Modulation Of Responsiveness Research Articles

Strength-training and balance activities in Canada: historical trends and current prevalence.

Muscle-strengthening and balance activities are associated with the prevention of illness and injury. Age-specific Canadian 24-Hour Movement Guidelines include recommendations for muscle/bone-strengthening and balance activities. From 2000-2014, the Canadian Community Health Survey (CCHS) included a module that assessed frequency in 22 physical activities. In 2020, a healthy living rapid response module (HLV-RR) on the CCHS asked new questions on the frequency of muscle/bonestrengthening and balance activities. The objectives of the study were to (1) estimate and characterize adherence to meeting the muscle/bone-strengthening and balance recommendations; (2) examine associations between muscle/bone-strengthening and balance activities with physical and mental health; and (3) examine trends (2000-2014) in adherence to recommendations. Using data from the 2020 CCHS HLV-RR, we estimated age-specific prevalence of meeting recommendations. Multivariate logistic regressions examined associations with physical and mental health. Using data from the 2000-2014 CCHS, sex-specific temporal trends in recommendation adherence were explored using logistic regression. Youth aged 12 to 17 years (56.6%, 95% CI: 52.4-60.8) and adults aged 18 to 64 years (54.9%, 95% CI: 53.1-56.8) had significantly greater adherence to the muscle/ bone-strengthening recommendation than adults aged 65 years and older (41.7%, 95% CI: 38.9-44.5). Only 16% of older adults met the balance recommendation. Meeting the recommendations was associated with better physical and mental health. The proportion of Canadians who met the recommendations increased between 2000 and 2014. Approximately half of Canadians met their age-specific muscle/bonestrengthening recommendations. Reporting on the muscle/bone-strengthening and balance recommendations elevates their importance alongside the already recognized aerobic recommendation.

An AI-Based Power Reserve Control Strategy for Photovoltaic Power Generation Systems Participating in Frequency Regulation of Microgrids

In this paper, a novel AI-based power reserve control strategy is proposed for photovoltaic (PV) power generation systems participating in the frequency regulation (FR) of microgrids. The proposed strategy uses a frequency response module to determine the target power reserve ratio of the PV system based on microgrid frequency deviation, as well as a power reserve control module to obtain the target duty cycle, which is input to the BOOST converter. The use of artificial neural networks (ANN) in the power reserve control module enables the PV system to work at a specified power reserve ratio, producing appropriate power and mitigating frequency fluctuations in the microgrid. Additionally, a deep reinforcement learning (DRL) algorithm is employed as the decision maker for variable step-size control and initial power reserve ratio determination. Simulations were performed to validate the effectiveness of the proposed method, demonstrating a significant reduction in average frequency deviation by 72.36% when subjected to random variations in irradiance intensity and load conditions. Overall, the proposed AI-based power reserve control strategy has good potential for practical applications in real-world microgrids, promoting the absorption of new energy led by PV and reducing the phenomenon of light abandonment.

Clinical Signs of Kawasaki Disease from the Perspective of Epithelial-to-Mesenchymal Transition Recruiting Erythrocytes: A Literature Review.

Kawasaki disease (KD) is a systemic vasculitis affecting children younger than 5 years of age. Early period in life is marked by rapid somatic growth with cell proliferation and immaturity of the immunity with dominant innate immune system. Coronary complications in KD are the most common acquired heart disease in children, yet the diagnosis of KD still depends on the clinical diagnostic criteria. Glossy red lips and conjunctival injection are characteristic signs enabling pediatricians to make the initial diagnosis of KD; however, little is known why these are so characteristic. The diagnostic criteria of KD seem to be scattered in seemingly irrelevant body systems such as the eyes, lips, skin, and heart. KD is classified as a connective tissue disease. Recently, red blood cells (RBCs) have emerged as important modulators in innate immune response. RBCs are reported to participate in extracellular matrix remodeling and upregulating matrix metalloproteinase (MMP) expression in dermal fibroblasts. Also, fibroblast growth factors and microRNAs associated with fibrosis are drawing attention in KD. The cardinal signs of KD appear at the border of muco-cutaneous junction. Head and neck regions are abundant in tissues undergoing epithelial-to-mesenchymal transition (EMT). Interstitial carditis and valve insufficiency as well as coronary arterial lesions may complicate KD, and these lesions present in tissues that originated from epicardial progenitor cells by EMT. Having reviewed the recent research on KD, we presume that the signs of KD present at borders between keratinized and non-keratinized stratified squamous epithelium where the EMT is still ongoing for the rapid somatic growth where RBCs are recruited as an innate immune response and to prevent excessive fibrosis in mucosa. KD presents scarcely in adults with somatic growth and immune maturation completed. In this review, we attempted to explain the reasons for the clinical manifestations of KD and to search for a link among the diagnostic clues in the perspective of EMT during the somatic growth and immune system maturation in children with KD.

Rational Engineering Docetaxel Prodrug Nanoassemblies: Response Modules Guiding Efficacy Enhancement and Toxicity Reduction.

Prodrug-based nanoassemblies have been developed to solve the bottlenecks of chemotherapeutic drugs. The fabricated prodrugs usually consist of active drug modules, response modules, and modification modules. Among three modules, the response modules play a vital role in controlling the intelligent drug release at tumor sites. Herein, various locations of disulfide bond linkages were selected as response modules to construct three Docetaxel (DTX) prodrugs. Interestingly, the small structural difference caused by the length of response modules endowed corresponding prodrug nanoassemblies with unique characteristic. α-DTX-OD nanoparticles (NPs) possessed the advantages of high redox-responsiveness due to their shortest linkages. However, they were too sensitive to retain the intact structure in the blood circulation, leading to severe systematic toxicity. β-DTX-OD NPs significantly improved the pharmacokinetics of DTX but may induce damage to the liver. In comparison, γ-DTX-OD NPs with the longest linkages greatly ameliorated the delivery efficiency of DTX as well as improved DTX's tolerance dose.

Design and implementation of a VoIP PBX integrated Vietnamese virtual assistant: a case study

ABSTRACT As digitization is integrated into daily life, media are increasingly transferred over the Internet. Voice-over-Internet Protocol (VoIP), the most popular media transfer technology, is attracting many researchers and investments. The application of Artificial Intelligence (AI) technology into the Private Branch Exchange (PBX) has played a pivotal role in enhancing the customer experience and is able to unite employees in any company. One technology application used to optimize customer experience in a call centre is the use of an automatic PBX integrated with a Virtual Assistant (VA), which interacts directly with the PBX through voice and in multiple languages without any keystrokes. The Interactive Voice Response (IVR) module forwards the customer’s call to an operator or supports automatic processing. This solution can help businesses to handle thousands of calls per day with optimal performance, thus creating a customer care campaign that quickly reaches many users. A PBX integrated with Vietnamese Virtual Assistants (VVA) on an AI technology platform will also help businesses to cut down on operator costs with automated calls. Through comparison with a traditional PBX, this article analyzes, evaluates and optimizes an automatic PBX system with integrated VVA, thereby offering efficient solutions for interest companies.

Identification and characterization of CircRNA-associated CeRNA networks in moso bamboo under nitrogen stress

BackgroundNitrogen is a macronutrient element for plant growth and development. Circular RNAs (circRNAs) serve as pivotal regulators for the coordination between nutrient supply and plant demand. Moso bamboo (Phyllostachys edulis) is an excellent plant with fast growth, and the mechanism of the circRNA-target module in response to nitrogen remains unclear.ResultsDeep small RNA sequencing results of moso bamboo seedlings under different concentrations of KNO3 (N0 = 0 mM, N6 = 6 mM, N18 = 18 mM) were used to identify circRNAs. A total of 549 circRNAs were obtained, of which 309 were generated from corresponding parental coding genes including 66 new ones. A total of 536 circRNA-parent genes were unevenly distributed in 24 scaffolds and were associated with root growth and development. Furthermore, 52 differentially expressed circRNAs (DECs) were obtained, including 24, 33 and 15 DECs from three comparisons of N0 vs. N6, N0 vs. N18 and N6 vs. N18, respectively. Based on integrative analyses of the identified DECs, differentially expressed mRNAs (DEGs), and miRNAs (DEMs), a competitive endogenous RNA (ceRNA) network was constructed, including five DECs, eight DEMs and 32 DEGs. A regulatory module of PeSca_6:12,316,320|12,372,905-novel_miR156-PH02Gene35622 was further verified by qPCR and dual-luciferase reporter assays.ConclusionThe results indicated that circRNAs could participate in multiple biological processes as miRNA sponges, including organ nitrogen compound biosynthesis and metabolic process regulation in moso bamboo. Our results provide valuable information for further study of circRNAs in moso bamboo under fluctuating nitrogen conditions.

The abscisic acid–responsive element binding factors MAPKKK18 module regulates abscisic acid–induced leaf senescence in Arabidopsis

The mitogen-activated protein kinase kinase kinase 18 (MAPKKK18) has been reported to play a role in abiotic stress priming in long-term abscisic acid (ABA) response including drought tolerance and leaf senescence. However, the upstream transcriptional regulators of MAPKKK18 remain to be determined. Here, we report ABA-responsive element binding factors (ABFs) as upstream transcription factors of MAPKKK18 expression. Mutants of abf2, abf3, abf4, and abf2abf3abf4 dramatically reduced the transcription of MAPKKK18. Our electrophoresis mobility shift assay and dual-luciferase reporter assay demonstrated that ABF2, ABF3, and ABF4 bound to ABA-responsive element cis-elements within the promoter of MAPKKK18 to transactivate its expression. Furthermore, enrichments of the promoter region of MAPKKK18 by ABF2, ABF3, and ABF4 were confirmed by invivo chromatin immunoprecipitation coupled with quantitative PCR. In addition, we found that mutants of mapkkk18 exhibited obvious delayed leaf senescence. Moreover, a genetic study showed that overexpression of ABF2, ABF3, and ABF4 in the background of mapkkk18 mostly phenocopied the stay-green phenotype of mapkkk18 and, expression levels of five target genes of ABFs, that is, NYE1, NYE2, NYC1, PAO, and SAG29, were attenuated as a result of MAPKKK18 mutation. These findings demonstrate that ABF2, ABF3, and ABF4 act as transcription regulators of MAPKKK18 and also suggest that, at least in part, ABA acts in priming leaf senescence via ABF-induced expression of MAPKKK18.

Uganda's experience in establishing an electronic compendium for public health emergencies.

Uganda has implemented several interventions that have contributed to prevention, early detection, and effective response to Public Health Emergencies (PHEs). However, there are gaps in collecting and documenting data on the overall response to these PHEs. We set out to establish a comprehensive electronic database of PHEs that occurred in Uganda since 2000. We constituted a core development team, developed a data dictionary, and worked with Health Information Systems Program (HISP)-Uganda to develop and customize a compendium of PHEs using the electronic Integrated Disease Surveillance and Response (eIDSR) module on the District Health Information Software version 2 (DHIS2) platform. We reviewed literature for retrospective data on PHEs for the compendium. Working with the Uganda Public Health Emergency Operations Center (PHEOC), we prospectively updated the compendium with real-time data on reported PHEs. We developed a user's guide to support future data entry teams. An operational compendium was developed within the eIDSR module of the DHIS2 platform. The variables for PHEs data collection include those that identify the type, location, nature and time to response of each PHE. The compendium has been updated with retrospective PHE data and real-time prospective data collection is ongoing. Data within this compendium is being used to generate information that can guide future outbreak response and management. The compendium development highlights the importance of documenting outbreak detection and response data in a central location for future reference. This data provides an opportunity to evaluate and inform improvements in PHEs response.

CAR-T Cell Therapy and the Gut Microbiota.

Chimeric antigen receptor (CAR) - T cell cancer therapy has yielded promising results in treating hematologic malignancies in clinical studies, and a growing number of CAR-T regimens are approved for clinical usage. While the therapy is considered of great potential in expanding the cancer immunotherapy arsenal, more than half of patients receiving CAR-T infusions do not respond, while others develop significant adverse effects, collectively indicating a need for optimization of CAR-T treatment to the individual. The microbiota is increasingly suggested as a major modulator of immunotherapy responsiveness. Studying causal microbiota roles possibly contributing to CAR-T therapy efficacy, adverse effects reduction, and prediction of patient responsiveness constitutes an exciting area of active research. Herein, we discuss the latest developments implicating human microbiota involvement in CAR-T therapy, while highlighting challenges and promises in harnessing the microbiota as a predictor and modifier of CAR-T treatment towards optimized efficacy and minimization of treatment-related adverse effects.

Highly Responsive Plasmon Modulation in Dopant-Segregated Nanocrystals.

Electron transfer to and from metal oxide nanocrystals (NCs) modulates their infrared localized surface plasmon resonance (LSPR), revealing fundamental aspects of their photophysics and enabling dynamic optical applications. We synthesized and chemically reduced dopant-segregated Sn-doped In2O3 NCs, investigating the influence of radial dopant segregation on LSPR modulation and near-field enhancement (NFE). We found that core-doped NCs show large LSPR shifts and NFE change during chemical titration, enabling broadband modulation in LSPR energy of over 1000 cm-1 and of peak extinction over 300%. Simulations reveal that the evolution of the LSPR spectra during chemical reduction results from raising the surface Fermi level and increasing the donor defect density in the shell region. These results establish dopant segregation as a useful strategy to engineer the dynamic optical modulation in plasmonic semiconductor NC heterostructures going beyond what is possible with conventional plasmonic metals.

Immersive security personnel training module for active shooter events

There is a need to prepare for emergencies such as active shooter events. Emergency response training drills and exercises are necessary to train for such events as we are unable to predict when emergencies do occur. There has been progress in understanding human behavior, unpredictability, human motion synthesis, crowd dynamics, and their relationships with active shooter events, but challenges remain. This paper presents an immersive security personnel training module for active shooter events in an indoor building. We have created an experimental platform for conducting active shooter drills for training that gives a fully immersive feel of the situation and allow one to perform virtual evacuation drills. The security personnel training module also incorporates four sub-modules namely 1) Situational assessment module, 2) Individual officer intervention module, 3) Team Response Module, and 4) Rescue Task Force module. We have developed an immersive virtual reality training module for active shooter events using an Oculus for course of action, visualization, and situational awareness for active shooter events as shown in Fig.1. The immersive security personnel training module aims to get information about the emergency situation inside the building. The dispatched officer will verify the active shooter situation in the building. The security personnel should find a safe zone in the building and secure the people in that area. The security personnel should also find the number and location of persons in possible jeopardy. Upon completion of the initial assessment, the first security personnel shall advise communications and request resources as deemed necessary. This will allow determining whether to take immediate action alone or with another officer or wait until additional resources are available. After successfully gathering the information, the personnel needs to update the info to their officer through a communication device.

Immersive security personnel training module for active shooter events

There is a need to prepare for emergencies such as active shooter events. Emergency response training drills and exercises are necessary to train for such events as we are unable to predict when emergencies do occur. There has been progress in understanding human behavior, unpredictability, human motion synthesis, crowd dynamics, and their relationships with active shooter events, but challenges remain. This paper presents an immersive security personnel training module for active shooter events in an indoor building. We have created an experimental platform for conducting active shooter drills for training that gives a fully immersive feel of the situation and allow one to perform virtual evacuation drills. The security personnel training module also incorporates four sub-modules namely 1) Situational assessment module, 2) Individual officer intervention module, 3) Team Response Module, and 4) Rescue Task Force module. We have developed an immersive virtual reality training module for active shooter events using an Oculus for course of action, visualization, and situational awareness for active shooter events as shown in Fig.1. The immersive security personnel training module aims to get information about the emergency situation inside the building. The dispatched officer will verify the active shooter situation in the building. The security personnel should find a safe zone in the building and secure the people in that area. The security personnel should also find the number and location of persons in possible jeopardy. Upon completion of the initial assessment, the first security personnel shall advise communications and request resources as deemed necessary. This will allow determining whether to take immediate action alone or with another officer or wait until additional resources are available. After successfully gathering the information, the personnel needs to update the info to their officer through a communication device.

Exploring release mechanisms by disrupting π-π stacking regions in stable micelles.

π-π stacking strategies can enhance the stability performance of delivery platforms but are often restricted by incomplete drug release performance, even with the help of crosslinking strategies. Therefore, there has been considerable interest in enhancing the drug release performance by disrupting the π-π stacking region (structural rearrangements). Herein, we synthesized poly(3-(isobutyloxy)-2-oxopropyl benzoate)-b-poly(2-hydroxybutyl methacrylate)-co-poly((ethylene glycol)methylether methacrylate) [PBOOPMA-b-P(HBMA-co-PEGMA), PHB] and revealed the drug release mechanism of PHB-based micelles. The structural rearrangements derived from the crosslinking strategy were revealed to improve the early release performance by 43-55% using micellar dissolutions. Moreover, the esterase-responsive strategy was elucidated to induce reassembly with 77-79% size variation, intensifying the structural rearrangements, which was also synergistic with the crosslinking strategy. Based on the advantages of improving drug release performance, the esterase-responsive strategy was considered a promising candidate for enhancing late release performance. Meanwhile, it is believed that such responsive modulation (crosslinking, esterase-responsive) in the π-π stacking region will become highly promising for subsequent research. Finally, the biosafety of 95.81% at 400 mg L-1 and drug cytotoxicity of IC50 ≈ 2.5 mg L-1 of PHB-EDE@CPT were also validated, confirming the broad application prospects of PHB-based crosslinked micelles.

Mechanism underlying the modulation of milk production by incomplete milking.

Mammary gland secretory activity is modulated by systemic and local factors; however, the relationship between these factors is unknown. The aim of this study was to determine how a local factor, such as incomplete milking, affects mammary epithelial cell activity, number, and responsiveness to blood prolactin (PRL). Eight cows in mid-lactation were differentially milked (i.e., their right quarters were milked incompletely at approximately 70%, and their left quarters were milked completely, twice daily for 4 wk). Throughout the experiment, milk yield was measured at the quarter level. Milk samples were collected from each quarter once a week to assess the milk components, and epithelial cell concentrations, as well as to isolate milk fat globule RNA. In the weeks before and after the experiment, mammary gland functional capacity was evaluated by measuring the volume of milk harvested after complete filling of the gland. At the end of the last experimental week, mammary gland biopsies were performed on each rear quarter. The milk production of quarters milked completely remained stable during the treatment period, whereas, as expected, the milk production of quarters milked incompletely was only 53% of completely milked quarters at the end of the period. Accordingly, the expression of genes related to milk synthesis (CSN2, LALBA, and ACACA) in milk fat was lower in the quarters that were milked incompletely. Incomplete milking decreased the milk lactose content, indicating a loss of integrity of tight junctions. The total yield of epithelial cells in milk was not affected, but their concentration in milk, the BAX:BCL2 gene expression ratio, and the loss of mammary functional capacity were greater in the quarters milked incompletely, suggesting an acceleration of involution in those quarters. The expression of the short isoform of the PRL receptor gene (PRLR) tended to be lower, and the expression of STAT5A and STAT5B tended to decline in the quarters milked incompletely. In mammary gland biopsy samples, the number of both short and long isoforms of the PRLR were not affected, nor were the amount and activation of STAT3 and STAT5. However, the ratio of PRLR short isoform to PRLR long isoform was lower in the quarters milked incompletely. The decrease in milk yield induced by incomplete milking is rapid and associated with a decrease in mammary epithelial cell activity and a decrease in the number of secretory epithelial cells. The results of this experiment provide only limited support for the hypothesis that modulation of the mammary gland's responsiveness to PRL is part of the mechanism by which local factors, such as incomplete milking, modulate milk synthesis.

Multi-Label Speech Emotion Recognition via Inter-Class Difference Loss Under Response Residual Network

Speech emotion recognition has always been a challenging task due to the difference in emotion expression and perception. Currently, in the supervised speech emotion recognition systems, the soft label overcomes the disadvantage of the hard label losing annotations variability and emotion perception subjectivity, but it only considers the emotion perceptions of a few annotators and thus still brings high statistical error. For this issue, this paper redefines the target and designs a novel loss function (denoted as inter-class difference loss), which enables the network to adaptively learn an emotion distribution in all utterances. This not only restricts the negative class probability less than the positive class probability, but also limits the negative class probability close to zero. To make the speech emotion recognition system more efficient, this paper proposes an end-to-end network, called response residual network (R-ResNet), which incorporates the ResNet for features extraction, together with the emotion response module for data augmentation and variable-length data processing. Finally, the experimental results not only demonstrate the advanced performance of our work, but also confirm that the ambiguous utterances contain emotional characteristics. In addition, another interesting finding is that, on the unbalanced dataset, the batch normalization (BN) after addition performs better than BN before addition.

Sensitivity of lower-limb joint mechanics to prosthetic forefoot stiffness with a variable stiffness foot in level-ground walking

This paper presents the effectsof the Variable Stiffness Foot (VSF) on lower-limb joint mechanics in level-ground walking. Persons with transtibial amputations use lower-limb prostheses to restore level-ground walking, and foot stiffness and geometry have been shown to be the main factors for evaluating foot prostheses. Previous studies have validated the semi-active and stiffness modulation capabilities of the VSF. The core aim of this study is to investigate the mechanical effects of adjusting stiffness on knee and ankle mechanics for prosthetic users wearing the VSF. For this study, seven human participants walked with three different stiffnesses (compliant, medium, stiff) of the VSF across two force plates in a motion capture lab. Linear mixed models were utilized to estimate the significance and coefficients of determinations for the regression of stiffness on several biomechanical metrics. A stiffer VSF led to decreased ankle dorsiflexion angle (p < 0.0001, r2 = 0.90), increased ankle plantarflexor moment (p = 0.016, r2 = 0.40), increased knee extension (p = 0.021, r2 = 0.37), increased knee flexor moment (p = 0.0007, r2 = 0.63), and decreased magnitudes of prosthetic energy storage (p < 0.0001, r2 = 0.90), energy return (p = 0.0003, r2 = 0.67), and power (p < 0.0001, r2 = 0.74). These results imply lower ankle, knee, and hip moments, and more ankle angle range of motion using a less stiff VSF, which may be advantageous to persons walking with lower-limb prostheses. Responsive modulation of the VSF stiffness, according to these findings, could help overcome gait deviations associated with different slopes, terrain characteristics, or footwear.

Growth-regulating factor 15-mediated gene regulatory network enhances salt tolerance in poplar.

Soil salinity is an important determinant of crop productivity and triggers salt stress response pathways in plants. The salt stress response is controlled by transcriptional regulatory networks that maintain regulatory homeostasis through combinations of transcription factor (TF)-DNA and TF-TF interactions. We investigated the transcriptome of poplar 84 K (Populus alba × Populus glandulosa) under salt stress using samples collected at 4- or 6-h intervals within 2 days of salt stress treatment. We detected 24,973 differentially expressed genes, including 2,231 TFs that might be responsive to salt stress. To explore these interactions and targets of TFs in perennial woody plants, we combined gene regulatory networks, DNA affinity purification sequencing, yeast two-hybrid-sequencing, and multi-gene association approaches. Growth-regulating factor 15 (PagGRF15) and its target, high-affinity K+ transporter 6 (PagHAK6), were identified as an important regulatory module in the salt stress response. Overexpression of PagGRF15 and PagHAK6 in transgenic lines improved salt tolerance by enhancing Na+ transport and modulating H2O2 accumulation in poplar. Yeast two-hybrid assays identified more than 420 PagGRF15-interacting proteins, including ETHYLENE RESPONSE FACTOR TFs and a zinc finger protein (C2H2) that are produced in response to a variety of phytohormones and environmental signals and are likely involved in abiotic stress. Therefore, our findings demonstrate that PagGRF15 is a multifunctional TF involved in growth, development, and salt stress tolerance, highlighting the capability of a multifaceted approach in identifying regulatory nodes in plants.

SlGATA17, A tomato GATA protein, interacts with SlHY5 to modulate salinity tolerance and germination

The GATA transcription factor family participates in plant biological processes and abiotic stress across various crop species, but their function in response to salinity stress remains unexplored, particularly in tomato. Here, a tomato (Solanum lycopersicum) GATA gene, SlGATA17, was characterized in the tolerance to salinity stress. SlGATA17 had transcription activity in yeast, and the transcriptional activation domain was location on 32–60 amino acids of the N-terminal. SlGATA17 expression was induced by heat, cold, ABA, ACC and IAA treatments, but inhibited by NaCl and PEG treatments. In this study, the Slgata17 mutant plants showed slight injury symptoms compared to wild-type plants under salinity stress, and higher expression levels of stress-related marker genes (SlDREB2A, SlAREB1, SlRD29A and SlP5CS1). Heterologous expression of SlGATA17 in Arabidopsis promoted seed germination under NaCl, ABA and mannitol conditions, and inhibited ABA content and the expression levels of ABA related genes (AtNCED3, AtNCED5, AtNCED9, AtABI3, AtEM1 and AtEM6). However, SlGATA17 transgenic Arabidopsis were hypersensitive to NaCl at the post-germination stage. Yeast two assay and BiFC assay showed that tomato transcription factor ELONGATED HYPOCOTYL (SlHY5) interacts with SlGATA17. Yeast one assay and Dual-Luc assay showed that SlHY5 negatively regulated SlGATA17 expression via binding to the GATA-box of SlGATA17 promoter. SlHY5-SlGATA17 might function as a regulatory module in response to abiotic stress.

Kinase MxMPK4-1 and calmodulin-binding protein MxIQM3 enhance apple root acidification during Fe deficiency.

Iron (Fe) deficiency is a long-standing issue in plant mineral nutrition. Ca2+ signals and the mitogen-activated protein kinase (MAPK) cascade are frequently activated in parallel to perceive external cues, but their interplay under Fe deficiency stress remains largely unclear. Here, the kinase MxMPK4-1, which is induced during the response to Fe deficiency stress in apple rootstock Malus xiaojinensis, cooperates with IQ-motif containing protein3 (MxIQM3). MxIQM3 gene expression, protein abundance, and phosphorylation level increased under Fe deficiency stress. The overexpression of MxIQM3 in apple calli and rootstocks mitigated the Fe deficiency phenotype and improved stress tolerance, whereas RNA interference or silencing of MxIQM3 in apple calli and rootstocks, respectively, worsened the phenotype and reduced tolerance to Fe deficiency. MxMPK4-1 interacted with MxIQM3 and subsequently phosphorylated MxIQM3 at Ser393, and co-expression of MxMPK4-1 and MxIQM3 in apple calli and rootstocks enhanced Fe deficiency responses. Furthermore, MxIQM3 interacted with the central-loop region of the plasma membrane (PM) H+-ATPase MxHA2. Phospho-mimicking mutation of MxIQM3 at Ser393 inhibited binding to MxHA2, but phospho-abolishing mutation promoted interaction with both the central-loop and C terminus of MxHA2, demonstrating phosphorylation of MxIQM3 caused dissociation from MxHA2 and therefore increased H+ secretion. Moreover, Ca2+/MxCAM7 (Calmodulin7) regulated the MxMPK4-1-MxIQM3 module in response to Fe deficiency stress. Overall, our results demonstrate that MxMPK4-1-MxIQM3 forms a functional complex and positively regulates PM H+-ATPase activity in Fe deficiency responses, revealing a versatile mechanism of Ca2+/MxCAM7 signaling and MAPK cascade under Fe deficiency stress.

The module triad: a novel network biology approach to utilize patients’ multi-omics data for target discovery in ulcerative colitis

Tumor necrosis factor-alpha inhibitors (TNFi) have been a standard treatment in ulcerative colitis (UC) for nearly 20 years. However, insufficient response rate to TNFi therapies along with concerns around their immunogenicity and inconvenience of drug delivery through injections calls for development of UC drugs targeting alternative proteins. Here, we propose a multi-omic network biology method for prioritization of protein targets for UC treatment. Our method identifies network modules on the Human Interactome—a network of protein-protein interactions in human cells—consisting of genes contributing to the predisposition to UC (Genotype module), genes whose expression needs to be modulated to achieve low disease activity (Response module), and proteins whose perturbation alters expression of the Response module genes to a healthy state (Treatment module). Targets are prioritized based on their topological relevance to the Genotype module and functional similarity to the Treatment module. We demonstrate utility of our method in UC and other complex diseases by efficiently recovering the protein targets associated with compounds in clinical trials and on the market . The proposed method may help to reduce cost and time of drug development by offering a computational screening tool for identification of novel and repurposing therapeutic opportunities in UC and other complex diseases.