C. elegans

Systematic functional profiling of the gene set that directs embryonic development is an important challenge. To tackle this challenge, we used 4D imaging of C. elegans embryogenesis to capture the effects of 500 gene knockdowns and developed an automated approach to compare developmental phenotypes. The automated approach quantifies features-including germ layer cell numbers, tissue position, and tissue shape-to generate temporal curves whose parameterization yields numerical phenotypic signatures. In conjunction with a new similarity metric that operates across phenotypic space, these signatures enabled the generation of ranked lists of genes predicted to have similar functions, accessible in the PhenoBank web portal, for ∼25% of essential development genes...

BACKGROUND: Caenorhabditis elegans is a widely used model animal. Chemotaxis assay is one of the experiments that study the effects of different chemicals on nematodes. It is mainly used to study the effects of different chemicals on the perception behavior of nematodes. By conducting this experiment, not only can the neurotoxicity of chemicals be reflected, but also the impact of chemicals on physiological functions regulated by the nervous system, such as nematode feeding behavior and basic motor ability...

Computational super-resolution methods, including conventional analytical algorithms and deep learning models, have substantially improved optical microscopy. Among them, supervised deep neural networks have demonstrated outstanding performance, however, demanding abundant high-quality training data, which are laborious and even impractical to acquire due to the high dynamics of living cells. Here, we develop zero-shot deconvolution networks (ZS-DeconvNet) that instantly enhance the resolution of microscope images by more than 1...

Photodynamic therapy is a noninvasive treatment in which specific photosensitizers and light are used to produce high amounts of reactive oxygen species (ROS), which can be employed for targeted tissue destruction in cancer treatment or antimicrobial therapy. However, it remains unknown whether lower amounts of ROS produced by mild photodynamic therapy increase lifespan and stress resistance at the organism level. Here, we introduce a novel photodynamic treatment (PDTr) that uses 20 μM hypericin, a photosensitizer that originates from Hypericum perforatum, and orange light (590 nm, 5...

Four Ru(II) complexes (A2-A5) were synthesized from the reaction of coumarin Schiff base ligands (7da2-tsc, 7da3-mtsc, 7da4-etsc and 7da5-ptsc) with [RuHCl(CO)(PPh3 )3 ]. The compounds were characterized by FT-IR, UV-Vis, 1 H, 13 C and 31 P NMR, mass spectrometry and crystallographic analysis. Calf Thymus DNA (CT-DNA) binding studies revealed the intercalative mode of binding of the complexes with DNA. The results of Bovine serum albumin (BSA) binding studies established the interaction between BSA followed static quenching mechanism...

Although iron (Fe) is the most biologically abundant transition metal, it is highly toxic when it accumulates as Fe2+, forming a labile Fe pool and favoring the Fenton reaction. This oxidative scenario leads to a type of caspase-independent programmed cell death, referred to as ferroptosis, where following processes take place: 1) Fe2+ overload; 2) glutathione peroxidase 4 inactivation; 3) lipid peroxidation and 4) glutathione depletion. The present study sought to evaluate the consequences of Fe2+ administration on ferroptosis induction in Caenorhabditis elegans...

Multicellular organisms are composed of many tissue types that have distinct morphologies and functions, which are largely driven by specialized proteomes and interactomes. To define the proteome and interactome of a specific type of tissue in an intact animal, we developed a localized proteomics approach called Methionine Analog-based Cell-Specific Proteomics and Interactomics (MACSPI). This method uses the tissue-specific expression of an engineered methionyl-tRNA synthetase to label proteins with a bifunctional amino acid 2-amino-5-diazirinylnonynoic acid in selected cells...

While depolarization of the neuronal membrane is known to evoke the neurotransmitter release from synaptic vesicles, hyperpolarization is regarded as a resting state of chemical neurotransmission. Here, we report that hyperpolarizing neurons can actively signal neural information by employing undocked hemichannels. We show that UNC-7, a member of the innexin family in Caenorhabditis elegans, functions as a hemichannel in thermosensory neurons and transmits temperature information from the thermosensory neurons to their postsynaptic interneurons...

Loss of proteostasis is a highly conserved feature of aging across model organisms and results in the accumulation of insoluble protein aggregates. Protein insolubility is also a unifying feature of major age-related neurodegenerative diseases, including Alzheimer's Disease (AD), in which hundreds of insoluble proteins associate with aggregated amyloid beta (Aβ) in senile plaques. Despite the connection between aging and AD risk, therapeutic approaches to date have overlooked aging-driven generalized protein insolubility as a contributing factor...

Pathogen avoidance behaviour has been observed across animal taxa as a vital host-microbe interaction mechanism. The nematode Caenorhabditis elegans has evolved multiple diverse mechanisms for pathogen avoidance under natural selection pressure. We summarise the current knowledge of the stimuli that trigger pathogen avoidance, including alterations in aerotaxis, intestinal bloating, and metabolites. We then survey the neural circuits involved in pathogen avoidance, transgenerational epigenetic inheritance of pathogen avoidance, signalling crosstalk between pathogen avoidance and innate immunity, and C...

Borate glass transforms into hydroxycarbonate apatite more rapidly than silicate glass. This research aims to evaluate strontium's structural and biological effects on borate bioactive glass (BBG) and the influence of strontium concentrations (0%, 5%, 10%, and 15% Sr) prepared via the sol-gel method. The study reveals significant findings related to the physicochemical properties of the glass. Immersion of the glass powders in a simulated body fluid (SBF) led to the development of a hydroxyapatite (HAP) layer on the glass surfaces...

Candida species have been responsible for a high number of invasive infections worldwide. In this sense, Rottlerin has demonstrated a wide range of pharmacological activities. Therefore, this study aimed to evaluate the antifungal, antibiofilm and antivirulence activity of Rottlerin in vitro against Candida spp. and its toxicity and antifungal activity in vivo. Rottlerin showed antifungal activity against all yeasts evaluated, presenting Minimum Inhibitory and Fungicidal Concentration (MIC and MFC) values of 7...

Amyotrophic lateral sclerosis can be caused by abnormal accumulation of TAR DNA-binding protein 43 (TDP-43) in the cytoplasm of neurons. Here, we use a C. elegans model for TDP-43-induced toxicity to identify the biological mechanisms that lead to disease-related phenotypes. By applying deep behavioral phenotyping and subsequent dissection of the neuromuscular circuit, we show that TDP-43 worms have profound defects in GABA neurons. Moreover, acetylcholine neurons appear functionally silenced. Enhancing functional output of repressed acetylcholine neurons at the level of, among others, G-protein-coupled receptors restores neurotransmission, but inefficiently rescues locomotion...

Invertebrates use the endoribonuclease Dicer to cleave viral dsRNA during antiviral defense, while vertebrates use RIG-I-like Receptors (RLRs), which bind viral dsRNA to trigger an interferon response. While some invertebrate Dicers act alone during antiviral defense, Caenorhabditis elegans Dicer acts in a complex with a dsRNA binding protein called RDE-4, and an RLR ortholog called DRH-1. We used biochemical and structural techniques to provide mechanistic insight into how these proteins function together...

Mitochondrial function relies on the coordinated transcription of mitochondrial and nuclear genomes to assemble respiratory chain complexes. Across species, the SIN3 coregulator influences mitochondrial functions, but how its loss impacts mitochondrial homeostasis and metabolism in the context of a whole organism is unknown. Exploring this link is important because SIN3 haploinsufficiency causes intellectual disability/autism syndromes and SIN3 plays a role in tumor biology. Here we show that loss of C. elegans SIN-3 results in transcriptional deregulation of mitochondrial- and nuclear-encoded mitochondrial genes, potentially leading to mito-nuclear imbalance...

The gut microbiome has been proposed to influence many aspects of animal development and physiology. However, both the specific bacterial species and the molecular mechanisms by which bacteria exert these effects are unknown in most cases. Here, we established a high throughput screening platform using the model animal Caenorhabditis elegans for identifying bacterial species and mechanisms that influence animal development and physiology. From our initial screens we found that many Bacillus species can restore normal animal development to insulin signaling mutant animals that otherwise do not develop to adulthood...

Heritable gene silencing has been proposed to rely on DNA methylation, histone modifications, and/or non-coding RNAs in different organisms. Here we demonstrate that multiple RNA-mediated mechanisms with distinct and easily detectable molecular signatures can underlie heritable silencing of the same open-reading frame in the nematode C. elegans . Using two-gene operons, we reveal three cases of gene-selective silencing that provide support for the transmission of heritable epigenetic changes through different mechanisms of RNA silencing independent of changes in chromatin that would affect all genes of an operon equally...

We develop a data harmonization approach for C. elegans volumetric microscopy data, still or video, consisting of a standardized format, data pre-processing techniques, and a set of human-in-the-loop machine learning based analysis software tools. We unify a diverse collection of 118 whole-brain neural activity imaging datasets from 5 labs, storing these and accompanying tools in an online repository called WormID ( wormid.org ). We use this repository to generate a statistical atlas that, for the first time, enables accurate automated cellular identification that generalizes across labs, approaching human performance in some cases...

Progress in biology has generated numerous lists of genes that share some property. But, advancing from the initial implication of a set of genes in a process to understanding their roles in the process is slow and unsystematic. Here we use RNA silencing in C. elegans to illustrate a general approach for comparing lists of data accumulated by a field to prioritize genes for detailed study given limited resources. The partially subjective relationships between genes forged by both functional relatedness of the genes and biased progress in the field was captured as historical mutual information (HMI) and used as a quantitative measure for clustering genes...

Centrioles organize centrosomes, the cell's primary microtubule-organizing centers (MTOCs). Centrioles double in number each cell cycle, and mis-regulation of this process is linked to diseases such as cancer and microcephaly. In C. elegans, centriole assembly is controlled by the Plk4 related-kinase ZYG-1, which recruits the SAS-5-SAS-6 complex. While the kinase activity of ZYG-1 is required for centriole assembly, how it functions has not been established. Here we report that ZYG-1 physically interacts with and phosphorylates SAS-5 on 17 conserved serine and threonine residues in vitro...