the molecular processes of enhanced drought tolerance is required to tailor key networks for improved crop protection. During summer, prolonged periods of drought are the major reason for economic yield losses of sugar beet (Beta vulgaris) in Europe. A drought stress and recovery time course experiment was carried out under controlled environmental conditions. In order to find regulatory key mechanisms enabling plants to rapidly react to periodic stress events, beets were either subjected to 11 days of progressive drought, or were drought stressed for 9 days followed by gradual rewatering for 14 days. Based on physiological measurements of leaf water relations and changes in different stress indicators, plants experienced a switch from moderate to severe water stress between day 9 and 11 of drought. The leaf proteome was analyzed, revealing induced protein pre-adjustment (prior to severe stress) and putative stress endurance processes. Three key protein targets, regulatory relevant during drought stress and with lingering levels of abundance upon rewatering were further exploited through their transcript performance. These three targets consist of a jasmonate induced, a salt-stress enhanced and a phosphatidylethanolamine-binding protein. The data demonstrate delayed protein responses to stress compared to their transcripts and indicate that the lingering mechanism is post-transcriptionally regulated. A set of lingering proteins is discussed with respect to a possible involvement in drought stress acclimation and memory effects