Systems Biology

Seiðr: Efficient calculation of robust ensemble gene networks

Wed, 2023-06-14 06:00

Heliyon. 2023 May 31;9(6):e16811. doi: 10.1016/j.heliyon.2023.e16811. eCollection 2023 Jun.

ABSTRACT

Gene regulatory and gene co-expression networks are powerful research tools for identifying biological signal within high-dimensional gene expression data. In recent years, research has focused on addressing shortcomings of these techniques with regard to the low signal-to-noise ratio, non-linear interactions and dataset dependent biases of published methods. Furthermore, it has been shown that aggregating networks from multiple methods provides improved results. Despite this, few useable and scalable software tools have been implemented to perform such best-practice analyses. Here, we present Seidr (stylized Seiðr), a software toolkit designed to assist scientists in gene regulatory and gene co-expression network inference. Seidr creates community networks to reduce algorithmic bias and utilizes noise corrected network backboning to prune noisy edges in the networks. Using benchmarks in real-world conditions across three eukaryotic model organisms, Saccharomyces cerevisiae, Drosophila melanogaster, and Arabidopsis thaliana, we show that individual algorithms are biased toward functional evidence for certain gene-gene interactions. We further demonstrate that the community network is less biased, providing robust performance across different standards and comparisons for the model organisms. Finally, we apply Seidr to a network of drought stress in Norway spruce (Picea abies (L.) H. Krast) as an example application in a non-model species. We demonstrate the use of a network inferred using Seidr for identifying key components, communities and suggesting gene function for non-annotated genes.

PMID:37313140 | PMC:PMC10258422 | DOI:10.1016/j.heliyon.2023.e16811

Categories: Literature Watch

Genome-wide association study for biomass accumulation traits in soybean

Wed, 2023-06-14 06:00

Mol Breed. 2023 Apr 21;43(5):33. doi: 10.1007/s11032-023-01380-6. eCollection 2023 May.

ABSTRACT

Soybean is one of the most versatile crops for oil production, human diets, and feedstocks. The vegetative biomass of soybean is an important determinant of seed yield and is crucial for the forage usages. However, the genetic control of soybean biomass is not well explained. In this work, we used a soybean germplasm population, including 231 improved cultivars, 207 landraces, and 121 wild soybeans, to investigate the genetic basis of biomass accumulation of soybean plants at the V6 stage. We found that biomass-related traits, including NDW (nodule dry weight), RDW (root dry weight), SDW (shoot dry weight), and TDW (total dry weight), were domesticated during soybean evolution. In total, 10 loci, encompassing 47 putative candidate genes, were detected for all biomass-related traits by a genome-wide association study. Among these loci, seven domestication sweeps and six improvement sweeps were identified. Glyma.05G047900, a purple acid phosphatase, was a strong candidate gene to improve biomass for future soybean breeding. This study provided new insights into the genetic basis of biomass accumulation during soybean evolution.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11032-023-01380-6.

PMID:37312748 | PMC:PMC10248709 | DOI:10.1007/s11032-023-01380-6

Categories: Literature Watch

Non-alcoholic fatty liver disease mediates the effect of obesity on arterial hypertension

Wed, 2023-06-14 06:00

Liver Int. 2023 Jun 13. doi: 10.1111/liv.15643. Online ahead of print.

ABSTRACT

BACKGROUND: It has been consistently shown that obesity contributes directly to arterial hypertension and cardiovascular disease (CVD), independently of other risk factors. Likewise, non-alcoholic fatty liver disease (NAFLD) is acknowledged as a contributor and a risk enhancer for CVD.

OBJECTIVES: We tested the hypothesis of a causal role of NAFLD in the effect of obesity on arterial hypertension.

METHODS: Using causal mediation analysis, we quantified the magnitude of the body mass index (BMI) effect on arterial hypertension and CV-traits mediated by NAFLD. First, we analysed data from 1348 young adults in the Bogalusa Heart Study (BHS), a cohort aimed at assessing the natural history of CVD. Then, we used data from 3359 participants of the National Health and Nutrition Examination Survey (2017-2018 cycle, NHANES) to replicate the findings.

RESULTS: We found that roughly 92% of the effects of BMI on arterial hypertension in the BHS and 51% in the NHANES population are mediated by NAFLD. In addition, indirect effects of BMI on systolic (SBP) and diastolic (DBP) blood pressure, and heart rate (HR) through NAFLD explained up to 91%, 93%, and 100% of the total effect, respectively, in the BHS. In the NHANES survey, indirect effects of BMI through NAFLD on CV traits explain a significant proportion of the total effects (SBP = 60.4%, HR = 100%, and pulse pressure = 88%).

CONCLUSION: NAFLD mediates a substantial proportion of the effect of obesity on the presence of hypertension and CV-parameters independently of relevant covariates. This conclusion has implications for clinical management.

PMID:37312639 | DOI:10.1111/liv.15643

Categories: Literature Watch

Three R2R3-MYB transcription factors from banana (Musa acuminata) activate structural anthocyanin biosynthesis genes as part of an MBW complex

Tue, 2023-06-13 06:00

BMC Res Notes. 2023 Jun 13;16(1):103. doi: 10.1186/s13104-023-06375-2.

ABSTRACT

OBJECTIVE: Bananas are one of the most popular fruits in the world, providing food security and employment opportunities in several developing countries. Increasing the anthocyanin content of banana fruit could improve the health-promoting properties. Anthocyanin biosynthesis is largely regulated at the transcriptional level. However, relatively little is known about the transcriptional activation of anthocyanin biosynthesis in banana.

RESULTS: We analysed the regulatory activity of three Musa acuminata MYBs that were predicted by bioinformatic analysis to transcriptionally regulate anthocyanin biosynthesis in banana. MaMYBA1, MaMYBA2 and MaMYBPA2 did not complement the anthocyanin-deficient phenotype of the Arabidopsis thaliana pap1/pap2 mutant. However, co-transfection experiments in A. thaliana protoplasts showed that MaMYBA1, MaMYBA2 and MaMYBPA2 function as components of a transcription factor complex with a bHLH and WD40 protein, the so called MBW complex, resulting in the activation of the A. thaliana ANTHOCYANIDIN SYNTHASE and DIHYDROFLAVONOL 4-REDUCTASE promoters. The activation potential of MaMYBA1, MaMYBA2 and MaMYBPA2 was increased when combined with the monocot Zea mays bHLH ZmR instead of the dicot AtEGL3. This work paves the path towards decoding the MBW complex-mediated transcriptional activation of anthocyanin biosynthesis in banana. It will also facilitate research towards increased anthocyanin content in banana and other monocot crops.

PMID:37312204 | DOI:10.1186/s13104-023-06375-2

Categories: Literature Watch

Synthase-selected sorting approach identifies a beta-lactone synthase in a nudibranch symbiotic bacterium

Tue, 2023-06-13 06:00

Microbiome. 2023 Jun 13;11(1):130. doi: 10.1186/s40168-023-01560-8.

ABSTRACT

BACKGROUND: Nudibranchs comprise a group of > 6000 marine soft-bodied mollusk species known to use secondary metabolites (natural products) for chemical defense. The full diversity of these metabolites and whether symbiotic microbes are responsible for their synthesis remains unexplored. Another issue in searching for undiscovered natural products is that computational analysis of genomes of uncultured microbes can result in detection of novel biosynthetic gene clusters; however, their in vivo functionality is not guaranteed which limits further exploration of their pharmaceutical or industrial potential. To overcome these challenges, we used a fluorescent pantetheine probe, which produces a fluorescent CoA-analog employed in biosynthesis of secondary metabolites, to label and capture bacterial symbionts actively producing these compounds in the mantle of the nudibranch Doriopsilla fulva.

RESULTS: We recovered the genome of Candidatus Doriopsillibacter californiensis from the Ca. Tethybacterales order, an uncultured lineage of sponge symbionts not found in nudibranchs previously. It forms part of the core skin microbiome of D. fulva and is nearly absent in its internal organs. We showed that crude extracts of D. fulva contained secondary metabolites that were consistent with the presence of a beta-lactone encoded in Ca. D. californiensis genome. Beta-lactones represent an underexplored group of secondary metabolites with pharmaceutical potential that have not been reported in nudibranchs previously.

CONCLUSIONS: Altogether, this study shows how probe-based, targeted sorting approaches can capture bacterial symbionts producing secondary metabolites in vivo. Video Abstract.

PMID:37312139 | DOI:10.1186/s40168-023-01560-8

Categories: Literature Watch

SBMLKinetics: a tool for annotation-independent classification of reaction kinetics for SBML models

Tue, 2023-06-13 06:00

BMC Bioinformatics. 2023 Jun 13;24(1):248. doi: 10.1186/s12859-023-05380-3.

ABSTRACT

BACKGROUND: Reaction networks are widely used as mechanistic models in systems biology to reveal principles of biological systems. Reactions are governed by kinetic laws that describe reaction rates. Selecting the appropriate kinetic laws is difficult for many modelers. There exist tools that attempt to find the correct kinetic laws based on annotations. Here, I developed annotation-independent technologies that assist modelers by focusing on finding kinetic laws commonly used for similar reactions.

RESULTS: Recommending kinetic laws and other analyses of reaction networks can be viewed as a classification problem. Existing approaches to determining similar reactions rely heavily on having good annotations, a condition that is often unsatisfied in model repositories such as BioModels. I developed an annotation-independent approach to find similar reactions via reaction classifications. I proposed a two-dimensional kinetics classification scheme (2DK) that analyzed reactions along the dimensions of kinetics type (K type) and reaction type (R type). I identified approximately ten mutually exclusive K types, including zeroth order, mass action, Michaelis-Menten, Hill kinetics, and others. R types were organized by the number of distinct reactants and the number of distinct products in reactions. I constructed a tool, SBMLKinetics, that inputted a collection of SBML models and then calculated reaction classifications as the probability of each 2DK class. The effectiveness of 2DK was evaluated on BioModels, and the scheme classified over 95% of the reactions.

CONCLUSIONS: 2DK had many applications. It provided a data-driven annotation-independent approach to recommending kinetic laws by using type common for the kind of models in combination with the R type of the reactions. Alternatively, 2DK could also be used to alert users that a kinetic law was unusual for the K type and R type. Last, 2DK provided a way to analyze groups of models to compare their kinetic laws. I applied 2DK to BioModels to compare the kinetics of signaling networks with the kinetics of metabolic networks and found significant differences in K type distributions.

PMID:37312031 | DOI:10.1186/s12859-023-05380-3

Categories: Literature Watch

Mining proteomics data to extract post-translational modifications associated with gastric cancer

Tue, 2023-06-13 06:00

Amino Acids. 2023 Jun 13. doi: 10.1007/s00726-023-03287-0. Online ahead of print.

ABSTRACT

Gastric cancers are highly heterogeneous, deep-seated tumours associated with late diagnosis and poor prognosis. Post-translational modifications (PTMs) of proteins are known to be well-associated with oncogenesis and metastasis in most cancers. Several enzymes which drive PTMs have also been used as theranostics in cancers of the breast, ovary, prostate and bladder. However, there is limited data on PTMs in gastric cancers. Considering that experimental protocols for simultaneous analysis of multiple PTMs are being explored, a data-driven approach involving reanalysis of mass spectrometry-derived data is useful in cataloguing altered PTMs. We subjected publicly available mass spectrometry data on gastric cancer to an iterative searching strategy for fetching PTMs including phosphorylation, acetylation, citrullination, methylation and crotonylation. These PTMs were catalogued and further analyzed for their functional enrichment through motif analysis. This value-added approach delivered identification of 21,710 unique modification sites on 16,364 modified peptides. Interestingly, we observed 278 peptides corresponding to 184 proteins to be differentially abundant. Using bioinformatics approaches, we observed that majority of these altered PTMs/proteins belonged to cytoskeletal and extracellular matrix proteins, which are known to be perturbed in gastric cancer. The dataset derived by this mutiPTM investigation can provide leads to further investigate the potential role of altered PTMs in gastric cancer management.

PMID:37311859 | DOI:10.1007/s00726-023-03287-0

Categories: Literature Watch

Transformative Materials to Create 3D Functional Human Tissue Models In Vitro in a Reproducible Manner

Tue, 2023-06-13 06:00

Adv Healthc Mater. 2023 Jun 13:e2301030. doi: 10.1002/adhm.202301030. Online ahead of print.

ABSTRACT

Recreating human tissues and organs in the petri dish to establish models as tools in biomedical sciences has gained momentum. These models can provide insight into mechanisms of human physiology, disease onset, and progression, and improve drug target validation, as well as the development of new medical therapeutics. Transformative materials play an important role in this evolution, as they can be programmed to direct cell behavior and fate by controlling the activity of bioactive molecules and material properties. Using nature as an inspiration, scientists are creating materials that incorporate specific biological processes observed during human organogenesis and tissue regeneration. This article presents the reader with state-of-the-art developments in the field of in vitro tissue engineering and the challenges related to the design, production, and translation of these transformative materials. Advances regarding (stem) cell sources, expansion, and differentiation, and how novel responsive materials, automated and large-scale fabrication processes, culture conditions, in situ monitoring systems, and computer simulations are required to create functional human tissue models that are relevant and efficient for drug discovery, are described. This paper illustrates how these different technologies need to converge to generate in vitro life-like human tissue models that provide a platform to answer health-based scientific questions.

PMID:37311209 | DOI:10.1002/adhm.202301030

Categories: Literature Watch

Adoption of a National Prophylactic Anticoagulation Guideline for Hospitalized Pregnant Women with COVID-19: Retrospective Cohort Study

Tue, 2023-06-13 06:00

JMIR Public Health Surveill. 2023 Jun 13. doi: 10.2196/45586. Online ahead of print.

ABSTRACT

BACKGROUND: Both COVID-19 and pregnancy are associated with hypercoagulability. Due to increased risk for thrombosis, the United States National Institute of Health's recommendation for prophylactic anticoagulant use for pregnant patients has expanded from patients hospitalized for severe COVID-19 manifestation to all patients hospitalized for the manifestation of COVID-19 (no guideline: ~12-26-2020, first update: 12-27-2020~02-23-2022, second update: 02-24-2022~present). However, no study has evaluated this recommendation.

OBJECTIVE: The objective of this study was to characterize prophylactic anticoagulant use among hospitalized pregnant people with COVID-19 from 03-20-2020~10-19-2022.

METHODS: This was a retrospective cohort study in large US healthcare systems across seven states. The cohort of interest was pregnant patients who were hospitalized with COVID-19, without prior coagulopathy or contraindication to anticoagulants (n=2,767). The treatment group consisted of patients prescribed prophylactic dose anticoagulation during -2~+14 days from COVID-19 treatment onset (n=191). The control group was patients with no anticoagulant exposure during -14~+60 days of the SARS-CoV-2 infection date (n=2,534). We ascertained the use of prophylactic anticoagulants with attention to the updates in guidelines and emerging SARS-CoV-2 variants. We propensity score matched the treatment and control group 1:1 on the most important features contributing to the prophylactic anticoagulant administration status classification. Outcome measures included coagulopathy, bleeding, COVID-19-related complications, and maternal-fetal health outcomes. Additionally, the inpatient anticoagulant administration rate was validated in a nationwide population from Truveta, a collective of 700 hospitals across the United States.

RESULTS: The overall administration rate of prophylactic anticoagulants was 7.0% (191/2,725). It was lowest after the second guideline update (no guideline: 10.4%, first update: 9.0%, second update: 2.5%; P<.05) and during the omicron-dominant period (WT:8.3%, Alpha:14.0%, Delta:16.6%, Omicron:3.5%; P<.05). Models developed on retrospective data showed that the variable most associated with administration of inpatient prophylactic anticoagulant. The patients who administered prophylactic anticoagulant were also more likely to receive supplementary oxygen (33.0% versus 4.8%; P<.05). There was no statistical difference in new diagnosis of coagulopathy, bleeding, or maternal-fetal health outcomes between those who received treatment and the matched control group.

CONCLUSIONS: Most hospitalized pregnant COVID-19 patients did not receive prophylactic anticoagulants across healthcare systems as recommended by guidelines. Guideline recommended treatment was administered more frequently to patients with greater COVID-19 illness severity. Given the low rate of administration and differences between treated and untreated cohorts, efficacy could not be assessed.

PMID:37311123 | DOI:10.2196/45586

Categories: Literature Watch

Modulation of the substrate specificity of the kinase PDK1 by distinct conformations of the full-length protein

Tue, 2023-06-13 06:00

Sci Signal. 2023 Jun 13;16(789):eadd3184. doi: 10.1126/scisignal.add3184. Epub 2023 Jun 13.

ABSTRACT

The activation of at least 23 different mammalian kinases requires the phosphorylation of their hydrophobic motifs by the kinase PDK1. A linker connects the phosphoinositide-binding PH domain to the catalytic domain, which contains a docking site for substrates called the PIF pocket. Here, we used a chemical biology approach to show that PDK1 existed in equilibrium between at least three distinct conformations with differing substrate specificities. The inositol polyphosphate derivative HYG8 bound to the PH domain and disrupted PDK1 dimerization by stabilizing a monomeric conformation in which the PH domain associated with the catalytic domain and the PIF pocket was accessible. In the absence of lipids, HYG8 potently inhibited the phosphorylation of Akt (also termed PKB) but did not affect the intrinsic activity of PDK1 or the phosphorylation of SGK, which requires docking to the PIF pocket. In contrast, the small-molecule valsartan bound to the PIF pocket and stabilized a second distinct monomeric conformation. Our study reveals dynamic conformations of full-length PDK1 in which the location of the linker and the PH domain relative to the catalytic domain determines the selective phosphorylation of PDK1 substrates. The study further suggests new approaches for the design of drugs to selectively modulate signaling downstream of PDK1.

PMID:37311034 | DOI:10.1126/scisignal.add3184

Categories: Literature Watch

TMELand: An end-to-end Pipeline for Quantification and Visualization of Waddington's Epigenetic Landscape based on Gene Regulatory Network

Tue, 2023-06-13 06:00

IEEE/ACM Trans Comput Biol Bioinform. 2023 Jun 13;PP. doi: 10.1109/TCBB.2023.3285395. Online ahead of print.

ABSTRACT

Waddington's epigenetic landscape is a framework depicting the processes of cell differentiation and reprogramming under the control of a gene regulatory network (GRN). Traditional model-driven methods for landscape quantification focus on the Boolean network or differential equation-based models of GRN, which need sophisticated prior knowledge and hence hamper their practical applications. To resolve this problem, we combine data-driven methods for inferring GRNs from gene expression data with model-driven approach to the landscape mapping. Specifically, we build an end-to-end pipeline to link data-driven and model-driven methods and develop a software tool named TMELand for GRN inference, visualizing Waddington's epigenetic landscape, and calculating state transition paths between attractors to uncover the intrinsic mechanism of cellular transition dynamics. By integrating GRN inference from real transcriptomic data with landscape modeling, TMELand can facilitate studies of computational systems biology, such as predicting cellular states and visualizing the dynamical trends of cell fate determination and transition dynamics from single-cell transcriptomic data. The source code of TMELand, a user manual, and model files of case studies can be downloaded freely from https://github.com/JieZheng-ShanghaiTech/TMELand.

PMID:37310837 | DOI:10.1109/TCBB.2023.3285395

Categories: Literature Watch

Elucidating the CodY regulon in <em>Staphylococcus aureus</em> USA300 substrains TCH1516 and LAC

Tue, 2023-06-13 06:00

mSystems. 2023 Jun 13:e0027923. doi: 10.1128/msystems.00279-23. Online ahead of print.

ABSTRACT

CodY is a conserved broad-acting transcription factor that regulates the expression of genes related to amino acid metabolism and virulence in Gram-positive bacteria. Here, we performed the first in vivo determination of CodY target genes using a novel CodY monoclonal antibody in methicillin-resistant Staphylococcus aureus (MRSA) USA300. Our results showed (i) the same 135 CodY promoter binding sites regulating the 165 target genes identified in two closely related virulent S. aureus USA300 TCH1516 and LAC strains; (ii) the differential binding intensity for the same target genes under the same conditions was due to sequence differences in the same CodY-binding site in the two strains; (iii) a CodY regulon comprising 72 target genes that are differentially regulated relative to a CodY deletion strain, representing genes that are mainly involved in amino acid transport and metabolism, inorganic ion transport and metabolism, transcription and translation, and virulence, all based on transcriptomic data; and (iv) CodY systematically regulated central metabolic flux to generate branched-chain amino acids (BCAAs) by mapping the CodY regulon onto a genome-scale metabolic model of S. aureus. Our study performed the first system-level analysis of CodY in two closely related USA300 TCH1516 and LAC strains, revealing new insights into the similarities and differences of CodY regulatory roles between the closely related strains. IMPORTANCE With the increasing availability of whole-genome sequences for many strains within the same pathogenic species, a comparative analysis of key regulators is needed to understand how the different strains uniquely coordinate metabolism and expression of virulence. To successfully infect the human host, Staphylococcus aureus USA300 relies on the transcription factor CodY to reorganize metabolism and express virulence factors. While CodY is a known key transcription factor, its target genes are not characterized on a genome-wide basis. We performed a comparative analysis to describe the transcriptional regulation of CodY between two dominant USA300 strains. This study motivates the characterization of common pathogenic strains and an evaluation of the possibility of developing specialized treatments for major strains circulating in the population.

PMID:37310465 | DOI:10.1128/msystems.00279-23

Categories: Literature Watch

Genome-wide association studies dissect the G × E interaction for agronomic traits in a worldwide collection of safflowers (<em>Carthamus tinctorius</em> L.)

Tue, 2023-06-13 06:00

Mol Breed. 2022 Apr 12;42(4):24. doi: 10.1007/s11032-022-01295-8. eCollection 2022 Apr.

ABSTRACT

Genome-wide association studies were conducted using a globally diverse safflower (Carthamus tinctorius L.) Genebank collection for grain yield (YP), days to flowering (DF), plant height (PH), 500 seed weight (SW), seed oil content (OL), and crude protein content (PR) in four environments (sites) that differed in water availability. Phenotypic variation was observed for all traits. YP exhibited low overall genetic correlations (rGoverall) across sites, while SW and OL had high rGoverall and high pairwise genetic correlations (rGij) across all pairwise sites. In total, 92 marker-trait associations (MTAs) were identified using three methods, single locus genome-wide association studies (GWAS) using a mixed linear model (MLM), the Bayesian multi-locus method (BayesR), and meta-GWAS. MTAs with large effects across all sites were detected for OL, SW, and PR, and MTAs specific for the different water stress sites were identified for all traits. Five MTAs were associated with multiple traits; 4 of 5 MTAs were variously associated with the three traits of SW, OL, and PR. This study provided insights into the phenotypic variability and genetic architecture of important safflower agronomic traits under different environments.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11032-022-01295-8.

PMID:37309464 | PMC:PMC10248593 | DOI:10.1007/s11032-022-01295-8

Categories: Literature Watch

MFI2 upregulation promotes malignant progression through EGF/FAK signaling in oral cavity squamous cell carcinoma

Mon, 2023-06-12 06:00

Cancer Cell Int. 2023 Jun 12;23(1):112. doi: 10.1186/s12935-023-02956-0.

ABSTRACT

Oral squamous cell carcinoma (OSCC) is the predominant histological type of the head and neck squamous cell carcinoma (HNSCC). By comparing the differentially expressed genes (DEGs) in OSCC-TCGA patients with copy number variations (CNVs) that we identify in OSCC-OncoScan dataset, we herein identified 37 dysregulated candidate genes. Among these potential candidate genes, 26 have been previously reported as dysregulated proteins or genes in HNSCC. Among 11 novel candidates, the overall survival analysis revealed that melanotransferrin (MFI2) is the most significant prognostic molecular in OSCC-TCGA patients. Another independent Taiwanese cohort confirmed that higher MFI2 transcript levels were significantly associated with poor prognosis. Mechanistically, we found that knockdown of MFI2 reduced cell viability, migration and invasion via modulating EGF/FAK signaling in OSCC cells. Collectively, our results support a mechanistic understanding of a novel role for MFI2 in promoting cell invasiveness in OSCC.

PMID:37309001 | DOI:10.1186/s12935-023-02956-0

Categories: Literature Watch

Recent five-year progress in the impact of gut microbiota on vaccination and possible mechanisms

Mon, 2023-06-12 06:00

Gut Pathog. 2023 Jun 12;15(1):27. doi: 10.1186/s13099-023-00547-y.

ABSTRACT

Vaccine is the most effective way to prevent the spread of communicable diseases, but the immune response induced by it varies greatly between individuals and populations in different regions of the world. Current studies have identified the composition and function of the gut microbiota as key factors in modulating the immune response to vaccination. This article mainly reviews the differences in gut microbiota among different groups of vaccinated people and animals, explores the possible mechanism of vaccine immunity affected by gut microbiota, and reviews the strategies for targeting gut microbiota to improve vaccine efficacy.

PMID:37308966 | DOI:10.1186/s13099-023-00547-y

Categories: Literature Watch

Itaconate trims the fat

Mon, 2023-06-12 06:00

Nat Metab. 2023 Jun 12. doi: 10.1038/s42255-023-00819-6. Online ahead of print.

NO ABSTRACT

PMID:37308725 | DOI:10.1038/s42255-023-00819-6

Categories: Literature Watch

The design of mapping populations: Impacts of geographic scale on genetic architecture and mapping efficacy for defense and immunity

Mon, 2023-06-12 06:00

Curr Opin Plant Biol. 2023 Jun 10;74:102399. doi: 10.1016/j.pbi.2023.102399. Online ahead of print.

ABSTRACT

Genome-wide association studies (GWAS) have yielded tremendous insight into the genetic architecture of trait variation. However, the collections of loci they uncover are far from exhaustive. As many of the complicating factors that confound or limit the efficacy of GWAS are exaggerated over broad geographic scales, a shift toward more analyses using mapping panels sampled from narrow geographic localities ("local" populations) could provide novel, complementary insights. Here, we present an overview of the major complicating factors, review mounting evidence from genomic analyses that these factors are pervasive, and synthesize theoretical and empirical evidence for the power of GWAS in local populations.

PMID:37307746 | DOI:10.1016/j.pbi.2023.102399

Categories: Literature Watch

Decomposition decreases molecular diversity and ecosystem similarity of soil organic matter

Mon, 2023-06-12 06:00

Proc Natl Acad Sci U S A. 2023 Jun 20;120(25):e2303335120. doi: 10.1073/pnas.2303335120. Epub 2023 Jun 12.

ABSTRACT

Soil organic matter (SOM) is comprised of a diverse array of reactive carbon molecules, including hydrophilic and hydrophobic compounds, that impact rates of SOM formation and persistence. Despite clear importance to ecosystem science, little is known about broad-scale controls on SOM diversity and variability in soil. Here, we show that microbial decomposition drives significant variability in the molecular richness and diversity of SOM between soil horizons and across a continental-scale gradient in climate and ecosystem type (arid shrubs, coniferous, deciduous, and mixed forests, grasslands, and tundra sedges). The molecular dissimilarity of SOM was strongly influenced by ecosystem type (hydrophilic compounds: 17%, P < 0.001; hydrophobic compounds: 10% P < 0.001) and soil horizon (hydrophilic compounds: 17%, P < 0.001; hydrophobic compounds: 21%, P < 0.001), as assessed using metabolomic analysis of hydrophilic and hydrophobic metabolites. While the proportion of shared molecular features was significantly higher in the litter layer than subsoil C horizons across ecosystems (12 times and 4 times higher for hydrophilic and hydrophobic compounds, respectively), the proportion of site-specific molecular features nearly doubled from the litter layer to the subsoil horizon, suggesting greater differentiation of compounds after microbial decomposition within each ecosystem. Together, these results suggest that microbial decomposition of plant litter leads to a decrease in SOM α-molecular diversity, yet an increase in β-molecular diversity across ecosystems. The degree of microbial degradation, determined by the position in the soil profile, exerts a greater control on SOM molecular diversity than environmental factors, such as soil texture, moisture, and ecosystem type.

PMID:37307452 | DOI:10.1073/pnas.2303335120

Categories: Literature Watch

Fertility loss in senescing Arabidopsis ovules is controlled by the maternal sporophyte via a NAC transcription factor triad

Mon, 2023-06-12 06:00

Proc Natl Acad Sci U S A. 2023 Jun 20;120(25):e2219868120. doi: 10.1073/pnas.2219868120. Epub 2023 Jun 12.

ABSTRACT

Flowers have a species-specific fertile period during which pollination and fertilization have to occur to initiate seed and fruit development. Unpollinated flowers remain receptive for mere hours in some species, and up to several weeks in others before flower senescence terminates fertility. As such, floral longevity is a key trait subject to both natural selection and plant breeding. Within the flower, the life span of the ovule containing the female gametophyte is decisive for fertilization and the initiation of seed development. Here, we show that unfertilized ovules in Arabidopsis thaliana undergo a senescence program that generates morphological and molecular hallmarks of canonical programmed cell death processes in the sporophytically derived ovule integuments. Transcriptome profiling of isolated aging ovules revealed substantial transcriptomic reprogramming during ovule senescence, and identified up-regulated transcription factors as candidate regulators of these processes. Combined mutation of three most-up-regulated NAC (NAM, ATAF1/2, and CUC2) transcription factors, NAP/ANAC029, SHYG/ANAC047, and ORE1/ANAC092, caused a substantial delay in ovule senescence and an extension of fertility in Arabidopsis ovules. These results suggest that timing of ovule senescence and duration of gametophyte receptivity are subject to genetic regulation controlled by the maternal sporophyte.

PMID:37307449 | DOI:10.1073/pnas.2219868120

Categories: Literature Watch

Unraveling female communication through scent marks in the Norway rat

Mon, 2023-06-12 06:00

Proc Natl Acad Sci U S A. 2023 Jun 20;120(25):e2300794120. doi: 10.1073/pnas.2300794120. Epub 2023 Jun 12.

ABSTRACT

Chemical communication by females remains poorly understood, with most attention focused on female advertisement of sexual receptivity to males or mother-offspring communication. However, in social species, scents are likely to be important for mediating competition and cooperation between females determining individual reproductive success. Here, we explore chemical signaling by female laboratory rats (Rattus norvegicus) to test i) whether females target their deployment of scent information differentially according to their sexual receptivity and the genetic identity of both female and male conspecifics signaling in the local environment and ii) whether females are attracted to gain the same or different information from female scents compared to males. Consistent with targeting of scent information to colony members of similar genetic background, female rats increased scent marking in response to scents from females of the same strain. Females also suppressed scent marking in response to male scent from a genetically foreign strain while sexually receptive. Proteomic analysis of female scent deposits revealed a complex protein profile, contributed from several sources but dominated by clitoral gland secretion. In particular, female scent marks contained a series of clitoral-derived hydrolases and proteolytically truncated major urinary proteins (MUPs). Manipulated blends of clitoral secretion and urine from estrus females were strongly attractive to both sexes, while voided urine alone stimulated no interest. Our study reveals that information about female receptive status is shared between females as well as with males, while clitoral secretions containing a complex set of truncated MUPs and other proteins play a key role in female communication.

PMID:37307448 | DOI:10.1073/pnas.2300794120

Categories: Literature Watch

Pages