Malaria, caused by the protozoan parasite Plasmodium and transmitted by Anopheles mosquitoes, represents a major threat to human health. Plasmodium's infection cycle in the Anopheles vector is ...critical for transmission of the parasite between humans. The midgut-stage bottleneck of infection is largely imposed by the mosquito's innate immune system. microRNAs (miRNAs, small noncoding RNAs that bind to target RNAs to regulate gene expression) are also involved in regulating immunity and the anti-Plasmodium defense in mosquitoes. Here, we characterized the mosquito's miRNA responses to Plasmodium infection using an improved crosslinking and immunoprecipitation (CLIP) method, termed covalent ligation of endogenous Argonaute-bound RNAs (CLEAR)-CLIP. Three candidate miRNAs' influence on P. falciparum infection and midgut microbiota was studied through transgenically expressed miRNA sponges (miR-SPs) in midgut and fat body tissues. MiR-SPs mediated conditional depletion of aga-miR-14 or aga-miR-305, but not aga-miR-8, increased mosquito resistance to both P. falciparum and P. berghei infection, and enhanced the mosquitoes' antibacterial defenses. Transcriptome analysis revealed that depletion of aga-miR-14 or aga-miR-305 resulted in an increased expression of multiple immunity-related and anti-Plasmodium genes in mosquito midguts. The overall fitness cost of conditionally expressed miR-SPs was low, with only one of eight fitness parameters being adversely affected. Taken together, our results demonstrate that targeting mosquito miRNA by conditional expression of miR-SPs may have potential for the development of malaria control through genetically engineered mosquitoes.
Molecular interplay between host epigenetic factors and viral proteins constitutes an intriguing mechanism for sustaining hepatitis B virus (HBV) life cycle and its chronic infection. HBV encodes a ...regulatory protein, HBx, which activates transcription and replication of HBV genome organized as covalently closed circular (ccc) DNA minichromosome. Here we illustrate how HBx accomplishes its task by hijacking Spindlin1, an epigenetic reader comprising three consecutive Tudor domains. Our biochemical and structural studies have revealed that the highly conserved N-terminal 2-21 segment of HBx (HBx
) associates intimately with Tudor 3 of Spindlin1, enhancing histone H3 "K4me3-K9me3" readout by Tudors 2 and 1. Functionally, Spindlin1-HBx engagement promotes gene expression from the chromatinized cccDNA, accompanied by an epigenetic switch from an H3K9me3-enriched repressive state to an H3K4me3-marked active state, as well as a conformational switch of HBx that may occur in coordination with other HBx-binding factors, such as DDB1. Despite a proposed transrepression activity of HBx
, our study reveals a key role of Spindlin1 in derepressing this conserved motif, thereby promoting HBV transcription from its chromatinized genome.
•The p160 coactivator FISC is a DNA-binding partner of the juvenile hormone receptor Met.•Binding to juvenile hormone response elements requires intact DNA-binding domains of Met and FISC.•Met and ...FISC are sufficient to bind to a consensus motif GCACGTG.•This study reveals mechanistic details in a key step in signal transduction of juvenile hormone.
Methoprene-tolerant (Met) protein is a juvenile hormone (JH) receptor in insects. JH-bound Met forms a complex with the βFtz-F1-interacting steroid receptor coactivator (FISC) and together they regulate JH response genes in mosquitoes. Both proteins contain basic helix–loop–helix (bHLH) and PAS motifs. Here we demonstrated that FISC is the obligatory partner of Met for binding to JH-response elements (JHREs). Met or FISC alone could not bind a previously characterized JHRE, while formation of the Met–FISC complex was necessary and sufficient to bind to the JHRE. This binding required participation of the DNA-binding domains of both Met and FISC. The optimal DNA sequence recognized by Met and FISC contained a core consensus sequence GCACGTG. While formation of the Met–FISC complex in mosquito cells was induced by JH, heterodimerization and DNA binding of bacterially expressed Met and FISC were JH-independent, implying that additional mosquito proteins were required to modulate formation of the receptor complex.
A novel type of coplanar plasmonic laser based on an edge-coupled hybrid plasmonic waveguide is proposed and analyzed theoretically. This structure enables the realization of an air gap between the ...nanowire and the metal layer that could facilitate enhanced field confinement. By simulating the modal properties and the lasing threshold under different geometric parameters, it is demonstrated that with smaller gap widths and metal films of a larger rounded-corner radius, the lasing threshold could be reduced significantly. The structure could enable deep-subwavelength lasing with low pump thresholds and be readily integrated with other plasmonic structures for future coplanar active plasmonic circuits.
The quadriceps tendon, crucial for body movement, is among the body's strongest tendons. Factors like diabetes or hormone use can weaken it, making even minor trauma potentially causing rupture. ...Bilateral spontaneous quadriceps tendon rupture, where both tendons tear simultaneously, is rare. Prompt diagnosis and treatment are crucial. We present a case of a 44-year-old woman who experienced bilateral rupture after falling while doing chores. She had immediate pain and limited knee movement. Diagnosis via physical examination and CT/MRI scans confirmed the rupture. Surgical repair followed by rehabilitation led to significant pain reduction and improved function within two months. Overall, her postoperative outcome was satisfactory. This study underscores the importance of clear diagnosis, timely surgery, and thorough rehabilitation for optimal patient recovery from bilateral quadriceps tendon rupture.
Transportation efficiency is a problem of particular interest in multi-channel confluent water supply engineering. Transportation efficiency depends not only on the system control strategy but also ...on the pressure loss (pressure difference between the inlet and outlet) and pressure drop (amplitude of outlet pressure fluctuations) of its structure. In this article, sensitivity analyses of the pressure loss and pressure drop to changes in multi-channel confluent water supply geometry are presented. An experimental set-up was established to validate computational fluid dynamic (CFD) predictions and obtain the boundary conditions for two-channel synchronous switching. The influences of the geometric structure varies by the clustered pipe diameter (40 mm < Dc < 80 mm), main pipe diameter (30 mm < Do < 80 mm), channel pitch (60 mm < L < 400 mm) and number of channels (2 ≤ n ≤ 4); those variables were investigated with the help of CFD simulations. The results showed that configuration “C” can be considered a costless method of decreasing pressure loss (βC(2.05) < βA(2.42) < βB(2.64)) and that the different configurations are insensitive to pressure drop. The variations of the influence of channel pitch and clustered pipe diameter on pressure loss have extremes at L/d = 5 and Dc/d = 2.5, respectively, but the effect on pressure drop is not obvious. The main pipe diameter and the inlet velocity have more significant influences on efficiency. The results can be used to choose the proper geometry of multi-channel confluent water supply to enable energy savings.
Exposure of adult mosquitoes to pyriproxyfen (PPF), an analog of insect juvenile hormone (JH), has shown promise to effectively sterilize female mosquitoes. However, the underlying mechanisms of the ...PPF-induced decrease in mosquito fecundity are largely unknown. We performed a comprehensive study to dissect the mode of PPF action in Aedes aegypti mosquitoes. Exposure to PPF prompted the overgrowth of primary follicles in sugar-fed Ae. aegypti females but blocked the development of primary follicles at Christopher's Stage III after blood feeding. Secondary follicles were precociously activated in PPF-treated mosquitoes. Moreover, PPF substantially altered the expression of many genes that are essential for mosquito physiology and oocyte development in the fat body and ovary. In particular, many metabolic genes were differentially expressed in response to PPF treatment, thereby affecting the mobilization and utilization of energy reserves. Furthermore, PPF treatment on the previtellogenic female adults considerably modified mosquito responses to JH and 20-hydroxyecdysone (20E), two major hormones that govern mosquito reproduction. Krüppel homolog 1, a JH-inducible transcriptional regulator, showed consistently elevated expression after PPF exposure. Conversely, PPF upregulated the expression of several key players of the 20E regulatory cascades, including HR3 and E75A, in the previtellogenic stage. After blood-feeding, the expression of these 20E response genes was significantly weaker in PPF-treated mosquitoes than the solvent-treated control groups. RNAi-mediated knockdown of the Methoprene-tolerant (Met) protein, the JH receptor, partially rescued the impaired follicular development after PPF exposure and substantially increased the hatching of the eggs produced by PPF-treated female mosquitoes. Thus, the results suggested that PPF relied on Met to exert its sterilizing effects on female mosquitoes. In summary, this study finds that PPF exposure disturbs normal hormonal responses and metabolism in Ae. aegypti, shedding light on the molecular targets and the downstream signaling pathways activated by PPF.
During the multi-channel confluent water supply process, the pressure control of the main pipe is often held back by such problems as non-linearity, hysteresis and parameter uncertainty, its own ...unique load dynamic changes, channel switching disturbance and other system characteristics caused by the actual working conditions. Moreover, pressure fluctuations in the main pipe will lead to a reduction in the service life of fire-fighting equipment, an increase in the failure rate, and even an interruption of the fire-fighting water supply. Therefore, a master and auxiliary control strategy is proposed to stabilize the pressure change in the process of multi-channel concentrated water supply switching, by using variable universe fuzzy proportional integral derivative (PID) control as the main controller on the main pipe and traditional PID control as the subsidiary controller on the channel. The control strategy is verified by the co-simulation platforms of LabVIEW and AMESim. Simulation results show that the variable universe fuzzy PID control and the master and auxiliary compound control based on the variable universe fuzzy PID control have advantages in step response, tracking response and anti-interference, respectively. The parameters obtained in the co-simulation are used in the experimental system. The experimental results show that the maximum deviation rate of main pipe pressure can be reduced by about 10% compared with other control methods under different loads. In conclusion, the proposed control strategy has strong anti-interference ability, fast dynamic response speed, high stability and good peak shaving effect.
•CNN models for predicting creep and shrinkage of concrete are researched.•The constitutive law of concrete based on the proposed CNN models is presented.•An ABAQUS user subroutine of concrete creep ...and shrinkage is developed.•The performance of CNN models is better than the B4 model.•Developed user subroutine predicts well the long-term deformation of a RC beam.
The problem of long-term deformation caused by creep and shrinkage (C&S) needs to be concerned in the design and service of concrete structures. Although various models have been developed to predict the C&S of concrete, more accurate and reliable prediction methods are still needed. The models of C&S based on convolutional neural networks (CNNs) are proposed in the study. The performance of the CNN models is verified by using 906 sets of creep experiment data and 1114 sets of shrinkage experiment data in the Northwestern University (NU) database. Besides, the K-means clustering algorithm is introduced to divide the data set into the training set, validation set, and test set, and the problem of uneven distribution of the data set on the time scale is overcome. Finally, the incremental viscoelastic constitutive law of concrete based on the developed CNN models is proposed, and the ABAQUS user subroutine for simulating C&S of concrete is developed. The availability of the user subroutine is validated by the creep and shrinkage test of a reinforced concrete beam. The research can provide reliable methods for the rapid prediction of C&S of concrete and the simulation analysis of long-term deformation of concrete structures.
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