Mechanical Response Research Articles

Hydroponic Culture of Rice Seedlings for Stress Response Assay.

The major environmental factors limiting rice growth and production are osmotic stresses such as drought and high salinity. High osmotic stresses directly disrupt cellular activities, leading to plant growth retardation or death. Plants have various response mechanisms to survive under such stresses. Understanding rice's stress response mechanisms is necessary to enhance the osmotic stress tolerance of rice. However, assessing specific physiological responses to osmotic stresses is difficult because multiple environmental factors affect rice growth. Here, we describe a simple method for analyzing the osmotic stress responses of rice plants using a hydroponic culture system. This method allows comprehensive gene expression and phenotypic analyses under osmotic stress conditions in rice. Various osmotic stress conditions and samples can be tested simultaneously because this method is small-scale. In addition, the procedure is easy, and highly reproductive results can be obtained.

Understanding cold stress response mechanisms in plants: an overview

Low-temperature stress significantly impacts plant growth, development, yield, and geographical distribution. However, during the long-term process of evolution, plants have evolved complicated mechanisms to resist low-temperature stress. The cold tolerance trait is regulated by multiple pathways, such as the Ca2+ signaling cascade, mitogen-activated protein kinase (MAPK) cascade, inducer of CBF expression 1 (ICE1)-C-repeat binding factor (CBF)-cold-reulated gene (COR) transcriptional cascade, reactive oxygen species (ROS) homeostasis regulation, and plant hormone signaling. However, the specific responses of these pathways to cold stress and their interactions are not fully understood. This review summarizes the response mechanisms of plants to cold stress from four aspects, including cold signal perception and transduction, ICE1-CBF-COR transcription cascade regulation, ROS homeostasis regulation and plant hormone signal regulation. It also elucidates the mechanism of cold stress perception and Ca2+ signal transduction in plants, and proposes the important roles of transcription factors (TFs), post-translational modifications (PTMs), light signals, circadian clock factors, and interaction proteins in the ICE1-CBF-COR transcription cascade. Additionally, we analyze the importance of ROS homeostasis and plant hormone signaling pathways in plant cold stress response, and explore the cross interconnections among the ICE1-CBF-COR cascade, ROS homeostasis, and plant hormone signaling. This comprehensive review enhances our understanding of the mechanism of plant cold tolerance and provides a molecular basis for genetic strategies to improve plant cold tolerance.

Expression Analysis of the Extensive Regulation of Mitogen-Activated Protein Kinase (MAPK) Family Genes in Buckwheat (Fagopyrum tataricum) During Organ Differentiation and Stress Response

The mitogen-activated protein kinase (MAPK) signaling cascade is a unique and relatively conserved signaling pathway in eukaryotes, transmitting extracellular signals into cells through successive phosphorylation and eliciting appropriate responses from the organism. While its mechanism in plant immune response has been partially elucidated in Arabidopsis, it has been rarely examined in Tartary buckwheat (Fagopyrum tataricum). Based on the conserved MAPK domain, we identified 16 MAPK family genes in Tartary buckwheat. The FtMAPKs have similar structures and motif compositions, indicating that this gene family is conserved yet functionally diverse. Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis, we observed significant expression variation in 15 genes across different organs, except for FtMAPK12. FtMAPK9 showed specific expression in vegetative organs, FtMAPK4 in reproductive organs, and FtMAPK1 and FtMAPK10 in leaves and flowers, respectively, indicating their regulatory roles in Tartary buckwheat development. Following drought and salt stress treatments, 12 and 14 FtMAPKs, respectively, showed significantly altered expression in leaves exhibiting notable biological oxidation. Among these, FtMAPK3, FtMAPK4, and FtMAPK8 demonstrated highly significant changes across both treatments. Transcriptome analysis confirmed these findings, suggesting that these three genes play pivotal roles in Tartary buckwheat’s response to abiotic stress and hold potential for molecular breeding improvements.

Environmental and Molecular Regulation of Flowering in Cultivated Strawberry (Fragaria x ananassa)

Abstract Cultivated strawberry (Fragaria x ananassa) is a globally important fruit crop which shows promise as a candidate for various methods of controlled environment production. However, a better understanding of the mechanisms of the regulation of flowering is needed, as more frequent or consistent flowering would be advantageous in controlled production. It is well understood that flowering in F. x ananassa responds to both photoperiod and temperature, however, the mechanism behind this response is not fully understood, particularly in perpetually flowering cultivars. While some genes of interest have been identified, a more complete model has not been established. This is largely due to the complexity of the octoploid genome and a lack of current knowledge on the mechanism of temperature response in both seasonal- and perpetual-flowering F. x ananassa. A starting point for developing a better model of flowering response in cultivated strawberries lies in the simpler Fragaria vesca, which indicates a FvCO-FvFT1-FvSOC1-FvTFL1 module for control of seasonal flowering and a lack of functional FvTFL1 responsible for perpetual flowering. However, there are some key differences when discussing F. x ananassa's perpetual flowering characteristics. Recent studies have helped to elucidate some of these differences, allowing for a putative model of seasonal flowering in F. x ananassa, as well as indicating where further questions need to be asked regarding perpetually flowering cultivars.

Cyclic stretch regulates epithelial cell migration in a frequency dependent manner via intercellular vinculin recruitment

AbstractThe epithelial microenvironment is incredibly dynamic, subjected to mechanical cues including cyclic stretch. While cyclic cell stretching platforms have revealed epithelial cell reorientation and gap formation, few studies have investigated the long-term effects of cyclic stretch on cell migration. We measured the migratory response of the epithelium to a range of physiologically relevant frequencies and stretch. Our results indicate that lower stretch frequencies (i.e., 0.1 Hz) suppress epithelial migration, accompanied by cell reorientation and high cell shape solidity. We found that this response is also accompanied by increased recruitment of vinculin to cell-cell contacts, and this recruitment is necessary to suppress cell movements. These results confirm the mechanosensitive nature of vinculin within the adherens junction, but independently reveal a novel mechanism of low frequency stress response in supporting epithelial integrity by suppressing cell migration.

Effect of Structure on Osteogenesis of Bone Scaffold: Simulation Analysis Based on Mechanobiology and Animal Experiment Verification

Porous scaffolds, whose mechanical and biological properties are greatly affected by structure, are new treatments for bone defects. Since bone repair is related to biomechanics, analyzing the osteogenesis in scaffolds based on mechanical stimulation may become a more effective method than traditional biological experiments. A tissue regeneration algorithm based on mechanical regulation theory was implemented in this study to evaluate the osteogenesis of classical scaffolds (Gyroid, I-WP, and Diamond). In vivo experiments were used to verify and supplement the simulation results. Different approaches to describing osteogenesis were discussed. Bone formation was more obvious inside the Gyroid scaffold and outside the I-WP scaffold, while the new bone was more sufficient and evenly distributed in the Diamond scaffold. The osteogenesis pattern of the bone scaffold in the simulation analysis was consistent with the results of animal experiments, and the bone volume calculated by the tissue fraction threshold method and the elastic modulus threshold method was very similar to the in vivo experiment. The mechanical responses mediated by structure affect the osteogenesis of bone scaffolds. This study provided and confirmed a simulation analysis method based on mechanical regulation theory, which is more efficient and economical for analyzing tissue healing in bioengineering.

Data-Driven Surrogate Modeling with Microstructure-Sensitivity of Viscoplastic Creep in Grade 91 Steel

AbstractTo support the development of advanced steel alloys tailored to withstand extreme conditions, it is imperative to account for the mechanical performance of components, while considering the influence of local microstructure on the macroscopic response. To this end, this study focuses on the development of microstructure-sensitive constitutive models for the mechanical response of Grade 91 steel exposed to extreme thermo-mechanical environments. Polynomial chaos expansion (PCE) surrogates are used to emulate high-fidelity polycrystal simulations of the viscoplastic response of Grade 91 steel as a function of the microstructure fingerprint (e.g., dislocations and precipitates). To cover a wide temperature–stress domain, two separate PCE surrogates—one that captures softening and the other that captures hardening behavior—are combined using another (sparse) Gaussian process regression model. The resulting constitutive creep surrogate model is integrated within the MOOSE finite element framework to simulate the intricate effects of microstructure, in particular MX-phase precipitates, on a component with a graded microstructure. Surrogate sensitivity analysis is applied to quantify the relevant impact of spatially varying microstructure on the creep response in a test-case involving a Grade 91 alloy with a prototypical weld.

Sedimentary Environment Reconstruction and Organic Matter Enrichment Mechanisms in Various Lithofacies of the Lacustrine Shale: A Case Study of the Da’anzhai Member, Central Sichuan Basin, China

Jurassic lacustrine shale in the Sichuan Basin is a focal exploration area in China, while the pronounced heterogeneity presents challenges, necessitating detailed research as a prerequisite. This study aims at the Jurassic Ziliujing Formation Da’anzhai shale in the central Sichuan Basin, systematically characterizing its geological features. Employing geochemical methods, we reconstructed the paleo-sedimentary environments and explored the mechanisms behind the organic matter enrichment. The findings reveal that the Da’anzhai shale exhibits three lithofacies: organic-rich argillaceous shale (ORA), organic-poor argillaceous shale (OPA), and organic-rich mixed shale (ORM). The sedimentary period was marked by a warm and humid climate, predominantly depositing in anoxic environments with freshwater to brackish conditions. The watershed areas that are provenance sources for the shale clastics are experiencing strong weathering. Significant differences in the sedimentary environments of various lithofacies’ shale were observed. Redox conditions and paleoclimate were identified as the primary factors controlling organic matter enrichment in the Da’anzhai shale of the study area. Salinity also played a role in organic matter enrichment, while terrigenous debris influx and paleo-productivity did not exert a significant controlling effect on organic matter enrichment. Utilizing the reconstructed ancient sedimentary environments, we developed sedimentary models for different lithofacies’ shale, contributing to a deeper understanding of lithofacies’ diversity and the mechanisms governing organic matter enrichment in lacustrine environments. This study provides new information for further understanding the response mechanism of lacustrine shales to the Toarcian Oceanic Anoxic Event in the Early Jurassic from the perspective of elemental geochemistry.

Strain-Induced Tunable Enhancement of Piezoelectricity in a Novel Molecular Multiferroic Material.

Multiferroics are appealing because of application potentials in data storage devices, sensors, transducers, and energy harvesters. Molecular multiferroics emerge as a promising alternative to inorganic multiferroics due to flexibility, light weight, low toxicity, solution processing, structural diversity, and chemical tunability. While researches have predominantly focused on perovskite structures, studies on molecular ionic multiferroics remain relatively limited. It is urgent to creatively build a novel platform for studying and developing the coupling and interaction between the stress, electricity, and magnetism. Knowing this, the work focuses on a novel organic-inorganic hybrid multiferroic N-ethyl-N-(fluoromethyl)-N-methylethylammonium tetrabromoferrate (III) showing coexisting magnetic and electric orderings. It undergoes antiferromagnetic, ferroelectric, and ferroelastic transitions. Notably, under a strain of 2.0%, the piezoelectric response increases tenfold, and the coercive field of ferroelectric polarization is reduced by half. The strain-induced enhancement of piezoelectricity is rarely reported in molecular multiferroics. Density functional theory is employed to predict that the mechanism of the large piezoelectric response under strain engineering is related to the cation rotation and phase switching between the stable phase and an energetically competitive metastable phase. This study creates a new paradigm to develop molecular multiferroics and future microelectronic devices for energy conversion.

Forced Vibration Induced by Dynamic Response Under Different Inlet Distortion Intensities

Boundary layer ingestion propulsion systems have attracted much attention due to their significant potential to reduce the fuel consumption of future commercial aircraft. However, the aeroelastic stability of the fan blade is affected by the continuous non-uniform incoming flow induced by the ingestion of the boundary layer. When the fan blades rotate in the junction area between the distorted area and the clean area, blade pressure fluctuations occur. This phenomenon triggers a dynamic response process in the blade. Previous numerical investigations explored the influence of the distorted inflow on the blade vibration amplitude, and found that there are two sources of low-order excitation to the blades: the distorted inflow and the dynamic response of the blade. The results show that the low-order excitation existing in the distorted inflow varies sinusoidally with the distortion extent. However, as a new source of excitation, the key influence mechanism of dynamic response is still unclear. To explore this issue, calculations and analyses were conducted for different distorted inflow intensities. The results show that the blade vibration amplitude increases with the rise in distortion intensity. The total pressure at the leading and trailing edge of the rotor blade was extracted for analysis. It was found that when the blade enters or leaves the distorted area, there is a consistent lag in the change in total pressure at the trailing edge compared to the leading edge. This lag leads to an abrupt variation in the total pressure ratio, which constitutes the dynamic response process of the rotor blade. This periodic change generates a second-order excitation that causes the blade to vibrate.

Sex Differences in Blood Accumulation of Neurodegenerative-Related Proteins and Antioxidant Responses to Regular Physical Exercise

Physical activity has been demonstrated to improve cognitive function, thereby preventing/slowing neurodegenerative diseases (NDs). Biological responses to physical activity and vulnerabilities to NDs are emerging to be gender-related. Herein, known ND-associated markers (β-amyloid, tau, α-synuclein), main sex steroid hormones, antioxidant responses, and key gene transcription modulators were evaluated in the blood of physically active and sedentary women and men. In our hands, females presented higher basal erythrocytes β-amyloid and α-synuclein amounts than males. Regular physical activity was able to significantly reduce the erythrocyte content of β-amyloid in females and the tau levels in males, suggesting that these differences may be mediated by organizational actions of sex steroid hormones during development. Furthermore, despite a comparable plasma antioxidant capability (AOC) between males and females, in the latter group, physical activity significantly enhances AOC versus peroxynitrite radicals only. Finally, regular physical activity modulated the levels of transcription factor Nrf2 in erythrocytes, as well as the plasma concentration of the microRNA miR-195 and miR-153, suggesting the promotion of antioxidant/autophagic processes associated with ND-related proteins. Overall, these results could shed light on how cerebral adaptations to physical activity differ between males and females, especially with regard to blood accumulation of ND proteins and mechanisms of antioxidant responses to regular exercise.

Fiscal consolidation plans with underground economy

AbstractFiscal consolidation literature often neglects that there are economies characterized by sizable underground sectors, with their mechanisms of response to fiscal policy shocks. Therefore, reliable analyses of fiscal consolidation plans call for the decomposition of Gross Domestic Product in its regular and hidden components. We investigate fiscal consolidation effects in the context of tax evasion for the Italian economy. Results show that a temporary cut in public spending associated with a permanent drop in tax rate yet entails tax evasion reduction. The main underlying mechanism is the strong responsiveness of the underground sector, implying a reallocation of resources toward the regular sector.

Self-Healing and Mechanical Behaviour of Fibre-Reinforced Ultra-High-Performance Concrete Incorporating Superabsorbent Polymer Under Repeated and Sustained Loadings

This study investigated the mechanical responses and self-healing capability of incorporating superabsorbent polymer (SAP) particles in Fibre-Reinforced Ultra-High-Performance Concrete (UHPC) mixes under repetitive flexural and sustained tensile loadings. UHPC with SAP addition of 0.3% and 0.4% of the binder ratio were studied along with a control UHPC mix. The methodology included investigating the mechanical properties of these mixes under ambient, water, and 100% of relative humidity (RH) curing conditions. In addition, the mechanical performance of ambient-, water-, and 100% RH-cured prismatic specimens (100 mm × 100 mm × 500 mm) under repeated load was studied under the same curing conditions. Prismatic specimens (75 mm × 75 mm × 500 mm) were kept under cure conditions of wet and dry cycles with applied tensile load for 28 days for the sustained tensile load. The results showed that incorporating SAP into UHPC enhances the elastic modulus, flexural strength, and tensile strength. Also, mixes with SAP have exhibited compressive strength above 120 MPa after 90 days. Furthermore, the load recovery of the prisms under repetitive flexural load and prisms under sustained tensile loading demonstrated the self-healing efficiency of SAP incorporated into the UHPC mixes higher than the control mix specimens.

Recent Advances in Additive Manufacturing of Fibre-Reinforced Materials: A Comprehensive Review

Additive manufacturing (AM) plays a significant role in the 4th Industrial Revolution due to its flexibility, allowing AM equipment to be connected, monitored, and controlled in real time. In advance, the minimum waste of material, the agility of manufacturing complex geometries, and the ability to use recycled materials can provide an advantage to this manufacturing method. On the other hand, the poor strength and durability of the thermoplastics used in the manufacturing process are the major drawback that keeps AM behind common production methods such as casting and machining. Fibre-reinforced polymers can enhance mechanical properties, advance AM from the commonly used polymers, and make AM competitive against conventional production methods. The main focus of the current review is to examine the work conducted in the field of reinforced additively manufactured technologies in the literature of recent years. More specifically, this review discusses the conducted research in the composite fibre coextrusion (CFC) additive manufacturing techniques developed over the past years and the materials that can be used. In addition, this study includes an up-to-date comprehensive review of the evaluation of fibre-reinforced 3D printing along with its benefits in terms of mechanical response, namely tensile, flexural, compression and energy absorption, anisotropy, and dynamic properties. Finally, this review highlights possible research gaps regarding fibre-reinforced AM and proposes future directions, such as deeper investigations into energy absorption and anisotropy, to position fibre-reinforced AM as a preferred fabrication method for ready-to-use parts in cutting-edge industries, including automotive, aerospace, and biomedical sectors.

To the top or into the dark? Relationships between elevational and canopy cover distribution shifts in mountain forests

Numerous studies have reported that observed species shifts in mountain areas lag behind expectations under current warming trends, however, the mechanisms remain poorly understood. One important mechanism might be microclimatic heterogeneity causing migration of species to cooler conditions under closed forest canopies, but evidence is scarce. We here compared the distributions of 710 species (11 taxonomic groups including fungi, plants, and animals) along an elevation gradient (287–1419 m a.s.l.) in a temperate low mountain range between 2006–2008 and 2016–2017 to address this open question. We characterized each species' distribution (peak and breadth) based on their abundance along two environmental gradients: elevation and canopy cover. We then analysed changes in species' distribution peaks, asking whether shifts in canopy distribution and initial distribution characteristics explain variation in elevational distribution shifts. Across all taxa, the mean shift in elevational distribution peak was + 35.3 m (i.e. upslope). Species' baseline distribution peaks were strong predictors of elevational distribution shifts with stronger upslope shifts in low‐elevation and open‐forest species. Even though we observed considerable variation in the responses among species, canopy distribution shifts had a significant negative effect on elevational distribution shifts overall and in six taxonomic groups. We suggest that this is related to cooler microclimatic conditions under closed compared to open forest canopies. Shifts to closed‐canopy forests may thus partly compensate for elevational distribution shifts, highlighting the conservation value of heterogeneous landscapes featuring microclimatic refugia. Yet, it is likely that other mechanisms, such as habitat limitation, are also at play. Future studies need to quantify the potential of microclimatic refugia under accelerating forest dynamics, considering the interplay of canopy cover and other factors driving microclimate, and to illuminate the complex climate change response mechanisms among species and taxonomic groups.

Spatiotemporal Variations and Driving Factors of Ecological Sensitivity in the West Qinling Mountains, China, Under the Optimal Scale

This study selected the five indicators of soil erosion, climate environment, geological hazards, biodiversity, and human disturbances and uses the entropy weight method to calculate the ecological sensitivity of the West Qinling Mountains from 2000 to 2020. The analysis produced a spatiotemporal distribution of ecological sensitivity over the 20-year period. An equal step size of 500 m was used to progressively increase the spatial scale from 500 m to 6 km. The optimal scale for the spatial differentiation of ecological sensitivity in the West Qinling Mountains was determined by analyzing the characteristics of changes at different scales, response mechanisms, and optimal parameters for geographical detector spatial scale identification. Based on this scale, the change in intensity and pattern and the influencing factors of ecological sensitivity were analyzed. The results show the following: (1) The 5.5 km spatial scale balances the requirements of accuracy, spatial heterogeneity, and data adequacy, making it the optimal scale for analyzing the spatiotemporal variation patterns of ecological sensitivity in the West Qinling Mountains. (2) From 2000 to 2020, the mean ecological sensitivity in the West Qinling Mountains exhibited a decreasing trend, indicating an improvement in the ecological environment. Spatially, the ecological sensitivity of the West Qinling Mountains showed a spatial distribution pattern of “low in the west and high in the east, low in the south and high in the north”. During the study period, the ecological sensitivity in the West Qinling region remained generally stable, with no high-frequency changes observed. (3) Population density is the primary driving factor of spatial differentiation of ecological sensitivity in the West Qinling Mountains, while GDP serves as a secondary factor. Overall, socioeconomic factors have the most significant impact on ecological sensitivity. (4) Over 75% of the ecological sensitivity trends exhibit patterns of perennial unchanged and fluctuating unchanged trends, with areas of fluctuating increase smaller than areas of fluctuating decrease. Regions of perennial high sensitivity are primarily concentrated in the northeastern part of the West Qinling Mountains, while areas with increased fluctuation in ecological sensitivity are mainly located in the western and southern parts of the West Qinling Mountains. Future efforts should focus on these regions.

Hypoxia stress: plant's sensing, responses, and tolerance mechanisms.

Oxygen (O2) is an inhibiting factor for plant growth and development in submerged and flooding environments. Plants experience different O2 concentrations, such as normoxia, hypoxia, and anoxia, which can change over space and time. Plants have evolved various morphological, physiological, and biochemical adaptations to withstand low O2 stress, many of which have been well investigated. This review provides a detailed analysis of how plants respond to hypoxia, a significant stress factor primarily caused by flooding. Hypoxia affects plants at various cellular, developmental, and environmental levels. This review highlights genetic, molecular, and metabolic adaptations crops employ to cope with O2 deficiency. The roles of various transcription factors (TFs) and gene regulation mechanisms in enabling plants to modulate their physiological responses under hypoxic conditions are notable. The review also identifies a significant gap in research on plant responses during reoxygenation, the phase of returning to normal O2 levels, especially under natural lighting conditions. This transition poses ROS generation and photoinhibition challenges, affecting plant recovery post-hypoxia. We discuss various strategies to enhance plant hypoxia tolerance, including traditional breeding, genetic modification, and grafting techniques. It emphasizes integrating these approaches with a comprehensive understanding of hypoxia sensing and response mechanisms. We underscore the complexity of plant adaptations to hypoxia and the need for continued research in this field, especially in the face of global climate change. This is vital for developing sustainable agricultural practices and ensuring future food security.

Identification of virus epitopes and reactive T-cell receptors from memory T cells without peptide synthesis

Identifying epitopes and their corresponding T-cell receptor (TCR) sequences is crucial in the face of rapidly mutating viruses. Peptide synthesis is often required to confirm the exact epitope sequences, which is time-consuming and expensive. In this study, we introduce a scalable workflow to identify the exact sequences of virus epitopes and reactive TCRs targeting the epitopes from memory T cells. Following the narrowing down of epitopes to specific regions via the tandem minigene (TMG) system, our workflow incorporates the utilization of peptide-major histocompatibility complex-displaying yeasts (pMHC-displaying yeasts) to rapidly screen immunogenic epitopes’ precise sequences, obviating the necessity for the chemical synthesis of peptides. Focusing on SARS-CoV-2, we identify the precise sequences of reactive TCRs, targeting conserved epitopes across the Coronaviridae family, from the blood of COVID-19-recovered individuals over 8 months. Notably, we reveal that at least 75% (6/8) of the tested donors harbor T cells targeting a shared epitope, KTFPPTEPK, derived from the N protein. Furthermore, several identified TCRs exhibit cross-reactivity to mutant epitopes, suggesting a potential mechanism for sustained T-cell responses against emerging SARS-CoV-2 variants.

Proteome Profiling of Cucurbita pepo Phyllosphere After Infection by Podosphaera xanthii and Application of Reynoutria sachalinensis Extract

Podosphaera xanthii is the main causal agent of powdery mildew (PM) disease for Cucurbita pepo. Disease control is attained principally by applications of chemical fungicides, along with parallel use of tolerant crop varieties and alternate application of elicitors to control development of disease resistance. To get insight into C. pepo molecular responses to P. xanthii infection and elicitor treatment we studied the proteomic profile differences at the phyllosphere of a zucchini cultivar susceptible to PM, at the onset of P. xanthii (PX) infection and after application of Reynoutria sachalinensis (RS) plant extract, respectively, using a nano-LC-HRMS/MS, Q-Exactive-Orbitrap approach. Analysis of peptide sequences regarding four treatment groups (Control; PX; RS; and RSPX (PX-infected priorly treated with RS)) resulted in 2070 CuGenDB annotations. Three comparisons (treatments vs. Control) encompassed most of the Differentially Expressed Proteins (DEPs). In these three comparisons, KEGG and Gene Ontology functional analyses highlighted unique differentially enriched pathways—some of which included highly expressed proteins—in PX-related (proteasome, pentose phosphate pathway, and carbon fixation), RS-related (biosynthesis of secondary metabolites, flavonoids, and starch and sucrose metabolism), and RSPX-related (pyruvate metabolism and polycomb repressive complex) comparisons, respectively, suggesting distinct mechanisms of early plant responses modulated by PX and RS. Furthermore, in four out of six comparisons the thiamine metabolism pathway was found to be enriched, suggesting a pivotal role in PX-induced responses.

Circulating microRNAs associated with bronchodilator response in childhood asthma

BackgroundBronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology.ObjectiveThe purpose of this study is to identify circulating miRNAs associated with bronchodilator response in asthma and decipher possible mechanism of bronchodilator response variation.MethodsWe used available small RNA sequencing on blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We filtered the participants into the highest and lowest bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N = 277) vs. low (N = 278) BDR group. Replication was carried out in the Leukotriene modifier Or Corticosteroids or Corticosteroid-Salmeterol trial (LOCCS), an adult asthma cohort. The putative target genes of DE miRNAs were identified, and pathway enrichment analysis was performed.ResultsWe identified 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR = 2.26) between high and low BDR group. These were assessed for replication in the LOCCS cohort, where two miRNAs (miR-200b-3p and miR-1246) were associated. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways.ConclusionMiRNAs miR-1246 and miR-200b-3p are associated with both childhood and adult asthma BDR. Our findings add to the growing body of evidence that miRNAs play a significant role in the difference of asthma treatment response among patients as it points to genomic regulatory machinery underlying difference in bronchodilator response among patients.Trial registrationLOCCS cohort [ClinicalTrials.gov number NCT00156819, Registration date 20050912], GACRS cohort [ClinicalTrials.gov number NCT00021840].