Oxygen is Toxic in the Cold in C. elegans. DOI

Cameron M. Suraci,

Michael L. Morrison, Mark B. Roth

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 22, 2024

Abstract Temperature and oxygen are two factors that profoundly affect survival limits of animals; too much or little either is lethal. However, both humans animals can exhibit exceptional when temperature simultaneously low. To better understand this apparent synergistic interaction between temperature, we assayed the Caenorhabditis elegans in experimental environments at different temperatures concentrations. While nematodes cannot survive a day room air 2 °C (cold shock), found low, 200-fold less than air, they for 48 hours. Consistent with this, worms exposed to high concentrations, 35 times greater more sensitive low air. These results show normal atmospheric levels toxic cold. Using these assays, cold acclimatization protects from lethal effects oxygen, mutations pathway tolerance, naturally occurring physiologically relevant compounds glucose, manganese (II), ascorbate improve supplied early life. interdependence on C. based part shared physiological mechanisms involved response environmental stressors. The evolution natural history stress responses suggest similar phenomena may function humans.

Language: Английский

The uses of zebrafish (Danio rerio) as an in vivo model for toxicological studies: A review based on bibliometrics DOI Creative Commons
Weichao Zhao,

Y.-W. Chen,

Nan Hu

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 272, P. 116023 - 116023

Published: Jan. 30, 2024

An in vivo model is necessary for toxicology. This review analyzed the uses of zebrafish (Danio rerio) toxicology based on bibliometrics. Totally 56,816 publications about from 2002 to 2023 were found Web Science Core Collection, with Toxicology as top 6 among all disciplines. Accordingly, bibliometric map reveals that "toxicity" has become a hot keyword. It further most common exposure types include acute, chronic, and combined exposure. The toxicological effects behavioral, intestinal, cardiovascular, hepatic, endocrine toxicity, neurotoxicity, immunotoxicity, genotoxicity, reproductive transgenerational toxicity. mechanisms oxidative stress, inflammation, autophagy, dysbiosis gut microbiota. toxicants commonly evaluated by using nanomaterials, arsenic, metals, bisphenol, dioxin. Overall, provide unique well-accepted investigate mechanisms. We also discussed possible ways address some limitations model, such combination human organoids avoid species differences.

Language: Английский

Citations

31
Updates to the Alliance of Genome Resources central infrastructure DOI Creative Commons
Suzi Aleksander, Anna V. Anagnostopoulos, Giulia Antonazzo

et al.

Genetics, Journal Year: 2024, Volume and Issue: 227(1)

Published: March 29, 2024

Abstract The Alliance of Genome Resources (Alliance) is an extensible coalition knowledgebases focused on the genetics and genomics intensively studied model organisms. organized as individual knowledge centers with strong connections to their research communities a centralized software infrastructure, discussed here. Model organisms currently represented in are budding yeast, Caenorhabditis elegans, Drosophila, zebrafish, frog, laboratory mouse, rat, Gene Ontology Consortium. project rapid development phase harmonize knowledge, store it, analyze present it community through web portal, direct downloads, application programming interfaces (APIs). Here, we focus developments over last 2 years. Specifically, added enhanced tools for browsing genome (JBrowse), downloading sequences, mining complex data (AllianceMine), visualizing pathways, full-text searching literature (Textpresso), sequence similarity (SequenceServer). We existing interactive tables table paralogs complement our representation orthology. To support organism communities, implemented species-specific “landing pages” will add disease-specific portals soon; addition, common forum Discourse software. describe progress toward central persistent database curation, modeling that underpins harmonization, state-of-the-art curation system integrated artificial intelligence machine learning (AI/ML).

Language: Английский

Citations

19
Multi-omics-based mapping of decidualization resistance in patients with a history of severe preeclampsia DOI Creative Commons
Irene Muñoz-Blat, Raúl Pérez-Moraga, Nerea Castillo-Marco

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Endometrial decidualization resistance (DR) is implicated in various gynecological and obstetric conditions. Here, using a multi-omic strategy, we unraveled the cellular molecular characteristics of DR patients who have suffered severe preeclampsia (sPE). Morphological analysis unveiled significant glandular anatomical abnormalities, confirmed histologically quantified by digitization hematoxylin eosin-stained tissue sections. Single-cell RNA sequencing (scRNA-seq) endometrial samples from with sPE (n = 11) controls 12) revealed sPE-associated shifts cell composition, manifesting as stromal mosaic state characterized proliferative cells (MMP11 SFRP4) alongside IGFBP1+ decidualized cells, concurrent epithelial mosaicism dearth epithelial–stromal transition associated decidualization. Cell–cell communication network mapping underscored aberrant crosstalk among specific types, implicating crucial pathways such endoglin, WNT SPP1. Spatial transcriptomics replication cohort validated DR-associated features. Laser capture microdissection/mass spectrometry second corroborated several scRNA-seq findings, notably absence to at pathway level, indicating disrupted response steroid hormones, particularly estrogens. These insights shed light on potential mechanisms underpinning pathogenesis context sPE. A multi-omics resistance, which conditions, history defects stroma, epithelium epithelial-to-stromal transition, findings separate cohort.

Language: Английский

Citations

2
Characterization of the Pristionchus pacificus “epigenetic toolkit” reveals the evolutionary loss of the histone methyltransferase complex PRC2 DOI Creative Commons
Audrey Brown, Adriaan B. Meiborg,

Mirita Franz‐Wachtel

et al.

Genetics, Journal Year: 2024, Volume and Issue: 227(1)

Published: March 21, 2024

Abstract Comparative approaches have revealed both divergent and convergent paths to achieving shared developmental outcomes. Thus, only through assembling multiple case studies can we understand biological principles. Yet, despite appreciating the conservation—or lack thereof—of networks, conservation of epigenetic mechanisms regulating these networks is poorly understood. The nematode Pristionchus pacificus has emerged as a model system plasticity regulation it exhibits bacterivorous or omnivorous morph depending on its environment. Here, determined “epigenetic toolkit” available P. resource for future functional work plasticity, comparison with Caenorhabditis elegans investigate mechanisms. Broadly, observed similar cast genes putative function between C. pacificus. However, also found striking differences. Most notably, histone methyltransferase complex PRC2 appears be missing in We described deletion/pseudogenization mes-2 mes-6 concluded that were lost last common ancestor related species arcanus. Interestingly, enzymatic product (H3K27me3) by mass spectrometry immunofluorescence, suggesting currently unknown been co-opted heterochromatin silencing. Altogether, provided an inventory compare elegans. This will enable reverse-genetic experiments first loss multicellular organism.

Language: Английский

Citations

6
Single-tissue proteomics in Caenorhabditis elegans reveals proteins resident in intestinal lysosome-related organelles DOI Creative Commons
Chieh-Hsiang Tan, Ting‐Yu Wang, Heenam Park

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(25)

Published: June 11, 2024

The nematode intestine is the primary site for nutrient uptake and storage as well synthesis of biomolecules; lysosome-related organelles known gut granules are important many these functions. Aspects biology not understood, including export nutrients it imports molecules synthesizes, complete functions protein content granules. Here, we report a mass spectrometry (MS)–based proteomic analysis Caenorhabditis elegans its Overall, identified approximately 5,000 proteins each in gonad showed that most can be detected samples extracted from single worm, suggesting feasibility individual-level genetic using proteomes. Comparing proteomes published transcriptomes gonad, appear to synthesized then transferred gonad. To identify granule proteins, compared proteome individual intestines deficient wild type. includes exclusively localized additional putative proteins. We selected two validation via immunohistochemistry, our successful confirmation both suggests strategy was effective identifying proteome. Our results demonstrate practicability single-tissue MS–based small organisms future utility.

Language: Английский

Citations

6
Genetic Insights into Brain Morphology: a Genome-Wide Association Study of Cortical Thickness and T1-Weighted MRI Gray Matter-White Matter Intensity Contrast DOI Creative Commons
Nicholas Kim, Nahian F. Chowdhury, Kenneth H. Buetow

et al.

Neuroinformatics, Journal Year: 2025, Volume and Issue: 23(2)

Published: April 1, 2025

In T1-weighted magnetic resonance imaging (MRI), cortical thickness (CT) and gray-white matter contrast (GWC) capture brain morphological traits vary with age-related disease. To gain insight into genetic factors underlying structure dynamics observed during neurodegeneration, this genome-wide association study (GWAS) quantifies the relationship between single nucleotide polymorphisms (SNPs) both CT GWC in UK Biobank participants (N = 43,002). our knowledge, is first GWAS to investigate determinants of T1-MRI humans. We found 251 SNPs associated or for at least 1% locations, including 42 GWC; 127 only CT; 82 GWC. Identified include rs1080066 (THSB1, featuring strongest GWC), rs13107325 (SLC39A8, linked largest number locations), rs864736 (KCNK2, locations). Dimensionality reduction reveals three major gene ontologies constraining (neural signaling, ion transport, cell migration) four development, cellular homeostasis, tissue repair, transport). Our findings provide CT, highlighting pathways anatomy neurodegeneration. These insights can assist development therapies treatments targeting diseases.

Language: Английский

Citations

0
Sex-biased gene expression during neural differentiation of human embryonic stem cells DOI Creative Commons
Philipp Pottmeier,

Danai Nikolantonaki,

Fredrik Lanner

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: May 1, 2024

Sex differences in the developing human brain are primarily attributed to hormonal influence. Recently however, genetic and their impact on nervous system have attracted increased attention. To understand genetically driven sexual dimorphisms neurodevelopment, we investigated genome-wide gene expression an

Language: Английский

Citations

4
The sodium leak channel NALCN is regulated by neuronal SNARE complex proteins DOI Creative Commons
Samuel Usher, Estelle Toulmé, Roberta Florea

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(11)

Published: March 14, 2025

NALCN (sodium leak channel, nonselective) is vital for regulating electrical activity in neurons and other excitable cells, mutations the channel or its auxiliary proteins lead to severe neurodevelopmental disorders. Here, we show that neuronal SNARE (soluble N -ethylmaleimide–sensitive factor attachment protein receptors) complex syntaxin SNAP25 (synaptosome-associated 25), which enable synaptic transmission nervous system, inhibit of both heterologous systems primary neurons. The existence this interaction suggests neurotransmitter release machinery can regulate signaling directly therefore modulate threshold own activity. We further find reduction currents sufficient promote cell survival syntaxin-depleted cells. This disinhibited may cause puzzling phenomenon rapid death absence syntaxin. could offer opportunities future drug development against genetic diseases linked NALCN- protein–containing complexes.

Language: Английский

Citations

0
Ribonucleases in Mendelian disease: Characterization and insight from model organisms DOI Creative Commons
Anirban Dutta, A. Zaremba, Paulina Jackowiak

et al.

Genes & Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 101613 - 101613

Published: March 1, 2025

Language: Английский

Citations

0
Emerging roles of ATG9/ATG9A in autophagy: implications for cell and neurobiology DOI Creative Commons
Ji-Young Choi,

Haeun Jang,

Xuan Zhao

et al.

Autophagy, Journal Year: 2024, Volume and Issue: 20(11), P. 2373 - 2387

Published: Aug. 4, 2024

Atg9, the only transmembrane protein among many autophagy-related proteins, was first identified in year 2000 yeast. Two homologs of ATG9A and ATG9B, have been found mammals. While ATG9B shows a tissue-specific expression pattern, such as placenta pituitary gland, is ubiquitously expressed. Additionally, deficiency leads to severe defects not at molecular cellular levels but also organismal level, suggesting key fundamental roles for ATG9A. The subcellular localization on small vesicles its functional relevance autophagy suggested potential role lipid supply during autophagosome biogenesis. Nevertheless, precise autophagic process has remained long-standing mystery, especially neurons. Recent findings, however, including structural, proteomic, biochemical analyses, provided new insights into function expansion phagophore membrane. In this review, we aim understand various aspects ATG9 (in invertebrates plants)/ATG9A mammals), localization, trafficking, other functions, nonneuronal cells neurons by comparing recent discoveries related ATG9/ATG9A proposing directions future research.

Language: Английский

Citations

2