Age-Dependent Changes in Transcription Factor FOXO Targeting in Female Drosophila

FOXO transcription factors have long been associated with longevity control and tissue homeostasis. Although the transcriptional regulation of FOXO have been previously characterized (especially in long-lived insulin mutants and under stress conditions), how normal aging impacts the transcriptional activity of FOXO is poorly understood. Here, we conducted a chromatin immunoprecipitation sequencing (ChIP-Seq) analysis in both young (2-week-old) and aged (5-week-old) wild-type female fruit flies, Drosophila melanogaster, to evaluate the dynamics of FOXO gene targeting during aging. Intriguingly, the number of FOXO-bound genes dramatically decreases with age (from 2617 to 224). Consistent to the reduction of FOXO binding activity, many genes targeted by FOXO in young flies are transcriptionally altered with age, either up-regulated (FOXOrepressing genes) or down-regulated (FOXO-activating genes) in adult head tissue. In addition, we show that many FOXO-bound genes in wild-type flies are unique from those in insulin receptor substrate chico mutants. Distinct from chico mutants, FOXO targets specific cellular processes (e.g., actin cytoskeleton) and signaling pathways (e.g., Hippo, MAPK) in young wild-type female flies. FOXO targeting on these pathways decreases with age. Interestingly, FOXO targets in aged flies are enriched in cellular processes like chromatin organization and nucleosome assembly. Furthermore, FOXO binding to core histone genes is well maintained at aged flies. Together, our findings provide new insights into dynamic FOXO targeting under normal aging and highlight the diverse and understudied regulatory mechanisms for FOXO transcriptional activity

LAPP: Layer Adaptive Progressive Pruning for Compressing CNNs from Scratch

Structured pruning is a commonly used convolutional neural network (CNN) compression approach. Pruning rate setting is a fundamental problem in structured pruning. Most existing works introduce too many additional learnable parameters to assign different pruning rates across different layers in CNN or cannot control the compression rate explicitly. Since too narrow network blocks information flow for training, automatic pruning rate setting cannot explore a high pruning rate for a specific layer. To overcome these limitations, we propose a novel framework named Layer Adaptive Progressive Pruning (LAPP), which gradually compresses the network during initial training of a few epochs from scratch. In particular, LAPP designs an effective and efficient pruning strategy that introduces a learnable threshold for each layer and FLOPs constraints for network. Guided by both task loss and FLOPs constraints, the learnable thresholds are dynamically and gradually updated to accommodate changes of importance scores during training. Therefore the pruning strategy can gradually prune the network and automatically determine the appropriate pruning rates for each layer. What's more, in order to maintain the expressive power of the pruned layer, before training starts, we introduce an additional lightweight bypass for each convolutional layer to be pruned, which only adds relatively few additional burdens. Our method demonstrates superior performance gains over previous compression methods on various datasets and backbone architectures. For example, on CIFAR-10, our method compresses ResNet-20 to 40.3% without accuracy drop. 55.6% of FLOPs of ResNet-18 are reduced with 0.21% top-1 accuracy increase and 0.40% top-5 accuracy increase on ImageNet.Comment: 12 pages, 8 tables, 3 figure

Proteomics Landscape of Host-Pathogen Interaction in Acinetobacter baumannii Infected Mouse Lung

Acinetobacter baumannii is an important pathogen of nosocomial infection worldwide, which can primarily cause pneumonia, bloodstream infection, and urinary tract infection. The increasing drug resistance rate of A. baumannii and the slow development of new antibacterial drugs brought great challenges for clinical treatment. Host immunity is crucial to the defense of A. baumannii infection, and understanding the mechanisms of immune response can facilitate the development of new therapeutic strategies. To characterize the system-level changes of host proteome in immune response, we used tandem mass tag (TMT) labeling quantitative proteomics to compare the proteome changes of lungs from A. baumannii infected mice with control mice 6 h after infection. A total of 6,218 proteins were identified in which 6,172 could be quantified. With threshold p 1.2 or < 0.83, we found 120 differentially expressed proteins. Bioinformatics analysis showed that differentially expressed proteins after infection were associated with receptor recognition, NADPH oxidase (NOX) activation and antimicrobial peptides. These differentially expressed proteins were involved in the pathways including leukocyte transendothelial migration, phagocyte, neutrophil degranulation, and antimicrobial peptides. In conclusion, our study showed proteome changes in mouse lung tissue due to A. baumannii infection and suggested the important roles of NOX, neutrophils, and antimicrobial peptides in host response. Our results provide a potential list of protein candidates for the further study of host-bacteria interaction in A. baumannii infection. Data are available via ProteomeXchange with identifier PXD020640

Baculovirus superinfection: a probable restriction factor on the surface display of proteins for library screening

In addition to the expression of recombinant proteins, baculoviruses have been developed as a platform for the display of complex eukaryotic proteins on the surface of virus particles or infected insect cells. Surface display has been used extensively for antigen presentation and targeted gene delivery but is also a candidate for the display of protein libraries for molecular screening. However, although baculovirus gene libraries can be efficiently expressed and displayed on the surface of insect cells, target gene selection is inefficient probably due to super-infection which gives rise to cells expressing more than one protein. In this report baculovirus superinfection of Sf9 cells has been investigated by the use of two recombinant multiple nucleopolyhedrovirus carrying green or red fluorescent proteins under the control of both early and late promoters (vAcBacGFP and vAcBacDsRed). The reporter gene expression was detected 8 hours after the infection of vAcBacGFP and cells in early and late phases of infection could be distinguished by the fluorescence intensity of the expressed protein. Simultaneous infection with vAcBacGFP and vAcBacDsRed viruses each at 0.5 MOI resulted in 80% of infected cells coexpressing the two fluorescent proteins at 48 hours post infection (hpi), and subsequent infection with the two viruses resulted in similar co-infection rate. Most Sf9 cells were re-infectable within the first several hours post infection, but the reinfection rate then decreased to a very low level by 16 hpi. Our data demonstrate that Sf9 cells were easily super-infectable during baculovirus infection, and super-infection could occur simultaneously at the time of the primary infection or subsequently during secondary infection by progeny viruses. The efficiency of super-infection may explain the difficulties of baculovirus display library screening but would benefit the production of complex proteins requiring co-expression of multiple polypeptides

Electrogenic Na/HCO3 Cotransporter (NBCe1) Variants Expressed in Xenopus Oocytes: Functional Comparison and Roles of the Amino and Carboxy Termini

Using pH- and voltage-sensitive microelectrodes, as well as the two-electrode voltage-clamp and macropatch techniques, we compared the functional properties of the three NBCe1 variants (NBCe1-A, -B, and -C) with different amino and/or carboxy termini expressed in Xenopus laevis oocytes. Oocytes expressing rat brain NBCe1-B and exposed to a CO2/HCO3− solution displayed all the hallmarks of an electrogenic Na+/HCO3− cotransporter: (a) a DIDS-sensitive pHi recovery following the initial CO2-induced acidification, (b) an instantaneous hyperpolarization, and (c) an instantaneous Na+-dependent outward current under voltage-clamp conditions (−60 mV). All three variants had similar external HCO3− dependencies (apparent KM of 4–6 mM) and external Na+ dependencies (apparent KM of 21–36 mM), as well as similar voltage dependencies. However, voltage-clamped oocytes (−60 mV) expressing NBCe1-A exhibited peak HCO3−-stimulated NBC currents that were 4.3-fold larger than the currents seen in oocytes expressing the most dissimilar C variant. Larger NBCe1-A currents were also observed in current–voltage relationships. Plasma membrane expression levels as assessed by single oocyte chemiluminescence with hemagglutinin-tagged NBCs were similar for the three variants. In whole-cell experiments (Vm = −60 mV), removing the unique amino terminus of NBCe1-A reduced the mean HCO3−-induced NBC current 55%, whereas removing the different amino terminus of NBCe1-C increased the mean NBC current 2.7-fold. A similar pattern was observed in macropatch experiments. Thus, the unique amino terminus of NBCe1-A stimulates transporter activity, whereas the different amino terminus of the B and C variants inhibits activity. One or more cytosolic factors may also contribute to NBCe1 activity based on discrepancies between macropatch and whole-cell currents. While the amino termini influence transporter function, the carboxy termini influence plasma membrane expression. Removing the entire cytosolic carboxy terminus of NBCe1-C, or the different carboxy terminus of the A/B variants, causes a loss of NBC activity due to low expression at the plasma membrane

Global stability and optimal vaccination control of SVIR models

Vaccination is widely acknowledged as an affordable and cost-effective approach to guard against infectious diseases. It is important to take vaccination rate, vaccine effectiveness, and vaccine-induced immune decline into account in epidemic dynamical modeling. In this paper, an epidemic dynamical model of vaccination is developed. This model provides a framework of the infectious disease transmission dynamics model through qualitative and quantitative analysis. The result shows that the system may have multiple equilibria. We used the next-generation operator approach to calculate the maximum spectral radius, that is, basic reproduction number ${R_{vac}}$. Next, by dividing the model into infected and uninfected subjects, we can prove that the disease-free equilibrium is globally asymptotically stable when {R_{vac}} < 1 , provided certain assumptions are satisfied. When {R_{vac}} > 1 , there exists a unique endemic equilibrium. Using geometric methods, we calculate the second compound matrix and demonstrate the Lozinskii measure $\bar q \leqslant 0$, which is equivalent to the unique endemic equilibrium, which is globally asymptotically stable. Then, using center manifold theory, we justify the existence of forward bifurcation. As the vaccination rate decreases, the likelihood of forward bifurcation increases. We also theoretically show the presence of Hopf bifurcation. Then, we performed sensitivity analysis and found that increasing the vaccine effectiveness rate can curb the propagation of disease effectively. To examine the influence of vaccination on disease control, we chose the vaccination rate as the optimal vaccination control parameter, using the Pontryagin maximum principle, and we found that increasing vaccination rates reduces the number of infected individuals. Finally, we ran a numerical simulation to finalize the theoretical results

Sull. 1)

ABSTRACT Response surface methodology(RSM) was employed to optimize conditions for ultrasound-assisted extraction(UAE) of antioxidantive components from Arundinagraminifolia. 1,1-diphenyl-2-picryl-hydrazyl(DPPH) free radical scavenging assay was used to evaluate the activity of antioxidative components. Based on the single-factor test, we identified extraction time, ethanol volume fraction, extraction temperature and liquid-solid ratio as the main variables that influence DPPH free radical scavenging activity of A. graminifolia extract. The optimal conditions to achieve the maximum activity were determined as follows: extraction time 35 min, extraction temperature46ºC, ethanol volume fraction 74%and liquid-solidratio27 mL.g -1 . The scavenging rateof 78.71%was achieved under the optimal extraction conditions, which was well in agreement with the optimal predicted values (79.16%). This extraction method was simple and efficient and provided a method of sample preparation to determine DPPH radical scavenging activity of total antioxidative components from A. graminifolia. The research also provided a reference for full utilization of A. graminifolia and identified a technique to extract antioxidative components

Extraction of Prostatic Lumina and Automated Recognition for Prostatic Calculus Image Using PCA-SVM

Identification of prostatic calculi is an important basis for determining the tissue origin. Computation-assistant diagnosis of prostatic calculi may have promising potential but is currently still less studied. We studied the extraction of prostatic lumina and automated recognition for calculus images. Extraction of lumina from prostate histology images was based on local entropy and Otsu threshold recognition using PCA-SVM and based on the texture features of prostatic calculus. The SVM classifier showed an average time 0.1432 second, an average training accuracy of 100%, an average test accuracy of 93.12%, a sensitivity of 87.74%, and a specificity of 94.82%. We concluded that the algorithm, based on texture features and PCA-SVM, can recognize the concentric structure and visualized features easily. Therefore, this method is effective for the automated recognition of prostatic calculi

Molecular Optical Imaging with Radioactive Probes

Background: Optical imaging (OI) techniques such as bioluminescence and fluorescence imaging have been widely used to track diseases in a non-invasive manner within living subjects. These techniques generally require bioluminescent and fluorescent probes. Here we demonstrate the feasibility of using radioactive probes for in vivo molecular OI. Methodology/Principal Findings: By taking the advantages of low energy window of light (1.2–3.1 eV, 400–1000 nm) resulting from radiation, radionuclides that emit charged particles such as b + and b 2 can be successfully imaged with an OI instrument. In vivo optical images can be obtained for several radioactive probes including 2-deoxy-2- [ 18 F]fluoro-D-glucos