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Autophagy is the major lysosomal pathway for the clearance of proteins, organelles and microbes in eukaryotic cells. Therefore, autophagic dysfunction can lead to numerous human diseases, like cancer or neurodegeneration, and may facilitate infections by pathogens. However, despite tremendous advances in the understanding of autophagy over the past decades, the functions and regulations of autophagy-related proteins in canonical and non-canonical autophagy are still not fully resolved. The Special Issue “Model Organisms to Study Autophagy” organized by Cells includes six original articles and one review that show the latest achievements in autophagy research using different model organisms. The Special Issue summarizes and discusses different aspects of autophagy that open new avenues in understanding autophagy functions and mechanisms.

Summary: The Dp(10)2Yey mouse carries a ∼2.3-Mb intra-chromosomal duplication of mouse chromosome 10 (Mmu10) that has homology to human chromosome 21, making it an essential model for aspects of Down syndrome (DS, trisomy 21). In this study, we investigated neuronal dysfunction in the Dp(10)2Yey mouse and report spatial memory impairment and anxiety-like behavior alongside altered neural activity in the medial prefrontal cortex (mPFC) and hippocampus (HPC). Specifically, Dp(10)2Yey mice showed impaired spatial alternation associated with increased sharp-wave ripple activity in mPFC during a period of memory consolidation, and reduced mobility in a novel environment accompanied by reduced theta-gamma phase-amplitude coupling in HPC. Finally, we found alterations in the number of interneuron subtypes in mPFC and HPC that may contribute to the observed phenotypes and highlight potential approaches to ameliorate the effects of human trisomy 21.

Intestinal barrier dysfunction is an evolutionarily conserved hallmark of aging, which has been linked to microbial dysbiosis, altered expression of occluding junction proteins, and impending mortality. However, the interplay between intestinal junction proteins, age-onset dysbiosis, and lifespan determination remains unclear. Here, we show that altered expression of Snakeskin (Ssk), a septate junction-specific protein, can modulate intestinal homeostasis, microbial dynamics, immune activity, and lifespan in Drosophila. Loss of Ssk leads to rapid and reversible intestinal barrier dysfunction, altered gut morphology, dysbiosis, and dramatically reduced lifespan. Remarkably, restoration of Ssk expression in flies showing intestinal barrier dysfunction rescues each of these phenotypes previously linked to aging. Intestinal up-regulation of Ssk protects against microbial translocation following oral infection with pathogenic bacteria. Furthermore, intestinal up-regulation of Ssk improves intestinal barrier function during aging, limits dysbiosis, and extends lifespan. Our findings indicate that intestinal occluding junctions may represent prolongevity targets in mammals.

Cephalopod research remains limited by the inability to culture species under laboratory conditions for multiple generations to provide continuous access to animals at all stages of the life cycle. Here, we describe a multi-generational laboratory culture system for two emerging cephalopod models: the hummingbird or Berry’s bobtail squid, Euprymna berryi Sasaki, 1929, and Morse’s bobtail squid, Euprymna morsei Verrill, 1881, which are primarily found off mainland Japan. E. berryi wild adults were spawned and raised to the third filial generation, and E. morsei wild adults were spawned and raised to the second filial generation in a closed system at 20°C. We report growth and survivorship data for a cohort of 30 individuals across the first generation raised in captivity. E. berryi and E. morsei grew exponentially during the first 90 and 60 days post-hatching, respectively. Survivorship at the first spawning event for E. berryi and E. morsei was 90% and 77%. E. berryi and E. morsei females spawned after days 112 and 71 days post-hatching, respectively. We describe the life history of each species and how to distinguish sexes. We discuss the challenges of cephalopod culture and how culturing these species address those problems.

Fish has emerged as an alternative model organism in biomedical research for conducting experimental pharmacological and toxicological studies. As a vertebrate, it shares many conserved physiological and molecular features with humans making it a valuable model for diagnosing, investigating disease states and testing drugs to check toxicity and therapeutic activity against the target. Zebrafish and medaka are mainstream models that are widely employed in pharmaceutical research. This study aims to highlight the probability and potential of fish as an alternative model organism in biomedical research, drug discovery and development. Further, it discusses the limitations of fish models in experimental pharmacological and toxicological studies considering the changes in the residing environment, physiology, metabolism, unpredictable inter-individual variability due to diseases, variable conditioning, and interspecific and intraspecific variability. [ABSTRACT FROM AUTHOR]

Regulation of inflammation is a critical process for maintaining physiological homeostasis. The λ-carrageenan (λ-CGN) is a mucopolysaccharide extracted from the cell wall of red algae (Chondrus crispus) capable of inducing acute intestinal inflammation, which is translated into the production of acute phase reactants secreted into the blood circulation. However, the associated mechanisms in vertebrates are not well understood. Here, we investigated the crucial factors behind the inflammatory milieu of λ-CGN-mediated inflammation administered at 0, 1.75, and 3.5% (v/w) by i.p. injection into the peritoneal cavity of adult zebrafish (ZF) (Danio rerio). We found that polymorphonuclear leukocytes (neutrophils) and lymphocytes infiltrating the ZF peritoneal cavity had short-term persistence. Nevertheless, they generate a strong pattern of inflammation that affects systemically and is enough to produce edema in the cavity. Consistent with these findings, cell infiltration, which causes notable tissue changes, resulted in the overexpression of several acute inflammatory markers at the protein level. Using reversed-phase high-performance liquid chromatography followed by a hybrid linear ion-trap mass spectrometry shotgun proteomic approach, we identified 2938 plasma proteins among the animals injected with PBS and 3.5% λ-CGN. First, the bioinformatic analysis revealed the composition of the plasma proteome. Interestingly, 72 commonly expressed proteins were recorded among the treated and control groups, but, surprisingly, 2830 novel proteins were differentially expressed exclusively in the λ-CGN-induced group. Furthermore, from the commonly expressed proteins, compared to the control group 62 proteins got a significant (p < 0.05) upregulation in the λ-CGN-treated group, while the remaining ten proteins were downregulated. Next, we obtained the major protein-protein interaction networks between hub protein clusters in the blood plasma of the λ-CGN induced group. Moreover, to understand the molecular underpinnings of these effects based on the unveiled protein sets, we performed a bioinformatic structural similarity analysis and generated overlapping 3D reconstructions between ZF and humans during acute inflammation. Biological pathway analysis pointed to the activation and abundance of diverse classical immune and acute phase reactants, several catalytic enzymes, and varied proteins supporting the immune response. Together, this information can be used for testing and finding novel pharmacological targets to treat human intestinal inflammatory diseases. [ABSTRACT FROM AUTHOR]

Demosponges of the genus Halichondria Fleming (1828) are common in coastal marine ecosystems worldwide and have been well-studied over the last decades. As ecologically important filter feeders, Halichondria species represent potentially suitable model organisms to link and fill in existing knowledge gaps in sponge biology, providing important novel insights into the physiology and evolution of the sponge holobiont. Here we review studies on the morphology, taxonomy, geographic distribution, associated fauna, life history, hydrodynamic characteristics, and coordinated behavior of Halichondria species. [ABSTRACT FROM AUTHOR]

Routine histochemical techniques are capable of producing vast amount of information from diverse sample types, but these techniques are limited in their ability to generate 3D information. Autofluorescence imaging can be used to analyse samples in 3D but it suffers from weak/low signal intensities. Here, we describe a simple chemical treatment with glutaraldehyde to enhance autofluorescence for 3D fluorescence imaging and to generate detailed morphological images on whole-mount samples. This methodology is straightforward and cost-effective to implement, suitable for a wide range of organisms and sample types. Furthermore, it can be readily integrated with standard confocal and fluorescence microscopes for analysis. This approach has the potential to facilitate the analysis of biological 3D structures and research in developmental biology, including studies on model and non-model organisms., Competing Interests: Competing interests University of Turku has registered a trademark 3DFLUOHISTO®. University of Turku, IP and MN are preparing commercialization of the 3DFLUOHISTO® method for 3D morphological imaging of biological samples., (© 2024. Published by The Company of Biologists Ltd.)

The yellow dung fly Scathophaga stercoraria is a widely distributed species in high-altitude regions of the Northern Hemisphere. It plays important roles as a decomposer, predator, and pollinator in the ecosystem. As a staple model organism, S. stercoraria serves as a standard test species for assessing the toxicity of drug residues in livestock dung and has been the focus of numerous studies. The genetic mechanisms underlying the ecological adaptability of S. stercoraria remain poorly understood. To fill the gap, we first assembled a high-quality chromosome-level genome of S. stercoraria, resulting in a final assembly size of 549.64 Mb, with a contig N50 of 4.06 Mb, and 92.53 % of the sequence anchored to six chromosomes. Gene family analysis revealed an expansion of Toll (Toll1), GNBP3, Cyp303a1, Cyp4d14, Cyp6g1, OR67d, and yolk protein genes in the S. stercoraria genome. Transcriptome analysis indicated that most genes in the trypsin and carboxypeptidase gene families are predominantly expressed during the larval stage, whereas the α-Amylase gene family is mainly expressed during the adult stage. Additionally, PGRP-SC is highly expressed during the larval stage, OBPs are primarily expressed during the adult stage, and yolk protein genes exhibit female-biased expression. Our study not only provides a new resource for the dung flies genomic pool, but also identifies the expression patterns of key ecologically adaptative genes and gene families at the developmental stages, which provides new insights into the ecological adaptive evolution of dung flies., Competing Interests: Declaration of competing interest The authors have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The inwardly rectifying K + channel K ir 5.1 ( Kcnj16 ) is essential in renal salt handling and blood pressure control. However, the underlying mechanisms are not fully understood. Here, we integrated transcriptomics and metabolomics to comprehensively profile the changes in genes and metabolites in the Dahl salt-sensitive (SS) rat lacking Kcnj16 to identify potential mechanisms. Consistent with the phenotype of knockout (KO) rats, the transcriptomic profile predicted reduced blood pressure, kidney damage, and increased ion transport. Canonical pathway analysis suggested activation of metabolic-related pathways while suppression of immune response-related pathways in KO rats. Untargeted metabolomic analysis revealed different metabolic profiles between wild-type (WT) and KO rats. Integration of transcriptomic and metabolomic profiles suggested altered tricarboxylic acid (TCA) cycle, amino acid metabolism, and reactive oxygen species (ROS) metabolism that are related to SS hypertension. In conclusion, besides increased ion transport, our data suggest suppressed immune response-related and altered metabolic-related pathways of SS rats lacking K ir 5.1., Competing Interests: The authors declare no competing interests.

Objective: Under the guidance of model organism Caenorhabditis elegans with fine olfactory system, small molecular metabolites sensitive to high dose radiation were screened as biomarkers of acute radiation-induced injury, and their metabolic pathways were elucidated by enrichment. Methods: Rats were irradiated with 12 ​Gy γ-rays to establish an acute radiation injury model, and their urine was fingerprinted using UPLC-Q/TOF-MS. Further, under the guidance of Caenorhabditis elegans as olfactory-sensitive model organism, the key differential metabolites in urine were found as biomarkers of radiation-induced injury. Results: After rats were irradiated, the radiation injury urine showed a difference from control (sham-irradiated) urine, which could be distinguished by Caenorhabditis elegans. Based on metabolomics analysis, a total of 21 key differential metabolites with P value ​2 or

Untargeted metabolomics studies are unbiased but identifying the same feature across studies is complicated by environmental variation, batch effects, and instrument variability. Ideally, several studies that assay the same set of metabolic features would be used to select recurring features to pursue for identification. Here, we developed an anchored experimental design. This generalizable approach enabled us to integrate three genetic studies consisting of 14 test strains of Caenorhabditis elegans prior to the compound identification process. An anchor strain, PD1074, was included in every sample collection, resulting in a large set of biological replicates of a genetically identical strain that anchored each study. This enables us to estimate treatment effects within each batch and apply straightforward meta-analytic approaches to combine treatment effects across batches without the need for estimation of batch effects and complex normalization strategies. We collected 104 test samples for three genetic studies across six batches to produce five analytical datasets from two complementary technologies commonly used in untargeted metabolomics. Here, we use the model system C. elegans to demonstrate that an augmented design combined with experimental blocks and other metabolomic QC approaches can be used to anchor studies and enable comparisons of stable spectral features across time without the need for compound identification. This approach is generalizable to systems where the same genotype can be assayed in multiple environments and provides biologically relevant features for downstream compound identification efforts. All methods are included in the newest release of the publicly available SECIMTools based on the open-source Galaxy platform.

Summary: Age-related diseases are major concern in developed countries. To avoid disabilities that accompany increased lifespan, pharmaceutical approaches are considered. Therefore, appropriate animal models are required for a better understanding of aging processes and potential in vivo assays to evaluate the impact of molecules that may delay the occurrence of age-related diseases. Few mouse models exhibiting pathological aging exist, but currently, none of them reproducibly mimics human diseases like osteoporosis, cognitive dysfunctions or sarcopenia that can be seen in some, but not all, elders. Here, we describe the premature aging phenotypes of Dicer-deficient mature animals, which exhibit an overall deterioration of many organs and tissues (skin, heart, and adipose tissue) ultimately leading to a significant reduction of their lifespan. Molecular characterization of transcriptional responses focused on the adipose tissue suggested that both canonical and non-canonical functions of DICER are involved in this process and highlight potential actionable pathways to revert it.

Summary: Classical swine fever virus (CSFV), a classic swine fever pathogen, causes severe economic losses worldwide. Poly (rC)-binding protein 1 (PCBP1), which interacts with Npro of CSFV, plays a vital role in CSFV growth. We are the first to report the generation of PCBP1-deficient pigs via gene-editing technology. The PCBP1-deficient pigs exhibited normal birth weight and reproductive-performance traits and developed normally. Viral challenge experiments indicated that primary cells isolated from F0- and F1-generation pigs exhibited significantly reduced CSFV infection. Additional mechanistic exploration further confirmed that the PCBP1 deficiency-mediated antiviral effect is related to the activation of type I interferon (IFN). Besides showing that a gene-editing strategy could be used to generate PCBP1-deficient pigs, our study introduces a valuable animal model for further investigating the infection mechanisms of CSFV that will help to develop better antiviral solutions.

Summary: The disintegrin and metalloproteinase Adam10 is a membrane-bound sheddase that regulates Notch signaling and ensures epidermal integrity. To address the function of Adam10 in the continuously growing incisors, we used Keratin14Cre/+;Adam10fl/fl transgenic mice, in which Adam10 is conditionally deleted in the dental epithelium. Keratin14Cre/+;Adam10fl/fl mice exhibited severe abnormalities, including defective enamel formation reminiscent of human enamel pathologies. Histological analyses of mutant incisors revealed absence of stratum intermedium, and severe disorganization of enamel-secreting ameloblasts. In situ hybridization and immunostaining analyses in the Keratin14Cre/+;Adam10fl/fl incisors showed strong Notch1 downregulation in dental epithelium and ectopic distribution of enamel-specific molecules, including ameloblastin and amelogenin. Lineage tracing studies using Notch1CreERT2;R26mT/mG mice demonstrated that loss of the stratum intermedium cells was due to their fate switch toward the ameloblast lineage. Overall, our data reveal that in the continuously growing incisors the Adam10/Notch axis controls dental epithelial cell boundaries, cell fate switch and proper enamel formation.

Regulation of inflammation is a critical process for maintaining physiological homeostasis. The λ-carrageenan (λ-CGN) is a mucopolysaccharide extracted from the cell wall of red algae (Chondrus crispus) capable of inducing acute intestinal inflammation, which is translated into the production of acute phase reactants secreted into the blood circulation. However, the associated mechanisms in vertebrates are not well understood. Here, we investigated the crucial factors behind the inflammatory milieu of λ-CGN-mediated inflammation administered at 0, 1.75, and 3.5% (v/w) by i.p. injection into the peritoneal cavity of adult zebrafish (ZF) (Danio rerio). We found that polymorphonuclear leukocytes (neutrophils) and lymphocytes infiltrating the ZF peritoneal cavity had short-term persistence. Nevertheless, they generate a strong pattern of inflammation that affects systemically and is enough to produce edema in the cavity. Consistent with these findings, cell infiltration, which causes notable tissue changes, resulted in the overexpression of several acute inflammatory markers at the protein level. Using reversed-phase high-performance liquid chromatography followed by a hybrid linear ion-trap mass spectrometry shotgun proteomic approach, we identified 2938 plasma proteins among the animals injected with PBS and 3.5% λ-CGN. First, the bioinformatic analysis revealed the composition of the plasma proteome. Interestingly, 72 commonly expressed proteins were recorded among the treated and control groups, but, surprisingly, 2830 novel proteins were differentially expressed exclusively in the λ-CGN-induced group. Furthermore, from the commonly expressed proteins, compared to the control group 62 proteins got a significant (p < 0.05) upregulation in the λ-CGN-treated group, while the remaining ten proteins were downregulated. Next, we obtained the major protein-protein interaction networks between hub protein clusters in the blood plasma of the λ-CGN induced group. Moreover, to understand the molecular underpinnings of these effects based on the unveiled protein sets, we performed a bioinformatic structural similarity analysis and generated overlapping 3D reconstructions between ZF and humans during acute inflammation. Biological pathway analysis pointed to the activation and abundance of diverse classical immune and acute phase reactants, several catalytic enzymes, and varied proteins supporting the immune response. Together, this information can be used for testing and finding novel pharmacological targets to treat human intestinal inflammatory diseases.

Summary: Idiopathic scoliosis (IS) refers to abnormal spinal curvatures that occur in the absence of vertebral or neuromuscular defects. IS accounts for 80% of human spinal deformity, afflicts ∼3% of children worldwide, yet pathogenic mechanisms are poorly understood. A key role for cerebrospinal fluid (CSF) homeostasis in zebrafish spine development has been identified. Specifically, defects in cilia motility of brain ependymal cells (EC), CSF flow, and/or Reissner fiber (RF) assembly are observed to induce neuroinflammation, oxidative stress, abnormal CSF-contacting neuron activity, and urotensin peptide expression, all associating with scoliosis. However, the functional relevance of these observations to IS remains unclear. Here we characterize zebrafish katnb1 mutants as a new IS model. We define essential roles for Katnb1 in motile ciliated lineages, uncouple EC cilia and RF formation defects from spinal curvature, and identify abnormal CSF flow and cell stress responses as shared pathogenic signatures associated with scoliosis across diverse zebrafish models.

In vitro systems have been mainly promoted by authorities to sustain research by following the 3Rs principle, but continuously increasing amounts of evidence point out that in vivo experimentation is also of extreme relevance. Xenopus laevis, an anuran amphibian, is a significant model organism in the study of evolutionary developmental biology, toxicology, ethology, neurobiology, endocrinology, immunology and tumor biology; thanks to the recent development of genome editing, it has also acquired a relevant position in the field of genetics. For these reasons, X. laevis appears to be a powerful and alternative model to the zebrafish for environmental and biomedical studies. Its life cycle, as well as the possibility to obtain gametes from adults during the whole year and embryos by in vitro fertilization, allows experimental studies of several biological endpoints, such as gametogenesis, embryogenesis, larval growth, metamorphosis and, of course, the young and adult stages. Moreover, with respect to alternative invertebrate and even vertebrate animal models, the X. laevis genome displays a higher degree of similarity with that of mammals. Here, we have reviewed the main available literature on the use of X. laevis in the biosciences and, inspired by Feymann’s revised view, “Plenty of room for biology at the bottom”, suggest that X. laevis is a very useful model for all possible studies.

Eusocial bumble and honey bees are important pollinators for global ecology and the agricultural economy. Although both the bumble and honey bees possess similar and host‐restricted gut microbiota, they differ in aspects of morphology, autonomy, physiology, behavior, and life cycle. The social bee gut bacteria exhibit host specificity that is likely a result of long‐term co‐evolution. The unique life cycle of bumblebees is key for the acquisition and development of their gut microbiota, and affects the strain‐level diversity of the core bacterial species. Studies on bumblebee gut bacteria show that they retain less functional capacity for carbohydrate metabolism compared with that of the honeybee. We discuss the potential roles of the bumblebee gut microbiota against pathogenic threats and the application of host‐specific probiotics for bumblebees. Given the advantages of the bumblebee microbiome, including the simple structure and host specificity, and the ease of manipulating bumblebee colonies, we propose that bumblebees may provide a valuable system for understanding the general principles of host–microbe interactions, gut–brain axis, and vertical transmission. [ABSTRACT FROM AUTHOR]

Temperature drives performance and therefore adaptation; to interpret and understand these, thermal performance curves (TPC) are used, often through meta‐analyses, revealing trends across divergent taxa. Four discrete hypotheses—thermodynamic‐constraint; biochemical‐adaptation (hotter is not better); specialist‐generalist; thermal‐trade‐off—have arisen to explain cross‐phyletic trends. In contrast, detailed comparisons of closely related taxa are rare, yet trends arising from these should reveal mechanisms of adaptation, as taxa diverge. Here, we combine experimental work with TPC theory to assess if the current hypotheses apply equally to closely related taxa. We established TPC for six species (and two strains of one species) of the animal model Tetrahymena (Ciliophora)—characterized by SSU rDNA/COX1 sequences—by examining specific growth rate (r), size (V), production (P = rV), and metabolic rate (rV−0.25) across 15–20 temperatures. Using parameters derived from the mechanistic "Sharpe and DeMichele" function, we established a framework to test which hypothesis best represented the data. We conclude that superficially the "hotter is not better" hypothesis is best but argue that the mechanistic theory underlying it cannot apply at the genus level: trends are likely to arise from little rather than substantial adaptation. Our further analysis suggests: (1) upward shift in the maximum‐functioning temperature (Tmax) is more constrained than the optimal temperature (Topt), leading to a decreased safety margin (Topt−Tmax) and suggesting that species initially succeed in warmer environments through an increase in Topt, followed by increasing Tmax; and (2) thermal performance traits are correlated with phylogeny for closely related species, suggesting that species gradually adapt to new thermal environments. [ABSTRACT FROM AUTHOR]

The growing use of genomics in diverse organisms provides the basis for identifying genomic and transcriptional differences across species and experimental conditions. Databases containing genomic and functional data have played critical roles in the development of numerous genetic models but most emerging models lack such databases. The Mexican tetra, Astyanax mexicanus exists as 2 morphs: surface-dwelling and cave-dwelling. There exist at least 30 cave populations, providing a system to study convergent evolution. We have generated a web-based analysis suite that integrates datasets from different studies to identify how gene transcription and genetic markers of selection differ between populations and across experimental contexts. Results of diverse studies can be analyzed in conjunction with other genetic data (e.g. Gene Ontology information), to enable biological inference from cross-study patterns and identify future avenues of research. Furthermore, the framework that we have built for A. mexicanus can be adapted for other emerging model systems. [ABSTRACT FROM AUTHOR]

Lipidomics analysis of zebrafish tissues has shown promising results to understand disease‐related outcomes of exposure to toxic substances at a molecular level. However, knowledge about their lipidome is limited, as most untargeted studies only identify the lipids that are statistically significant in their setup. In this work, liquid chromatography‐high resolution mass spectrometry was used to study different aspects of the analytical workflow, that is, extraction solvents (methanol/chloroform/water (3/2/2, v/v/v), methanol/dichloromethane/water (2/3/2, v/v/v) and methanol/methyl‐tert‐butyl ether/water (3/10/2.5, v/v/v), instrumental response, and strategies used for lipid annotation. The number of high‐quality features (relative standard deviation of the intensity values ≤ 10% in the range 103−107 counts) was affected by the dilution of lipid extracts, indicating that it is an important parameter for developing untargeted methods. The workflows used allowed the selection of a dilution factor to annotate 712 lipid species (507 bulk lipids) in zebrafish liver using four software (LipidMatch, LipidHunter, MS‐DIAL, and Lipostar). Retention time mapping was a valuable tool to filter lipid annotations obtained from automatic software annotations. The lipid profiling of zebrafish livers will help in a better understanding of the true constitution of their lipidome at the species level, as well as in the use of zebrafish in toxicological studies. [ABSTRACT FROM AUTHOR]

Sepiolidae (Cephalopoda: Sepiolida) are growing in popularity as model organisms, not least because of their well-studied symbiotic relationship with light producing bacteria. Their easy maintenance and cultivation requirements in captivity have further facilitated their use in a wide range of developmental, anatomical, neurophysiological, behavioural and genetic studies, exhibiting promising opportunities for these cephalopods in research. Considering the rising interest in sepiolids, a detailed overview of their behavioural ecology is necessary to understand their evolution and conservation, as well as to aid establishment of good welfare practice when held in captivity. To date, not all aspects of the sepiolid ecology have been investigated in detail, and our current knowledge of their behavioural ecology is, for the most part, restricted to descriptions from less than 10 of the approximately 80 species, occasionally resulting in a generalisation of specific observations across species, genera, or even subfamilies. This review summarises current knowledge on sepiolid behavioural ecology and life history, including discussions on their habitat, life span, activity patterns, hunting and feeding behaviour, anti-predator behaviour, burying behaviour, and reproductive behaviour. Moreover, future directions as well as areas of interest for upcoming research studies are highlighted. [ABSTRACT FROM AUTHOR]

Background: Hox genes are key regulators of appendage development in the insect body plan. The body plan of mayfly (Ephemeroptera) nymphs differs due to the presence of abdominal appendages called gills. Despite mayflies' phylogenetic position in Paleoptera and novel morphology amongst insects, little is known of their developmental genetics, such as the appendage-regulating Hox genes. To address this issue we present an annotated, early instar transcriptome and embryonic expression profiles for Antennapedia, Ultrabithorax, and Abdominal A proteins in the mayfly Hexagenia limbata, identify putative Hox protein sequences in the mayflies H. limbata, Cloeon dipterum, and Ephemera danica, and describe the genomic organization of the Hox gene cluster in E. danica. Results: Transcriptomic sequencing of early instar H. limbata nymphs yielded a high-quality assembly of 83,795 contigs, of which 22,975 were annotated against Folsomia candida, Nilaparvata lugens, Zootermopsis nevadensis and UniRef90 protein databases. Homeodomain protein phylogeny and peptide annotations identified coding sequences for eight of the ten canonical Hox genes (excluding zerknüllt/Hox3 and fushi tarazu) in H. limbata and C. dipterum, and all ten in E. danica. Mayfly Hox protein sequences and embryonic expression patterns of Antp, Ubx, and Abd-A appear highly conserved with those seen in other non-holometabolan insects. Similarly, the genomic organization of the Hox cluster in E. danica resembles that seen in most insects. Conclusions: We present evidence that mayfly Hox peptide sequences and the embryonic expression patterns for Antp, Ubx, and Abd-A are extensively conserved with other insects, as is organization of the mayfly Hox gene cluster. The protein data suggest mayfly Antp, Ubx, and Abd-A play appendage promoting and repressing roles during embryogenesis in the thorax and abdomen, respectively, as in other insects. The identified expression of eight Hox genes, including Ubx and abd-A, in early instar nymphs further indicates a post-embryonic role, possibly in gill development. These data provide a basis for H. limbata as a complementary Ephemeridae model to the growing repertoire of mayfly model species and molecular techniques. [ABSTRACT FROM AUTHOR]

During the past three decades, mice, zebrafish, fruit flies, and Caenorhabditis elegans have been the primary model organisms used for the study of various biological phenomena. These models have also been adopted and developed to investigate the physiological roles of carbonic anhydrases (CAs) and carbonic anhydrase-related proteins (CARPs). These proteins belong to eight CA families and are identified by Greek letters: α, β, γ, δ, ζ, η, θ, and ι. Studies using model organisms have focused on two CA families, α-CAs and β-CAs, which are expressed in both prokaryotic and eukaryotic organisms with species-specific distribution patterns and unique functions. This review covers the biological roles of CAs and CARPs in light of investigations performed in model organisms. Functional studies demonstrate that CAs are not only linked to the regulation of pH homeostasis, the classical role of CAs, but also contribute to a plethora of previously undescribed functions. [ABSTRACT FROM AUTHOR]

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Neuroscience lacks a diverse repertoire of model organisms, resulting in an incomplete understanding of the general principles of neural function. Ctenophores display many neurobiological and experimental features which make them a promising candidate to fill this gap. They possess a nerve net distributed across their body surface in the epithelial layer. There is a long‐held assumption that nerve nets are "simple" and lack distinct organizational principles. We want to challenge this assumption and determine how stereotyped the structure of this network is. We estimated body surface area in Pleurobrachia pileus using custom optical projection tomography and light sheet morphometry imaging systems. Using an antibody against tyrosinated α‐tubulin, we visualized the nerve net in situ and quantified the geometric properties using an automated segmentation approach. We characterized organizational rules of the epithelial nerve net in animals of different sizes and at different regions of the body. We found that specific morphological features within the nerve net are largely unchanged during growth. These properties must be essential to the functionality of the nervous system and therefore are maintained during a change in body size. We have also established the principles of organization of the network and showed that some of the geometric properties are variable across different parts of the body. This suggests that there may be different functions occurring in regions with different structural characteristics. This is the most comprehensive structural description of a ctenophore nerve net to date and demonstrates the amenability of P. pileus for whole organism network analysis. [ABSTRACT FROM AUTHOR]

Despite its limitations, Drosophila shall be a promising complementary model system to explore vector competence, parasites biology and their related behaviors inside the vector, and hopefully at the same time might provide a glimpse of evidence for uncharted antiparasitic immunity of the metazoan host. Keywords: fruit fly; model organism; infection; parasite biology; drug discovery; drug repurposing EN fruit fly model organism infection parasite biology drug discovery drug repurposing 1 4 4 06/07/22 20220602 NES 220602 Introduction In the past decades, insect vector-borne parasitic diseases (VBDs), such as malaria, leishmaniasis, and lymphatic filariasis, have caused a devastating health problem, threatening for over 250 million lives worldwide ([22]). Infection, drug discovery, drug repurposing, fruit fly, model organism, parasite biology. [Extracted from the article]

Science popularisation festivals attract more and more people every year, showing that there is a need to satisfy public curiosity. Such events are good occasions to disseminate knowledge to a large audience. The results of scientific research bring advances for mankind. Since research mostly depends on public funds, it is important to gain understanding and support for it. Scientists are also responsible for educating people in important aspects of science. In a wider perspective, science popularisation may be relevant to influencing decision-making government agencies e.g. regarding legislation about the use of animals in biomedical research. In this paper, we present one of the approaches to knowledge dissemination, namely the independent educational project, which has a more flexible formula, and may give more benefits than science festivals. Based on our experience in implementing educational projects connected with biology, we provide examples of the workflow of such a project and some useful tips. We show some quantitative data underlining the significant educational effect of this specific approach. Science popularisation in this form not only provides significant benefits both for the participants and the tutor, such as satisfaction and inspiration, but also a well-heard voice in public debate and/or useful preliminary experimental research results. [ABSTRACT FROM AUTHOR]

Freshwater salinization is a global ecological concern because of the alarming biodiversity declines associated with increases in major ion concentrations. Loss of mayfly diversity appears to be a common ecological response to anthropogenic salinization worldwide. Remarkably few regulatory standards exist to protect aquatic life from major ions, and antiquated approaches for setting such standards rely on traditional laboratory toxicity tests, which do not address sensitivities of mayflies at different larval stages. The lab-reared mayfly Neocloeon triangulifer (McDunnough, 1931) has emerged as one of the very few useful aquatic insect models for studying the effects of environmental stressors, including salinity, in the laboratory. Here, we asked if different larval life stages are differentially sensitivity to ion concentrations by conducting traditional 96-h toxicity tests with NaCl, CaCl2, and Ca/MgSO4. We used a general linear model to determine if survivorship differed among larval stages as well as ion type and concentration. We also calculated median lethal concentrations (LC50) for each larval stage. Larval sensitivity to NaCl decreased slightly with age (2–6, 9–13, and 17–21 d, with LC50 values of 401, 441, and 570 mg/L, respectively, when expressed as Na concentrations). Similarly, larval sensitivity to Ca/MgSO4 differed slightly among age groups (LC50 = 748, 1503, and 1439 mg/L, respectively, when expressed as SO4 concentrations). Reliable confidence intervals on LC50 values for CaCl2 could not be calculated because of high survivorship. However, our general linear model revealed that age played a moderate role in survival (p = 0.0065) across all salts of interest. To assess the potential changes in ion flux between larval stages, we used radiotracers (22Na, 35SO4, or 45Ca) in 18- and 25-d-old larvae and found no strong differences in ion uptake rates. We also qualitatively examined morphological differences between larval life stages, including the appearance of gills and number of ionocytes. Our results indicate that younger N. triangulifer larvae may be more sensitive to major ions than mature larvae. These results should be considered when experimentally using larger, late-stage N. triangulifer larvae to study the physiological effects and acute toxicity of salinity. [ABSTRACT FROM AUTHOR]

African trypanosomes are early branching protists that cause human and animal diseases, termed trypanosomiases. They have been under intensive study for more than 100 years and have contributed significantly to our understanding of eukaryotic biology. The combination of conserved and parasite‐specific features mean that their flagellum has gained particular attention. Here, we discuss the different structural features of the flagellum and their role in transmission and virulence. We highlight the possibilities of targeting flagellar function to cure trypanosome infections and help in the fight to eliminate trypanosomiases. [ABSTRACT FROM AUTHOR]

With a century-old history of fundamental discoveries, the fruit fly has long been a favored experimental organism for a wide range of scientific inquiries. But Drosophila is not a "legacy" model organism; technical and intellectual innovations continue to revitalize fly research and drive advances in our understanding of conserved mechanisms of animal biology. Here, we provide an overview of this "ecosystem" and discuss how to address emerging challenges to ensure its continued productivity. Drosophila researchers are fortunate to have a sophisticated and ever-growing toolkit for the analysis of gene function. Access to these tools depends upon continued support for both physical and informational resources. Uncertainty regarding stable support for bioinformatic databases is a particular concern, at a time when there is the need to make the vast knowledge of functional biology provided by this model animal accessible to scientists studying other organisms. Communication and advocacy efforts will promote appreciation of the value of the fly in delivering biomedically important insights. Well-tended traditions of large-scale tool development, open sharing of reagents, and community engagement provide a strong basis for coordinated and proactive initiatives to improve the fly research ecosystem. Overall, there has never been a better time to be a fly pusher.

Summary: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with high genetic heterogeneity, affecting one in 44 children in the United States. Recent genomic sequencing studies from autistic human individuals indicate that PARK2, a gene that has long been considered in the pathogenesis of Parkinson's disease, is involved in ASD. Here, we report that Prkn knockout (KO) mice demonstrate autistic-like behaviors including impaired social interaction, elevated repetitive behaviors, and deficits in communication. In addition, Prkn KO mice show reduced neuronal activity in the context of sociability in the prelimbic cortex. Cell morphological examination of layer 5 prelimbic cortical neurons shows a reduction in dendritic arborization and spine number. Furthermore, biochemistry and immunocytochemistry analyses reveal alterations in synapse density and the molecular composition of synapses. These findings indicate that Prkn is implicated in brain development and suggest the potential use of the Prkn KO mouse as a model for autism research.

Computing phenotypic similarity helps identify new disease genes and diagnose rare diseases. Genotype–phenotype data from orthologous genes in model organisms can compensate for lack of human data and increase genome coverage. In the past decade, cross-species phenotype comparisons have proven valuble, and several ontologies have been developed for this purpose. The relative contribution of different model organisms to computational identification of disease-associated genes is not fully explored. We used phenotype ontologies to semantically relate phenotypes resulting from loss-of-function mutations in model organisms to disease-associated phenotypes in humans. Semantic machine learning methods were used to measure the contribution of different model organisms to the identification of known human gene–disease associations. We found that mouse genotype–phenotype data provided the most important dataset in the identification of human disease genes by semantic similarity and machine learning over phenotype ontologies. Other model organisms' data did not improve identification over that obtained using the mouse alone, and therefore did not contribute significantly to this task. Our work impacts on the development of integrated phenotype ontologies, as well as for the use of model organism phenotypes in human genetic variant interpretation. This article has an associated First Person interview with the first author of the paper.

Environmental pollution is a global concern because of its associated risks to human health and ecosystem. The bio-monitoring of environmental health has attracted much attention in recent years and efforts to minimize environmental contamination as well as to delineate toxicological mechanisms related to toxic exposure are essential to improve the health conditions of both humans and animals. This review aims to substantiate the need and advantages in utilizing cockroaches as a complementary, non-mammalian model to further understand the noxious impact of environmental contaminants on humans and animals. We discuss recent advances in neurotoxicology, immunotoxicology, reproductive and developmental toxicology, environmental forensic entomotoxicology, and environmental toxicology that corroborate the utility of the cockroach (Periplaneta americana, Blaptica dubia, Blattella germanica and Nauphoeta cinerea) in addressing toxicological mechanisms as well as a sensor of environmental pollution. Indeed, recent improvements in behavioural assessment and the detection of potential biomarkers allow for the recognition of phenotypic alterations in cockroaches following exposure to toxic chemicals namely saxitoxin, methylmercury, polychlorinated biphenyls, electromagnetic fields, pharmaceuticals, polycyclic aromatic hydrocarbon, chemical warfare agents and nanoparticles. The review provides a state-of-the-art update on the current utility of cockroach models in various aspects of toxicology as well as discusses the potential limitations and future perspectives.

Summary: Recent studies showed that SARS-CoV-2 can infect adult human pancreas and trigger pancreatic damage. Here, using human fetal pancreas samples and 3D differentiation of human pluripotent cells into pancreatic endocrine cells, we determined that SARS-CoV-2 receptors ACE2, TMPRSS2, and NRP1 are expressed in precursors of insulin-producing pancreatic β-cells, rendering them permissive to SARS-CoV-2 infection. We also show that SARS-CoV-2 enters and undergoes efficient replication in human multipotent pancreatic and endocrine progenitors in vitro. Moreover, we investigated mechanisms by which SARS-CoV-2 enters pancreatic cells, and found that ACE2 mediates the entry, while NRP1 and TMPRSS2 do not. Surprisingly, we found that in pancreatic progenitors, SARS-CoV-2 enters cells via cathepsin-dependent endocytosis, which is a different route than in respiratory tract. Therefore, pancreatic spheroids might serve as a model to study candidate drugs for endocytosis-mediated viral entry inhibition and to investigate whether SARS-CoV-2 infection may affect pancreas development, possibly causing lifelong health consequences.

Of all the non-human primate species studied by researchers, the rhesus macaque (Macaca mulatta) is likely the most widely used across biological disciplines. Rhesus macaques have thrived during the Anthropocene and now have the largest natural range of any non-human primate. They are highly social, exhibit marked genetic diversity, and display remarkable niche flexibility (which allows them to live in a range of habitats and survive on a variety of diets). These characteristics mean that rhesus macaques are well-suited for understanding the links between sociality, health and fitness, and also for investigating intra-specific variation, adaptation and other topics in evolutionary ecology.

Hundreds of millions of people worldwide are infected by various species of parasitic flatworms. Without treatment, acute and chronical infections frequently lead to the development of severe pathologies and even death. Emerging data on a decreasing eff iciency of some important anthelmintic compounds and the emergence of resistance to them force the search for alternative drugs. Parasitic flatworms have complex life cycles, are laborious and expensive in culturing, and have a range of anatomic and physiological adaptations that complicate the application of standard molecular-biological methods. On the other hand, free-living flatworm species, evolutionarily close to parasitic flatworms, do not have the abovementioned diff iculties, which makes them potential alternative models to search for and study homologous genes. In this review, we describe the use of the basal free-living flatworm Macrostomum lignano as such a model. M. lignano has a number of convenient biological and experimental properties, such as fast reproduction, easy and non-expensive laboratory culturing, optical body transparency, obligatory sexual reproduction, annotated genome and transcriptome assemblies, and the availability of modern molecular methods, including transgenesis, gene knockdown by RNA interference, and in situ hybridization. All this makes M. lignano amenable to the most modern approaches of forward and reverse genetics, such as transposon insertional mutagenesis and methods of targeted genome editing by the CRISPR/Cas9 system. Due to the availability of an increasing number of genome and transcriptome assemblies of different parasitic flatworm species, new knowledge generated by studying M. lignano can be easily translated to parasitic f latworms with the help of modern bioinformatic methods of comparative genomics and transcriptomics. In support of this, we provide the results of our bioinformatics search and analysis of genes homologous between M. lignano and parasitic flatworms, which predicts a list of promising gene targets for subsequent research.

Today, Alzheimer’s disease (AD)—the most common neurodegenerative disorder, which affects 50 million people—remains incurable. Several studies suggest that one of the main pathological hallmarks of AD is the accumulation of abnormal amyloid beta (Aβ) aggregates; therefore, many therapeutic approaches focus on anti-Aβ aggregation inhibitors. Taking into consideration that plant-derived secondary metabolites seem to have neuroprotective effects, we attempted to assess the effects of two flavones—eupatorin and scutellarein—on the amyloidogenesis of Aβ peptides. Biophysical experimental methods were employed to inspect the aggregation process of Aβ after its incubation with each natural product, while we monitored their interactions with the oligomerized Aβ through molecular dynamics simulations. More importantly, we validated our in vitro and in silico results in a multicellular organismal model—namely, Caenorhabditis elegans—and we concluded that eupatorin is indeed able to delay the amyloidogenesis of Aβ peptides in a concentration-dependent manner. Finally, we propose that further investigation could lead to the exploitation of eupatorin or its analogues as potential drug candidates.

Simple Summary: The standardization of husbandry conditions, feeding regimens, and diets is the prerequisite for the comparability of results generated by the use of laboratory animals. Compared to rodents, which account for the largest proportion of laboratory animals worldwide, standardization is still inadequate for aquatic species, especially clawed frogs (Xenopus laevis). In this context, species-specific feeding is important for standardization and animal health and welfare. However, the current feeding recommendations for Xenopus are extrapolated from other species' nutrient requirements. In addition, the feeding regimen itself affects animal behavior. In particular, the feed intake seems to be influenced by the type of feed. Using a questionnaire, the most common methods of husbandry and feeding of Xenopus laevis in laboratory settings were recorded, and the feeds were compared to the recommendations by Ferrie. The results showed variations with regard to husbandry and feeding concepts between facilities. Commercial Xenopus diets and fish feed were the most commonly used feeds, all meeting the recommendation for protein content but differing considerably in mineral content (based on labelled information). It appears that the feed composition and feeding regimen need to be the focus of further research to ensure that feeding and husbandry are adapted to nutritional and behavioral needs. African clawed frogs are common animal models used in various research areas. However, husbandry and especially feeding regimens are not nearly as standardized as is established for other laboratory animals. We recorded the diets and feeding protocols commonly used in laboratory practice in a questionnaire (18 responses). The survey revealed a wide variety of housing conditions. Feeding protocols and, in particular, diet composition varied considerably between facilities. While diets tailored to Xenopus were used in the majority, differences in feeding frequency and dietary components were noted. From five responses, the weekly feed intake per frog could be calculated, showing considerable differences in dry matter intake (1.37–5.4 g). The labelled nutrient content of the diets fed in the facilities (n = 10) met the recommendations in most cases, with protein as the major energy source. However, the mineral content varied markedly between diets. Both floating and sinking diets were used, while quickly sinking diets were associated with feed leftovers. Feed processing may likely influence feed intake behavior. Further research is needed to ensure standardization for aquatic species with respect to husbandry systems, feeding regimens, and especially the nutrient composition of feeds. Furthermore, this work will contribute positively to animal welfare and the comparability of research results. [ABSTRACT FROM AUTHOR]