Pest management facing warming and chemical stresses: Multi-stress effects on the biological agent Trichogramma oleae.

Global change is affecting plant-insect interactions in agroecosystems and can have dramatic consequences on yields when causing non-targeted pest outbreaks and threatening the use of pest natural enemies for biocontrol. The vineyard agroecosystem is an interesting system to study multi-stress conditions: on the one hand, agricultural intensification comes with high inputs of copper-based fungicides and, on the other hand, temperatures are rising due to climate change. We investigated interactive and bottom-up effects of both temperature increase and copper-based fungicides exposure on the important Lepidopteran vineyard pest Lobesia botrana and its natural enemy, the oophagous parasitoid Trichogramma oleae. We exposed L. botrana larvae to three increasing copper sulfate concentrations under two fluctuating thermal regimes, one current and one future. Eggs produced by L. botrana were then exposed to T. oleae. Our results showed that the survival of L. botrana, was only reduced by the highest copper sulfate concentration and improved under the warmer regime. The development time of L. botrana was strongly reduced by the warmer regime but increased with increasing copper sulfate concentrations, whereas pupal mass was reduced by both thermal regime and copper sulfate. T. oleae F1 emergence rate was reduced and their development time increased by combined effects of the warmer regime and increasing copper sulfate concentrations. Size, longevity and fecundity of T. oleae F1 decreased with high copper sulfate concentrations. These effects on the moth pest and its natural enemy are probably the result of trade-offs between the survival and the development of L. botrana facing multi-stress conditions and implicate potential consequences for future biological pest control. Our study supplies valuable data on how the interaction between pests and biological control agents is affected by multi-stress conditions.

Acute Effects of Growth Hormone on the Cellular Immunologic Landscape in Pediatric Patients.

INTRODUCTION: Growth hormone (GH) and the immune system have multiple bidirectional interactions. Data about the acute effects of GH on the immune system are lacking. The objective of our study was to evaluate the acute effects of GH on the immune system using time-of-flight mass cytometry. METHODS: This was a prospective study of pediatric patients who were being evaluated for short stature and underwent a GH stimulation test at a tertiary care center. Blood samples for immunologic markers, i.e., complete blood count (CBC) and time of flight mass cytometry (CyTOF), were collected at baseline (T0) and over the course of three hours (T3) of the test. Differences in immune profiling in patients by timepoint (T0, T3) and GH response (growth hormone sufficient (GHS) versus growth hormone deficient (GHD)) were calculated using a two-way ANOVA test.  Results: A total of 54 patients (39 boys and 15 girls) aged five to 18 years were recruited. Twenty-two participants tested GHD (peak GH <10 ng/ml). The CyTOF analysis showed a significant increase from T0 to T3 in granulocyte percentage, monocyte count, and dendritic cell (DC) count; in contrast, a significant decrease was seen in T lymphocytes (helper and cytotoxic) and IgD+ B lymphocytes. The CBC analysis supported these findings: an increase in total white blood cell count, absolute neutrophil count, and neutrophil percentage; a decrease in absolute lymphocyte count, lymphocyte percentage, absolute eosinophil count, and absolute monocyte count. No significant differences were found between CBC/CyTOF measurements and GH status at either time. CONCLUSIONS: This study provides the first high-resolution map of acute changes in the immune system with GH stimulation. This implies a key role for GH in immunomodulatory function.

Inflammatory plasma signature of chronic hand eczema: Associations with aetiological and clinical subtypes.

BACKGROUND: Chronic hand eczema (CHE) is a highly prevalent, heterogeneous, skin disease that encompasses different aetiological and clinical subtypes. Severe CHE without atopic dermatitis has been associated with systemic inflammation; yet it remains unknown if specific CHE subtypes leave distinct, systemic, molecular signatures. OBJECTIVES: To characterize the inflammatory plasma signature of different aetiological and clinical CHE subtypes. METHODS: We assessed expression levels of 266 inflammatory and cardiovascular disease risk plasma proteins as well as filaggrin gene mutation status in 51 well-characterized CHE patients without concomitant atopic dermatitis and 40 healthy controls. Plasma protein expression was compared between aetiological and clinical CHE subgroups and controls both overall and according to clinical CHE severity. Correlation analyses for biomarkers, clinical and self-reported variables were performed. RESULTS: Very severe, chronic allergic contact dermatitis (ACD) on the hands was associated with a mixed Type 1/Type 2 systemic immune activation as compared with controls. Circulating levels of Type 1/Type 2 inflammatory biomarkers correlated positively with clinical disease severity among CHE patients with ACD. No biomarkers were found, that could discriminate between aetiological subtypes, for example, between ACD and irritant contact dermatitis. Hyperkeratotic CHE showed a distinct, non-atopic dermatitis-like, systemic footprint with upregulation of markers associated with Type 1 inflammation and tumour necrosis factor alpha, but not Type 2 inflammation. Increased levels of CCL19 and CXCL9/10 could discriminate hyperkeratotic CHE from both vesicular and chronic fissured CHE, whereas no difference was found between the latter two subtypes. CONCLUSION: Profiling of systemic biomarkers showed potential for identifying certain CHE subtypes. Peripheral blood levels of inflammatory biomarkers were associated and correlated with the clinical disease severity of chronic ACD on the hands, underlining that this is a systemic disease. We question whether hyperkeratotic CHE should be classified as eczema.

Circulating biomarkers are associated with disease severity of chronic hand eczema and atopic dermatitis.

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.

Altered volatile emission of pear trees under elevated atmospheric CO2 levels has no relevance to pear psyllid host choice.

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.

Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal disorder. Two U.S. Food and Drug Administration-approved antifibrotic drugs, nintedanib and pirfenidone, slow the rate of decline in lung function, but responses are variable and side effects are common. Objectives: 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. Methods: We investigated the antifibrotic efficacy of saracatinib relative to nintedanib and pirfenidone in three preclinical models: 1) in vitro in normal human lung fibroblasts; 2) in vivo in bleomycin and recombinant Ad-TGF-ß (adenovirus transforming growth factor-ß) murine models of pulmonary fibrosis; and 3) ex vivo in mice and human precision-cut lung slices from these two murine models as well as patients with IPF and healthy donors. Measurements and Main Results: In each model, the effectiveness of saracatinib in blocking fibrogenic responses was equal or superior to nintedanib and pirfenidone. Transcriptomic analyses of TGF-ß-stimulated normal human lung fibroblasts identified specific gene sets associated with fibrosis, including epithelial-mesenchymal transition, TGF-ß, and WNT signaling that was uniquely altered by saracatinib. Transcriptomic analysis of whole-lung extracts from the two animal models of pulmonary fibrosis revealed that saracatinib reverted many fibrogenic pathways, including epithelial-mesenchymal transition, immune responses, and extracellular matrix organization. Amelioration of fibrosis and inflammatory cascades in human precision-cut lung slices confirmed the potential therapeutic efficacy of saracatinib in human lung fibrosis. Conclusions: These studies identify novel Src-dependent fibrogenic pathways and support the study of the therapeutic effectiveness of saracatinib in IPF treatment.

IL-17 Pathway Members as Potential Biomarkers of Effective Systemic Treatment and Cardiovascular Disease in Patients with Moderate-to-Severe Psoriasis.

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.

Biomarkers of subclinical atherosclerosis in patients with psoriasis.

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.

Neutrophil Pathways of Inflammation Characterize the Blood Transcriptomic Signature of Patients with Psoriasis and Cardiovascular Disease.

BACKGROUND: Patients with psoriasis have an increased risk of atherosclerotic cardiovascular disease (CVD). The molecular mechanisms behind this connection are not fully understood, but the involvement of neutrophils have drawn attention as a shared inflammatory factor. METHODS: RNA sequencing using the Illumina platform was performed on blood from 38 patients with moderate to severe psoriasis; approximately half had prior CVD. The neutrophil to lymphocyte ratio (NLR) was obtained from blood samples. Subclinical atherosclerosis was assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and ultrasound imaging. Transcriptomic analysis for differential expression and functional enrichment were performed, followed by correlation analyses of differentially expressed genes (DEGs), NLR and subclinical measurers of CVD. RESULTS: 291 genes were differentially expressed between patients with psoriasis with and without CVD. These included 208 upregulated and 83 downregulated DEGs. Neutrophil degranulation was identified as the most significant process related to the upregulated DEGs. Genes for the neutrophil-associated markers MPO, MMP9, LCN2, CEACAM1, CEACAM6 and CEACAM8 were identified as being of special interest and their mRNA levels correlated with NLR, high-sensitive C-reactive protein and markers of subclinical CVD. CONCLUSIONS: Patients with psoriasis and CVD had an increased expression of genes related to neutrophil degranulation in their blood transcriptome compared with patients with psoriasis without CVD. NLR may be a potential biomarker of subclinical CVD in psoriasis.

Repositioning of a novel GABA-B receptor agonist, AZD3355 (Lesogaberan), for the treatment of non-alcoholic steatohepatitis.

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.

Multiscale Biology of Cardiovascular Risk in Psoriasis: Protocol for a Case-Control Study.

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<.001), subcutaneous adipose tissue (P=.007), pericardial adipose tissue (P<.001), spleen (P=.001), and bone marrow (P<.001). 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.

Feeding guild determines strength of top-down forces in multitrophic system experiencing bottom-up constraints.

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 system, 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 carbon concentration), direct defense (alkaloids and phenolics), and indirect defense (plant volatile organic compounds); 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 parasitoid 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.

Association between Vascular Inflammation and Inflammation in Adipose Tissue, Spleen, and Bone Marrow in Patients with Psoriasis.

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 (ß = 0.26; p < 0.001), SAT (ß = 0.28; p < 0.001), PAT (ß = 0.24; p < 0.001), spleen (ß = 1.35; p = 0.001), and bone marrow (ß = 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.

Identification of therapeutic targets from genetic association studies using hierarchical component analysis.

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.

CD82 controls CpG-dependent TLR9 signaling.

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-κB 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.

Global change-driven modulation of bottom-up forces and cascading effects on biocontrol services.

Abiotic and biotic factors affect plants in various ways which in turn affect associated arthropod communities through direct and/or indirect bottom-up interactions. Several review articles have synthesized studies examining the indirect effects of abiotic factors on plant-arthropod interactions, mainly focusing on soil nitrogen, soil water status, and climate change. However, these studies have mostly focused on bitrophic interactions, whereas most ecological systems are composed of at least three trophic levels. Lately, research on plant-mediated multitrophic interactions in plant-arthropod food web has received increasing interest. Both the intensification of agriculture and the global climate change have the potential to trigger bottom-up effects that cascade through trophic links. In this review article, we synthesize the most recent studies describing how abiotic changes could modulate plant-mediated bottom-up forces and how it could affect arthropod communities and associated biocontrol services. We discuss potential for increasing the sustainability of managed and natural ecosystems, and highlight road maps for future studies.

Flavonoid, Nitrate and Glucosinolate Concentrations in Brassica Species Are Differentially Affected by Photosynthetically Active Radiation, Phosphate and Phosphite.

We evaluated the effects of phosphate (Pi-deficiency: 0.1 mM; Pi-sufficiency: 0.5 mM), phosphite (low-Phi: 0.1 mM; medium-Phi: 0.5 mM; and high-Phi: 2.5 mM), and two mean daily photosynthetically active radiations (lower PAR: 22.2 mol ⋅ m-2 ⋅ d-1; higher PAR: 29.7 mol ⋅ m-2 ⋅ d-1), as well as their interactions, on flavonoid, nitrate and glucosinolate (GL) concentrations and growth characteristics in hydroponically grown Brassica campestris cv. Mibuna Early and Brassica juncea cv. Red Giant. As expected, higher PAR increased dry matter and contrariwise decreased number of leaves but only in B. campestris. Total flavonoid and individual flavonoid compounds increased with the higher PAR value in B. campestris. Pi-sufficiency resulted in a lower quercetin concentration in both species, the isorhamnetin and total flavonoid concentrations in B. campestris, and the cyanidin concentration in B. juncea, in comparison to Pi-deficiency. Similarly, Pi-sufficient plants exhibited lower GL concentration, especially alkyl-GLs in B. campestris and alkenyl-GLs and an aryl-GL in B. juncea. Pi did not affect the nitrate concentration in either species, and nor did Phi influence the flavonoid concentrations in either species. In B. campestris, medium Phi (0.5 mM) increased the 1-methoxyindol-3-ylmethyl GL concentration by 28.3%, as compared to that observed at low Phi. In B. juncea, high Phi level increased the but-3-enyl-GL concentration by 18.9%, in comparison to values recorded at medium Phi. B. campestris plants exposed to higher PAR increased total flavonoids concentration. In both Brassica species, higher PAR stimulated the alkyl-, alkenyl-, and indole-GLs. The interaction of lower PAR and increasing Phi significantly decreased flavonoid concentration in B. juncea, whereas increasing Phi at higher PAR increased such concentration in this species. The same combination reduced the concentration of 2-phenylethyl- and indol-3-ylmethyl-GL in B. juncea. The highest indol-3-ylmethyl-GL concentration was observed when Pi was deficient combined with medium Phi in B. juncea. Thus, PAR, Pi and Phi may modulate flavonoid, GL and nitrate concentrations in Brassica species, which may be a useful tool to improve the nutraceutical quality of these leafy vegetables if properly managed.

Automated cell type discovery and classification through knowledge transfer.

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 utomated ell-type iscovery and lassification (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 . CONTACT: brian.kidd@mssm.edu or joel.dudley@mssm.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.