Systems Biology

Polyploidy and hybridization in the Mediterranean: unravelling the evolutionary history of Centaurium (Gentianaceae)

Tue, 2024-04-30 06:00

Ann Bot. 2024 Apr 30:mcae066. doi: 10.1093/aob/mcae066. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Polyploidy is considered one of the main mechanisms of plant evolution and speciation. In the Mediterranean basin, polyploidy has contributed to making this region a biodiversity hotspot, along with its geological and climatic history and other ecological and biogeographic factors. The Mediterranean genus Centaurium Hill (Gentianaceae) comprises ca. 25 species, of which 60% are polyploids, including tetraploids and hexaploids. To date, the evolutionary history of centauries has been studied using Sanger sequencing phylogenies, which have been insufficient to fully understand the phylogenetic relationships in this lineage. The goal of this study is to gain a better understanding of the evolutionary history of Centaurium by exploring the mechanisms that have driven its diversification, specifically hybridization and polyploidy. We aim at identifying the parentage of hybrid species, at the species or clade level, as well as assessing whether morphological traits are associated with particular ploidy levels.

METHODS: We sequenced RADseq markers from 42 samples of 28 Centaurium taxa, and performed phylogenomic analyses using maximum likelihood, summary coalescent SVDquartets and NeighborNet approaches. To identify hybrid taxa, we used Phylonetworks and the fastStructure algorithm. To infer the putative parental species of the allopolyploids, we employed genomic analyses (SNIPloid). The association between different traits and particular ploidy levels was explored with NMDS.

KEY RESULTS: Our phylogenetic analyses confirmed the long-suspected occurrence of recurrent hybridization. The allopolyploid origin of the tetraploid C. serpentinicola and the hexaploids C. mairei, C. malzacianum and C. centaurioides were also confirmed, unlike that of C. discolor. We inferred additional signatures of hybridization events within the genus and identified morphological traits differentially distributed in different ploidy levels.

CONCLUSIONS: This study highlights the important role that hybridization has played in the evolution of a Mediterranean genus such as Centaurium, leading to a polyploid complex, which facilitated its diversification and may exemplify that of other Mediterranean groups.

PMID:38687133 | DOI:10.1093/aob/mcae066

Categories: Literature Watch

CAM evolution is associated with gene family expansion in an explosive bromeliad radiation

Tue, 2024-04-30 06:00

Plant Cell. 2024 Apr 30:koae130. doi: 10.1093/plcell/koae130. Online ahead of print.

ABSTRACT

The subgenus Tillandsia (Bromeliaceae) belongs to one of the fastest radiating clades in the plant kingdom and is characterised by the repeated evolution of Crassulacean acid metabolism (CAM). Despite its complex genetic basis, this water-conserving trait has evolved independently across many plant families and is regarded as a key innovation trait and driver of ecological diversification in Bromeliaceae. By producing high-quality genome assemblies of a Tillandsia species pair displaying divergent photosynthetic phenotypes, and combining genome-wide investigations of synteny, transposable element (TE) dynamics, sequence evolution, gene family evolution and temporal differential expression, we were able to pinpoint the genomic drivers of CAM evolution in Tillandsia. Several large-scale rearrangements associated with karyotype changes between the two genomes and a highly dynamic TE landscape shaped the genomes of Tillandsia. However, our analyses show that rewiring of photosynthetic metabolism is mainly obtained through regulatory evolution rather than coding sequence evolution, as CAM-related genes are differentially expressed across a 24-hour cycle between the two species but are not candidates of positive selection. Gene orthology analyses reveal that CAM-related gene families manifesting differential expression underwent accelerated gene family expansion in the constitutive CAM species, further supporting the view of gene family evolution as a driver of CAM evolution.

PMID:38686825 | DOI:10.1093/plcell/koae130

Categories: Literature Watch

Ca<sup>2+</sup> homeostasis and male fertility: a target for a new male contraceptive system

Tue, 2024-04-30 06:00

Anim Cells Syst (Seoul). 2024 Apr 28;28(1):171-183. doi: 10.1080/19768354.2024.2345647. eCollection 2024.

ABSTRACT

Ca2+ is a key secondary messenger that determines sperm motility patterns. Mammalian sperm undergo capacitation, a process to acquire fertilizing ability, in the female reproductive tract. Capacitated sperm change their flagellar waveform to develop hyperactivated motility, which is crucial for successful sperm navigation to the eggs and fertilization. The sperm-specific channel, CATSPER, and an ATPase transporter, PMCA4, serve as major paths for Ca2+ influx and efflux, respectively, in sperm. The ionic paths coordinate Ca2+ homeostasis in the sperm, and their loss-of-function impairs sperm motility, to cause male infertility. In this review, we summarize the physiological significance of these two Ca2+ gates and suggest their potential applications in novel male contraceptives.

PMID:38686363 | PMC:PMC11057403 | DOI:10.1080/19768354.2024.2345647

Categories: Literature Watch

Antitumor effects of a novel photosensitizer-mediated photodynamic therapy and its influence on the cell transcriptome

Tue, 2024-04-30 06:00

Oncol Res. 2024 Apr 23;32(5):911-923. doi: 10.32604/or.2023.042384. eCollection 2024.

ABSTRACT

Photodynamic therapy (PDT) is a promising cancer treatment. This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]-10,15,20-triphenyl-porphyrin (DTP) mediated PDT (DTP-PDT). Cell viability, reactive oxygen species (ROS), and apoptosis were measured with a Cell Counting Kit-8 assay, DCFH-DA fluorescent probe, and Hoechst staining, respectively. Cell apoptosis- and autophagy-related proteins were examined using western blotting. RNA sequencing was used to screen differentially expressed mRNAs (DERs), and bioinformatic analysis was performed to identify the major biological events after DTP-PDT. Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity. DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2, which could also be inhibited by NAC or SB203580. The level of LC3B-II, a marker of autophagy, was increased by DTP-PDT. A total of 3496 DERs were obtained after DTP-PDT. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes, the nuclear lumen, protein binding, cell cycle, protein targeting to the endoplasmic reticulum, and ribosomal DNA replication. Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints. Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes. Therefore, DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy, partly through ROS and the P38 MAPK signaling pathway. Genes associated with the cell cycle, ribosomes, DNA replication, and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.

PMID:38686054 | PMC:PMC11055994 | DOI:10.32604/or.2023.042384

Categories: Literature Watch

Early administration of Wumei Wan inhibit myeloid-derived suppressor cells via PI3K/Akt pathway and amino acids metabolism to prevent Colitis-associated Colorectal Cancer

Tue, 2024-04-30 06:00

J Ethnopharmacol. 2024 Apr 27:118260. doi: 10.1016/j.jep.2024.118260. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Wumei Wan (WMW), a traditional Chinese medicine prescription, has been proved to be effective in treating Colitis-associated colorectal cancer (CAC), but it has not been proven to be effective in different stages of CAC.

AIM OF THE STUDY: The purpose of our study is to investigate the therapeutic effect and mechanism of WMW on the progression of CAC.

MATERIALS AND METHODS: Azioximethane (AOM) and dextran sulfate sodium (DSS) were used to treat mice for the purpose of establishing CAC models. WMW was administered in different stages of CAC. The presentative chemical components in WMW were confirmed by UHPLCQTOF/MS under the optimized conditions. The detection of inflammatory cytokines in the serum and colon of mice were estimated by qRT-PCR and ELISA. The changes of T cells and myeloid-derived suppressor cells (MDSCs) in each group were detected by flow cytometry. The metabolic components in serum of mice were detected by UPLC-MS/MS. Expression of genes and proteins were detected by eukaryotic transcriptomics and western blot to explore the key pathway of WMW in preventing CAC.

RESULTS: WMW had significant effect on inhibiting inflammatory responses and tumors during the early development stage of CAC when compared to other times. WMW increased the length of mice's colons, reduced the level of IL-1β, IL-6, TNF-α in colon tissues, and effectively alleviated colonic inflammation, and improved the pathological damage of colon tissues. WMW could significantly reduce the infiltration of MDSCs in the spleen, increase CD4+ T cells and CD8+ T cells in the spleen of CAC mice, and effectively reform the immune microenvironment in CAC mice. Transcriptomics analysis revealed that 2204 genes had different patterns of overlap in the colon tissues of mice between control group, AOM+DSS group, and early administration of WMW group. And KEGG enrichment analysis showed that PI3K/Akt signaling pathway, ECM-receptor interaction, IL-17 signaling pathway, MAPK signaling pathway, pancreatic secretion, thermogenesis, and Rap1 signaling pathway were all involved. The serum metabolomics results of WMW showed that the metabolic compositions of the control group, AOM+DSS group and the early stage of WMW were different, and 42 differential metabolites with the opposite trends of changes were screened. The metabolic pathways mainly included pyrimidine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, and purine metabolism. And amino acids and related metabolites may play an important role in WMW prevention of CAC.

CONCLUSION: WMW can effectively prevent the occurrence and development of CAC, especially in the initial stage. WMW can reduce the immune infiltration of MDSCs in the early stage. Early intervention of WMW can improve the metabolic disorder caused by AOM+DSS, especially correct the amino acid metabolism. PI3K/Akt signaling pathway was inhabited in early administration of WMW, which can regulate the amplification and function of MDSCs.

PMID:38685367 | DOI:10.1016/j.jep.2024.118260

Categories: Literature Watch

Pro197Ser and the new Trp574Leu mutations together with enhanced metabolism contribute to cross-resistance to ALS inhibiting herbicides in Sinapis alba

Tue, 2024-04-30 06:00

Pestic Biochem Physiol. 2024 May;201:105882. doi: 10.1016/j.pestbp.2024.105882. Epub 2024 Mar 19.

ABSTRACT

White mustard, (Sinapis alba), a problematic broadleaf weed in many Mediterranean countries in arable fields has been detected as resistant to tribenuron-methyl in Tunisia. Greenhouse and laboratory studies were conducted to characterize Target-Site Resistance (TSR) and the Non-Target Site Resistance (NTSR) mechanisms in two suspected white mustard biotypes. Herbicide dose-response experiments confirmed that the two S. alba biotypes were resistant to four dissimilar acetolactate synthase (ALS)-pinhibiting herbicide chemistries indicating the presence of cross-resistance mechanisms. The highest resistance factor (>144) was attributed to tribenuron-methyl herbicide and both R populations survived up to 64-fold the recommended field dose (18.7 g ai ha-1). In this study, the metabolism experiments with malathion (a cytochrome P450 inhibitor) showed that malathion reduced resistance to tribenuron-methyl and imazamox in both populations, indicating that P450 may be involved in the resistance. Sequence analysis of the ALS gene detected target site mutations in the two R biotypes, with amino acid substitutions Trp574Leu, the first report for the species, and Pro197Ser. Molecular docking analysis showed that ALSPro197Ser enzyme cannot properly bind to tribenuron-methyl's aromatic ring due to a reduction in the number of hydrogen bonds, while imazamox can still bind. However, Trp574Leu can weaken the binding affinity between the mutated ALS enzyme and both herbicides with the loss of crucial interactions. This investigation provides substantial evidence for the risk of evolving multiple resistance in S. alba to auxin herbicides while deciphering the TSR and NTSR mechanisms conferring cross resistance to ALS inhibitors.

PMID:38685248 | DOI:10.1016/j.pestbp.2024.105882

Categories: Literature Watch

Structural basis of closed groove scrambling by a TMEM16 protein

Mon, 2024-04-29 06:00

Nat Struct Mol Biol. 2024 Apr 29. doi: 10.1038/s41594-024-01284-9. Online ahead of print.

ABSTRACT

Activation of Ca2+-dependent TMEM16 scramblases induces phosphatidylserine externalization, a key step in multiple signaling processes. Current models suggest that the TMEM16s scramble lipids by deforming the membrane near a hydrophilic groove and that Ca2+ dependence arises from the different association of lipids with an open or closed groove. However, the molecular rearrangements underlying groove opening and how lipids reorganize outside the closed groove remain unknown. Here we directly visualize how lipids associate at the closed groove of Ca2+-bound fungal nhTMEM16 in nanodiscs using cryo-EM. Functional experiments pinpoint lipid-protein interaction sites critical for closed groove scrambling. Structural and functional analyses suggest groove opening entails the sequential appearance of two π-helical turns in the groove-lining TM6 helix and identify critical rearrangements. Finally, we show that the choice of scaffold protein and lipids affects the conformations of nhTMEM16 and their distribution, highlighting a key role of these factors in cryo-EM structure determination.

PMID:38684930 | DOI:10.1038/s41594-024-01284-9

Categories: Literature Watch

Author Correction: Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI/SNF

Mon, 2024-04-29 06:00

Nature. 2024 Apr 29. doi: 10.1038/s41586-024-07402-3. Online ahead of print.

NO ABSTRACT

PMID:38684813 | DOI:10.1038/s41586-024-07402-3

Categories: Literature Watch

Antigen presentation plays positive roles in the regenerative response to cardiac injury in zebrafish

Mon, 2024-04-29 06:00

Nat Commun. 2024 Apr 29;15(1):3637. doi: 10.1038/s41467-024-47430-1.

ABSTRACT

In contrast to adult mammals, adult zebrafish can fully regenerate injured cardiac tissue, and this regeneration process requires an adequate and tightly controlled immune response. However, which components of the immune response are required during regeneration is unclear. Here, we report positive roles for the antigen presentation-adaptive immunity axis during zebrafish cardiac regeneration. We find that following the initial innate immune response, activated endocardial cells (EdCs), as well as immune cells, start expressing antigen presentation genes. We also observe that T helper cells, a.k.a. Cd4+ T cells, lie in close physical proximity to these antigen-presenting EdCs. We targeted Major Histocompatibility Complex (MHC) class II antigen presentation by generating cd74a; cd74b mutants, which display a defective immune response. In these mutants, Cd4+ T cells and activated EdCs fail to efficiently populate the injured tissue and EdC proliferation is significantly decreased. cd74a; cd74b mutants exhibit additional defects in cardiac regeneration including reduced cardiomyocyte dedifferentiation and proliferation. Notably, Cd74 also becomes activated in neonatal mouse EdCs following cardiac injury. Altogether, these findings point to positive roles for antigen presentation during cardiac regeneration, potentially involving interactions between activated EdCs, classical antigen-presenting cells, and Cd4+ T cells.

PMID:38684665 | DOI:10.1038/s41467-024-47430-1

Categories: Literature Watch

The Role of HSP90 and TRAP1 Targets on Treatment in Hepatocellular Carcinoma

Mon, 2024-04-29 06:00

Mol Biotechnol. 2024 Apr 29. doi: 10.1007/s12033-024-01151-4. Online ahead of print.

ABSTRACT

Hepatocellular Carcinoma (HCC) is the predominant form of liver cancer and arises due to dysregulation of the cell cycle control machinery. Heat Shock Protein 90 (HSP90) and mitochondrial HSP90, also referred to as TRAP1 are important critical chaperone target receptors for early diagnosis and targeting HCC. Both HSP90 and TRAP1 expression was found to be higher in HCC patients. Hence, the importance of HSP90 and TRAP1 inhibitors mechanism and mitochondrial targeted delivery of those inhibitors function is widely studied. This review also focuses on importance of protein-protein interactions of HSP90 and TRAP1 targets and association of its interacting proteins in various pathways of HCC. To further elucidate the mechanism, systems biology approaches and computational biology approach studies are well explored in the association of inhibition of herbal plant molecules with HSP90 and its mitochondrial type in HCC.

PMID:38684604 | DOI:10.1007/s12033-024-01151-4

Categories: Literature Watch

Development and evaluation of genomics informed real-time PCR assays for the detection and strain typing of mycobacterium avium subsp. Paratuberculosis

Mon, 2024-04-29 06:00

J Appl Microbiol. 2024 Apr 29:lxae107. doi: 10.1093/jambio/lxae107. Online ahead of print.

ABSTRACT

AIMS: This study aimed to identify specific genomic targets for the detection and strain typing of Map and analyse their sensitivity and specificity and to detect Map directly from faeces.

METHODS AND RESULTS: A comparative genomics approach was used to identify specific genomic targets for the detection and strain typing of Map. A Map specific qPCR using the primer pair 7132 that targets a DNA segregation ATPase protein was able to detect all strains of Map and is more sensitive than the current Johne's disease PCR assays with a sensitivity of 0.0002 fg µl-1. A strain specific qPCR using the Atsa primer pair that targets the arylsulfase gene was able to differentiate between Type S and Type C strains of Map and is more sensitive than the IS1311 PCR and REA with a sensitivity of 40fg µl-1 and was specific for Type S Map. Both assays successfully detected Map directly from faeces.

CONCLUSION: This study developed and validated two genomics informed qPCR assays, 7132B Map and Atsa Type S and found both assays to be highly specific and sensitive for the detection of Map from culture and directly from faeces. This is the first time that a probe-based qPCR has been designed and developed for Map strain typing which will greatly improve the response time during outbreak investigations.

PMID:38684472 | DOI:10.1093/jambio/lxae107

Categories: Literature Watch

A time-resolved single-cell roadmap of the logic driving anterior neural crest diversification from neural border to migration stages

Mon, 2024-04-29 06:00

Proc Natl Acad Sci U S A. 2024 May 7;121(19):e2311685121. doi: 10.1073/pnas.2311685121. Epub 2024 Apr 29.

ABSTRACT

Neural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of early molecular choices orchestrating the emergence of neural crest heterogeneity from the embryonic ectoderm remains elusive. Gene-regulatory-networks (GRN) govern early development and cell specification toward definitive neural crest. Here, we combine ultradense single-cell transcriptomes with machine-learning and large-scale transcriptomic and epigenomic experimental validation of selected trajectories, to provide the general principles and highlight specific features of the GRN underlying neural crest fate diversification from induction to early migration stages using Xenopus frog embryos as a model. During gastrulation, a transient neural border zone state precedes the choice between neural crest and placodes which includes multiple converging gene programs. During neurulation, transcription factor connectome, and bifurcation analyses demonstrate the early emergence of neural crest fates at the neural plate stage, alongside an unbiased multipotent-like lineage persisting until epithelial-mesenchymal transition stage. We also decipher circuits driving cranial and vagal neural crest formation and provide a broadly applicable high-throughput validation strategy for investigating single-cell transcriptomes in vertebrate GRNs in development, evolution, and disease.

PMID:38683994 | DOI:10.1073/pnas.2311685121

Categories: Literature Watch

Proteolytic stability and aggregation in a key metabolic enzyme of bacteria

Mon, 2024-04-29 06:00

Proc Natl Acad Sci U S A. 2024 May 7;121(19):e2301458121. doi: 10.1073/pnas.2301458121. Epub 2024 Apr 29.

ABSTRACT

Proteins that are kinetically stable are thought to be less prone to both aggregation and proteolysis. We demonstrate that the classical lac system of Escherichia coli can be leveraged as a model system to study this relation. β-galactosidase (LacZ) plays a critical role in lactose metabolism and is an extremely stable protein that can persist in growing cells for multiple generations after expression has stopped. By attaching degradation tags to the LacZ protein, we find that LacZ can be transiently degraded during lac operon expression but once expression has stopped functional LacZ is protected from degradation. We reversibly destabilize its tetrameric assembly using α-complementation, and show that unassembled LacZ monomers and dimers can either be degraded or lead to formation of aggregates within cells, while the tetrameric state protects against proteolysis and aggregation. We show that the presence of aggregates is associated with cell death, and that these proteotoxic stress phenotypes can be alleviated by attaching an ssrA tag to LacZ monomers which leads to their degradation. We unify our findings using a biophysical model that enables the interplay of protein assembly, degradation, and aggregation to be studied quantitatively in vivo. This work may yield approaches to reversing and preventing protein-misfolding disease states, while elucidating the functions of proteolytic stability in constant and fluctuating environments.

PMID:38683989 | DOI:10.1073/pnas.2301458121

Categories: Literature Watch

The C-terminus of the prototypical M2 muscarinic receptor localizes to the mitochondria and regulates cell respiration under stress conditions

Mon, 2024-04-29 06:00

PLoS Biol. 2024 Apr 29;22(4):e3002582. doi: 10.1371/journal.pbio.3002582. Online ahead of print.

ABSTRACT

Muscarinic acetylcholine receptors are prototypical G protein-coupled receptors (GPCRs), members of a large family of 7 transmembrane receptors mediating a wide variety of extracellular signals. We show here, in cultured cells and in a murine model, that the carboxyl terminal fragment of the muscarinic M2 receptor, comprising the transmembrane regions 6 and 7 (M2tail), is expressed by virtue of an internal ribosome entry site localized in the third intracellular loop. Single-cell imaging and import in isolated yeast mitochondria reveals that M2tail, whose expression is up-regulated in cells undergoing integrated stress response, does not follow the normal route to the plasma membrane, but is almost exclusively sorted to the mitochondria inner membrane: here, it controls oxygen consumption, cell proliferation, and the formation of reactive oxygen species (ROS) by reducing oxidative phosphorylation. Crispr/Cas9 editing of the key methionine where cap-independent translation begins in human-induced pluripotent stem cells (hiPSCs), reveals the physiological role of this process in influencing cell proliferation and oxygen consumption at the endogenous level. The expression of the C-terminal domain of a GPCR, capable of regulating mitochondrial function, constitutes a hitherto unknown mechanism notably unrelated to its canonical signaling function as a GPCR at the plasma membrane. This work thus highlights a potential novel mechanism that cells may use for controlling their metabolism under variable environmental conditions, notably as a negative regulator of cell respiration.

PMID:38683874 | DOI:10.1371/journal.pbio.3002582

Categories: Literature Watch

Insights into Molecular Interactions between a GAPDH-Related Fish Antimicrobial Peptide, Analogs Thereof, and Bacterial Membranes

Mon, 2024-04-29 06:00

Biochemistry. 2024 Apr 29. doi: 10.1021/acs.biochem.4c00049. Online ahead of print.

ABSTRACT

Interactions between SJGAP (skipjack tuna GAPDH-related antimicrobial peptide) and four analogs thereof with model bacterial membranes were studied using Fourier-transform infrared spectroscopy (FTIR) and molecular dynamics (MD) simulations. MD trajectory analyses showed that the N-terminal segment of the peptide analogs has many contacts with the polar heads of membrane phospholipids, while the central α helix interacts strongly with the hydrophobic core of the membranes. The peptides also had a marked influence on the wave numbers associated with the phase transition of phospholipids organized as liposomes in both the interface and aliphatic chain regions of the infrared spectra, supporting the interactions observed in the MD trajectories. In addition, interesting links were found between peptide interactions with the aliphatic chains of membrane phospholipids, as determined by FTIR and from the MD trajectories, and the membrane permeabilization capacity of these peptide analogs, as previously demonstrated. To summarize, the combined experimental and computational efforts have provided insights into crucial aspects of the interactions between the investigated peptides and bacterial membranes. This work thus makes an original contribution to our understanding of the molecular interactions underlying the antimicrobial activity of these GAPDH-related antimicrobial peptides from Scombridae.

PMID:38683758 | DOI:10.1021/acs.biochem.4c00049

Categories: Literature Watch

ROP signalling and their activating ROPGEFs - Specificity in cellular signal transduction of plants

Mon, 2024-04-29 06:00

J Exp Bot. 2024 Apr 29:erae196. doi: 10.1093/jxb/erae196. Online ahead of print.

ABSTRACT

Every cell constantly receives signals from its neighbours or the environment. In plants, most signals are perceived by RECEPTOR-LIKE KINASES (RLKs) and then transmitted into the cell. The molecular switches RHO OF PLANTS (ROP) are critical proteins for polar signal transduction and regulate multiple cell polarity processes downstream of RLKs. Many ROPregulating proteins and scaffold proteins of the ROP complex are known. However, the spatiotemporal ROP signalling complex composition still needs to be understood. Moreover, how specificity is achieved in different ROP signalling pathways within one cell still needs to be determined. This review gives an overview of the recent advances in ROP signalling and how specificity by downstream scaffold proteins can be achieved. The composition of the ROP signalling complexes is discussed, focusing on the possibility of the simultaneous presence of ROP activators and inactivators within the same complex to balance ROP activity. Furthermore, this review highlights the function of plant-specific ROPGEFs polarising ROP signalling and defining the specificity of the initiated ROP signalling pathway.

PMID:38683617 | DOI:10.1093/jxb/erae196

Categories: Literature Watch

HCMMD: systematic evaluation of metabolites in body fluids as liquid biopsy biomarker for human cancers

Mon, 2024-04-29 06:00

Aging (Albany NY). 2024 Apr 26;16. doi: 10.18632/aging.205779. Online ahead of print.

ABSTRACT

Metabolomics is a rapidly expanding field in systems biology used to measure alterations of metabolites and identify metabolic biomarkers in response to disease processes. The discovery of metabolic biomarkers can improve early diagnosis, prognostic prediction, and therapeutic intervention for cancers. However, there are currently no databases that provide a comprehensive evaluation of the relationship between metabolites and cancer processes. In this review, we summarize reported metabolites in body fluids across pan-cancers and characterize their clinical applications in liquid biopsy. We conducted a search for metabolic biomarkers using the keywords ("metabolomics" OR "metabolite") AND "cancer" in PubMed. Of the 22,254 articles retrieved, 792 were deemed potentially relevant for further review. Ultimately, we included data from 573,300 samples and 17,083 metabolic biomarkers. We collected information on cancer types, sample size, the human metabolome database (HMDB) ID, metabolic pathway, area under the curve (AUC), sensitivity and specificity of metabolites, sample source, detection method, and clinical features were collected. Finally, we developed a user-friendly online database, the Human Cancer Metabolic Markers Database (HCMMD), which allows users to query, browse, and download metabolite information. In conclusion, HCMMD provides an important resource to assist researchers in reviewing metabolic biomarkers for diagnosis and progression of cancers.

PMID:38683118 | DOI:10.18632/aging.205779

Categories: Literature Watch

Development of equation of motion deciphering locomotion including omega turns of <em>Caenorhabditis elegans</em>

Mon, 2024-04-29 06:00

Elife. 2024 Apr 29;12:RP92562. doi: 10.7554/eLife.92562.

ABSTRACT

Locomotion is a fundamental behavior of Caenorhabditis elegans (C. elegans). Previous works on kinetic simulations of animals helped researchers understand the physical mechanisms of locomotion and the muscle-controlling principles of neuronal circuits as an actuator part. It has yet to be understood how C. elegans utilizes the frictional forces caused by the tension of its muscles to perform sequenced locomotive behaviors. Here, we present a two-dimensional rigid body chain model for the locomotion of C. elegans by developing Newtonian equations of motion for each body segment of C. elegans. Having accounted for friction-coefficients of the surrounding environment, elastic constants of C. elegans, and its kymogram from experiments, our kinetic model (ElegansBot) reproduced various locomotion of C. elegans such as, but not limited to, forward-backward-(omega turn)-forward locomotion constituting escaping behavior and delta-turn navigation. Additionally, ElegansBot precisely quantified the forces acting on each body segment of C. elegans to allow investigation of the force distribution. This model will facilitate our understanding of the detailed mechanism of various locomotive behaviors at any given friction-coefficients of the surrounding environment. Furthermore, as the model ensures the performance of realistic behavior, it can be used to research actuator-controller interaction between muscles and neuronal circuits.

PMID:38682888 | DOI:10.7554/eLife.92562

Categories: Literature Watch

Causal Associations between Posttraumatic Stress Disorder and COVID-19

Mon, 2024-04-29 06:00

J Integr Neurosci. 2024 Apr 1;23(4):68. doi: 10.31083/j.jin2304068.

ABSTRACT

OBJECTIVE: We aimed to evaluate bidirectional genetic relationships between posttraumatic stress disorder (PTSD) and COVID-19.

METHODS: We investigated potential causal associations between PTSD and two COVID-19 conditions (COVID-19 hospitalization and SARS-CoV-2 infection) via Mendelian randomization (MR) analyses. Three genome-wide association study (GWAS) summary datasets were used in the study, including PTSD (N = 174,659), SARS-CoV-2 infection (N = 2,597,856), and COVID-19 hospitalization (N = 2,095,324). We performed a literature-based analysis to uncover molecular pathways connecting PTSD and COVID-19.

RESULTS: We found that PTSD exerts a causal effect on SARS-CoV-2 infection (odds ratio (OR): 1.10, 95% confidence interval (CI): 1.00-1.21, p = 0.048) and hospitalized COVID-19 (OR: 1.34, 95% CI: 1.07-1.67, p = 0.001). However, both SARS-CoV-2 infection and hospitalized COVID-19 were not associated with the risk of PTSD. Pathway analysis revealed that several immunity-related genes may link PTSD to COVID-19.

CONCLUSIONS: Our study suggests that PTSD was associated with increased risks for COVID-19 susceptibility and severity. Early diagnosis and effective treatment of PTSD in individuals infected with the coronavirus may improve the management of the outcomes of COVID-19.

PMID:38682223 | DOI:10.31083/j.jin2304068

Categories: Literature Watch

Pony feeding management: the role of morphology and hay feeding methods on intake rate, ingestive behaviors and mouth shaping

Mon, 2024-04-29 06:00

Front Vet Sci. 2024 Apr 12;11:1332207. doi: 10.3389/fvets.2024.1332207. eCollection 2024.

ABSTRACT

In the last decade, haynets and slow feeders have been promoted as sustainable tools to improve the feeding management of horses and reduce forage waste, but little is known about their effects on ponies. Therefore, the aim of this study was to analyze the effects of different hay feeding methods on the ingestive behaviors, intake rate and mouth shaping of ponies belonging to two breed types, which are characterized by different head morphologies. Shetland type (SH, n = 5) and Welsh/Cob type (WC, n = 4) ponies were fed hay using four feeding methods: on the ground (G), a fully filled haynet (HF), a partially filled haynet (HL), and a slow-feeder hay box (HB). Head morphology was measured for each pony. Video recordings were then made to apply geometric morphometrics and to perform behavioral analysis. The intake rate was measured for each pony and each feeding method. Data obtained with geometric morphometrics were analyzed using principal component analysis (PCA) and canonical variate analysis (CVA). Behavioral data and intake rate measurements were analyzed using a mixed model, a post-hoc Tukey's test, a Pearson's correlation test, and a stepwise regression model. The geometric morphometrics results demonstrated that feeding method influenced mouth shaping (36% for G, 78% for HB, 77% for HF, 83% for HL, considering the total variance of shape) and affected the intake rate. Differences in mouth shaping and ingestive behaviors in SH and WC ponies also confirmed the role of morphology in feeding management. The HL proved to be the most effective tool to increase feeding consumption time when needed (5 h/kg for SH ponies and 3 h/kg for WC ponies, considering the intake time), although the HB may be the optimal choice to reduce the intake rate while maintaining a more natural posture. Future studies are suggested to fully understand how body size and morphology influence feeding in equine species.

PMID:38681853 | PMC:PMC11046934 | DOI:10.3389/fvets.2024.1332207

Categories: Literature Watch

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