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The successful, area-wide application of the mating disruption (MD) technique, an insect sex pheromone-based biotechnological pest control method, against the European grapevine moth Lobesia botrana and the European grape berry moth Eupoecilia ambiguella, has led to drastic reductions in insecticide application in vineyards. However, since insect pheromone perception and emission can be affected by abiotic conditions, the future success of MD may be affected by climate change. At the same time, politics and society are calling for drastic and sustainable reductions in pesticide application, making highly specific, efficient, and environmentally friendly pest control techniques like MD more important than ever. To anticipate whether climate change factors will interfere with the MD of L. botrana and E. ambiguella in vineyards, we conducted field experiments in the Geisenheim VineyardFACE (Free-Air Carbon dioxide Enrichment) facility. The insects were raised at ambient or elevated temperatures in the lab and male moths were released in cages installed in the VineyardFACE facility. Trap recapture rates obtained by pheromone lures or female moths under elevated or ambient CO2 in areas with and without MD were evaluated. Our results did not indicate a reduced efficacy ofL. botrana or E. ambiguella MD at elevated CO2 concentrations, irrespective of the temperature the moths were raised under. From a practical point of view—and especially from an ecological one—our results are good news. They indicate that MD will not be negatively affected by future elevated CO2 concentrations.

The impact of climate change drivers on cultivated plants and pest insects has come into research focus. One of the most significant drivers is atmospheric carbon dioxide, which is converted into primary plant metabolites by photosynthesis. Increased atmospheric CO2 concentrations therefore affect plant chemistry. The chemical composition of non-volatile and volatile organic compounds of plants is used by insects to locate and identify suitable host plants for feeding and reproduction. We investigated whether elevated CO2 concentrations in the atmosphere affect the plant-pest interaction in a fruit crop of high economic importance in Europe. Therefore, potted pear trees were cultivated under specified CO2 conditions in a Free-Air Carbon dioxide Enrichment (FACE) facility at Geisenheim University in Germany for up to 14 weeks, beginning from bud swelling. We compared emitted volatiles from these pear trees cultivated for 7 and 14 weeks under two different CO2 levels (ambient: ca. 400 ppm and elevated: ca. 450 ppm CO2) and their impact on pest insect behavior. In total, we detected and analyzed 76 VOCs from pear trees. While we did not detect an overall change in VOC compositions, the relative release of single compounds changed in response to CO2 increase. Differences in VOC release were inconsistent over time (phenology stages) and between study years, indicating interactions with other climate parameters, such as temperature. Even though insect-plant interaction can rely on specific volatile compounds and specific mixtures of compounds, respectively, the changes of VOC patterns in our field study did not impact the host choice behavior of C. pyri females. In olfactometer trials, 64% and 60% of the females preferred the odor of pear trees cultivated under elevated CO2 for 7 and 14 weeks, respectively, over the odor from pear trees cultivated under ambient CO2. In binary-choice oviposition assays, C. pyri females laid most eggs on pears during April 2020; on average, 51.9 (± 51.3) eggs were laid on pears cultivated under eCO2 and 60.3 (± 48.7) eggs on aCO2.

Climate change can affect biological pest control by altering trophic interactions. Elevated carbon dioxide (CO2) concentrations can reduce host plant quality and, in turn, alter herbivore and natural enemy preference and performance. Using the Geisenheim VineyardFACE (free-air carbon dioxide enrichment) facility, we studied plant- and herbivore-mediated bottom-up effects of elevated CO2 concentration on the European grapevine moth, Lobesia botrana, and the parasitoid Trichogramma cacoeciae. Grapevine inflorescences of two cultivars cultivated at ambient or elevated CO2 (aCO2 and eCO2: 400 and 480 ppm) in the VineyardFACE were incorporated into L. botrana artificial diet. Eggs laid by the respective adults were parasitized by T. cacoeciae. Egg size and emergence rate of L. botrana as well as parasitism rate, parasitoid emergence rate and egg size preference of T. cacoeciae were evaluated. We observed an indirect grapevine cultivar-dependent bottom-up effect of CO2 on both herbivore and egg parasitoid. Compared to aCO2, eCO2 resulted in larger host eggs and higher parasitism rates regarding Riesling-feeding but not regarding Cabernet Sauvignon-feeding L. botrana larvae. Parasitoid emergence rate was higher when L. botrana had fed on Riesling compared to Cabernet Sauvignon-diet. Egg size preference depended on the host’s diet: T. cacoeciae preferred larger L. botrana eggs when the larvae had fed on grapevine-containing diet but not when they fed on standard artificial diet. Our results highlight the importance of the host’s diet for the parasitoid’s preference and performance. They furthermore suggest that the future efficiency of L. botrana-biocontrol by T. cacoeciae will not decrease under elevated CO2 concentrations.

Background Although chronic hand eczema (CHE) is a highly prevalent and disabling skin disease, it is currently unknown if CHE is associated with systemic inflammation. Objectives To characterize the plasma inflammatory signature of CHE. Methods Using Proximity Extension Assay technology, we assessed 266 inflammatory and cardiovascular disease risk proteins in the plasma of 40 healthy controls, 57 patients with atopic dermatitis (AD) with active lesions, 11 with CHE and a history of AD (CHEPREVIOUS_AD), and 40 with CHE and no history of AD (CHENO_AD). Filaggrin gene mutation status was also assessed. Protein expression was compared between groups and according to disease severity. Correlation analyses for biomarkers, and clinical- and self-reported variables, were performed. Results Very severe CHENO_AD was associated with systemic inflammation when compared with controls. Levels of T helper (Th)2- and Th1-, general inflammation and eosinophil activation markers increased with severity of CHENO_AD, primarily being significantly increased in very severe disease. Significant, positive correlations were found between markers from these pathways and severity of CHENO_AD. Moderate-to-severe but not mild AD displayed systemic inflammation. The Th2 markers C-C motif chemokine (CCL)17 and CCL13 (also known as monocyte chemotactic protein 4) were the top differentially expressed proteins in both very severe CHENO_AD and moderate-to-severe AD, showing a higher fold change and significance in AD. CCL17 and CCL13 levels further correlated positively with disease severity in both CHENO_AD and AD. Conclusions Systemic Th2-driven inflammation is shared between very severe CHE with no history of AD, and moderate-to-severe AD, suggesting that Th2 cell targeting could be effective in several CHE subtypes.

Im Fremdsprachenunterricht ist es gang und gäbe, dass Lehrende und Lernende persönliche Erlebnisse und Erfahrungen narrativieren, zum Beispiel, wenn sie über das letzte Wochenende, Traditionen des Herkunftslandes oder ihre Familie erzählen. Bislang wurde jedoch nur in Ansätzen untersucht, was und wie Lernende Erfahrungen in Interaktionen mit anderen Lernenden oder den Lehrenden teilen. Ausgehend von empirischen Daten aus einem telekollaborativen Austausch zwischen Fremdsprachenlernenden in Deutschland und Schweden werden in diesem Beitrag Fragen beantwortet, die zum einen den konkreten Bezug zur Unterrichtspraxis haben, zum anderen aber auch das Potenzial des Erzählens für kulturbezogenes Lernen ausleuchten.

PurposeThe purpose of this paper is to identify which plant protection practices consumers prefer and why. The authors focused on beneficial insects, genetically modified (GM) plants, synthetic chemical pesticides, biological plant protection, mechanical-physical plant protection as well as biotechnical plant protection. The authors studied the effects of the risk perception and both subjective and objective knowledge on preference.Design/methodology/approachThe authors collected cross-sectional data from n = 1,223 people living in Germany. For this, the authors used an online panel and quoted participation after age, gender, income and region. The authors used multiple regression analyses and also explored moderation effects of knowledge on risk perception to explain participants' preferences.FindingsThe most preferred plant protection practice in the study sample was the application of beneficial insects. The authors found evidence that risk perception, as well as objective and subjective knowledge, can have a pivotal direct effect on preferences. Additionally, subjective as well as objective knowledge typically moderated the effect of risk perception, depending on the plant protection practice in focus. Overall, the authors found that levels of subjective and objective knowledge of plant protection practices were rather low among German participants.Originality/valueWhile studies on consumer preferences for GM or organic food are abundant, preferences regarding other types of common plant protection practices are hardly investigated. To tackle this research gap, the authors focused on six different and common plant protection practices and compare results.

Zusammenfassung Hintergrund Übergewicht und Adipositas bestimmen zunehmend unseren Alltag. In Deutschland ist mehr als jeder Zweite übergewichtig, fast jeder Vierte adipös. Normalgewicht weist weniger als die Hälfte der Bevölkerung auf. Adipositas nimmt insbesondere in den jungen Altersklassen zu, sodass immer mehr eine adipöse Gesellschaft heranwächst. Dies stellt unsere Gesellschaft, den Arbeitsmarkt sowie das Gesundheits- und Sozialsystem vor neue Herausforderungen. Um diesen Entwicklungen nachhaltig begegnen zu können, sind alltagstaugliche Maßnahmen notwendig. Material und Methodik 5-Jahres-Ergebnisse einer multizentrischen Erhebung von 135 adipösen Teilnehmern (46 Männer [34,1 %], 89 Frauen [65,9 %]) an einem 12-wöchigen, ambulanten, ärztlich betreuten Adipositastherapieprogramm. Anschließend besteht die Möglichkeit zur Teilnahme an einer Langzeitbetreuung. Die Kombination von Ernährungsumstellung, Verhaltensänderung und Steigerung der Bewegungsaktivität bilden die Programmschwerpunkte. Vorgestellt werden die Veränderungen von Körpergewicht, BMI und Körperzusammensetzung. Ergebnisse Alle Gruppen (Gesamtgruppe, Männer, Frauen) erzielten eine kontinuierliche Gewichtsabnahme über mindestens 6 Monate – und damit über den 12-wöchigen Kursverlauf hinaus. Trotz Wiederzunahmen befand sich das mittlere Körpergewicht zu jedem Messzeitpunkt in allen Gruppen unter den Ausgangswerten. Nach 5 Jahren bestand in der Gesamtgruppe noch ein mittlerer Gewichtsverlust von 3,8 kg/3,6 % (P Schlussfolgerung Das vorgestellte, ambulante, ärztlich betreute Adipositastherapieprogramm bietet auch über 5 Jahre – und damit deutlich über den regulären Kurszeitraum hinaus – die Möglichkeit für eine deutliche Gewichtsabnahme, die überwiegend über Körperfett erfolgt.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal disorder. Two FDA approved anti-fibrotic drugs, nintedanib and pirfenidone, slow the rate of decline in lung function, but responses are variable and side effects are common. Using an in-silico data-driven approach, we identified a robust connection between the transcriptomic perturbations in IPF disease and those induced by saracatinib, a selective Src kinase inhibitor, originally developed for oncological indications. Based on these observations, we hypothesized that saracatinib would be effective at attenuating pulmonary fibrosis. We investigated the anti-fibrotic efficacy of saracatinib relative to nintedanib and pirfenidone in three preclinical models: (i) in vitro in normal human lung fibroblasts (NHLFs); (ii) in vivo in bleomycin and recombinant adenovirus transforming growth factor-beta (Ad-TGF-β) murine models of pulmonary fibrosis; and (iii) ex vivo in precision cut lung slices from these mouse models. In each model, the effectiveness of saracatinib in blocking fibrogenic responses was equal or superior to nintedanib and pirfenidone.

Psoriasis is linked with increased risk of cardiovascular disease (CVD) that is underestimated by traditional risk stratification. We conducted a large-scale plasma proteomic analysis by use of a proximity extension assay in 85 patients with a history of moderate-to-severe psoriasis with or without established atherosclerotic CVD. Differentially expressed proteins associated with CVD were correlated with subclinical atherosclerotic markers including vascular inflammation determined by 18F-fluorodeoxyglucose positron emission tomography/computed tomography, carotid intima-media thickness (CIMT), carotid artery plaques, and coronary artery calcium score (CCS) in the patients without CVD and statin treatment. We also examined the association between the neutrophil-to-lymphocyte ratio (NLR) and subclinical atherosclerosis. In unadjusted analyses, growth differentiation factor-15 (GDF-15) levels and NLR were increased, while tumor necrosis factor (TNF)-related activation-inducing ligand (TRANCE) and TNF-related apoptosis-induced ligand (TRAIL) levels were decreased in patients with established CVD compared to those without CVD. Among patients with psoriasis without CVD and statin treatment, GDF-15 levels were negatively associated with vascular inflammation in the ascending aorta and entire aorta, and positively associated with CIMT and CCS. NLR was positively associated with vascular inflammation in the carotid arteries. Our data suggest that circulating GDF-15 levels and NLR might serve as biomarkers of subclinical atherosclerosis in patients with psoriasis.

Non-alcoholic steatohepatitis (NASH) is a rising health challenge, with no approved drugs. We used a computational drug repositioning strategy to uncover a novel therapy for NASH, identifying a GABA-B receptor agonist, AZD3355 (Lesogaberan) previously evaluated as a therapy for esophageal reflux. AZD3355’s potential efficacy in NASH was tested in human stellate cells, human precision cut liver slices (hPCLS), and in vivo in a well-validated murine model of NASH. In human stellate cells AZD3355 significantly downregulated profibrotic gene and protein expression. Transcriptomic analysis of these responses identified key regulatory nodes impacted by AZD3355, including Myc, as well as MAP and ERK kinases. In PCLS, AZD3355 down-regulated collagen1α1, αSMA and TNF-α mRNAs as well as secreted collagen1α1. In vivo, the drug significantly improved histology, profibrogenic gene expression, and tumor development, which was comparable to activity of obeticholic acid in a robust mouse model of NASH, but awaits further testing to determine its relative efficacy in patients. These data identify a well-tolerated clinical stage asset as a novel candidate therapy for human NASH through its hepatoprotective, anti-inflammatory and antifibrotic mechanisms of action. The approach validates computational methods to identify novel therapies in NASH in uncovering new pathways of disease development that can be rapidly translated into clinical trials.

Any academic working on a contemporary topic fears significant developments coming along shortly after publishing a book. Michael Serazio was braced for this possibility, as he expressed in an earl...

The tetraspanin CD82 is a potent suppressor of tumor metastasis and regulates several processes including signal transduction, cell adhesion, motility, and aggregation. However, the mechanisms by which CD82 participates in innate immunity are unknown. We report that CD82 is a key regulator of TLR9 trafficking and signaling. TLR9 recognizes unmethylated cytosine-phosphate-guanine (CpG) motifs present in viral, bacterial, and fungal DNA. We demonstrate that TLR9 and CD82 associate in macrophages, which occurs in the endoplasmic reticulum (ER) and post-ER. Moreover, CD82 is essential for TLR9-dependent myddosome formation in response to CpG stimulation. Finally, CD82 modulates TLR9-dependent NF-��B nuclear translocation, which is critical for inflammatory cytokine production. To our knowledge, this is the first time a tetraspanin has been implicated as a key regulator of TLR signaling. Collectively, our study demonstrates that CD82 is a specific regulator of TLR9 signaling, which may be critical in cancer immunotherapy approaches and coordinating the innate immune response to pathogens.-Khan, N. S., Lukason, D. P., Feliu, M., Ward, R. A., Lord, A. K., Reedy, J. L., Ramirez-Ortiz, Z. G., Tam, J. M., Kasperkovitz, P. V., Negoro, P. E., Vyas, T. D., Xu, S., Brinkmann, M. M., Acharaya, M., Artavanis-Tsakonas, K., Frickel, E.-M., Becker, C. E., Dagher, Z., Kim, Y.-M., Latz, E., Ploegh, H. L., Mansour, M. K., Miranti, C. K., Levitz, S. M., Vyas, J. M. CD82 controls CpG-dependent TLR9 signaling.

Background. Current lipid-lowering drugs often leave significant residual risk for adverse outcomes. Identification of previously approved drugs for new indications, drug repurposing, may provide a cost effective alternative to de novo drug developing.Objectives. We combined clinical, transcriptomic, computational, and experimental strategies to explore lipid-lowering and plaque-stabilizing effects of atypical antidepressant trazodone.Methods. First, a connectivity mapping strategy was used to match rosuvastatin gene expression signature derived from a clinical trial of 85 patients with to the expression patterns of 1,309 different small molecules to discover a similarity between the rosuvastatin and trazodone gene expression signatures. Then, we assessed the lipid-lowering ability of trazodone in vitro using HepG2 cells and in vivo using molecular imaging of rabbit atherosclerotic lesions. In addition, we analyzed electronic medical records of patients from three large medical centers who had a prescription for trazodone and lipid laboratory measurements available.Results. Trazodone significantly reduced cholesterol levels in the HepG2 human hepatocyte model, decreased atherosclerotic plaque burden in a rabbit model and lowered low-density lipoprotein (LDL) cholesterol levels in patients.Conclusion. Our results indicate that trazodone may be a promising candidate for adjunctive lipid lowering therapy. It may provide significant benefits to patients with hyperlipidemia, including lipid level reduction and formation of a more favorable atherosclerotic plaque morphology. Patients diagnosed with major depressive disorder requiring better lipid control would benefit the most from the for adjunctive lipid lowering therapy.

Non-alcoholic steatohepatitis (NASH) is a rising health challenge, with no approved drugs. We used a computational drug repositioning strategy to uncover a novel therapy for NASH, identifying a GABA-B receptor agonist, AZD3355 (lesogaberan) previously evaluated as a therapy for esophageal reflux. AZD3355’s potential efficacy in NASH was tested in human stellate cells, human precision cut liver slices (hPCLS), and in vivo in a well-validated murine model of NASH. In human stellate cells AZD3355 significantly downregulated profibrotic gene and protein expression. Transcriptomic analysis of these responses identified key regulatory nodes impacted by AZD3355, including Myc, as well as MAP and ERK kinases. In PCLS, AZD3355 down-regulated collagen1α1, aSMA and TNF-a mRNA as well as secreted collagen1a1. In vivo, the drug significantly improved histology, profibrogenic gene expression, and tumor development in a robust murine model of NASH, which was comparable to activity of obeticholic acid, an advanced investigational therapy for this disease. These data identify a well-tolerated clinical stage asset as a novel therapy for human NASH through its hepatoprotective, anti-inflammatory and antifibrotic mechanisms of action. The approach validates computational methods to identify novel therapies in NASH in uncovering new pathways of disease development that can be rapidly translated into clinical trials.

BACKGROUND Patients with psoriasis have increased risk of cardiovascular disease (CVD) independent of traditional risk factors. The molecular mechanisms underlying the psoriasis-CVD connection are not fully understood. Advances in high-throughput molecular profiling technologies and computational analysis techniques offer new opportunities to improve the understanding of disease connections. OBJECTIVE We aim to characterize the complexity of cardiovascular risk in patients with psoriasis by integrating deep phenotypic data with systems biology techniques to perform comprehensive multiomic analyses and construct network models of the two interacting diseases. METHODS The study aims to include 120 adult patients with psoriasis (60 with prior atherosclerotic CVD and 60 without CVD). Half of the patients are already receiving systemic antipsoriatic treatment. All patients complete a questionnaire, and a medical interview is conducted to collect medical history and information on, for example, socioeconomics, mental health, diet, and physical exercise. Participants are examined clinically with assessment of the Psoriasis Area and Severity Index and undergo imaging by transthoracic echocardiography, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT), and carotid artery ultrasonography. Skin swabs are collected for analysis of microbiome metagenomics; skin biopsies and blood samples are collected for transcriptomic profiling by RNA sequencing; skin biopsies are collected for immunohistochemistry; plasma samples are collected for analyses of proteomics, lipidomics, and metabolomics; blood samples are collected for high-dimensional mass cytometry; and feces samples are collected for gut microbiome metagenomics. Bioinformatics and systems biology techniques are utilized to analyze the multiomic data and to integrate data into a network model of CVD in patients with psoriasis. RESULTS Recruitment was completed in September 2020. Preliminary results of 18F-FDG-PET/CT data have recently been published, where vascular inflammation was reduced in the ascending aorta (P=.046) and aortic arch (P=.04) in patients treated with statins and was positively associated with inflammation in the visceral adipose tissue (PP=.007), pericardial adipose tissue (PP=.001), and bone marrow (P CONCLUSIONS This systems biology approach with integration of multiomics and clinical data in patients with psoriasis with or without CVD is likely to provide novel insights into the biological mechanisms underlying these diseases and their interplay that can impact future treatment. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/28669

Background Patients with psoriasis have increased risk of cardiovascular disease (CVD) independent of traditional risk factors. The molecular mechanisms underlying the psoriasis-CVD connection are not fully understood. Advances in high-throughput molecular profiling technologies and computational analysis techniques offer new opportunities to improve the understanding of disease connections. Objective We aim to characterize the complexity of cardiovascular risk in patients with psoriasis by integrating deep phenotypic data with systems biology techniques to perform comprehensive multiomic analyses and construct network models of the two interacting diseases. Methods The study aims to include 120 adult patients with psoriasis (60 with prior atherosclerotic CVD and 60 without CVD). Half of the patients are already receiving systemic antipsoriatic treatment. All patients complete a questionnaire, and a medical interview is conducted to collect medical history and information on, for example, socioeconomics, mental health, diet, and physical exercise. Participants are examined clinically with assessment of the Psoriasis Area and Severity Index and undergo imaging by transthoracic echocardiography, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT), and carotid artery ultrasonography. Skin swabs are collected for analysis of microbiome metagenomics; skin biopsies and blood samples are collected for transcriptomic profiling by RNA sequencing; skin biopsies are collected for immunohistochemistry; plasma samples are collected for analyses of proteomics, lipidomics, and metabolomics; blood samples are collected for high-dimensional mass cytometry; and feces samples are collected for gut microbiome metagenomics. Bioinformatics and systems biology techniques are utilized to analyze the multiomic data and to integrate data into a network model of CVD in patients with psoriasis. Results Recruitment was completed in September 2020. Preliminary results of 18F-FDG-PET/CT data have recently been published, where vascular inflammation was reduced in the ascending aorta (P=.046) and aortic arch (P=.04) in patients treated with statins and was positively associated with inflammation in the visceral adipose tissue (P Conclusions This systems biology approach with integration of multiomics and clinical data in patients with psoriasis with or without CVD is likely to provide novel insights into the biological mechanisms underlying these diseases and their interplay that can impact future treatment. International Registered Report Identifier (IRRID) DERR1-10.2196/28669

Psoriasis is associated with atherosclerotic cardiovascular disease (CVD) with significant overlap of inflammatory pathways. A link between vascular inflammation and inflammation in multiple adipose tissue types, spleen, and bone marrow may exist. Therefore, we investigated these associations using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in patients with psoriasis (n = 83) where half had established CVD. Carotid ultrasound imaging was also performed. Inflammation was measured by FDG uptake in the aorta, visceral- (VAT), subcutaneous- (SAT), and pericardial (PAT) adipose tissues, and spleen and bone marrow, respectively. Vascular inflammation was associated with FDG uptakes in all adipose tissues, including VAT (β = 0.26; p < 0.001), SAT (β = 0.28; p < 0.001), PAT (β = 0.24; p < 0.001), spleen (β = 1.35; p = 0.001), and bone marrow (β = 1.14; p < 0.001). Adjustments for age, sex, body mass index, and high sensitivity C-reactive protein did not change the results. These associations were generally preserved in the patients without prior CVD. No associations were observed between vascular inflammation and carotid intima-media thickness or presence of carotid plaques, respectively. The results suggest an inflammatory link between vascular and adipose tissues, spleen, and bone marrow in patients with psoriasis.

Background Mapping disease-associated genetic variants to complex disease pathophysiology is a major challenge in translating findings from genome-wide association studies into novel therapeutic opportunities. The difficulty lies in our limited understanding of how phenotypic traits arise from non-coding genetic variants in highly organized biological systems with heterogeneous gene expression across cells and tissues. Results We present a novel strategy, called GWAS component analysis, for transferring disease associations from single-nucleotide polymorphisms to co-expression modules by stacking models trained using reference genome and tissue-specific gene expression data. Application of this method to genome-wide association studies of blood cell counts confirmed that it could detect gene sets enriched in expected cell types. In addition, coupling of our method with Bayesian networks enables GWAS components to be used to discover drug targets. Conclusions We tested genome-wide associations of four disease phenotypes, including age-related macular degeneration, Crohn’s disease, ulcerative colitis and rheumatoid arthritis, and demonstrated the proposed method could select more functional genes than S-PrediXcan, the previous single-step model for predicting gene-level associations from SNP-level associations.

Psoriasis is a chronic inflammatory condition associated with atherosclerotic cardiovascular disease (CVD). Systemic anti-psoriatic treatments mainly include methotrexate and biological therapies targeting TNF, IL-12/23 and IL-17A. We profiled plasma proteins from patients with moderate-to-severe psoriasis to explore potential biomarkers of effective systemic treatment and their relationship to CVD. We found that systemically well-treated patients (PASI < 3.0, n = 36) had lower circulating levels of IL-17 pathway proteins compared to untreated patients (PASI > 10, n = 23). Notably, IL-17C and PI3 were decreased with all four examined systemic treatment types. Furthermore, in patients without CVD, we observed strong correlations among IL-17C/PI3/PASI (r ≥ 0.82, p ≤ 1.5 × 10−12) pairs or between IL-17A/PASI (r = 0.72, p = 9.3 × 10−8). In patients with CVD, the IL-17A/PASI correlation was abolished (r = 0.2, p = 0.24) and the other correlations were decreased, e.g., IL-17C/PI3 (r = 0.61, p = 4.5 × 10−5). Patients with moderate-to-severe psoriasis and CVD had lower levels of IL-17A compared to those without CVD (normalized protein expression [NPX] 2.02 vs. 2.55, p = 0.013), and lower IL-17A levels (NPX < 2.3) were associated with higher incidence of CVD (OR = 24.5, p = 0.0028, 95% CI 2.1–1425.1). As a result, in patients with moderate-to-severe psoriasis, we propose circulating IL-17C and PI3 as potential biomarkers of effective systemic anti-psoriatic treatment, and IL-17A as potential marker of CVD.

International audience; Nitrogen (N) and water are crucial in crop production but increasingly scarce environmental resources. Reducing their inputs can affect the whole plant-arthropod community including biocontrol agents. In a multitrophic sys-tem, we studied the interaction of the bottom-up effects of moderately reduced N concentration and/or water supply as well as the top-down effects of pests of different feeding guilds on plant nutritional quality (N and car-bon concentration), direct defense (alkaloids and phenolics), and indirect defense (plant volatile organic com-pounds); on herbivore performance and host quality (N and carbon) to parasitoids and the latter's performance. Studied organisms were tomato plants, the sap feeders Macrosiphum euphorbiae and Bemisia tabaci, the leaf chewers Tuta absoluta and Spodoptera littoralis, and the parasitic wasps Aphelinus abdominalis and Necremnus tutae. Resource limitation affected plant quality, triggering bottom-up effects on herbivore and para-sitoid performance, except for T. absoluta and N. tutae. Feeding guild had a major influence: bottom-up effects were stronger on sap feeders; N effects were stronger on sap feeders while water effects were stronger with leaf chewers (S. littoralis). Top-down effects of leaf chewer herbivory partly attenuated bottom-up effects and partly suppressed plant defenses. Bottom-up effects weakened when cascading up trophic levels. In summary, the interaction between plants, pests, and beneficial insects was modulated by abiotic factors, affecting insect performance. Simultaneous abiotic and biotic impact shaped plant biochemistry depending on the feeding guild: the biotic top-down effect of leaf chewer herbivory attenuated the bottom-up effects of plant nutrition and hence dominated the plant biochemical profile whereas in sap feeder infested leaves, it corresponded to the abiotic impact. This study highlights the plant's finely tuned regulatory system facilitating response prioritization. It offers perspectives on how smart manipulation of plant nutrient solutions might save resources while maintaining efficient biocontrol in crop production.

The effect of suboptimal supply of nitrogen (N) and of replacing nitrate in the nutrient solution with ammonia on growth, yield, and nitrate concentration in green and red leaf lettuce was evaluated over two seasons (autumn and spring) using multiple regression analysis. The plants were grown in a greenhouse on a Nutrient Film Technique (NFT) system. Nitrogen concentrations in the nutrient solution were either 3 mM or 12 mM, and the form of N was varied as follows: 100% NO3, 50% NO3 + 50% NH4, and 100% NH4. In both seasons, the biomass (fresh weight) of lettuce heads increased with increasing NO3 concentrations and in autumn, NO3 even at 1.5 mM was sufficient for high yield. However, head dry weight was affected neither by the season nor by changes in the composition of the nutrient solution. The concentration of NO3 had no effect on root dry weight, but it decreased at higher concentrations of NH4. The number of leaves increased as the ratio of NO3 to NH4 in the nutrient solution increased and was higher in autumn because of the longer growth period. Increasing the concentration of NO3 in nutrient solution increased both total N and nitrate concentration in lettuce heads (dry weight) but decreased the concentration of total C. Also, leaf nitrate concentration was lower in spring than in autumn and decreased with increasing NH4 concentration. Nitrogen utilization efficiency was maximum when NH4 levels in the nutrient solution were either 0% or 50% irrespective of the season. Our results thus show that suboptimal N supply in autumn will not affect lettuce yield, and that nitrate concentration in leaves is lower when NH4 concentrations in nutrient solution are higher and also much lower in red lettuce than in green lettuce.

DeutschIm Bereich der Kulturdidaktik findet seit einigen wenigen Jahren eine Auseinandersetzung mit dem Potenzial von Linguistic Landscapes fur den Fremdsprachenunterricht statt. Der Beitrag diskutiert, ausgehend von empirischen Daten aus dem universitaren DaF-Unterricht in Finnland und Schweden, die Deutung von nichtautorisierten Linguistic Landscapes durch die Studierenden, Rezeptionsmechanismen in der Auseinandersetzung und im Anschluss an einschlagige theoretische Arbeiten das Lehr- und Lernpotenzial in spezifischen Unterrichtskontexten. EnglishIn recent years an important discussion about the potential of linguistic landscapes in foreign language education has emerged in the field of cultural studies (Landeskunde). The aim of this study is to analyse how the meanings of unauthorised linguistic landscapes are adopted and reflected on in the teaching German as a foreign language. For this purpose, empirical data were collected in German language classrooms at universities in Finland and Sweden. The article discusses the teaching and learning potential of linguistic landscapes within specific language teaching contexts, based on theories and the empirical data collected.

Motivation Recent advances in mass cytometry allow simultaneous measurements of up to 50 markers at single-cell resolution. However, the high dimensionality of mass cytometry data introduces computational challenges for automated data analysis and hinders translation of new biological understanding into clinical applications. Previous studies have applied machine learning to facilitate processing of mass cytometry data. However, manual inspection is still inevitable and becoming the barrier to reliable large-scale analysis. Results We present a new algorithm called Automated Cell-type Discovery and Classification (ACDC) that fully automates the classification of canonical cell populations and highlights novel cell types in mass cytometry data. Evaluations on real-world data show ACDC provides accurate and reliable estimations compared to manual gating results. Additionally, ACDC automatically classifies previously ambiguous cell types to facilitate discovery. Our findings suggest that ACDC substantially improves both reliability and interpretability of results obtained from high-dimensional mass cytometry profiling data. Availability and Implementation A Python package (Python 3) and analysis scripts for reproducing the results are availability on https://bitbucket.org/dudleylab/acdc. Supplementary information Supplementary data are available at Bioinformatics online.

This chapter explores the corporate state of transatlantic television via a case study of BBC America, which is co-owned by the British BBC Worldwide and the American AMC Networks. The chapter details BBC America’s shift from an independent cable channel oriented around Britishness to an asset in AMC Networks’ portfolio, with a programming strategy more AMC than BBC. The study thereby illustrates that the value of a cable channel is no longer just in its individual brand; now its worth lies in the larger corporate network of program ownership and access to transnational platforms. BBC America’s prime-time scripted drama strategy is driven accordingly by the overarching goal to reach upscale, engaged viewers on both linear TV and video-on-demand platforms, in line with the global aspirations of its corporate parent.