Microbiol Resour Announc. 2024 Oct 21:e0093824. doi: 10.1128/mra.00938-24. Online ahead of print.

ABSTRACT

The genus Paenibacillus comprises facultatively anaerobic, endospore-forming, Gram-positive eubacteria known for efficiently producing a diverse array of exoenzymes. We isolated and sequenced the complete genomes of two Paenibacillus bacteria from the pegmatite surface in the fourth ore body in the mine Wagu Kannon Mine, Fukushima Prefecture.

PMID:39431869 | DOI:10.1128/mra.00938-24

Mol Biol Evol. 2024 Oct 21:msae200. doi: 10.1093/molbev/msae200. Online ahead of print.

ABSTRACT

Understanding the main determinants of protein evolution is a fundamental challenge in biology. Despite many decades of active research, the molecular and cellular mechanisms underlying the substantial variability of evolutionary rates across cellular proteins are not currently well understood. It also remains unclear how protein molecular function is optimized in the context of multicellular species and why many proteins, such as enzymes, are only moderately efficient on average. Our analysis of genomics and functional datasets reveals in multiple organisms a strong inverse relationship between the optimality of protein molecular function and the rate of protein evolution. Furthermore, we find that highly expressed proteins tend to be substantially more functionally optimized. These results suggest that cellular expression costs lead to more pronounced functional optimization of abundant proteins, and that the purifying selection to maintain high levels of functional optimality significantly slows protein evolution. We observe that in multicellular species both the rate of protein evolution and the degree of protein functional efficiency are primarily affected by expression in several distinct cell types and tissues. Specifically, in developed neurons with upregulated synaptic processes in animals and in young and fast-growing tissues in plants. Overall, our analysis reveals how various constraints from the molecular, cellular, and species' levels of biological organization jointly affect the rate of protein evolution and the level of protein functional adaptation.

PMID:39431545 | DOI:10.1093/molbev/msae200

Theranostics. 2024 Sep 16;14(16):6088-6108. doi: 10.7150/thno.96707. eCollection 2024.

ABSTRACT

Rationale: Alzheimer's disease (AD) is a progressive neurodegenerative disease accompanied by neurotoxicity, excessive inflammation, and cognitive impairment. The peroxisome proliferator-activated receptor (PPAR) δ is a potential target for AD. However, its regulatory mechanisms and therapeutic potential in AD remain unclear. We aimed to investigate if the activation of PPARδ using a highly selective and potent agonist could provide an effective therapeutic strategy against AD. Methods: We synthesized a novel PPARδ agonist, 5a, containing a selenazole group and determined the X-ray crystal structure of its complex with PPARδ. The drug-like properties of 5a were assessed by analyzing cytochrome P450 (CYP) inhibition, microsomal stability, pharmacokinetics, and mutagenicity. We investigated the anti-inflammatory effects of 5a using lipopolysaccharide (LPS)-stimulated BV-2 microglia and neuroinflammatory mouse model. The therapeutic efficacy of 5a was evaluated in AD mice with scopolamine-induced memory impairment and APP/PS1 by analyzing cognitive function, glial reactivity, and amyloid pathology. Results: Compound 5a, the most potent and selective PPARδ agonist, was confirmed to bind hPPARδ in a complex by X-ray crystallographic analysis. PPARδ activation using 5a showed potent anti-inflammatory effects in activated glial cells and mouse model of neuroinflammation. Administration of 5a inhibited amyloid plaque deposition by suppressing the expression of neuronal beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), and reduced abnormal glial hyperactivation and inflammatory responses, resulting in improved learning and memory in the APP/PS1 mouse model of AD. Conclusion: We identified that specific activation of PPARδ provides therapeutic effects on multiple pathogenic phenotypes of AD, including neuroinflammation and amyloid deposition. Our findings suggest the potential of PPARδ as a promising drug target for treating AD.

PMID:39431021 | PMC:PMC11488110 | DOI:10.7150/thno.96707

J Mol Cell Cardiol Plus. 2024 Jun;8:100073. doi: 10.1016/j.jmccpl.2024.100073. Epub 2024 Mar 31.

ABSTRACT

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) results from pathogenic variants in sarcomeric protein genes that increase myocyte energy demand and lead to cardiac hypertrophy. However, it is unknown whether a common metabolic trait underlies cardiac phenotype at the early disease stage. To address this question and define cardiac biochemical pathology in early-stage HCM, we studied two HCM mouse models that express pathogenic variants in cardiac troponin T (Tnt2) or myosin heavy chain (Myh6) genes, and have marked differences in cardiac imaging phenotype, mitochondrial function at early disease stage.

METHODS: We used a combination of echocardiography, transcriptomics, mass spectrometry-based untargeted metabolomics (GC-TOF, HILIC, CSH-QTOF), and computational modeling (CardioNet) to examine cardiac structural and metabolic remodeling at early disease stage (5 weeks of age) in R92W-TnT+/- and R403Q-MyHC+/- mutant mice. Data from mutants was compared with respective littermate controls (WT).

RESULTS: Allele-specific differences in cardiac phenotype, gene expression and metabolites were observed at early disease stage. LV diastolic dysfunction was prominent in TnT mutants. Differentially-expressed genes in TnT mutant hearts were predominantly enriched in the Krebs cycle, respiratory electron transport, and branched-chain amino acid metabolism, whereas MyHC mutants were enriched in mitochondrial biogenesis, calcium homeostasis, and liver-X-receptor signaling. Both mutant hearts demonstrated significant alterations in levels of purine nucleosides, trisaccharides, dicarboxylic acids, acylcarnitines, phosphatidylethanolamines, phosphatidylinositols, ceramides and triglycerides; 40.4 % of lipids and 24.7 % of metabolites were significantly different in TnT mutants, whereas 10.4 % of lipids and 5.8 % of metabolites were significantly different in MyHC mutants. Both mutant hearts had a lower abundance of unsaturated long-chain acyl-carnitines (18:1, 18:2, 20:1), but only TnT mutants showed enrichment of FA18:0 in ceramide and cardiolipin species. CardioNet predicted impaired energy substrate metabolism and greater phospholipid remodeling in TnT mutants than in MyHC mutants.

CONCLUSIONS: Our systems biology approach revealed marked differences in metabolic remodeling in R92W-TnT and R403Q-MyHC mutant hearts, with TnT mutants showing greater derangements than MyHC mutants, at early disease stage. Changes in cardiolipin composition in TnT mutants could contribute to impairment of energy metabolism and diastolic dysfunction observed in this study, and predispose to energetic stress, ventricular arrhythmias under high workloads such as exercise.

PMID:39430912 | PMC:PMC11485168 | DOI:10.1016/j.jmccpl.2024.100073

Brain Behav Immun Health. 2024 Oct 2;42:100879. doi: 10.1016/j.bbih.2024.100879. eCollection 2024 Dec.

ABSTRACT

Childhood overweight/obesity is associated with stress-related psychopathology, yet the pathways connecting childhood obesity to stress susceptibility are poorly understood. We employed a systems biology approach with 62 adolescent Lewis rats fed a Western-like high-saturated fat diet (WD, 41% kcal from fat) or a control diet (CD, 13% kcal from fat). A subset of rats underwent a 31-day model of predator exposures and social instability (PSS). Effects were assessed using behavioral tests, DTI (diffusion tensor imaging), NODDI (neurite orientation dispersion and density imaging), 16S rRNA gene sequencing for gut microbiome profiling, hippocampal microglia analysis, and targeted gene methylation. Parallel experiments on human microglia cells (HMC3) examined how palmitic acid influences cortisol-related inflammatory responses. Rats exposed to WD and PSS exhibited deficits in sociability, increased fear/anxiety-like behaviors, food consumption, and body weight. WD/PSS altered hippocampal microstructure (subiculum, CA1, dentate gyrus), and microbiome analysis showed a reduced abundance of members of the phylum Firmicutes. WD/PSS synergistically promoted neuroinflammatory changes in hippocampal microglia, linked with microbiome shifts and altered Fkbp5 expression/methylation. In HMC3, palmitate disrupted cortisol responses, affecting morphology, phagocytic markers, and cytokine release, partially mediated by FKBP5. This study identifies gene-environment interactions that influence microglia biology and may contribute to the connection between childhood obesity and stress-related psychopathology later in life.

PMID:39430879 | PMC:PMC11490928 | DOI:10.1016/j.bbih.2024.100879

JAMIA Open. 2024 Oct 18;7(4):ooae105. doi: 10.1093/jamiaopen/ooae105. eCollection 2024 Dec.

ABSTRACT

BACKGROUND: Procedural and reporting guidelines are crucial in framing scientific practices and communications among researchers and the broader community. These guidelines aim to ensure transparency, reproducibility, and reliability in scientific research. Despite several methodological frameworks proposed by various initiatives to foster reproducibility, challenges such as data leakage and reproducibility remain prevalent. Recent studies have highlighted the transformative potential of incorporating the FAIR (Findable, Accessible, Interoperable, and Reusable) principles into workflows, particularly in contexts like software and machine learning model development, to promote open science.

OBJECTIVE: This study aims to introduce a comprehensive framework, designed to calibrate existing reporting guidelines against the FAIR principles. The goal is to enhance reproducibility and promote open science by integrating these principles into the scientific reporting process.

METHODS: We employed the "Best fit" framework synthesis approach which involves systematically reviewing and synthesizing existing frameworks and guidelines to identify best practices and gaps. We then proposed a series of defined workflows to align reporting guidelines with FAIR principles. A use case was developed to demonstrate the practical application of the framework.

RESULTS: The integration of FAIR principles with established reporting guidelines through the framework effectively bridges the gap between FAIR metrics and traditional reporting standards. The framework provides a structured approach to enhance the findability, accessibility, interoperability, and reusability of scientific data and outputs. The use case demonstrated the practical benefits of the framework, showing improved data management and reporting practices.

DISCUSSION: The framework addresses critical challenges in scientific research, such as data leakage and reproducibility issues. By embedding FAIR principles into reporting guidelines, the framework ensures that scientific outputs are more transparent, reliable, and reusable. This integration not only benefits researchers by improving data management practices but also enhances the overall scientific process by promoting open science and collaboration.

CONCLUSION: The proposed framework successfully combines FAIR principles with reporting guidelines, offering a robust solution to enhance reproducibility and open science. This framework can be applied across various contexts, including software and machine learning model development stages, to foster a more transparent and collaborative scientific environment.

PMID:39430802 | PMC:PMC11488973 | DOI:10.1093/jamiaopen/ooae105

MethodsX. 2024 Sep 27;13:102982. doi: 10.1016/j.mex.2024.102982. eCollection 2024 Dec.

ABSTRACT

Aphids, as hemipteran insects, reproduce via parthenogenesis and viviparity, resulting in rapid and exponential offspring production. To investigate the molecular mechanisms underlying parthenogenetic viviparity in asexual aphids, precise protein detection through immunostaining is essential. Our previous research demonstrated the need for proteinase K (PK) treatment to improve tissue permeability, enabling antibodies targeting the germ-cell marker Ap-Vas1 to access gastrulating and later-stage embryos. However, optimal PK digestion protocols have not been thoroughly explored. In this study, we propose strategies to optimize PK digestion conditions for early, middle, and late-stage pea aphid embryos, which have varying tissue thicknesses. Additionally, we extend the application of PK treatment to salivary glands, a representative somatic tissue, by optimizing conditions for antibody penetration against the salivary gland marker C002. To enhance spatial precision in signal detection, we provide a detailed protocol for tissue dissection specific to pea aphids, focusing on the preservation of tissue integrity. These comprehensive guidelines, covering tissue dissection and PK titration, are expected to improve the specificity and intensity of protein signals in pea aphids and other aphid species.•Provide aphid-specific dissection methods to obtain intact embryos and salivary glands.•Present strategies for optimizing PK treatment conditions across different tissue types.

PMID:39430779 | PMC:PMC11489042 | DOI:10.1016/j.mex.2024.102982

Iran J Public Health. 2024 Jun;53(6):1332-1342.

ABSTRACT

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a common cancer with a poor prognosis and high recurrence rate. We aimed to identify potential biomarkers for LIHC by investigating the involvement of hub genes, microRNAs (miRNAs), transcription factors (TFs), and protein kinases (PKs) in its occurrence.

METHODS: we conducted a bioinformatics analysis using microarray datasets, the TCGA-LIHC dataset, and text mining to identify differentially expressed genes (DEGs) associated with LIHC. They then performed functional enrichment analysis and gene-disease association analysis. The protein-protein interaction network of the genes was established, and hub genes were identified. The expression levels and survival analysis of these hub genes were evaluated, and their association with miRNAs, TFs, and PKs was assessed.

RESULTS: The analysis identified 122 common genes involved in LIHC pathogenesis. Ten hub genes were filtered out, including CDK1, CCNB1, CCNB2, CCNA2, ASPM, NCAPG, BIRC5, RRM2, KIF20A, and CENPF. The expression level of all hub genes was confirmed, and high expression levels of all hub genes were correlated with poor overall survival of LIHC patients.

CONCLUSION: Identifying potential biomarkers for LIHC can aid in the design of targeted treatments and improve the survival of LIHC patients. The findings of this study provide a basis for further research in the field of LIHC and contribute to the understanding of its molecular pathogenesis.

PMID:39430152 | PMC:PMC11488550

F1000Res. 2024 Jan 18;13:77. doi: 10.12688/f1000research.146156.1. eCollection 2024.

ABSTRACT

Phosphatidylinositol-specific phospholipase C gamma 2 (PLC-gamma-2) is an enzyme that regulates the function of immune cells. PLC-gamma-2 has been implicated in neurodegenerative and autoimmune disorders, yet investigation of this protein has been limited by a lack of independently characterized antibodies. Here we have characterized eleven PLC-gamma-2 commercial antibodies for use in Western Blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.

PMID:39429638 | PMC:PMC11489847 | DOI:10.12688/f1000research.146156.1

Elife. 2024 Oct 21;13:RP93855. doi: 10.7554/eLife.93855.

ABSTRACT

Most of Earth's biomass is composed of polysaccharides. During biomass decomposition, polysaccharides are degraded by heterotrophic bacteria as a nutrient and energy source and are thereby partly remineralized into CO2. As polysaccharides are heterogeneously distributed in nature, following the colonization and degradation of a polysaccharide hotspot the cells need to reach new polysaccharide hotspots. Even though many studies indicate that these degradation-dispersal cycles contribute to the carbon flow in marine systems, we know little about how cells alternate between polysaccharide degradation and motility, and which environmental factors trigger this behavioral switch. Here, we studied the growth of the marine bacterium Vibrio cyclitrophicus ZF270 on the abundant marine polysaccharide alginate, both in its soluble polymeric form as well as on its breakdown products. We used microfluidics coupled to time-lapse microscopy to analyze motility and growth of individual cells, and RNA sequencing to study associated changes in gene expression. We found that single cells grow at reduced rate on alginate until they form large groups that cooperatively break down the polymer. Exposing cell groups to digested alginate accelerates cell growth and changes the expression of genes involved in alginate degradation and catabolism, central metabolism, ribosomal biosynthesis, and transport. However, exposure to digested alginate also triggers cells to become motile and disperse from cell groups, proportionally increasing with the group size before the nutrient switch, and this is accompanied by high expression of genes involved in flagellar assembly, chemotaxis, and quorum sensing. The motile cells chemotax toward polymeric but not digested alginate, likely enabling them to find new polysaccharide hotspots. Overall, our findings reveal cellular mechanisms that might also underlie bacterial degradation-dispersal cycles, which influence the remineralization of biomass in marine environments.

PMID:39429128 | DOI:10.7554/eLife.93855

Drug Dev Res. 2024 Nov;85(7):e70008. doi: 10.1002/ddr.70008.

ABSTRACT

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, driven mainly by chronic hepatitis infections and metabolic disorders, which highlights the urgent need for novel therapeutic strategies. Sirtuins, particularly SIRT1 are crucial in HCC pathogenesis, making it a promising drug target. Indole-based molecules show potential as therapeutic agents by interacting with key proteins like sirtuins involved in cancer progression. In this study, we designed and synthesized novel indole-based small molecules and investigated their potential sirtuin inhibitory action and anticancer activity on HCC cell lines. Four of the twenty-eight tested small molecules on different cancer types were selected (4 g, 4 h, 4o, and 7j) based on their structure-activity relationship and studied on a panel of HCC cell lines. Compounds had active drug-target interactions with SIRT1 or SIRT2 based on DEEPScreen DTI predictions and docking studies which confirmed that 4o, 4 g, and 7j were most potent in their interaction with SIRT1. Compound 4 g caused the highest sirtuin activity inhibition in vitro and induced G1 arrest and apoptosis in HCC cell lines.

PMID:39428864 | DOI:10.1002/ddr.70008

J Control Release. 2024 Oct 18:S0168-3659(24)00689-8. doi: 10.1016/j.jconrel.2024.10.018. Online ahead of print.

ABSTRACT

Non-adherence to antiretroviral treatment is a critical obstacle to effectively managing the progression of AIDS and reducing transmission and mortality rates. A promising strategy to address the clinical disadvantages of user-dependent dosing and decrease medication frequency is the development of long-acting antiretrovirals. In this study, we fabricated PLGA microspheres (MS) incorporating the lipopeptide LP-98 (LP-98-MS), which has previously exhibited potent anti-HIV efficacy. Our findings demonstrate that a single-dose injection of LP-98-MS in SHIV-infected rhesus macaques resulted in sustained and gradual release, maintaining antiviral effects at least 28 days. Notably, a single administration of LP-98-MS provided more than 28 days of sustained release, resulting in high-level pre-exposure prophylaxis (PrEP) for rhesus macaques, even providing complete protection when exposed to repeated intravaginal and intrarectal SHIV challenges. Overall, LP-98-MS holds significant potential in reducing medication frequency and shows promising prospects for further development.

PMID:39427773 | DOI:10.1016/j.jconrel.2024.10.018

Mol Cells. 2024 Oct 18:100131. doi: 10.1016/j.mocell.2024.100131. Online ahead of print.

ABSTRACT

Polycomb Group (PcG) proteins play key roles in development by repressing thousands of targets through histone modifications. However, how PcG is recruited to specific targets is poorly understood. In Arabidopsis, certain noncoding RNAs are necessary for recruiting the PcG protein CURLY LEAF (CLF) to its target sites. However, RNAs associated with CLF have not been analyzed on a genomic scale, thus it is unknown whether long noncoding RNA (lncRNA)-mediated PcG recruitment is a widespread mechanism. Here, we systematically searched for CLF-associated RNAs by RNA immunoprecipitation followed by deep sequencing. We identified 1299 genic and 138 intergenic regions that produced CLF-associated mRNAs and putative lncRNAs, respectively. The genes producing CLF-associated RNAs are depleted in PcG targets, carry active chromatin marks, and are highly expressed, suggesting that CLF may have a non-specific or promiscuous RNA-binding affinity, similar to animal PcG proteins. Notably, a significant portion of the CLF-associated lncRNAs is derived from the nuclear mitochondrial sequence, which is extensively marked by H3K27me3. These findings indicate that while CLF-RNA interactions are widespread, they may not always correlate with PcG target sites, highlighting the complexity of PcG recruitment mechanisms in Arabidopsis.

PMID:39427743 | DOI:10.1016/j.mocell.2024.100131

NPJ Parkinsons Dis. 2024 Oct 20;10(1):189. doi: 10.1038/s41531-024-00799-8.

ABSTRACT

Parkinson's disease (PD) is a neurodegenerative disorder marked by the loss of dopaminergic neurons in the substantia nigra. Despite progress, the pathogenesis remains unclear. Human midbrain organoids (hMLOs) have emerged as a promising model for studying PD, drug screening, and potential treatments. This review discusses the development of hMLOs, their application in PD research, and current challenges in organoid construction, highlighting possible optimization strategies.

PMID:39428415 | DOI:10.1038/s41531-024-00799-8

Cell Rep. 2024 Oct 19;43(11):114895. doi: 10.1016/j.celrep.2024.114895. Online ahead of print.

ABSTRACT

Hydroxycarboxylic acid receptor 3 (HCAR3), a class A G-protein-coupled receptor, is an important cellular energy metabolism sensor with a key role in the regulation of lipolysis in humans. HCAR3 is deeply involved in many physiological processes and serves as a valuable target for the treatment of metabolic diseases, tumors, and immune diseases. Here, we report four cryoelectron microscopy (cryo-EM) structures of human HCAR3-Gi1 complexes with or without agonists: the endogenous ligand 3-hydroxyoctanoic acid, the drug niacin, the highly subtype-specific agonist compound 5c (4-(n-propyl)amino-3-nitrobenzoic acid), and the apo form. Together with mutagenesis and functional analyses, we revealed the recognition mechanisms of HCAR3 for different agonists. In addition, the key residues that determine the ligand selectivity between HCAR2 and HCAR3 were also illuminated. Overall, these findings provide a structural basis for the ligand recognition, activation, and selectivity and G-protein coupling mechanisms of HCAR3, which contribute to the design of HCAR3-targeting drugs with high efficacy and selectivity.

PMID:39427321 | DOI:10.1016/j.celrep.2024.114895

Toxicology. 2024 Oct 17:153975. doi: 10.1016/j.tox.2024.153975. Online ahead of print.

ABSTRACT

The 9th German Pharm-Tox Summit (GPTS) and the 90th Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) took place in Munich from March 13-15, 2024. The event brought together over 700 participants from around the world to discuss cutting-edge developments in the fields of pharmacology and toxicology as well as scientific innovations and novel insights. A key focus of the conference was on the rapidly increasing role of computational toxicology, artificial intelligence (AI), and machine learning (ML) into the field, marking a shift away from traditional methods and allowing the reduction of animal testing as primary tool for toxicological risk assessment. Tools such as Toxometris.ai showcased the potential of AI-based risk assessments for predicting carcinogenicity, offering more ethical and efficient alternatives. Additionally, computer-driven models like computer-aided pattern analysis (C@PA) for drug toxicity prediction were presented, emphasizing the growing role of chem- and bioinformatic applications in computational sciences. Throughout the summit, there was a strong focus on the need for regulatory innovation to support the adoption of these advanced technologies and ensure the safety and sustainability of chemical substances and drugs.

PMID:39426660 | DOI:10.1016/j.tox.2024.153975

Food Chem. 2024 Oct 15;464(Pt 1):141667. doi: 10.1016/j.foodchem.2024.141667. Online ahead of print.

ABSTRACT

Humans have used Quercus ilex acorns as a staple food since ancient times. Recently, their nutritional and nutraceutical value has revived interest for human consumption. Ensuring their safety as food requires assessing their allergenic potential. In this work, we predicted the allergenic profile of acorns by in silico analysis of the Q. ilex genome and transcriptome. In addition, immunoblot analysis of pooled sera from patients allergic to various dry fruits was performed, with immunoreactive bands subjected to mass spectrometry analysis. The most remarkable allergens identified belong to the Bet v 1, profilin, prolamin, Hsp70 and cyclophilin families. Acorns from different mother trees exhibited also different IgE sensitization patterns. Thus, acorns from trees showing damage symptoms, and located in declined areas, had higher allergen contents than those from healthy ones, which corresponded to higher abundance of stress-related proteins.

PMID:39426264 | DOI:10.1016/j.foodchem.2024.141667

Phys Rev E. 2024 Sep;110(3-1):034309. doi: 10.1103/PhysRevE.110.034309.

ABSTRACT

Cells sense environmental signals and transmit information intracellularly through changes in the abundance of molecular components. Such molecular abundances can be measured in single cells and exhibit significant heterogeneity in clonal populations even in identical environments. Experimentally observed joint probability distributions can then be used to quantify the covariability and mutual information between molecular abundances along signaling cascades. However, because stationary state abundances along stochastic biochemical reaction cascades are not conditionally independent, their mutual information is not constrained by the data-processing inequality. Here, we report the conditions under which the mutual information between stationary state abundances increases along a cascade of biochemical reactions. This nonmonotonic behavior can be intuitively understood in terms of noise propagation and time-averaging stochastic fluctuations that are short-lived compared to an extrinsic signal. Our results reemphasize that mutual information measurements of stationary state distributions of cellular components may be of limited utility for characterizing cellular signaling processes because they do not measure information transfer.

PMID:39425385 | DOI:10.1103/PhysRevE.110.034309

Phys Rev E. 2024 Sep;110(3-1):034402. doi: 10.1103/PhysRevE.110.034402.

ABSTRACT

Many animals have patterned fur, feathers, or scales, such as the stripes of a zebra. Turing models, or reaction-diffusion systems, are a class of mathematical models of interacting species that have been successfully used to generate animal-like patterns for many species. When diffusion of the inhibitor is high enough relative to the activator, a diffusion-driven instability can spontaneously form patterns. However, it is not just the type of pattern but also the orientation that matters, and it remains unclear how patterns are oriented in practice. Here, we propose a mechanism by which the curvature of the surface influences the rate of diffusion, and can recapture the correct orientation of stripes on models of a zebra and of a cat in numerical simulations. Previous work has shown how anisotropic diffusion can give stripe forming reaction-diffusion systems a bias in orientation. From the observation that zebra stripes run around the direction of highest curvature, that is around the torso and legs, we apply this result by modifying the anisotropic diffusion rates based on the local curvature. These results show how local geometry can influence the reaction dynamics to give robust, global-scale patterns. Overall, this model proposes a coupling between the system geometry and reaction-diffusion dynamics that can give global control over the patterning by using only local curvature information. Such a model can give shape and positioning information in animal development without the need for spatially dependent morphogen gradients.

PMID:39425380 | DOI:10.1103/PhysRevE.110.034402

BMC Bioinformatics. 2024 Oct 18;25(1):334. doi: 10.1186/s12859-024-05948-7.

ABSTRACT

Traditional gene set enrichment analyses are typically limited to a few ontologies and do not account for the interdependence of gene sets or terms, resulting in overcorrected p-values. To address these challenges, we introduce mulea, an R package offering comprehensive overrepresentation and functional enrichment analysis. mulea employs a progressive empirical false discovery rate (eFDR) method, specifically designed for interconnected biological data, to accurately identify significant terms within diverse ontologies. mulea expands beyond traditional tools by incorporating a wide range of ontologies, encompassing Gene Ontology, pathways, regulatory elements, genomic locations, and protein domains. This flexibility enables researchers to tailor enrichment analysis to their specific questions, such as identifying enriched transcriptional regulators in gene expression data or overrepresented protein domains in protein sets. To facilitate seamless analysis, mulea provides gene sets (in standardised GMT format) for 27 model organisms, covering 22 ontology types from 16 databases and various identifiers resulting in almost 900 files. Additionally, the muleaData ExperimentData Bioconductor package simplifies access to these pre-defined ontologies. Finally, mulea's architecture allows for easy integration of user-defined ontologies, or GMT files from external sources (e.g., MSigDB or Enrichr), expanding its applicability across diverse research areas. mulea is distributed as a CRAN R package downloadable from https://cran.r-project.org/web/packages/mulea/ and https://github.com/ELTEbioinformatics/mulea . It offers researchers a powerful and flexible toolkit for functional enrichment analysis, addressing limitations of traditional tools with its progressive eFDR and by supporting a variety of ontologies. Overall, mulea fosters the exploration of diverse biological questions across various model organisms.

PMID:39425047 | DOI:10.1186/s12859-024-05948-7