Brain Behav Immun Health. 2024 Nov 28;43:100918. doi: 10.1016/j.bbih.2024.100918. eCollection 2025 Feb.

ABSTRACT

Prebiotic dietary fiber (PDF) may reduce feelings of stress or improve mood in healthy individuals. Yet gut intervention studies that focus on mood in daily life are lacking and few studies include extensive biological sample analyses to gain mechanistic insights. As part of a larger randomized placebo-controlled crossover study including healthy individuals, we explored the effects of 12 weeks of PDF (acacia gum and carrot powder) on everyday mood, as measured with ecological momentary assessment (EMA). Microbiome composition and levels of microbial metabolites, endocrine, and inflammatory markers were determined prior to and after both intervention phases. Fifty-four participants completed the study. The intervention significantly increased daily positive affect (PA) and reduced daily negative affect (NA) in female but not male participants. The intervention-induced reduction in NA was associated with an increase in microbial diversity in female participants. The intervention did not significantly affect levels of fecal short chain fatty acids, cortisol, and inflammatory markers. This is one of the first studies to show that a dietary fiber intervention can positively alter mood as it is experienced in everyday life. Overall, our findings may stimulate more targeted gut-microbiome interventions and detection of its mental health effects in real life.

PMID:39717875 | PMC:PMC11665422 | DOI:10.1016/j.bbih.2024.100918

Microlife. 2024 Dec 23;5:uqae025. doi: 10.1093/femsml/uqae025. eCollection 2024.

ABSTRACT

Evolutionary processes acting on populations of organized molecules preceded the origin of living organisms. These prebiotic entities were independently and repeatedly produced [i.e. (re)-produced] by the assembly of their components, following an iterative process giving rise to nearly but not fully identical replicas, allowing for a prebiotic form of Darwinian evolution. Natural selection favored the more persistent assemblies, some possibly modifying their own internal structure, or even their environment, thereby acquiring function. We refer to these assemblies as proto-organs. In association with other assemblies (e.g. in a coacervate or encapsulated within a vesicle), such proto-organs could evolve and acquire a role within the collective when their coexistence favored the selection of the ensemble. Along millions of years, an extraordinarily small number of successful combinations of those proto-organs co-occurring in spatially individualizing compartments might have co-evolved forming a proto-metabolic and proto-genetic informative network, eventually leading to the selfreplication of a very few. Thus, interactions between encapsulated proto-organs would have had a much higher probability of evolving into proto-organisms than interactions among simpler molecules. Multimolecular forms evolve functions; thus, functional organs would have preceded organisms.

PMID:39717754 | PMC:PMC11664216 | DOI:10.1093/femsml/uqae025

Onco Targets Ther. 2024 Dec 18;17:1197-1207. doi: 10.2147/OTT.S492659. eCollection 2024.

ABSTRACT

INTRODUCTION: The FGFR3-TACC3 fusion gene exists in a variety of malignant tumors, including bladder cancer. In our ongoing research on the CRISPR-Cas13a gene-editing system, we reported the use of CRISPR-Cas13a gene-editing system to knockout FGFR3-TACC3 and inhibit the proliferation of bladder tumor cells.

PURPOSE: This study aimed to use the CRISPR-Cas13a gene-editing system to target the FGFR3-TACC3 fusion gene in bladder cancer cells, which has the potential to be a new and effective treatment for bladder cancer.

MATERIALS AND METHODS: The efficacy of the CRISPR-Cas13a gene-editing system was analysed by qRT-PCR. The inhibitory effects of Cas13a-mediated knockdown of the FGFR3-TACC3 fusion gene on the proliferation of RT4 and RT112 cell lines were assessed utilizing CCK-8, EdU, and organoid formation assays. Subsequently, the comparative tumorigenic capability of RT4 cells with FGFR3-TACC3 knockdown achieved by Cas13a was examined in a nude mouse model.

RESULTS: At the cellular level, the comparative analysis of FGFR3-TACC3 knockdown efficacy between CRISPR-Cas13a and shRNA revealed a more pronounced reduction with the former. This knockdown effectively curtailed cellular proliferation, with CRISPR-Cas13a-mediated knockdown exhibiting a superior inhibitory effect over shRNA-mediated knockdown. In organoid cultures derived from RT4 cells, a similar trend was observed, with Cas13a-mediated knockdown of FGFR3-TACC3 leading to a more substantial suppression of proliferation compared to shRNA-mediated knockdown. In vivo tumor models corroborated these findings, demonstrating a significantly diminished tumor volume in the Cas13a-treated cohort relative to both the control and shRNA-treated groups.

CONCLUSION: The CRISPR-Cas13a gene-editing system has been demonstrated to significantly suppress tumor proliferation both in vitro and in vivo, thereby presenting itself as a promising candidate for a novel and efficacious therapeutic intervention in bladder cancer treatment.

PMID:39717713 | PMC:PMC11664097 | DOI:10.2147/OTT.S492659

Ecol Evol. 2024 Dec 22;14(12):e70760. doi: 10.1002/ece3.70760. eCollection 2024 Dec.

ABSTRACT

Long-term studies depicting the multicontinental invasion trajectories of species are often constrained by the scarcity of documented records, especially for invertebrates. The red swamp crayfish, Procambarus clarkii (Decapoda: Cambaridae), stands out as an uncommon example of hypersuccessful invasive species with a well-known invasion history at both regional and global levels. This allows for the use of its records to track distribution dynamics and bioclimatic preferences over time. Through multiple temporal comparisons, the global bioclimatic tendencies of the species have been explored over a period exceeding a century (1854-2023) using linear models with generalized least squares estimation and two-sample t-tests. This specific setup provides a rare focus on biological invasions at both broad temporal and spatial scales. The results highlight climatic trends in the invasion process of the species, including decreases in the values of bioclimatic variables associated with temperature and precipitation. This trend encompasses not only mean values but also both extreme (minimum and maximum) and is coupled with increases in elevation and aridity values in the areas with the presence of the species. The findings indicate that the species can engage in new ecological interactions and further affect range-restricted species in climatic refuges once considered protected. These findings help anticipate changes in the species' invasion trajectory, suggesting possible expansions into colder, less humid climates and higher altitudes. This knowledge supports effective monitoring and early detection for management and conservation efforts.

PMID:39717651 | PMC:PMC11663627 | DOI:10.1002/ece3.70760

Adv Sci (Weinh). 2024 Dec 23:e2404620. doi: 10.1002/advs.202404620. Online ahead of print.

ABSTRACT

Cell signaling pathways are enriched for biological processes crucial for cellular communication, response to external stimuli, and metabolism. Here, a cell signaling-focused CRISPR screen identified cytochrome c oxidase subunit 4 isoform 1 (COX4I1) as a novel vulnerability in acute myeloid leukemia (AML). Depletion of COX4I1 hindered leukemia cell proliferation and impacted in vivo AML progression. Mechanistically, loss of COX4I1 induced mitochondrial stress and ferroptosis, disrupting mitochondrial ultrastructure and oxidative phosphorylation. CRISPR gene tiling scans, coupled with mitochondrial proteomics, dissected critical regions within COX4I1 essential for leukemia cell survival, providing detailed insights into the mitochondrial Complex IV assembly network. Furthermore, COX4I1 depletion or pharmacological inhibition of Complex IV (using chlorpromazine) synergized with venetoclax, providing a promising avenue for improved leukemia therapy. This study highlights COX4I1, a nuclear encoded mitochondrial protein, as a critical mitochondrial checkpoint, offering insights into its functional significance and potential clinical implications in AML.

PMID:39716856 | DOI:10.1002/advs.202404620

Acta Paediatr. 2024 Dec 23. doi: 10.1111/apa.17553. Online ahead of print.

ABSTRACT

BACKGROUND: The Special Issue articles describe six systems of parental interventions and developmental care several differences among each of the approaches. Nevertheless, on a deeper level there are profound similarities shared across the six systems. These similarities are at the heart of developmental care in general and parental interventions in particular.

AIM: The aim of this paper is to highlight the commonalities of these systems of developmental processes and parental interventions.

MATERIALS AND METHODS: We discuss the concept of symbiosis as a theoretical framework for entering into a new understanding of mother-infant and family systems biology based on perspectives that share themes of interconnection and mutualism.

RESULTS: There are many rigorous, empirical studies of co-regulation, mutualism and interdependence in the human parent-offspring system that is moving us forward into this new territory. Perspectives that emphasize interconnection and interpenetration, reciprocity and mutualism, and integration over reduction are expanding to fill the spaces needed to answer today's questions.

DISCUSSION: Recent contributions of perspectives on neurocognitive development have buttressed the symbiosis view with constructs of prenatal origins, such as 'co-embodiment' and 'co-homeostasis', that illuminate maternal-fetal reciprocities seen to underlie initiation and maintenance of developmental trajectories essential to support fetuses born prematurely into a NICU environment.

CONCLUSION: The six systems of parental intervention and developmental care presented in this Special Issue represent foundational approaches to developmental care for prematurely born infants. All these approaches recognize forms of reciprocity and mutualism on many levels, always including the infants as active parts of multiple regulatory systems.

PMID:39716839 | DOI:10.1111/apa.17553

J Integr Bioinform. 2024 Dec 25. doi: 10.1515/jib-2022-0036. Online ahead of print.

ABSTRACT

Breast cancer has the highest incidence and is the fifth cause of death in cancers. Progression is one of the important features of breast cancer which makes it a life-threatening cancer. MicroRNAs are small RNA molecules that have pivotal roles in the regulation of gene expression and they control different properties in breast cancer such as progression. Recently, systems biology offers novel approaches to study complicated biological systems like miRNAs to find their regulatory roles. One of these approaches is analysis of weighted co-expression network in which genes with similar expression patterns are considered as a single module. Because the genes in one module have similar expression, it is rational to think the same regulatory elements such as miRNAs control their expression. Herein, we use WGCNA to find important modules related to breast cancer progression and use hypergeometric test to perform miRNA target enrichment analysis and find important miRNAs. Also, we use negative correlation between miRNA expression and modules as the second filter to ensure choosing the right candidate miRNAs regarding to important modules. We found hsa-mir-23b, hsa-let-7b and hsa-mir-30a are important miRNAs in breast cancer and also investigated their roles in breast cancer progression.

PMID:39716374 | DOI:10.1515/jib-2022-0036

BioData Min. 2024 Dec 24;17(1):60. doi: 10.1186/s13040-024-00416-7.

ABSTRACT

Pathway analysis is a powerful approach for elucidating insights from gene expression data and associating such changes with cellular phenotypes. The overarching objective of pathway research is to identify critical molecular drivers within a cellular context and uncover novel signaling networks from groups of relevant biomolecules. In this work, we present PathSingle, a Python-based pathway analysis tool tailored for single-cell data analysis. PathSingle employs a unique graph-based algorithm to enable the classification of diverse cellular states, such as T cell subtypes. Designed to be open-source, extensible, and computationally efficient, PathSingle is available at https://github.com/zurkin1/PathSingle under the MIT license. This tool provides researchers with a versatile framework for uncovering biologically meaningful insights from high-dimensional single-cell transcriptomics data, facilitating a deeper understanding of cellular regulation and function.

PMID:39716187 | DOI:10.1186/s13040-024-00416-7

ArXiv [Preprint]. 2024 Dec 13:arXiv:2412.10262v1.

ABSTRACT

Computational variant effect predictors (VEPs) are providing increasingly strong evidence to classify the pathogenicity of missense variants. Precision vs. recall analysis is useful in evaluating VEP performance, especially when adjusted for imbalanced test sets. Here, we describe VEPerform, a web-based tool for evaluating the performance of VEPs at the gene level using balanced precision vs. recall curve (BPRC) analysis.

PMID:39713801 | PMC:PMC11661297

Methods Mol Biol. 2025;2884:369-387. doi: 10.1007/978-1-0716-4298-6_22.

ABSTRACT

Amyloidosis diseases are characterized by protein misfolding, which forms insoluble beta-sheet fibrils progressively deposited in tissues. Deposition in the form of amyloid aggregates can occur in various organs, damaging their structure and function. The hallmark of amyloidosis is aberrant interactions leading to protein aggregation and proteotoxicity. Accordingly, amyloidosis-related samples represent a valuable source of information to generate new knowledge useful for diagnostic, prognostic, and therapeutic purposes. In this scenario, we outline the path to apply computational methods and strategies based on the combination of proteomics and systems biology approaches. In addition to algorithms useful for subtyping amyloid deposits or assessing proteome recovery after drug treatment, our chapter provides workflows based on protein-protein interaction and protein co-expression network models. In particular, the main steps to reconstruct and analyze them at both functional and topological levels are described. Our chapter aims to provide tools and instructions to identify and monitor prognostic, diagnostic, and therapeutic markers and to shed light on the processes, pathways, and functions affected by amyloidogenic proteins.

PMID:39716014 | DOI:10.1007/978-1-0716-4298-6_22

Nature. 2024 Dec 23. doi: 10.1038/s41586-024-08555-x. Online ahead of print.

NO ABSTRACT

PMID:39715925 | DOI:10.1038/s41586-024-08555-x

Genome Res. 2024 Dec 23:gr.279864.124. doi: 10.1101/gr.279864.124. Online ahead of print.

ABSTRACT

While the production of a draft genome has become more accessible due to long-read sequencing, the annotation of these new genomes has not been developed at the same pace. Long-read RNA sequencing (lrRNA-seq) offers a promising solution for enhancing gene annotation. In this study, we explore how sequencing platforms, Oxford Nanopore R9.4.1 chemistry or PacBio Sequel II CCS, and data processing methods influence evidence-driven genome annotation using long reads. Incorporating PacBio transcripts into our annotation pipeline significantly outperformed traditional methods, such as ab initio predictions and short-read-based annotations. We applied this strategy to a nonmodel species, the Florida manatee, and compared our results to existing short-read-based annotation. At the loci level, both annotations were highly concordant, with 90% agreement. However, at the transcript level, the agreement was only 35%. We identified 4,906 novel loci, represented by 5,707 isoforms, with 64% of these isoforms matching known sequences in other mammalian species. Overall, our findings underscore the importance of using high-quality curated transcript models in combination with ab initio methods for effective genome annotation.

PMID:39715684 | DOI:10.1101/gr.279864.124

BMJ Ment Health. 2024 Dec 22;27(1):e301333. doi: 10.1136/bmjment-2024-301333.

ABSTRACT

Data sharing is a cornerstone of modern scientific research, playing a critical role in fostering greater collaboration, enhancing reproducibility, transparency and efficiency of scientific discoveries, and integrating diverse data sources. In circadian rhythm research, data sharing is particularly important due to the complexity and heterogeneity of the data, which includes molecular profiles, physiological measurements, clinical data and sensor-based data. UK research funders, such as Medical Research Council, Wellcome Trust and UK Research and Innovation, have established data-sharing policies to promote open science and enhance research transparency. Despite these policies, a recent assessment within the UK Circadian Mental Health Network (CMHN), which incorporates an analysis of publications from several countries, revealed that data sharing remains limited. Significant challenges including data complexity, privacy and ethical considerations, technical issues and entrenched academic culture are major barriers to progress. This perspective article highlights the current state of data sharing in circadian and mental health research, identifies key obstacles and compares these practices with broader trends. We also provide insights from principal investigators within the CMHN on the reasons for limited data sharing. To address these challenges, researchers can foster a culture of openness by seeking training, planning ahead in ethics processes and data management plans and using data outputs in research assessment. We outline CMHN's future plans to deliver training on Findable, Accessible, Interoperable, Reusable principles, offer data curation services and provide ethical guidelines. By adopting these strategies, we aim to improve data-sharing practices, ultimately advancing our understanding of circadian rhythms and their implications for mental health.

PMID:39715637 | DOI:10.1136/bmjment-2024-301333

J Nat Prod. 2024 Dec 23. doi: 10.1021/acs.jnatprod.4c01128. Online ahead of print.

ABSTRACT

Nonenzymatic reactions, though critical in natural product biosynthesis, are significantly challenging to control. Adding 3% NaI to the culture medium of Penicillium janczewskii significantly increased pseurotin D (1) production and decreased pseurotin A (2) production. Previously, 1 and 2 were suggested to be produced via a nonenzymatic reaction, where the epoxide at C-10 undergoes SN2 (2) or SN2' (1) reactions. We confirmed that 1 was isolated as a 1:1 mixture of C-13 epimers by spectral elucidation via CP3 analysis aided by selective excitation NMR methods, which supported that 1 was produced through a nonenzymatic SN2' reaction. We propose that NaI increased the ratio of 1 by causing steric hindrance at the C-11 position of the transient intermediate, which makes C-13 more preferred in the SN2/SN2' competition.

PMID:39714233 | DOI:10.1021/acs.jnatprod.4c01128

ISME J. 2024 Dec 23:wrae257. doi: 10.1093/ismejo/wrae257. Online ahead of print.

ABSTRACT

Most of the microbes in nature infrequently receive nutrients and are thus in slow- or non-growing states. How quickly they can resume their growth upon an influx of new resources is crucial to occupy environmental niches. Isogenic microbial populations are known to harbor only a fraction of cells with rapid growth resumption, yet little is known about the physiological characteristics of those cells and their emergence in the population. Here, we tracked growth of individual Escherichia coli cells in populations under fluctuating nutrient conditions. We found that shifting from high- to low-nutrient conditions caused stalling of cell growth with few cells continuing to divide extremely slowly, a process which was dependent on lipid turnover. Resuming high-nutrient inflow after low-nutrient conditions resulted in cells resuming growth and division, but with different lag times and leading to varying progeny. The history of cell growth during low-nutrient but not high-nutrient conditions was determinant for resumption of growth, which cellular genealogy analysis suggested to originate from inherited physiological differences. Our results demonstrate that cellular growth dynamics become diverse by nutrient limitations, under which a fraction of cells experienced a particular growth history can reproduce progeny with new resources in the future.

PMID:39714219 | DOI:10.1093/ismejo/wrae257

mSystems. 2024 Dec 26:e0131524. doi: 10.1128/msystems.01315-24. Online ahead of print.

ABSTRACT

The composition of bacterial transcriptomes is determined by the transcriptional regulatory network (TRN). The TRN regulates the transition from one physiological state to another. Here, we use independent component analysis to monitor the composition of the transcriptome during the transition from the exponential growth phase to the stationary phase. With Escherichia coli K-12 MG1655 as a model strain, we trigger the transition using carbon, nitrogen, and sulfur starvation. We find that (i) the transition to the stationary phase accompanies common transcriptome changes, including increased stringent responses and reduced production of cellular building blocks and energy regardless of the limiting element; (ii) condition-specific changes are strongly associated with transcriptional regulators (e.g., Crp, NtrC, CysB, Cbl) responsible for metabolizing the limiting element; and (iii) the shortage of each limiting element differentially affects the production of amino acids and extracellular polymers. This study demonstrates how the combination of genome-scale datasets and new data analytics reveals the fundamental characteristics of a key transition in the life cycle of bacteria.

IMPORTANCE: Nutrient limitations are critical environmental perturbations in bacterial physiology. Despite its importance, a detailed understanding of how bacterial transcriptomes are adjusted has been limited. By utilizing independent component analysis (ICA) to decompose transcriptome data, this study reveals key regulatory events that enable bacteria to adapt to nutrient limitations. The findings not only highlight common responses, such as the stringent response, but also condition-specific regulatory shifts associated with carbon, nitrogen, and sulfur starvation. The insights gained from this work advance our knowledge of bacterial physiology, gene regulation, and metabolic adaptation.

PMID:39714213 | DOI:10.1128/msystems.01315-24

J Integr Plant Biol. 2024 Dec 23. doi: 10.1111/jipb.13817. Online ahead of print.

ABSTRACT

Stomata are epidermal pores that are essential for water evaporation and gas exchange in plants. Stomatal development is orchestrated by intrinsic developmental programs, hormonal controls, and environmental cues. The steroid hormone brassinosteroid (BR) inhibits stomatal lineage progression by regulating BIN2 and BSL proteins in leaves. Notably, BR is known to promote stomatal development in hypocotyls as opposed to leaves; however, its molecular mechanism remains elusive. Here, we show that BR signaling has a dual regulatory role in controlling stomatal development in Arabidopsis hypocotyls. We found that brassinolide (BL; the most active BR) regulates stomatal development differently in a concentration-dependent manner. At low and moderate concentrations, BL promoted stomatal formation by upregulating the expression of SPEECHLESS (SPCH) and its target genes independently of BIN2 regulation. In contrast, high concentrations of BL and bikinin, which is a specific inhibitor of BIN2 and its homologs, significantly reduced stomatal formation. Genetic analyses revealed that BIN2 regulates stomatal development in hypocotyls through molecular mechanisms distinct from the regulatory mechanism of the cotyledons. In hypocotyls, BIN2 promoted stomatal development by inactivating BZR1, which suppresses the expression of SPCH and its target genes. Taken together, our results suggest that BR precisely coordinates the stomatal development of hypocotyls using an antagonistic control of SPCH expression via BZR1-dependent and BZR1-independent transcriptional regulation.

PMID:39714086 | DOI:10.1111/jipb.13817

Evolution. 2024 Dec 23:qpae187. doi: 10.1093/evolut/qpae187. Online ahead of print.

ABSTRACT

Facultatively parthenogenetic animals could help reveal the role of sexual conflict in the evolution of sex. Although each female can reproduce both sexually (producing sons and daughters from fertilized eggs) and asexually (typically producing only daughters from unfertilized eggs), these animals often form distinct sexual and asexual populations. We hypothesized that asexual populations are maintained through female resistance as well as the decay of male traits. We tested this via experimental crosses between individuals descended from multiple natural sexual and asexual populations of the facultatively parthenogenic stick-insect Megacrania batesii. We found that male-paired females descended from asexual populations produced strongly female-biased offspring sex-ratios resulting from reduced fertilization rates. This effect was not driven by incompatibility between diverged genotypes but, rather, by both genotypic and maternal effects on fertilization rate. Furthermore, when females from asexual populations mated and produced sons, those sons had poor fertilization success when paired with resistant females, consistent with male trait decay. Our results suggest that resistance to fertilization resulting from both maternal and genotypic effects, along with male sexual trait decay, can hinder the invasion of asexual populations by males. Sexual conflict could thus play a role in the establishment and maintenance of asexual populations.

PMID:39713880 | DOI:10.1093/evolut/qpae187

ACS Nanosci Au. 2024 Nov 15;4(6):416-425. doi: 10.1021/acsnanoscienceau.4c00040. eCollection 2024 Dec 18.

ABSTRACT

RNA-based agents (siRNA, miRNA, and mRNA) can selectively manipulate gene expression/proteins and are set to revolutionize a variety of disease treatments. Nanoparticle (NP) platforms have been developed to deliver functional mRNA or siRNA inside cells to overcome their inherent limitations. Recent studies have focused on siRNA to knock down proteins causing drug resistance or mRNA technology to introduce tumor suppressors. However, cancer needs multitargeted approaches to selectively manipulate multiple gene expressions/proteins. In this proof-of-concept study, we developed NPs containing Luc-mRNA and siRNA-GFP as model agents ((M+S)-NPs) and showed that NPs can simultaneously deliver functional mRNA and siRNA and impact the expression of two genes/proteins in vitro. Additionally, after in vivo administration, (M+S)-NPs successfully knocked down GFP while introducing luciferase into a TNBC mouse model, indicating that our NPs have the potential to develop RNA-based anticancer therapeutics. These studies pave the way to develop RNA-based, multitargeted approaches for complex diseases like cancer.

PMID:39713729 | PMC:PMC11659891 | DOI:10.1021/acsnanoscienceau.4c00040

Bioscience. 2024 Oct 14;74(12):825-839. doi: 10.1093/biosci/biae084. eCollection 2024 Dec.

ABSTRACT

In a hyperconnected world, framing and managing biological invasions poses complex and contentious challenges, affecting socioeconomic and environmental sectors. This complexity distinguishes the field and fuels polarized debates. In the present article, we synthesize four contentious issues in invasion science that are rarely addressed together: vocabulary usage, the potential benefits of nonnative species, perceptions shifting because of global change, and rewilding practices and biological invasions. Researchers have predominantly focused on single issues; few have addressed multiple components of the debate within or across disciplinary boundaries. Ignoring the interconnected nature of these issues risks overlooking crucial cross-links. We advocate for interdisciplinary approaches that better integrate social and natural sciences. Although they are challenging, interdisciplinary collaborations offer hope to overcome polarization issues in invasion science. These may bridge disagreements, facilitate knowledge exchange, and reshape invasion science narratives. Finally, we present a contemporary agenda to advance future research, management, and constructive dialogue.

PMID:39713562 | PMC:PMC11660934 | DOI:10.1093/biosci/biae084