Systems Biology
The Human Pathology Atlas for deciphering the prognostic features of human cancers
EBioMedicine. 2024 Dec 10;111:105495. doi: 10.1016/j.ebiom.2024.105495. Online ahead of print.
ABSTRACT
BACKGROUND: Cancer is one of the leading causes of mortality worldwide, highlighting the urgent need for a deeper molecular understanding and the development of personalized treatments. The present study aims to establish a solid association between gene expression and patient survival outcomes to enhance the utility of the Human Pathology Atlas for cancer research.
METHODS: In this updated analysis, we examined the expression profiles of 6918 patients across 21 cancer types. We integrated data from 10 independent cancer cohorts, creating a cross-validated, reliable collection of prognostic genes. We applied systems biology approach to identify the association between gene expression profiles and patient survival outcomes. We further constructed prognostic regulatory networks for kidney renal clear cell carcinoma (KIRC) and liver hepatocellular carcinoma (LIHC), which elucidate the molecular underpinnings associated with patient survival in these cancers.
FINDINGS: We observed that gene expression during the transition from normal to tumorous tissue exhibited diverse shifting patterns in their original tissue locations. Significant correlations between gene expression and patient survival outcomes were identified in KIRC and LIHC among the major cancer types. Additionally, the prognostic regulatory network established for these two cancers showed the indicative capabilities of the Human Pathology Atlas and provides actionable insights for cancer research.
INTERPRETATION: The updated Human Pathology Atlas provides a significant foundation for precision oncology and the formulation of personalized treatment strategies. These findings deepen our understanding of cancer biology and have the potential to advance targeted therapeutic approaches in clinical practice.
FUNDING: The Knut and Alice Wallenberg Foundation (72110), the China Scholarship Council (Grant No. 202006940003).
PMID:39662180 | DOI:10.1016/j.ebiom.2024.105495
Skin immune-mesenchymal interplay within tertiarylymphoid structures promotes autoimmunepathogenesis in hidradenitis suppurativa
Immunity. 2024 Dec 10;57(12):2827-2842.e5. doi: 10.1016/j.immuni.2024.11.010.
ABSTRACT
Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disease characterized by keratinized epithelial tunnels that grow deeply into the dermis. Here, we examined the immune microenvironment within human HS lesions. Multi-omics profiling and multiplexed imaging identified tertiary lymphoid structures (TLSs) near HS tunnels. These TLSs were enriched with proliferative T cells, including follicular helper (Tfh), regulatory (Treg), and pathogenic T cells (IL17A+ and IFNG+), alongside extensive clonal expansion of plasma cells producing antibodies reactive to keratinocytes. HS fibroblasts express CXCL13 or CCL19 in response to immune cytokines. Using a microfluidic system to mimic TLS on a chip, we found that HS fibroblasts critically orchestrated lymphocyte aggregation via tumor necrosis factor alpha (TNF-α)-CXCL13 and TNF-α-CCL19 feedback loops with B and T cells, respectively; early TNF-α blockade suppressed aggregate initiation. Our findings provide insights into TLS formation in the skin, suggest therapeutic avenues for HS, and reveal mechanisms that may apply to other autoimmune settings, including Crohn's disease.
PMID:39662091 | DOI:10.1016/j.immuni.2024.11.010
Control of Cellular Differentiation Trajectories for Cancer Reversion
Adv Sci (Weinh). 2024 Dec 11:e2402132. doi: 10.1002/advs.202402132. Online ahead of print.
ABSTRACT
Cellular differentiation is controlled by intricate layers of gene regulation, involving the modulation of gene expression by various transcriptional regulators. Due to the complexity of gene regulation, identifying master regulators across the differentiation trajectory has been a longstanding challenge. To tackle this problem, a computational framework, single-cell Boolean network inference and control (BENEIN), is presented. Applying BENEIN to human large intestinal single-cell transcriptome data, MYB, HDAC2, and FOXA2 are identified as the master regulators whose inhibition induces enterocyte differentiation. It is found that simultaneous knockdown of these master regulators can revert colorectal cancer cells into normal-like enterocytes by synergistically inducing differentiation and suppressing malignancy, which is validated by in vitro and in vivo experiments.
PMID:39661721 | DOI:10.1002/advs.202402132
The BRAHMA-associated SWI/SNF chromatin remodeling complex controls Arabidopsis seed quality and physiology
Plant Physiol. 2024 Dec 11:kiae642. doi: 10.1093/plphys/kiae642. Online ahead of print.
ABSTRACT
The SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complex is involved in various aspects of plant development and stress responses. Here, we investigated the role of BRM (BRAHMA), a core catalytic subunit of the SWI/SNF complex, in Arabidopsis thaliana seed biology. brm-3 seeds exhibited enlarged size, reduced yield, increased longevity, and enhanced secondary dormancy, but did not show changes in primary dormancy or salt tolerance. Some of these phenotypes depended on the expression of DOG1, a key regulator of seed dormancy, as they were restored in the brm-3 dog1-4 double mutant. Transcriptomic and metabolomic analyses revealed that BRM and DOG1 synergistically modulate the expression of numerous genes. Some of the changes observed in the brm-3 mutant, including increased glutathione levels, depended on a functional DOG1. We demonstrated that the BRM-containing chromatin remodeling complex directly controls secondary dormancy through DOG1 by binding and remodeling its 3' region, where the promoter of the long non-coding RNA asDOG1 is located. Our results suggest that BRM and DOG1 cooperate to control seed physiological properties and that BRM regulates DOG1 expression through asDOG1. This study reveals chromatin remodeling at the DOG1 locus as a molecular mechanism controlling the interplay between seed viability and dormancy.
PMID:39661382 | DOI:10.1093/plphys/kiae642
Spatiotemporal evolution of heterogeneous structures in agarose gels revealed by particle tracking
Soft Matter. 2024 Dec 11. doi: 10.1039/d4sm01122h. Online ahead of print.
ABSTRACT
Upon decreasing the temperature, agarose solution exhibited gelation and phase separation, forming a cloudy gel consisting of agarose-rich and agarose-poor phases. Both phenomena contribute to the formation of a heterogeneous gel structure, but the primary influence of both processes on this heterogeneity remains unclear. In this study, we defined the specific gelation and phase separation temperatures of an agarose solution and examined the resulting gel structures with and without phase separation. Microscopic observation and colloid diffusion analysis revealed that phase separation leads to inhomogeneities several micrometers in size. Furthermore, we found that the distributions of colloidal diffusion coefficients and particle displacements strongly reflected the heterogeneity primarily induced by phase separation and gelation. Our findings contribute to the physicochemical understanding of the heterogeneous structures of various (bio) polymer gels associated with the phase separation of polymers.
PMID:39661144 | DOI:10.1039/d4sm01122h
Calcium signaling triggers early high humidity responses in <em>Arabidopsis thaliana</em>
Proc Natl Acad Sci U S A. 2024 Dec 17;121(51):e2416270121. doi: 10.1073/pnas.2416270121. Epub 2024 Dec 11.
ABSTRACT
Plants need to adapt to fluctuating atmospheric humidity and respond to both high and low humidity. Despite our substantial understanding of plant responses to low humidity, molecular mechanisms underlying the high humidity (HH) response are much less well understood. In this study, we investigated early responses to HH in Arabidopsis. Expression of CYP707A3, encoding an abscisic acid (ABA) 8'-hydroxylase, is induced by HH within 10 min, which leads to a decrease in foliar ABA level. We identified that the combined action of CAMTA3 and CAMTA2 transcription factors regulate this response. This regulation requires a calmodulin (CaM)-binding domain of CAMTA3. Transcriptomes of HH-regulated genes are enriched in those related to calcium signaling, including cyclic nucleotide-gated ion channels (CNGCs). Moreover, HH induces CNGC2- and CNGC4-mediated increases in cytosolic Ca2+ concentrations in leaves within a few minutes. We also found that CNGC2, CNGC4, and CAMTAs participate in HH-induced hyponastic movement of petioles. Taken together, our results indicate that CNGC2/CNGC4-Ca2+-CaM-CAMTA3/CAMTA2 acts as a primary regulatory module to trigger downstream HH responses.
PMID:39661062 | DOI:10.1073/pnas.2416270121
Artificial intelligence powers regenerative medicine into predictive realm
Regen Med. 2024 Dec 11:1-6. doi: 10.1080/17460751.2024.2437281. Online ahead of print.
ABSTRACT
The expanding regenerative medicine toolkit is reaching a record number of lives. There is a pressing need to enhance the precision, efficiency, and effectiveness of regenerative approaches and achieve reliable outcomes. While regenerative medicine has relied on an empiric paradigm, availability of big data along with advances in informatics and artificial intelligence offer the opportunity to inform the next generation of regenerative sciences along the discovery, translation, and application pathway. Artificial intelligence can streamline discovery and development of optimized biotherapeutics by aiding in the interpretation of readouts associated with optimal repair outcomes. In advanced biomanufacturing, artificial intelligence holds potential in ensuring quality control and assuring scalability through automated monitoring of process-critical variables mandatory for product consistency. In practice application, artificial intelligence can guide clinical trial design, patient selection, delivery strategies, and outcome assessment. As artificial intelligence transforms the regenerative horizon, caution is necessary to reduce bias, ensure generalizability, and mitigate ethical concerns with the goal of equitable access for patients and populations.
PMID:39660914 | DOI:10.1080/17460751.2024.2437281
Emergence of power-law distributions in protein-protein interaction networks through study bias
Elife. 2024 Dec 11;13:e99951. doi: 10.7554/eLife.99951. Online ahead of print.
ABSTRACT
Degree distributions in protein-protein interaction (PPI) networks are believed to follow a power law (PL). However, technical and study bias affect the experimental procedures for detecting PPIs. For instance, cancer-associated proteins have received disproportional attention. Moreover, bait proteins in large-scale experiments tend to have many false-positive interaction partners. Studying the degree distributions of thousands of PPI networks of controlled provenance, we address the question if PL distributions in observed PPI networks could be explained by these biases alone. Our findings are supported by mathematical models and extensive simulations and indicate that study bias and technical bias suffice to produce the observed PL distribution. It is, hence, problematic to derive hypotheses about the topology of the true biological interactome from the PL distributions in observed PPI networks. Our study casts doubt on the use of the PL property of biological networks as a modeling assumption or quality criterion in network biology.
PMID:39660719 | DOI:10.7554/eLife.99951
Novel class IIb microcins show activity against Gram-negative ESKAPE and plant pathogens
Elife. 2024 Dec 11;13:RP102912. doi: 10.7554/eLife.102912.
ABSTRACT
Interspecies interactions involving direct competition via bacteriocin production play a vital role in shaping ecological dynamics within microbial ecosystems. For instance, the ribosomally produced siderophore bacteriocins, known as class IIb microcins, affect the colonization of host-associated pathogenic Enterobacteriaceae species. Notably, to date, only five of these antimicrobials have been identified, all derived from specific Escherichia coli and Klebsiella pneumoniae strains. We hypothesized that class IIb microcin production extends beyond these specific compounds and organisms. With a customized informatics-driven approach, screening bacterial genomes in public databases with BLAST and manual curation, we have discovered 12 previously unknown class IIb microcins in seven additional Enterobacteriaceae species, encompassing phytopathogens and environmental isolates. We introduce three novel clades of microcins (MccW, MccX, and MccZ), while also identifying eight new variants of the five known class IIb microcins. To validate their antimicrobial potential, we heterologously expressed these microcins in E. coli and demonstrated efficacy against a variety of bacterial isolates, including plant pathogens from the genera Brenneria, Gibbsiella, and Rahnella. Two newly discovered microcins exhibit activity against Gram-negative ESKAPE pathogens, i.e., Acinetobacter baumannii or Pseudomonas aeruginosa, providing the first evidence that class IIb microcins can target bacteria outside of the Enterobacteriaceae family. This study underscores that class IIb microcin genes are more prevalent in the microbial world than previously recognized and that synthetic hybrid microcins can be a viable tool to target clinically relevant drug-resistant pathogens. Our findings hold significant promise for the development of innovative engineered live biotherapeutic products tailored to combat these resilient bacteria.
PMID:39660611 | DOI:10.7554/eLife.102912
AND Logic Based on Suppressor tRNAs Enables Stringent Control of Sliding Base Editors in <em>Pseudomonas putida</em>
ACS Synth Biol. 2024 Dec 11. doi: 10.1021/acssynbio.4c00640. Online ahead of print.
ABSTRACT
Base editors, e.g., cytosine deaminases, are powerful tools for precise DNA editing in vivo, enabling both targeted nucleotide conversions and segment-specific diversification of bacterial genomes. Yet, regulation of their spatiotemporal activity is crucial to avoid off-target effects and enabling controlled evolution of specific genes and pathways. This work reports a strategy for tight control of base-editing devices through subjecting their expression to a genetic AND logic gate in which two chemical inducer inputs are strictly required for cognate activity. The case study involves an archetypal genetic device consisting of a cytosine deaminase (pmCDA1) fused to a T7 RNA polymerase (RNAPT7), which cause intensive diversification of DNA portions bordered by a T7 promoter and a T7 terminator─but whose activity in vivo has been shown unattainable to govern with standard conditional expression systems. By encoding up to three UAG stop codons into the DNA sequence of the pmCDA1-RNAPT7 fusion, which is transcribed by the 3-methylbenzoate inducible promoter Pm, we first broke the structure of the hybrid protein. Then, to overcome the interruptions caused by UAG codons, we placed transcription of a supF tRNA under the control of a cyclohexanone-dependent system. When tested in the soil bacterium and metabolic engineering chassis Pseudomonas putida KT2440, these modifications changed the performance of the sliding base editor from a flawed YES logic to a precise AND logic. We also showed that such a 2-layer control brings about a minimal background activity as compared to a single-input digitalizer circuit. These results show the ability of suppressor tRNA-based logic gates for achieving stringent expression of otherwise difficult to control devices.
PMID:39660532 | DOI:10.1021/acssynbio.4c00640
Olfactory inputs regulate Drosophilamelanogaster oogenesis
J Exp Biol. 2024 Dec 15;227(24):jeb247234. doi: 10.1242/jeb.247234. Epub 2024 Dec 11.
ABSTRACT
Drosophila female germline development and maintenance require both local stem cell niche signaling and systemic regulation. Here, we show the indispensable function of the Drosophilamelanogaster olfactory circuit in normal oogenesis and fecundity. Lack of olfactory inputs during development causes a reduction in germline stem cells. Although germline stem cells proliferate normally, the germline cysts undergo caspase-mediated apoptosis, leading to decreased follicle production and egg-laying in flies with defective olfaction. Strikingly, activation of olfactory circuits is sufficient to boost egg production, demonstrating that chemosensory-activated brain-derived inputs promote gamete development. Given the energy demands of oogenesis and its direct consequence on fitness, we propose that olfactory-stimulated systemic regulation evolved tightly with downstream diet-responsive pathways to control germline physiology in response to nutritional status. Additionally, these findings raise the possibility that sensory-mediated stem cell maintenance is a generalizable mechanism spanning a myriad of neuronal circuits, systems and species.
PMID:39660407 | DOI:10.1242/jeb.247234
The causal relationship between the human gut microbiota and pyogenic arthritis: a Mendelian randomization study
Front Cell Infect Microbiol. 2024 Nov 26;14:1452480. doi: 10.3389/fcimb.2024.1452480. eCollection 2024.
ABSTRACT
BACKGROUND: Recent studies have indicated the role of the gut microbiota in the progression of osteoarticular diseases, however, the causal relationship between the gut microbiota and pyogenic arthritis remains unclear. There is also a lack of theoretical basis for the application of the gut microbiota in the treatment of pyogenic arthritis.
METHODS: In our study, we utilized the largest genome-wide association study (GWAS) data from the MiBioGen Consortium involving 13,400 participants and extracted summary statistical data of the microbiota metabolic pathways of 7,738 participants of European descent from the Dutch Microbiome Project (DMP) The data of pyogenic arthritis were derived from the FinnGen R10 database, including 1,086 patients and 147,221 controls. We employed the two-sample Mendelian randomization approach to investigate the causal association between the gut microbiota and pyogenic arthritis. Our methods comprised inverse variance weighting, Mendelian Randomization Egger regression, weighted median, and weighted modal methods. Subsequently, polygenic and heterogeneity analyses were conducted.
RESULTS: At the class level, β-proteobacteria is positively correlated with the risk of pyogenic arthritis. At the order level, Burkholderia is positively associated with the disease. At the genus level, the unclassified genus of Sutterellaceae is positively correlated with the disease, while the unnamed genus of Lachnospiraceae, Rothia, and the unnamed genus of Erysipelotrichaceae are negatively correlated with the disease. In addition, Faecalibacterium and Finegoldia are also negatively correlated with the disease. Sensitivity analysis did not show any abnormal evidence.
CONCLUSION: This study indicates that β-proteobacteria, Burkholderiales, and the unclassified genus of Sutterellaceae are associated with an increased risk of the disease, while the unnamed genus of Lachnospiraceae, Rothia, the unnamed genus of Erysipelotrichaceae, Faecalibacterium, and Finegoldia are related to a reduced risk. Future studies are needed to elucidate the specific mechanisms by which these specific bacterial groups affect pyogenic arthritis.
PMID:39660282 | PMC:PMC11629706 | DOI:10.3389/fcimb.2024.1452480
Artificial intelligence in tuberculosis: a new ally in disease control
Breathe (Sheff). 2024 Dec 10;20(3):240056. doi: 10.1183/20734735.0056-2024. eCollection 2024 Oct.
ABSTRACT
The challenges to effective tuberculosis (TB) disease control are considerable, and the current global targets for reductions in disease burden seem unattainable. The combination of complex pathophysiology and technical limitations results in difficulties in achieving consistent, reliable diagnoses, and long treatment regimens imply serious physiological and socioeconomic consequences for patients. Artificial intelligence (AI) applications in healthcare have significantly improved patient care regarding diagnostics, treatment and basic research. However, their success relies on infrastructures prioritising comprehensive data generation and collaborative research environments to foster stakeholder engagement. This viewpoint article briefly outlines the current and potential applications of advanced AI models in global TB control and the considerations and implications of adopting these tools within the public health community.
PMID:39660086 | PMC:PMC11629172 | DOI:10.1183/20734735.0056-2024
Disagreement on foundational principles of biological aging
PNAS Nexus. 2024 Dec 3;3(12):pgae499. doi: 10.1093/pnasnexus/pgae499. eCollection 2024 Dec.
ABSTRACT
To gain insight into how researchers of aging perceive the process they study, we conducted a survey among experts in the field. While highlighting some common features of aging, the survey exposed broad disagreement on the foundational issues. What is aging? What causes it? When does it begin? What constitutes rejuvenation? Not only was there no consensus on these and other core questions, but none of the questions received a majority opinion-even regarding the need for consensus itself. Despite many researchers believing they understand aging, their understanding diverges considerably. Importantly, as different processes are labeled as "aging" by researchers, different experimental approaches are prioritized. The survey shed light on the need to better define which aging processes this field should target and what its goals are. It also allowed us to categorize contemporary views on aging and rejuvenation, revealing critical, yet largely unanswered, questions that appear disconnected from the current research focus. Finally, we discuss ways to address the disagreement, which we hope will ultimately aid progress in the field.
PMID:39660064 | PMC:PMC11630784 | DOI:10.1093/pnasnexus/pgae499
Tracking the uptake of labelled host-derived extracellular vesicles by the human fungal pathogen <em>Aspergillus fumigatus</em>
Microlife. 2024 Nov 6;5:uqae022. doi: 10.1093/femsml/uqae022. eCollection 2024.
ABSTRACT
Extracellular vesicles (EVs) have gained attention as facilitators of intercellular as well as interkingdom communication during host-microbe interactions. Recently we showed that upon infection, host polymorphonuclear leukocytes produce antifungal EVs targeting the clinically important fungal pathogen Aspergillus fumigatus; however, the small size of EVs (<1 µm) complicates their functional analysis. Here, we employed a more tractable, reporter-based system to label host alveolar epithelial cell-derived EVs and enable their visualization during in vitro A. fumigatus interaction. Fusion of EV marker proteins (CD63, CD9, and CD81) with a Nanoluciferase (NLuc) and a green fluorescent protein (GFP) facilitated their relative quantification by luminescence and visualization by a fluorescence signal. The use of an NLuc fused with a GFP is advantageous as it allows for quantification and visualization of EVs simultaneously without additional external manipulation and to distinguish subpopulations of EVs. Using this system, visualization and tracking of EVs was possible using confocal laser scanning microscopy and advanced imaging analysis. These experiments revealed the propensity of host cell-derived EVs to associate with the fungal cell wall and ultimately colocalize with the cell membrane of A. fumigatus hyphae in large numbers. In conclusion, we have created a series of tools to better define the complex interplay of host-derived EVs with microbial pathogens.
PMID:39660046 | PMC:PMC11631206 | DOI:10.1093/femsml/uqae022
<em>Rubustingzhouensis</em> (Rosaceae), a new species from Fujian, China
PhytoKeys. 2024 Dec 2;249:251-267. doi: 10.3897/phytokeys.249.138951. eCollection 2024.
ABSTRACT
Rubustingzhouensis C.An & G.C.Lin, a newly-defined species within the family Rosaceae from Fujian Province, China, is formally described and illustrated here. R.tingzhouensis is morphologically similar to R.swinhoei, but can be distinguished by several key characteristics, such as long, reddish-purple stipitate glands, soft bristles, light yellow short trichomes (vs. shortly grey tomentose at the early stage, glabrescent) and scattered epidermal prickles (vs. few to many curved prickles). Furthermore, the stipules are pinnately deeply laciniate, measuring 1-1.5 cm (vs. ovate-oblong to ovate-lanceolate, 0.5-0.8 cm). Phylogenetic analyses, based on partial sequences and the complete plastome data, provide robust support for a close relationship between R.tingzhouensis and R.swinhoei, while also highlighting distinct genetic differentiation between these two species. The chloroplast genome of R.tingzhouensis is 156,311 bp in length and comprises 132 unique genes, including 86 protein-coding genes, 37 transfer RNAs, eight ribosomal RNAs and one pseudogene.
PMID:39659964 | PMC:PMC11629084 | DOI:10.3897/phytokeys.249.138951
OGT mediated HDAC5 O-GlcNAcylation promotes osteogenesis by regulating the homeostasis of epigenetic modifications and proteolysis
J Orthop Translat. 2024 Nov 25;50:14-29. doi: 10.1016/j.jot.2024.10.004. eCollection 2025 Jan.
ABSTRACT
BACKGROUND: O-GlcNAc transferase (OGT) is responsible for attaching O-linked N-acetylglucosamine (O-GlcNAc) to proteins, regulating diverse cellular processes ranging from transcription and translation to signaling and metabolism. This study focuses on the role and mechanisms of OGT in osteogenesis.
MATERIALS AND METHODS: We found that OGT is downregulated in osteoporosis by bioinformatics analysis, determined its role in osteogenic differentiation by using OGT inhibitors (or OGA inhibitors) as well as conditional knockout OGT mice in vitro and in vivo, and explored and specific mechanisms by quantitative proteomic analysis and RNA-seq, qRT-PCR, western blotting, immunofluorescence, H&E, ALP, ARS, Masson staining, IHC, micro CT, etc.
RESULTS: we revealed that OGT positively influenced osteogenesis and osteoblast differentiation in vitro as well as ovariectomy (OVX) mice in vivo. Consistently, mice with conditionally depleted OGT exhibited a reduction in bone mass, while O-GlcNAcylation enhancer could partially recover bone mass in ovariectomy (OVX) mice. Mechanistically, quantitative proteomic analysis and high-throughput RNAseq further reveals that HDAC5 is one of the endogenous O-GlcNAcylation substrates, and O-GlcNAcylation of HDAC5 on Thr934 promotes its translocation to lysosomes and subsequent degradation, thus, elevating the O-GlcNAcylation level of HDAC5 leads to its cytoplasmic cleavage, consequently diminished its nuclear entry and enhanced DNA transcription. The OGT-mediated O-GlcNAcylation of HDAC5 modulates the balance between its cytoplasmic proteolysis and nuclear entry, thereby impacting the Notch signaling pathway and DNA epigenetic modifications then playing a role in osteogenesis.
CONCLUSION: OGT is a regulator that promotes osteoblast differentiation and bone regeneration. Additionally, it highlights the critical function of HDAC5 O-GlcNAcylation in controlling epigenetics. This study offers fresh perspectives on osteogenesis and O-GlcNAcylation, proposing that the OGT-mediated O-GlcNAcylation of HDAC5 could be a promising target for osteoporosis treatment.
THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: On one side, OGT might potentially be used as a new biomarker for clinical diagnosis of osteoporosis (OP) in the future. On the other side, small molecule inhibitors of HDAC5, a glycosylation substrate of OGT, or OGT agonists such as silymarin, could all potentially serve as therapeutic targets for the prevention or treatment of OP in the future.
PMID:39659899 | PMC:PMC11626777 | DOI:10.1016/j.jot.2024.10.004
Editorial: Unveiling the potential of CTCs in drug resistance mechanisms and personalized medicine
Front Oncol. 2024 Nov 26;14:1519816. doi: 10.3389/fonc.2024.1519816. eCollection 2024.
NO ABSTRACT
PMID:39659796 | PMC:PMC11628518 | DOI:10.3389/fonc.2024.1519816
MeTEor: an R Shiny app for exploring longitudinal metabolomics data
Bioinform Adv. 2024 Nov 14;4(1):vbae178. doi: 10.1093/bioadv/vbae178. eCollection 2024.
ABSTRACT
MOTIVATION: The availability of longitudinal omics data is increasing in metabolomics research. Viewing metabolomics data over time provides detailed insight into biological processes and fosters understanding of how systems react over time. However, the analysis of longitudinal metabolomics data poses various challenges, both in terms of statistical evaluation and visualization.
RESULTS: To make explorative analysis of longitudinal data readily available to researchers without formal background in computer science and programming, we present MEtabolite Trajectory ExplORer (MeTEor). MeTEor is an R Shiny app providing a comprehensive set of statistical analysis methods. To demonstrate the capabilities of MeTEor, we replicated the analysis of metabolomics data from a previously published study on COVID-19 patients.
AVAILABILITY AND IMPLEMENTATION: MeTEor is available as an R package and as a Docker image. Source code and instructions for setting up the app can be found on GitHub (https://github.com/scibiome/meteor). The Docker image is available at Docker Hub (https://hub.docker.com/r/gordomics/meteor). MeTEor has been tested on Microsoft Windows, Unix/Linux, and macOS.
PMID:39659589 | PMC:PMC11631383 | DOI:10.1093/bioadv/vbae178
Plant growth-promoting effects of a novel <em>Lelliottia</em> sp. JS-SCA-14 and comparative genome analysis
Front Plant Sci. 2024 Nov 26;15:1484616. doi: 10.3389/fpls.2024.1484616. eCollection 2024.
ABSTRACT
Bacteria associated with plants play crucial roles in promoting plant growth and health by aiding in nutrient acquisition, including phosphorus. This study presents the isolation and genomic characterization of a potentially new bacterial strain, Lelliottia sp. JS-SCA-14, which exhibits significant plant growth-promoting effects through phosphorus solubilization. A comparative phylogenomic analysis of the complete genome of strain JS-SCA-14 and its closely related strains revealed a unique genomic profile, suggesting it could be a novel species. Genomic identity calculations indicated that JS-SCA-14 significantly deviates from strains belonging to closely related genera, such as Buttiauxella, Citrobacter, Enterobacter, Leclercia, and Lelliottia. A biochemical assay comparing JS-SCA-14 and a closely related strain, Lelliottia jeotgali PFL01T, showed differing patterns in carbon source utilization and enzyme activities. To assess the plant growth-promoting capabilities of strain JS-SCA-14, tests were conducted to evaluate its siderophore-producing and phosphate-solubilizing abilities. Seed germination assays demonstrated an improvement in germination, seedling length, and vigor compared to untreated controls. Notably, the phosphate-dissolving strain JS-SCA-14 led to a significant increase of 34.4% in fresh weight and 35.4% in dry weight of tomato plants compared to the negative control. These findings underscore the significant potential of strain JS-SCA-14 in solubilizing phosphate, thereby enhancing phosphorus availability in the rhizosphere and promoting plant growth and development. This study contributes to our understanding of plant-microbe interactions and suggests the potential application of strain JS-SCA-14 as a bioinoculant for sustainable agriculture and plant nutrient management strategies.
PMID:39659413 | PMC:PMC11628249 | DOI:10.3389/fpls.2024.1484616