PLoS One. 2023 Sep 1;18(9):e0290429. doi: 10.1371/journal.pone.0290429. eCollection 2023.

ABSTRACT

The improvement of crop yield is a major breeding target and there is a long history of research that has focussed on unravelling the mechanisms and processes that contribute to yield. Quantitative prediction of the interplay between morphological traits, and the effects of these trait-trait relationships on seed production remains, however, a challenge. Consequently, the extent to which crop varieties optimise their morphology for a given environment is largely unknown. This work presents a new combination of existing methodologies by framing crop breeding as an optimisation problem and evaluates the extent to which existing varieties exhibit optimal morphologies under the test conditions. In this proof-of-concept study using spring and winter oilseed rape plants grown under greenhouse conditions, we employ causal inference to model the hierarchically structured effects of 27 morphological yield traits on each other. We perform Bayesian optimisation of seed yield, to identify and quantify the morphologies of ideotype plants, which are expected to be higher yielding than the varieties in the studied panels. Under the tested growth conditions, we find that existing spring varieties occupy the optimal regions of trait-space, but that potentially high yielding strategies are unexplored in extant winter varieties. The same approach can be used to evaluate trait (morphology) space for any environment.

PMID:37656702 | DOI:10.1371/journal.pone.0290429

Elife. 2023 Sep 1;12:RP90773. doi: 10.7554/eLife.90773.

ABSTRACT

G-protein coupled receptors (GPCRs) present specific activation pathways and signaling among receptor subtypes. Hence, an extensive knowledge of the structural dynamics of the receptor is critical for the development of therapeutics. Here, we target the adenosine A1 receptor (A1R), for which a negligible number of drugs have been approved. We combine molecular dynamics simulations, enhanced sampling techniques, network theory and pocket detection to decipher the activation pathway of A1R, decode the allosteric networks and identify transient pockets. The A1R activation pathway reveal hidden intermediate and pre-active states together with the inactive and fully-active states observed experimentally. The protein energy networks computed throughout these conformational states successfully unravel the extra and intracellular allosteric centers and the communication pathways that couples them. We observe that the allosteric networks are dynamic, being increased along activation and fine-tuned in presence of the trimeric G-proteins. Overlap of transient pockets and energy networks uncover how the allosteric coupling between pockets and distinct functional regions of the receptor is altered along activation. By an in-depth analysis of the bridge between activation pathway, energy networks and transient pockets, we provide a further understanding of A1R. This information can be useful to ease the design of allosteric modulators for A1R.

PMID:37656635 | DOI:10.7554/eLife.90773

Med Oncol. 2023 Sep 1;40(10):287. doi: 10.1007/s12032-023-02163-x.

ABSTRACT

Sine oculis homeobox 4 (SIX4), a critical transcription factor modulating organ development, potentially participates in tumorigenesis through numerous pathways. Here, we investigated siRNA-mediated knockdown effects of SIX4 on pancreatic cancer cells and underlying molecular mechanisms. The expression of SIX4 in pancreatic cancer and adjacent tissues were investigated in clinical tissue samples and bioinformatically approved by gene expression omnibus (GEO) database. Appropriate siRNA transfected into PANC1 pancreatic cancer cells in order to SIX4 knockdown. The survival, migration, invasion, colony formation, mitochondrial membrane potential, apoptosis, autophagy, and cell cycle in the cancer cells were investigated after knockdown of SIX4. In addition, expression of genes involved in apoptosis and metastasis were assessed in the transfected cancer cells in mRNA and protein levels. High-throughput analysis using GEO database confirmed the overexpression of SIX4 in pancreatic cancer tissues by six independent pancreatic cancer microarrays. Knockdown of SIX4 by specific siRNA significantly decreased survival, colony formation, and mitochondrial membrane potential of the cancer cells. Further assessments demonstrated that knockdown of SIX4 increases the apoptosis and autophagy rates in the cancer cells through modifying the expression of related genes. Moreover, a significant decrease in migration and invasion rates were observed in SIX4 suppressed group. Furthermore, frequency of the cells transfected with SIX4 siRNA increased slightly in G1 and Sub-G1 phases of cell cycle. Our study suggested that siRNA-mediated knockdown of SIX4 increases the pancreatic cancer cells death and reduces the invasion and migration of the cancer cells through different molecular pathways.

PMID:37656231 | DOI:10.1007/s12032-023-02163-x

J Physiol. 2023 Sep 1. doi: 10.1113/JP284413. Online ahead of print.

ABSTRACT

Play is a suite of apparently non-functional, pleasurable behaviours observed in human and non-human animals. Although the phenomenon has been studied extensively, no adaptationist behavioural theory of how play evolved can be supported by the available evidence. However, the advancement of the extended evolutionary synthesis and developments in systems biology offer alternative avenues for non-adaptationist physiological hypotheses. I therefore propose a hypothesis of play, based upon a complex ACh activity that is under agential control of the organism, whereby play initiates ACh-mediated feedforward and feedback processes which act to: (i) regulate metabolic processes; (ii) form new ACh receptors via ACh mRNA activity; (iii) mediate attention, memory consolidation and learning; and (iv) mediate social behaviours, reproduction and embryonic development. However, play occurs across taxa, but does not occur across all taxonomic groups or within all species of a taxonomic group. Thus, to support the validity of the proposed hypothesis, I further propose potential explanations for this anomaly, which include sampling and observer biases, altricial versus precocial juvenile development, and the influence of habitat niche and environmental conditions on behaviour. The proposed hypothesis thus offers new avenues for study in both the biological and social sciences, in addition to having potential applications in applied sciences, such as animal welfare and biomedical research. Crucially, it is hoped that this hypothesis will promote further study of a valid and behaviourally significant, yet currently enigmatic, biological phenomenon.

PMID:37656171 | DOI:10.1113/JP284413

Appl Environ Microbiol. 2023 Sep 1:e0082623. doi: 10.1128/aem.00826-23. Online ahead of print.

ABSTRACT

Comparative proteomics and untargeted metabolomics were combined to study the physiological and metabolic adaptations of Rhodococcus qingshengii IGTS8 under biodesulfurization conditions. After growth in a chemically defined medium with either dibenzothiophene (DBT) or MgSO4 as the sulfur source, many differentially produced proteins and metabolites associated with several metabolic and physiological processes were detected including the metabolism of carbohydrates, amino acids, lipids, nucleotides, vitamins, protein synthesis, transcriptional regulation, cell envelope biogenesis, and cell division. Increased production of the redox cofactor mycofactocin and associated proteins was one of the most striking adaptations under biodesulfurization conditions. While most central metabolic enzymes were less abundant in the presence of DBT, a key enzyme of the glyoxylate shunt, isocitrate lyase, was up to 26-fold more abundant. Several C1 metabolism and oligotrophy-related enzymes were significantly more abundant in the biodesulfurizing culture. R. qingshengii IGTS8 exhibited oligotrophic growth in liquid and solid media under carbon starvation. Moreover, the oligotrophic growth was faster on the solid medium in the presence of DBT compared to MgSO4 cultures. In the DBT culture, the cell envelope and phospholipids were remodeled, with lower levels of phosphatidylethanolamine and unsaturated and short-chain fatty acids being the most prominent changes. Biodesulfurization increased the biosynthesis of osmoprotectants (ectoine and mannosylglycerate) as well as glutamate and induced the stringent response. Our findings reveal highly diverse and overlapping stress responses that could protect the biodesulfurizing culture not only from the associated sulfate limitation but also from chemical, oxidative, and osmotic stress, allowing efficient resource management. IMPORTANCE Despite decades of research, a commercially viable bioprocess for fuel desulfurization has not been developed yet. This is mainly due to lack of knowledge of the physiology and metabolism of fuel-biodesulfurizing bacteria. Being a stressful condition, biodesulfurization could provoke several stress responses that are not understood. This is particularly important because a thorough understanding of the microbial stress response is essential for the development of environmentally friendly and industrially efficient microbial biocatalysts. Our comparative systems biology studies provide a mechanistic understanding of the biology of biodesulfurization, which is crucial for informed developments through the rational design of recombinant biodesulfurizers and optimization of the bioprocess conditions. Our findings enhance the understanding of the physiology, metabolism, and stress response not only in biodesulfurizing bacteria but also in rhodococci, a precious group of biotechnologically important bacteria.

PMID:37655899 | DOI:10.1128/aem.00826-23

Front Mol Neurosci. 2023 Aug 16;16:1232805. doi: 10.3389/fnmol.2023.1232805. eCollection 2023.

ABSTRACT

Several studies found that most patients with Parkinson's disorder (PD) appear to have psychiatric symptoms such as depression, anxiety, hallucination, delusion, and cognitive dysfunction. Therefore, recognizing these psychiatrically symptoms of PD patients is crucial for both symptomatic therapy and better knowledge of the pathophysiology of PD. In order to address this issue, we created a bioinformatics framework to determine the effects of PD mRNA expression on understanding its relationship with psychiatric symptoms in PD patients. We have discovered a significant overlap between the sets of differentially expressed genes from PD exposed tissue and psychiatric disordered tissues using RNA-seq datasets. We have chosen Bipolar disorder and Schizophrenia as psychiatric disorders in our study. A number of significant correlations between PD and the occurrence of psychiatric diseases were also found by gene set enrichment analysis, investigations of the protein-protein interaction network, gene regulatory network, and protein-chemical agent interaction network. We anticipate that the results of this pathogenetic study will provide crucial information for understanding the intricate relationship between PD and psychiatric diseases.

PMID:37654790 | PMC:PMC10466791 | DOI:10.3389/fnmol.2023.1232805

Genome Res. 2023 Aug 31. doi: 10.1101/gr.277625.122. Online ahead of print.

ABSTRACT

Copy number variants (CNVs), duplications and deletions of genomic sequences, contribute to evolutionary adaptation but can also confer deleterious effects and cause disease. Whereas the effects of amplifying individual genes or whole chromosomes (i.e., aneuploidy) have been studied extensively, much less is known about the genetic and functional effects of CNVs of differing sizes and structures. Here, we investigated Saccharomyces cerevisiae (yeast) strains that acquired adaptive CNVs of variable structures and copy numbers following experimental evolution in glutamine-limited chemostats. Although beneficial in the selective environment, CNVs result in decreased fitness compared with the euploid ancestor in rich media. We used transposon mutagenesis to investigate mutational tolerance and genome-wide genetic interactions in CNV strains. We find that CNVs increase mutational target size, confer increased mutational tolerance in amplified essential genes, and result in novel genetic interactions with unlinked genes. We validated a novel genetic interaction between different CNVs and BMH1 that was common to multiple strains. We also analyzed global gene expression and found that transcriptional dosage compensation does not affect most genes amplified by CNVs, although gene-specific transcriptional dosage compensation does occur for ∼12% of amplified genes. Furthermore, we find that CNV strains do not show previously described transcriptional signatures of aneuploidy. Our study reveals the extent to which local and global mutational tolerance is modified by CNVs with implications for genome evolution and CNV-associated diseases, such as cancer.

PMID:37652668 | DOI:10.1101/gr.277625.122

Immunol Lett. 2023 Aug 29:S0165-2478(23)00142-6. doi: 10.1016/j.imlet.2023.08.004. Online ahead of print.

ABSTRACT

BACKGROUND: The rise of multi-drug resistant Acinetobacter baumannii poses a grave threat to hospital settings, resulting in increased mortality rates and garnering global attention. The formation of biofilms facilitated by biofilm-associated protein (Bap) and the iron absorption capabilities mediated by Baumannii acinetobactin Utilisation A (BauA) contribute to the persistence and survival of multidrug-resistant strains. In this study, we aimed to investigate the potential of disrupting the function of BauA and Bap simultaneously as a strategy for controlling A. baumannii.

METHODS: Recombinant Bap and BauA were expressed, purified, and subcutaneously administered individually and in combination to BALB/c mice. Subsequently, mice were intraperitoneally challenged with A. baumannii, and the bacterial load and tissue damage in the spleen, lung, and liver were assessed. Serum samples were evaluated to determine antibody titers in surviving mice.

RESULTS: Specific IgG antibodies were significantly increased. A combination of the antigens resulted in enhanced titer of specific IgGs in comparison to either BauA or Bap alone. The antibodies remained stable over a seven-month period. The combination of Bap and BauA exhibited superior immunoprotection against A. baumannii infection compared to individual administration, resulting in a further reduction in bacterial load in the liver, spleen, and lungs. The histopathological analysis demonstrated successful protection of the tissues against A. baumannii-induced damage upon administration of the two immunogens.

CONCLUSIONS: The combination of Bap and BauA has the potential to target a broader range of A. baumannii strains, including those expressing either Bap or BauA, thereby increasing its efficacy against a diverse array of strains.

PMID:37652189 | DOI:10.1016/j.imlet.2023.08.004

Mol Biol Evol. 2023 Aug 31:msad194. doi: 10.1093/molbev/msad194. Online ahead of print.

ABSTRACT

MADS-box transcription factors (TFs), among the first TFs extensively studied, exhibit a wide distribution across eukaryotes and play diverse functional roles. Varying by domain architecture, MADS-box TFs in land plants are categorized into Type I (M-type) and Type II (MIKC-type). Type I and II genes have been considered orthologous to the SRF and MEF2 genes in animals, respectively, presumably originating from a duplication before the divergence of eukaryotes. Here, we exploited the increasing availability of eukaryotic MADS-box sequences and reassessed their evolution. While supporting the ancient duplication giving rise to SRF- and MEF2-types, we found that Type I and II genes originated from the MEF2-type genes through another duplication in the most recent common ancestor (MRCA) of land plants. Protein structures predicted by AlphaFold2 and OmegaFold support our phylogenetic analyses, with plant Type I and II TFs resembling the MEF2-type structure, rather than SRFs. We hypothesize that the ancestral SRF-type TFs were lost in the MRCA of Archaeplastida (the kingdom Plantae sensu lato). The retained MEF2-type TFs acquired a Keratin-like domain and became MIKC-type before the divergence of Streptophyta. Subsequently in the MRCA of land plants, M-type TFs evolved from a duplicated MIKC-type precursor through loss of the Keratin-like domain, leading to the Type I clade. Both Type I and II TFs expanded and functionally differentiated in concert with the increasing complexity of land plant body architecture. The recruitment of these originally stress-responsive TFs into developmental programs, including those underlying reproduction, may have facilitated the adaptation to the terrestrial environment.

PMID:37652031 | DOI:10.1093/molbev/msad194

J Pharm Biomed Anal. 2023 Aug 21;236:115677. doi: 10.1016/j.jpba.2023.115677. Online ahead of print.

ABSTRACT

Bronchoalveolar lavage (BAL) has been widely applied for the diagnosis of pulmonary diseases in clinical as it was recognized as a minimally invasive, well-tolerated and easily performed procedure. Lipid analysis of BAL fluid is a comprehensive strategy to observe lipid phenotypes, explore potential biomarkers, and elucidate the biological mechanisms of respiratory diseases. However, the highly diverse concentration of lipids in BAL fluid due to the deviation between the retrieved and injected aliquot volumes during lavage raised a challenge in obtaining high-quality lipidomic data. Here, this study aims to investigate what volume of BAL fluid is suitable for lipidomic analysis. Specifically, the BAL fluid harvested from H1N1 infected mice and controls was concentrated to varying degrees by freeze-drying technique before preparation for lipidomic analysis. The optimal concentration multiple of BAL fluid was approved by comparing the coverage and quality of identified lipids, as well as the number of differentially expressed lipids in the H1N1 infection model. Sixty-two differential lipids were identified respectively in the positive and negative modes when the BAL fluid was condensed five times, and they were classified into glycerolipids, phospholipids and fatty acids. This study focuses on the alterations of phospholipids, since they are the main constituents of pulmonary surfactants. Several phospholipids significantly accumulated in the BAL fluid of H1N1-infected mice, while most of them contained omega-3 polyunsaturated fatty acids, indicating disrupted inflammatory homeostasis in lungs. This study recommends freeze-drying/reconstitution prior to lipid extraction from BAL fluid for lipidomic analysis, as this procedure increased the richness and abundance of lipids.

PMID:37651923 | DOI:10.1016/j.jpba.2023.115677

Biochem Biophys Res Commun. 2023 Aug 26;678:193-199. doi: 10.1016/j.bbrc.2023.08.055. Online ahead of print.

ABSTRACT

Severely immunodeficient mice are useful for understanding the pathogenesis of certain tumors and for developing therapeutic agents for such tumors. In addition, engraftment of these mice with human hematopoietic cells can yield information that helps us understand the in vivo molecular mechanisms underlying actual human viral infections. In our present research, we discovered a novel, severely immunodeficient strain of mice having a mutation in exon 57 of the Prkdc gene (PrkdcΔex57/Δex57) in an inbred colony of B10.S/SgSlc mice. Those PrkdcΔex57/Δex57 mice showed thymic hypoplasia and lack of mature T cells and B cells in peripheral lymphoid tissues, resulting in very low levels of production of serum immunoglobulins. In addition, those mice were highly susceptible to influenza viruses due to the lack of acquired immune cells. On the other hand, since they had sufficient numbers of NK cells, they rejected tumor transplants, similarly to Prkdc+/+ mice. Next, we generated Foxn1nu/nuPrkdcΔex57/Δex57Il2rg-/- (NPG) mice on the BALB/cSlc background, which lack all lymphocytes such as T cells, B cells and innate lymphoid cells, including NK cells. As expected, these mice were able to undergo engraftment of human tumor cell lines. These findings suggest that PrkdcΔex57/Δex57 mice will be useful as a novel model of immunodeficiency, while NPG mice will be useful for xenografting of various malignancies.

PMID:37651888 | DOI:10.1016/j.bbrc.2023.08.055

Geroscience. 2023 Aug 31. doi: 10.1007/s11357-023-00917-z. Online ahead of print.

ABSTRACT

Using mouse models and high-throughput proteomics, we conducted an in-depth analysis of the proteome changes induced in response to seven interventions known to increase mouse lifespan. This included two genetic mutations, a growth hormone receptor knockout (GHRKO mice) and a mutation in the Pit-1 locus (Snell dwarf mice), four drug treatments (rapamycin, acarbose, canagliflozin, and 17α-estradiol), and caloric restriction. Each of the interventions studied induced variable changes in the concentrations of proteins across liver, kidney, and gastrocnemius muscle tissue samples, with the strongest responses in the liver and limited concordance in protein responses across tissues. To the extent that these interventions promote longevity through common biological mechanisms, we anticipated that proteins associated with longevity could be identified by characterizing shared responses across all or multiple interventions. Many of the proteome alterations induced by each intervention were distinct, potentially implicating a variety of biological pathways as being related to lifespan extension. While we found no protein that was affected similarly by every intervention, we identified a set of proteins that responded to multiple interventions. These proteins were functionally diverse but tended to be involved in peroxisomal oxidation and metabolism of fatty acids. These results provide candidate proteins and biological mechanisms related to enhancing longevity that can inform research on therapeutic approaches to promote healthy aging.

PMID:37653270 | DOI:10.1007/s11357-023-00917-z

Nat Struct Mol Biol. 2023 Aug 31. doi: 10.1038/s41594-023-01078-5. Online ahead of print.

ABSTRACT

Ribosome assembly is orchestrated by many assembly factors, including ribosomal RNA methyltransferases, whose precise role is poorly understood. Here, we leverage the power of cryo-EM and machine learning to discover that the E. coli methyltransferase KsgA performs a 'proofreading' function in the assembly of the small ribosomal subunit by recognizing and partially disassembling particles that have matured but are not competent for translation. We propose that this activity allows inactive particles an opportunity to reassemble into an active state, thereby increasing overall assembly fidelity. Detailed structural quantifications in our datasets additionally enabled the expansion of the Nomura assembly map to highlight rRNA helix and r-protein interdependencies, detailing how the binding and docking of these elements are tightly coupled. These results have wide-ranging implications for our understanding of the quality-control mechanisms governing ribosome biogenesis and showcase the power of heterogeneity analysis in cryo-EM to unveil functionally relevant information in biological systems.

PMID:37653244 | DOI:10.1038/s41594-023-01078-5

Exp Mol Med. 2023 Sep 1. doi: 10.1038/s12276-023-01082-1. Online ahead of print.

ABSTRACT

Thus far, attempts to develop drugs that target corticotropin-releasing hormone receptor 1 (CRF1R), a drug target in stress-related therapy, have been unsuccessful. Studies have focused on using high-resolution G protein-coupled receptor (GPCR) structures to develop drugs. X-ray free-electron lasers (XFELs), which prevent radiation damage and provide access to high-resolution compositions, have helped accelerate GPCR structural studies. We elucidated the crystal structure of CRF1R complexed with a BMK-I-152 antagonist at 2.75 Å using fixed-target serial femtosecond crystallography. The results revealed that two unique hydrogen bonds are present in the hydrogen bond network, the stalk region forms an alpha helix and the hydrophobic network contains an antagonist binding site. We then developed two antagonists-BMK-C203 and BMK-C205-and determined the CRF1R/BMK-C203 and CRF1R/BMK-C205 complex structures at 2.6 and 2.2 Å, respectively. BMK-C205 exerted significant antidepressant effects in mice and, thus, may be utilized to effectively identify structure-based drugs against CRF1R.

PMID:37653040 | DOI:10.1038/s12276-023-01082-1

Nat Microbiol. 2023 Aug 31. doi: 10.1038/s41564-023-01458-z. Online ahead of print.

ABSTRACT

Heterotrophic bacteria-bacteria that utilize organic carbon sources-are taxonomically and functionally diverse across environments. It is challenging to map metabolic interactions and niches within microbial communities due to the large number of metabolites that could serve as potential carbon and energy sources for heterotrophs. Whether their metabolic niches can be understood using general principles, such as a small number of simplified metabolic categories, is unclear. Here we perform high-throughput metabolic profiling of 186 marine heterotrophic bacterial strains cultured in media containing one of 135 carbon substrates to determine growth rates, lag times and yields. We show that, despite high variability at all levels of taxonomy, the catabolic niches of heterotrophic bacteria can be understood in terms of their preference for either glycolytic (sugars) or gluconeogenic (amino and organic acids) carbon sources. This preference is encoded by the total number of genes found in pathways that feed into the two modes of carbon utilization and can be predicted using a simple linear model based on gene counts. This allows for coarse-grained descriptions of microbial communities in terms of prevalent modes of carbon catabolism. The sugar-acid preference is also associated with genomic GC content and thus with the carbon-nitrogen requirements of their encoded proteome. Our work reveals how the evolution of bacterial genomes is structured by fundamental constraints rooted in metabolism.

PMID:37653010 | DOI:10.1038/s41564-023-01458-z

Nat Microbiol. 2023 Aug 31. doi: 10.1038/s41564-023-01468-x. Online ahead of print.

ABSTRACT

Most microbes evolve faster than their hosts and should therefore drive evolution of host-microbe interactions. However, relatively little is known about the characteristics that define the adaptive path of microbes to host association. Here we identified microbial traits that mediate adaptation to hosts by experimentally evolving the free-living bacterium Pseudomonas lurida with the nematode Caenorhabditis elegans as its host. After ten passages, we repeatedly observed the evolution of beneficial host-specialist bacteria, with improved persistence in the nematode being associated with increased biofilm formation. Whole-genome sequencing revealed mutations that uniformly upregulate the bacterial second messenger, cyclic diguanylate (c-di-GMP). We subsequently generated mutants with upregulated c-di-GMP in different Pseudomonas strains and species, which consistently increased host association. Comparison of pseudomonad genomes from various environments revealed that c-di-GMP underlies adaptation to a variety of hosts, from plants to humans. This study indicates that c-di-GMP is fundamental for establishing host association.

PMID:37653009 | DOI:10.1038/s41564-023-01468-x

Nat Commun. 2023 Aug 31;14(1):5306. doi: 10.1038/s41467-023-41063-6.

ABSTRACT

Landscapes nearby glaciers are disproportionally affected by climate change, but we lack detailed information on microclimate variations that can modulate the impacts of global warming on proglacial ecosystems and their biodiversity. Here, we use near-subsurface soil temperatures in 175 stations from polar, equatorial and alpine glacier forelands to generate high-resolution temperature reconstructions, assess spatial variability in microclimate change from 2001 to 2020, and estimate whether microclimate heterogeneity might buffer the severity of warming trends. Temporal changes in microclimate are tightly linked to broad-scale conditions, but the rate of local warming shows great spatial heterogeneity, with faster warming nearby glaciers and during the warm season, and an extension of the snow-free season. Still, most of the fine-scale spatial variability of microclimate is one-to-ten times larger than the temporal change experienced during the past 20 years, indicating the potential for microclimate to buffer climate change, possibly allowing organisms to withstand, at least temporarily, the effects of warming.

PMID:37652908 | DOI:10.1038/s41467-023-41063-6

Trends Plant Sci. 2023 Aug 29:S1360-1385(23)00264-9. doi: 10.1016/j.tplants.2023.08.002. Online ahead of print.

ABSTRACT

We tell the story of the complex history and global distribution of the very popular banana and illustrate this with amazing depictions by artists and scientists. In addition, we discuss the major changes that occurred during domestication and the risks associated with maintaining a monoculture.

PMID:37652757 | DOI:10.1016/j.tplants.2023.08.002

Artif Cells Nanomed Biotechnol. 2023 Dec;51(1):453-465. doi: 10.1080/21691401.2023.2252477.

ABSTRACT

Perturbation of transcriptome in viral infection patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent transcriptome and identification of robust biomarkers is not complete. In this study, we manually collected 23 datasets related to 6,197 blood transcriptomes across 16 types of respiratory virus infections. We applied a comprehensive systems biology approach starting with whole-blood transcriptomes combined with multilevel bioinformatics analyses to characterize the expression, functional pathways, and protein-protein interaction (PPI) networks to identify robust biomarkers and disease comorbidities. Robust gene markers of infection with different viruses were identified, which can accurately classify the normal and infected patients in train and validation cohorts. The biological processes (BP) of different viruses showed great similarity and enriched in infection and immune response pathways. Network-based analyses revealed that a variety of viral infections were associated with nervous system diseases, neoplasms and metabolic diseases, and significantly correlated with brain tissues. In summary, our manually collected transcriptomes and comprehensive analyses reveal key molecular markers and disease comorbidities in the process of viral infection, which could provide a valuable theoretical basis for the prevention of subsequent public health events for respiratory virus infections.

PMID:37651591 | DOI:10.1080/21691401.2023.2252477

PLoS Genet. 2023 Aug 31;19(8):e1010909. doi: 10.1371/journal.pgen.1010909. Online ahead of print.

ABSTRACT

Trichoderma spp. are ubiquitous rhizosphere fungi capable of producing several classes of secondary metabolites that can modify the dynamics of the plant-associated microbiome. However, the bacterial-fungal mechanisms that mediate these interactions have not been fully characterized. Here, a random barcode transposon-site sequencing (RB-TnSeq) approach was employed to identify bacterial genes important for fitness in the presence of Trichoderma atroviride exudates. We selected three rhizosphere bacteria with RB-TnSeq mutant libraries that can promote plant growth: the nitrogen fixers Klebsiella michiganensis M5aI and Herbaspirillum seropedicae SmR1, and Pseudomonas simiae WCS417. As a non-rhizosphere species, Pseudomonas putida KT2440 was also included. From the RB-TnSeq data, nitrogen-fixing bacteria competed mainly for iron and required the siderophore transport system TonB/Exb for optimal fitness in the presence of T. atroviride exudates. In contrast, P. simiae and P. putida were highly dependent on mechanisms associated with membrane lipid modification that are required for resistance to cationic antimicrobial peptides (CAMPs). A mutant in the Hog1-MAP kinase (Δtmk3) gene of T. atroviride showed altered expression patterns of many nonribosomal peptide synthetase (NRPS) biosynthetic gene clusters with potential antibiotic activity. In contrast with exudates from wild-type T. atroviride, bacterial mutants containing lesions in genes associated with resistance to antibiotics did not show fitness defects when RB-TnSeq libraries were exposed to exudates from the Δtmk3 mutant. Unexpectedly, exudates from wild-type T. atroviride and the Δtmk3 mutant rescued purine auxotrophic mutants of H. seropedicae, K. michiganensis and P. simiae. Metabolomic analysis on exudates from wild-type T. atroviride and the Δtmk3 mutant showed that both strains excrete purines and complex metabolites; functional Tmk3 is required to produce some of these metabolites. This study highlights the complex interplay between Trichoderma-metabolites and soil bacteria, revealing both beneficial and antagonistic effects, and underscoring the intricate and multifaceted nature of this relationship.

PMID:37651474 | DOI:10.1371/journal.pgen.1010909