293 research outputs found
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
Oral nitrate-reducing bacteria as potential probiotics for blood pressure homeostasis
Hypertension is a leading cause of morbidity and mortality worldwide and poses a major risk factor for cardiovascular diseases and chronic kidney disease. Research has shown that nitric oxide (NO) is a vasodilator that regulates vascular tension and the decrease of NO bioactivity is considered one of the potential pathogenesis of essential hypertension. The L-arginine-nitric oxide synthase (NOS) pathway is the main source of endogenous NO production. However, with aging or the onset of diseases, the function of the NOS system becomes impaired, leading to insufficient NO production. The nitrate–nitrite–NO pathway allows for the generation of biologically active NO independent of the NOS system, by utilizing endogenous or dietary inorganic nitrate and nitrite through a series of reduction cycles. The oral cavity serves as an important interface between the body and the environment, and dysbiosis or disruption of the oral microbiota has negative effects on blood pressure regulation. In this review, we explore the role of oral microbiota in maintaining blood pressure homeostasis, particularly the connection between nitrate-reducing bacteria and the bioavailability of NO in the bloodstream and blood pressure changes. This review aims to elucidate the potential mechanisms by which oral nitrate-reducing bacteria contribute to blood pressure homeostasis and to highlight the use of oral nitrate-reducing bacteria as probiotics for oral microbiota intervention to prevent hypertension
Recommended from our members
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 . 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 , 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
- …