Systematic Screen for Drosophila Transcriptional Regulators Phosphorylated in Response to Insulin/mTOR Pathway

Insulin/insulin-like growth factor signaling (IIS) is a conserved mechanism to regulate animal physiology in response to nutrition. IIS activity controls gene expression, but only a subset of transcriptional regulators (TRs) targeted by the IIS pathway is currently known. Here we report the results of an unbiased screen forDrosophilaTRs phosphorylated in an IIS-dependent manner. To conduct the screen, we built a library of 857 V5/Strep-tagged TRs under the control of Copper-inducible metallothionein promoter (pMt). The insulin-induced phosphorylation changes were detected by using Phos-tag SDS-PAGE and Western blotting. Eight proteins were found to display increased phosphorylation after acute insulin treatment. In each case, the insulin-induced phosphorylation was abrogated by mTORC1 inhibitor rapamycin. The hits included two components of the NURF complex (NURF38 and NURF55), bHLHZip transcription factor Max, as well as theDrosophilaortholog of human proliferation-associated 2G4 (dPA2G4). Subsequent experiments revealed that the expression of thedPA2G4gene was promoted by the mTOR pathway, likely through transcription factor Myc. Furthermore, NURF38 was found to be necessary for growth in larvae, consistent with the role of IIS/mTOR pathway in growth control.Peer reviewe

How Does Triage by an Electronic Symptom Checker Match with Triage by a Nurse?

Publisher Copyright: © 2022 European Federation for Medical Informatics (EFMI) and IOS Press.Electronic symptom checkers (ESCs) have been developed to make triage for primary health care patients in Finland. Based on the analysis of the patient's responses to a set of questions, the ESC classifies him/her as emergent, urgent, not urgent, or advices on self-care. In this study the user answered the questions posed by the electronic symptom checker, after which a nurse assessed the urgency of the same user's symptom. The triage nurse was not allowed to know the result of the electronic symptom assessment until he or she had assessed the patient's condition. The level of triage was compared between ESC and nurse in each individual case. Findings from 825 individual cases were analyzed. The mean 'exactly matched' for all symptom estimates was 52.6%. The mean 'exactly matched' or 'overconservative but suitable' for all symptom assessments was 66.6%. Safe assessments of electronic symptom checkers accounted for 98.6% of all assessments. A case was defined as 'safe' if the recommendation for action given by the symptom assessment was at most one level less urgent than the nurse's triage assessment of the same case. The findings show that electronic symptom assessments are safe compared to the assessment of an experienced nurse Omaolo.Peer reviewe

Recognition of Indoor Scenes using 3D Scene Graphs

Scene recognition is a fundamental task in 3-D scene understanding. It answers the question, 'What is this place?' In an indoor environment, the answer can be an office, kitchen, lobby, and so on. As the number of point clouds increases, using embedded point information in scene recognition becomes computationally heavy to process. To achieve computational efficiency and accurate classification, our idea is to use an indoor scene graph that represents the 3-D spatial structures via object instances. The proposed method comprises two parts, namely: 1) construction of indoor scene graphs leveraging object instances and their spatial relationships and 2) classification of these graphs using a deep learning network. Specifically, each indoor scene is represented by a graph, where each node represents either a structural element (like a ceiling, a wall, or a floor) or a piece of furniture (like a chair or a table), and each edge encodes the spatial relationship between these elements. Then, these graphs are used as input for our proposed graph classification network to learn different scene representations. The public indoor dataset, ScanNet v2, with 625.53 million points, is selected to test our method. Experiments yield good results with up to 88.00% accuracy and 82.30% F1 score in the fixed validation dataset and 90.46% accuracy and 81.45% F1 score in the ten-fold cross-validation method; moreover, if some indoor objects cannot be successfully identified, the scene classification accuracy depends sublinearly on the rate of missing objects in the scene.</p

PWP1 promotes nutrient-responsive expression of 5S ribosomal RNA

Peer reviewe

Coordinated control of adiposity and growth by anti-anabolic kinase ERK7

Energy storage and growth are coordinated in response to nutrient status of animals. How nutrient-regulated signaling pathways control these processes in vivo remains insufficiently understood. Here, we establish an atypical MAP kinase, ERK7, as an inhibitor of adiposity and growth in Drosophila. ERK7 mutant larvae display elevated triacylglycerol (TAG) stores and accelerated growth rate, while overexpressed ERK7 is sufficient to inhibit lipid storage and growth. ERK7 expression is elevated upon fasting and ERK7 mutant larvae display impaired survival during nutrient deprivation. ERK7 acts in the fat body, the insect counterpart of liver and adipose tissue, where it controls the subcellular localization of chromatin-binding protein PWP1, a growth-promoting downstream effector of mTOR. PWP1 maintains the expression of sugarbabe, encoding a lipogenic Gli-similar family transcription factor. Both PWP1 and Sugarbabe are necessary for the increased growth and adiposity phenotypes of ERK7 loss-of-function animals. In conclusion, ERK7 is an anti-anabolic kinase that inhibits lipid storage and growth while promoting survival on fasting conditions.Peer reviewe

Human migration activities drive the fluctuation of ARGs : Case study of landfills in Nanjing, eastern China

Landfills are perfect sites to study the effect of human migration on fluctuation of antibiotic resistance genes (ARGs) as they are the final destination of municipal waste. For example, large-scale human migration during the holidays is often accompanied by changes in waste dumping having potential effects on ARG abundance. Three landfills were selected to examine fluctuation in the abundance of fifteen ARGs and Intl1 genes for 14 months in Nanjing, eastern China. Mass human migration, the amount of dumped waste and temperature exerted the most significant effects on bimonthly fluctuations of ARG levels in landfill sites. As a middle-sized cosmopolitan city in China, millions of college students and workers migrate during holidays, contributing to the dramatic increases in waste production and fluctuation in ARG abundances. In line with this, mass migration explained most of the variation in waste dumping. The waste dumping also affected the bioaccessibility of mixed-compound pollutants that further positively impacted the level of ARGs. The influence of various bioaccessible compounds on ARG abundance followed the order: antibiotics>nutrients>metals>organic pollutants. Concentrations of bioaccessible compounds were more strongly correlated with ARG levels compared to total compound concentrations. Improved waste classification and management strategies could thus help to decrease the amount of bioaccessible pollutants leading to more effective control for urban ARG dissemination

In vitro humanized 3D microfluidic chip for testing personalized immunotherapeutics for head and neck cancer patients

Objectives: Immunotherapy and personalized medicine therapeutics are emerging as promising approaches in the management of head and neck squamous cell carcinoma (HNSCC). In spite of that, there is yet no assay that could predict individual response to immunotherapy. Methods: We manufactured an in vitro 3D microfluidic chip to test the efficacy of immunotherapy. The assay was first tested using a tongue cancer cell line (HSC-3) embedded in a human tumour-derived matrix "Myogel/fibrin" and immune cells from three healthy donors. Next, the chips were used with freshly isolated cancer cells, patients' serum and immune cells. Chips were loaded with different immune checkpoint inhibitors, PD-L1 antibody and IDO 1 inhibitor. Migration of immune cells towards cancer cells and the cancer cell proliferation rate were evaluated. Results: Immune cell migration towards HSC-3 cells was cancer cell density dependent. IDO 1 inhibitor induced immune cells to migrate towards cancer cells both in HSC-3 and in two HNSCC patient samples. Efficacy of PD-L1 antibody and IDO 1 inhibitor was patient dependent. Conclusion: We introduced the first humanized in vitro microfluidic chip assay to test immunotherapeutic drugs against HNSCC patient samples. This assay could be used to predict the efficacy of immunotherapeutic drugs for individual patients.Peer reviewe

Image processing as state reconstruction in optics

The image reconstruction of partially coherent light is interpreted as the quantum state reconstruction. The efficient method based on maximum-likelihood estimation is proposed to acquire information from registered intensity measurements affected by noise. The connection with totally incoherent image restoration is pointed out. The feasibility of the method is demonstrated numerically. Spatial and correlation details significantly smaller than the diffraction limit are revealed in the reconstructed pattern.Comment: 10 pages, 5 figure