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International Journal of Molecular... Mar 2021is a dominant pathogen in people with cystic fibrosis (CF) contributing to morbidity and mortality. Its tremendous ability to adapt greatly facilitates its capacity to... (Review)
Review
is a dominant pathogen in people with cystic fibrosis (CF) contributing to morbidity and mortality. Its tremendous ability to adapt greatly facilitates its capacity to cause chronic infections. The adaptability and flexibility of the pathogen are afforded by the extensive number of virulence factors it has at its disposal, providing with the facility to tailor its response against the different stressors in the environment. A deep understanding of these virulence mechanisms is crucial for the design of therapeutic strategies and vaccines against this multi-resistant pathogen. Therefore, this review describes the main virulence factors of and the adaptations it undergoes to persist in hostile environments such as the CF respiratory tract. The very large genome (5 to 7 MB) contributes considerably to its adaptive capacity; consequently, genomic studies have provided significant insights into elucidating evolution and its interactions with the host throughout the course of infection.
Topics: Adaptation, Physiological; Animals; Biofilms; Humans; Lung; Pseudomonas aeruginosa; Quorum Sensing; Virulence Factors
PubMed: 33803907
DOI: 10.3390/ijms22063128 -
International Journal of Environmental... Mar 2023Strength training in prepubertal children is one of the topics that has aroused the most interest and controversy among training professionals in recent years.... (Review)
Review
Strength training in prepubertal children is one of the topics that has aroused the most interest and controversy among training professionals in recent years. Therefore, the aim of the present study was to analyze the available scientific evidence on the influence of strength training variables on morphological and/or neuromuscular adaptations in healthy prepubertal populations with no previous experience in this type of training according to the descriptive sample characteristics. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, 22 studies were selected after a systematic search and selection process using four electronic databases: Google Scholar, PubMed, Scopus, and SPORT Discus. Furthermore, the internal validity of the studies included was assessed using the modified PEDro scale. The sample consisted of 604 prepubertal children (age, 10.02 ± 0.75 years), of whom 473 were boys and 131 were girls, with 104 strength training programs recorded. Strength training resulted in a significant increase in jumping ( = 29) and sprinting ( = 13) abilities. Moreover, muscle strength was increased in 100% of the cases. Morphologically, strength training resulted in a decrease in body fat percentage ( = 19) and an increase in lean body mass ( = 17). With regard to gender, increases in general sport skills and basic physical abilities were significant in males but not in females. Thus, the results are more heterogeneous in girls due to the small number of studies carried out. Therefore, this research provides practical applications for coaches to design and implement more effective training programs to maximize adaptations, enhance physical performance, and reduce injury risk.
Topics: Male; Female; Humans; Child; Resistance Training; Muscle Strength; Sports; Adaptation, Physiological; Acclimatization
PubMed: 36981742
DOI: 10.3390/ijerph20064833 -
Cell Jan 2022Conifers dominate the world's forest ecosystems and are the most widely planted tree species. Their giant and complex genomes present great challenges for assembling a...
Conifers dominate the world's forest ecosystems and are the most widely planted tree species. Their giant and complex genomes present great challenges for assembling a complete reference genome for evolutionary and genomic studies. We present a 25.4-Gb chromosome-level assembly of Chinese pine (Pinus tabuliformis) and revealed that its genome size is mostly attributable to huge intergenic regions and long introns with high transposable element (TE) content. Large genes with long introns exhibited higher expressions levels. Despite a lack of recent whole-genome duplication, 91.2% of genes were duplicated through dispersed duplication, and expanded gene families are mainly related to stress responses, which may underpin conifers' adaptation, particularly in cold and/or arid conditions. The reproductive regulation network is distinct compared with angiosperms. Slow removal of TEs with high-level methylation may have contributed to genomic expansion. This study provides insights into conifer evolution and resources for advancing research on conifer adaptation and development.
Topics: Acclimatization; Chromosomes, Plant; Cycadopsida; DNA Transposable Elements; Epigenome; Evolution, Molecular; Forests; Gene Expression Regulation, Plant; Gene Regulatory Networks; Genes, Plant; Genome Size; Genomics; Introns; Magnoliopsida; Pinus
PubMed: 34965378
DOI: 10.1016/j.cell.2021.12.006 -
Journal of Integrative Plant Biology Mar 2024Excess soil salinity affects large regions of land and is a major hindrance to crop production worldwide. Therefore, understanding the molecular mechanisms of plant salt... (Review)
Review
Excess soil salinity affects large regions of land and is a major hindrance to crop production worldwide. Therefore, understanding the molecular mechanisms of plant salt tolerance has scientific importance and practical significance. In recent decades, studies have characterized hundreds of genes associated with plant responses to salt stress in different plant species. These studies have substantially advanced our molecular and genetic understanding of salt tolerance in plants and have introduced an era of molecular design breeding of salt-tolerant crops. This review summarizes our current knowledge of plant salt tolerance, emphasizing advances in elucidating the molecular mechanisms of osmotic stress tolerance, salt-ion transport and compartmentalization, oxidative stress tolerance, alkaline stress tolerance, and the trade-off between growth and salt tolerance. We also examine recent advances in understanding natural variation in the salt tolerance of crops and discuss possible strategies and challenges for designing salt stress-resilient crops. We focus on the model plant Arabidopsis (Arabidopsis thaliana) and the four most-studied crops: rice (Oryza sativa), wheat (Triticum aestivum), maize (Zea mays), and soybean (Glycine max).
Topics: Crops, Agricultural; Arabidopsis; Glycine max; Salt Tolerance; Salinity
PubMed: 38108117
DOI: 10.1111/jipb.13599 -
Proceedings of the National Academy of... Jun 2023As a crucial nitrogen source, nitrate (NO) is a key nutrient for plants. Accordingly, root systems adapt to maximize NO availability, a developmental regulation also...
As a crucial nitrogen source, nitrate (NO) is a key nutrient for plants. Accordingly, root systems adapt to maximize NO availability, a developmental regulation also involving the phytohormone auxin. Nonetheless, the molecular mechanisms underlying this regulation remain poorly understood. Here, we identify () in Arabidopsis (), whose root growth fails to adapt to low-NO conditions. is defective in the high-affinity NO transporter NRT2.1. () mutants exhibit defects in polar auxin transport, and their low-NO-induced root phenotype depends on the PIN7 auxin exporter activity. NRT2.1 directly associates with PIN7 and antagonizes PIN7-mediated auxin efflux depending on NO levels. These results reveal a mechanism by which NRT2.1 in response to NO limitation directly regulates auxin transport activity and, thus, root growth. This adaptive mechanism contributes to the root developmental plasticity to help plants cope with changes in NO availability.
Topics: Nitrate Transporters; Nitrates; Acclimatization; Biological Transport; Arabidopsis; Indoleacetic Acids
PubMed: 37307446
DOI: 10.1073/pnas.2221313120 -
Molecular Plant Sep 2023The shoot meristem generates the entire shoot system and is precisely maintained throughout the life cycle under various environmental challenges. In this study, we...
The shoot meristem generates the entire shoot system and is precisely maintained throughout the life cycle under various environmental challenges. In this study, we identified a prion-like domain (PrD) in the key shoot meristem regulator SHOOT MERISTEMLESS (STM), which distinguishes STM from other related KNOX1 proteins. We demonstrated that PrD stimulates STM to form nuclear condensates, which are required for maintaining the shoot meristem. STM nuclear condensate formation is stabilized by selected PrD-containing STM-interacting BELL proteins in vitro and in vivo. Moreover, condensation of STM promotes its interaction with the Mediator complex subunit MED8 and thereby enhances its transcriptional activity. Thus, condensate formation emerges as a novel regulatory mechanism of shoot meristem functions. Furthermore, we found that the formation of STM condensates is enhanced upon salt stress, which allows enhanced salt tolerance and increased shoot branching. Our findings highlight that the transcription factor partitioning plays an important role in cell fate determination and might also act as a tunable environmental acclimation mechanism.
Topics: Salt Tolerance; Arabidopsis; Meristem; Salt Stress; Cell Differentiation; Homeodomain Proteins; Arabidopsis Proteins
PubMed: 37674313
DOI: 10.1016/j.molp.2023.09.005 -
The New Phytologist Mar 2024Salt stress is a major challenge that has a negative impact on soybean growth and productivity. Therefore, it is important to understand the regulatory mechanism of salt...
Salt stress is a major challenge that has a negative impact on soybean growth and productivity. Therefore, it is important to understand the regulatory mechanism of salt response to ensure soybean yield under such conditions. In this study, we identified and characterized a miR160a-GmARF16-GmMYC2 module and its regulation during the salt-stress response in soybean. miR160a promotes salt tolerance by cleaving GmARF16 transcripts, members of the Auxin Response Factor (ARF) family, which negatively regulates salt tolerance. In turn, GmARF16 activates GmMYC2, encoding a bHLH transcription factor that reduces salinity tolerance by down-regulating proline biosynthesis. Genomic analysis among wild and cultivated soybean accessions identified four distinct GmARF16 haplotypes. Among them, the GmARF16 haplotype is preferentially enriched in localities with relatively saline soils, suggesting GmARF16 was artificially selected to improve salt tolerance. Our findings therefore provide insights into the molecular mechanisms underlying salt response in soybean and provide valuable genetic targets for the molecular breeding of salt tolerance.
Topics: Glycine max; Salt Tolerance; Haplotypes; Base Sequence; Gene Expression Regulation, Plant
PubMed: 38135657
DOI: 10.1111/nph.19503 -
Journal of Visualized Experiments : JoVE Jan 2023Festa, F., Labaer, J. Kinase inhibitor screening in self-assembled human protein microarrays. Journal of Visualized Experiments. 152, e59886 (2019). Stockman, B. J. et...
Festa, F., Labaer, J. Kinase inhibitor screening in self-assembled human protein microarrays. Journal of Visualized Experiments. 152, e59886 (2019). Stockman, B. J. et al. NMR-Based activity assays for determining compound inhibition, IC50 values, artifactual activity, and whole-cell activity of nucleoside ribohydrolases. Journal of Visualized Experiments. 148, e59928 (2019). Gao, S. et al. A high-throughput assay for the prediction of chemical toxicity by automated phenotypic profiling of Caenorhabditis elegans. Journal of Visualized Experiments. 145, e59082 (2019). Axelsson, H., Almqvist, H., Seashore-Ludlow, B. Using high content imaging to quantify target engagement in adherent cells. Journal of Visualized Experiments. 141, e58670 (2018). Chorba, J. S., Galvan, A. M., Shokat, K. M. A high-throughput luciferase assay to evaluate proteolysis of the single-turnover protease PCSK9. Journal of Visualized Experiments. 138, e58265 (2018). Sullivan, C. et al. Using zebrafish models of human influenza A virus infections to screen antiviral drugs and characterize host immune cell responses. Journal of Visualized Experiments. 119, e55235 (2017). Tiemann, K., Garri, C., Wang, J., Clarke, L., Kani, K. Assessment of resistance to tyrosine kinase inhibitors by an interrogation of signal transduction pathways by antibody arrays. Journal of Visualized Experiments. 139, e57779 (2018). Radnai, L., Stremel, R. F., Sellers, J. R., Rumbaugh, G., Miller, C. A. A semi-high-throughput adaptation of the NADH-coupled ATPase assay for screening small molecule inhibitors. Journal of Visualized Experiments. 150, e60017 (2019). Nandha Premnath, P., Craig, S., McInnes, C. Development of inhibitors of protein-protein interactions through REPLACE: Application to the design and development non-ATP competitive CDK inhibitors. Journal of Visualized Experiments. 104, e52441 (2015). Chen, E. W., Ke, C. Y., Brzostek, J., Gascoigne, N. R. J., Rybakin, V. Identification of mediators of T-cell receptor signaling via the screening of chemical inhibitor libraries. Journal of Visualized Experiments. 143, e58946 (2019). Takakusagi, Y. Biosensor-based high throughput biopanning and bioinformatics analysis strategy for the global validation of drug-protein interactions. Journal of Visualized Experiments. 166, e61873 (2020). Riching, K. M., Mahan, S. D., Urh, M., Daniels, D. L. High-Throughput cellular profiling of targeted protein degradation compounds using HiBiT CRISPR cell lines. Journal of Visualized Experiments. 165, e61787 (2020).
Topics: Humans; Animals; Proprotein Convertase 9; Zebrafish; Proteolysis; Acclimatization; Caenorhabditis elegans
PubMed: 37602881
DOI: 10.3791/64811 -
Annual Review of Statistics and Its... Mar 2021Adaptive enrichment designs for clinical trials may include rules that use interim data to identify treatment-sensitive patient subgroups, select or compare treatments,...
Adaptive enrichment designs for clinical trials may include rules that use interim data to identify treatment-sensitive patient subgroups, select or compare treatments, or change entry criteria. A common setting is a trial to compare a new biologically targeted agent to standard therapy. An enrichment design's structure depends on its goals, how it accounts for patient heterogeneity and treatment effects, and practical constraints. This article first covers basic concepts, including treatment-biomarker interaction, precision medicine, selection bias, and sequentially adaptive decision making, and briefly describes some different types of enrichment. Numerical illustrations are provided for qualitatively different cases involving treatment-biomarker interactions. Reviews are given of adaptive signature designs; a Bayesian design that uses a random partition to identify treatment-sensitive biomarker subgroups and assign treatments; and designs that enrich superior treatment sample sizes overall or within subgroups, make subgroup-specific decisions, or include outcome-adaptive randomization.
PubMed: 36212769
DOI: 10.1146/annurev-statistics-040720-032818 -
Therapeutic Innovation & Regulatory... Jan 2020In an adaptive trial, the researcher may have the option of responding to interim safety and efficacy data in a number of ways, including narrowing the study focus or... (Review)
Review
BACKGROUND
In an adaptive trial, the researcher may have the option of responding to interim safety and efficacy data in a number of ways, including narrowing the study focus or increasing the number of subjects, balancing treatment allocation or different forms of randomization based on responses of subjects prior to treatment. This research aims at compiling the technical, statistical, and regulatory implications of the employment of adaptive design in a clinical trial.
METHODS
Review of adaptive design clinical trials in Medline, PubMed, EU Clinical Trials Register, and ClinicalTrials.gov. Phase I and seamless phase I/II trials were excluded. We selected variables extracted from trials that included basic study characteristics, adaptive design features, size and use of independent data-monitoring committees (DMCs), and blinded interim analysis.
RESULTS
The research retrieved 336 results, from which 78 were selected for analysis. Sixty-seven were published articles, and 11 were guidelines, papers, and regulatory bills. The most prevalent type of adaptation was the seamless phase II/III design 23.1%, followed by adaptive dose progression 19.2%, pick the winner / drop the loser 16.7%, sample size re-estimation 10.3%, change in the study objective 9.0%, adaptive sequential design 9.0%, adaptive randomization 6.4%, biomarker adaptive design 3.8%, and endpoint adaptation 2.6%. Discussion DISCUSSION: It is possible to infer that the use of Adaptive Design is an ethical and scientific advantage when properly planned and applied, since it increases the flexibility of the trial, shortens the overall clinical investigation time of a drug, and reduces the risk of patient exposure to adverse effects related to the experimental drug. Its greater methodologic and analytic complexity requires an adequate statistical methodology.
CONCLUSIONS
The application of "adaptive clinical designs" for phase II/III studies appear to have been limited to trials with a small number of study centers, with smaller extensions of time and to experimental drugs with more immediate clinical effects that are amenable to risk/benefit decisions based on interim analyses. According to the reviewed studies, simple adaptive trial designs-such as early study terminations due to futility and sample size re-estimation-are becoming widely adopted throughout the pharmaceutical industry, especially in phase II and III studies. The pharmaceutical industry and contract research organizations (CROs) are implementing simple adaptations more frequently and the more complex adaptations-biomarker adaptive design, endpoint adaptation-are more sporadic.
Topics: Adaptive Clinical Trials as Topic; Drugs, Investigational; Humans; Research Design; Sample Size
PubMed: 32008232
DOI: 10.1007/s43441-019-00052-y