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International Journal For Parasitology.... Apr 2024Transmission of spp. in life cycles that involve mainly wildlife is well recognized for those species with small mammals as intermediate hosts (e. g. ), as well as for... (Review)
Review
Transmission of spp. in life cycles that involve mainly wildlife is well recognized for those species with small mammals as intermediate hosts (e. g. ), as well as for and the 'northern' genotypes of (G8 and G10). In contrast, the remaining taxa of sensu lato are best known for their domestic life cycles, and the numerous wild mammal species (mainly ungulates) that have been recorded with cystic echinococcosis in the past were mainly considered a result of spill-over from the dog-livestock transmission system. This view was challenged with the advent of molecular characterization, allowing discrimination of the metacestodes, although the contribution of wild mammals to various life cycles has remained uncertain for scarcity of wildlife studies. Numerous records of cysts in wild ungulates date back to the 20th century, but cannot with certainty be allocated to the species and genotypes that are recognized today. This means that our current knowledge is largely restricted to studies of the past two decades that kept adding gradually to our concepts of transmission in various geographic regions. In particular, new insights were gathered in the past years on s.l. in wildlife of sub-Saharan Africa, but also on transmission patterns of in previously neglected regions, e. g. North America. Here, an update is provided on the current state of knowledge on wild mammals as hosts for all species, listing >150 species of wild hosts with references, as well as estimates on their epidemiological impact and our current gaps of knowledge.
PubMed: 38405672
DOI: 10.1016/j.ijppaw.2024.100913 -
Frontiers in Immunology 2023RNA interference (RNAi) plays pleiotropic roles in animal cells, from the post-transcriptional control of gene expression via the production of micro-RNAs, to the... (Review)
Review
RNA interference (RNAi) plays pleiotropic roles in animal cells, from the post-transcriptional control of gene expression via the production of micro-RNAs, to the inhibition of RNA virus infection. We discuss here the role of RNAi in regulating the expression of self RNAs, and particularly transposable elements (TEs), which are genomic sequences capable of influencing gene expression and disrupting genome architecture. Dicer proteins act as the entry point of the RNAi pathway by detecting and degrading RNA of TE origin, ultimately leading to TE silencing. RNAi similarly targets cellular RNAs such as repeats transcribed from centrosomes. Dicer proteins are thus nucleic acid sensors that recognize self RNA in the form of double-stranded RNA, and trigger a silencing RNA interference response.
Topics: Animals; RNA Interference; RNA, Small Interfering; DNA Transposable Elements; RNA, Double-Stranded; Mammals
PubMed: 37475864
DOI: 10.3389/fimmu.2023.1212086 -
Aging Cell Nov 2023Although immunosenescence may result in increased morbidity and mortality, many mammals have evolved effective immune coping strategies to extend their lifespans. Thus,...
Although immunosenescence may result in increased morbidity and mortality, many mammals have evolved effective immune coping strategies to extend their lifespans. Thus, the immune systems of long-lived mammals present unique models to study healthy longevity. To identify the molecular clues of anti-immunosenescence, we first built high-quality reference genome for a long-lived myotis bat, and then compared three long-lived mammals (i.e., bat, naked mole rat, and human) versus the short-lived mammal, mouse, in splenic immune cells at single-cell resolution. A close relationship between B:T cell ratio and immunosenescence was detected, as B:T cell ratio was much higher in mouse than long-lived mammals and significantly increased during aging. Importantly, we identified several iron-related genes that could resist immunosenescence changes, especially the iron chaperon, PCBP1, which was upregulated in long-lived mammals but dramatically downregulated during aging in all splenic immune cell types. Supportively, immune cells of mouse spleens contained more free iron than those of bat spleens, suggesting higher level of ROS-induced damage in mouse. PCBP1 downregulation during aging was also detected in hepatic but not pulmonary immune cells, which is consistent with the crucial roles of spleen and liver in organismal iron recycling. Furthermore, PCBP1 perturbation in immune cell lines would result in cellular iron dyshomeostasis and senescence. Finally, we identified two transcription factors that could regulate PCBP1 during aging. Together, our findings highlight the importance of iron homeostasis in splenic anti-immunosenescence, and provide unique insight for improving human healthspan.
Topics: Humans; Animals; Mice; Immunosenescence; Chiroptera; Spleen; Aging; Mammals; Homeostasis
PubMed: 37681451
DOI: 10.1111/acel.13982 -
Clinical and Translational Medicine Oct 2023Background N6-methyladenosine (m6A), the most prevalent internal mRNA modification in eukaryotes, is added by m6A methyltransferases, removed by m6A demethylases and... (Review)
Review
Background N6-methyladenosine (m6A), the most prevalent internal mRNA modification in eukaryotes, is added by m6A methyltransferases, removed by m6A demethylases and recognised by m6A-binding proteins. This modification significantly influences carious facets of RNA metabolism and plays a pivotal role in cellular and physiological processes. Main body Pre-mRNA alternative splicing, a process that generates multiple splice isoforms from multi-exon genes, contributes significantly to the protein diversity in mammals. Moreover, the presence of crosstalk between m6A modification and alternative splicing, with m6A modifications on pre-mRNAs exerting regulatory control, has been established. The m6A modification modulates alternative splicing patterns by recruiting specific RNA-binding proteins (RBPs) that regulate alternative splicing or by directly influencing the interaction between RBPs and their target RNAs. Conversely, alternative splicing can impact the deposition or recognition of m6A modification on mRNAs. The integration of m6A modifications has expanded the scope of therapeutic strategies for cancer treatment, while alternative splicing offers novel insights into the mechanistic role of m6A methylation in cancer initiation and progression. Conclusion This review aims to highlight the biological functions of alternative splicing of m6A modification machinery and its implications in tumourigenesis. Furthermore, we discuss the clinical relevance of understanding m6A-dependent alternative splicing in tumour therapies.
Topics: Animals; Alternative Splicing; Neoplasms; RNA; Methylation; RNA, Messenger; RNA-Binding Proteins; Mammals
PubMed: 37850412
DOI: 10.1002/ctm2.1460 -
Current Opinion in Genetics &... Aug 2023X-chromosome inactivation (XCI) has evolved in mammals to compensate for the difference in X-chromosomal dosage between the sexes. In placental mammals, XCI is initiated... (Review)
Review
X-chromosome inactivation (XCI) has evolved in mammals to compensate for the difference in X-chromosomal dosage between the sexes. In placental mammals, XCI is initiated during early embryonic development through upregulation of the long noncoding RNA Xist from one randomly chosen X chromosome in each female cell. The Xist locus must thus integrate both X-linked and developmental trans-regulatory factors in a dosage-dependent manner. Furthermore, the two alleles must coordinate to ensure inactivation of exactly one X chromosome per cell. In this review, we summarize the regulatory principles that govern the onset of XCI. We go on to provide an overview over the factors that have been implicated in Xist regulation and discuss recent advances in our understanding of how Xist's cis-regulatory landscape integrates information in a precise fashion.
Topics: Pregnancy; Animals; Female; Placenta; X Chromosome Inactivation; X Chromosome; RNA, Long Noncoding; Mammals
PubMed: 37356341
DOI: 10.1016/j.gde.2023.102063 -
The Journal of Experimental Medicine Aug 2023There is unprecedented spread of highly pathogenic avian influenza A H5N1 viruses in bird species on five continents, and many reports of infections in mammals most...
There is unprecedented spread of highly pathogenic avian influenza A H5N1 viruses in bird species on five continents, and many reports of infections in mammals most likely resulting from consumption of infected birds. As H5N1 viruses infect more species, their geographical range increases and more viral variants are produced that could have new biological properties including adaptation to mammals and potentially to humans. This highlights the need to continually monitor and assess mammalian-origin H5N1 clade 2.3.4.4b viruses for the presence of mutations that could potentially increase their pandemic risk for humans. Fortunately, to date there have been a limited number of human cases, but infection of mammals increases the opportunity for the virus to acquire mutations that enhance efficient infection, replication, and spread in mammals, properties that have not been seen in these viruses in the past.
Topics: Animals; Humans; Influenza in Birds; Influenza A Virus, H5N1 Subtype; Pandemics; Influenza A virus; Birds; Mammals; Influenza, Human
PubMed: 37326966
DOI: 10.1084/jem.20230447 -
BioRxiv : the Preprint Server For... Jun 2023H5N1 highly pathogenic avian influenza viruses (HPAIV) emerged in wild birds in Chile in December 2022 and spilled over into poultry, marine mammals, and one human....
H5N1 highly pathogenic avian influenza viruses (HPAIV) emerged in wild birds in Chile in December 2022 and spilled over into poultry, marine mammals, and one human. Between December 9, 2022 - March 14, 2023, a coordinated government/academic response detected HPAIV by real-time RT-PCR in 8.5% (412/4735) of samples from 23 avian and 3 mammal orders. Whole-genome sequences obtained from 77 birds and 8 marine mammals revealed that all Chilean H5N1 viruses belong to lineage 2.3.4.4b and cluster monophyletically with viruses from Peru, indicating a single introduction from North America into Peru/Chile. Mammalian adaptations were identified in the PB2 segment: D701N in two sea lions, one human, and one shorebird, and Q591K in the human and one sea lion. Minor variant analysis revealed that D701N was present in 52.9 - 70.9% of sequence reads, indicating the presence of both genotypes within hosts. Further surveillance of spillover events is warranted to assess the emergence and potential onward transmission of mammalian adapted H5N1 HPAIV in South America.
PubMed: 37786724
DOI: 10.1101/2023.06.30.547205 -
Redox Biology Jul 2023Aminoacyl-tRNA synthetases (aaRSs) are indispensable players in translation. Usually, two or three genes encode cytoplasmic and mitochondrial threonyl-tRNA synthetases...
Aminoacyl-tRNA synthetases (aaRSs) are indispensable players in translation. Usually, two or three genes encode cytoplasmic and mitochondrial threonyl-tRNA synthetases (ThrRSs) in eukaryotes. Here, we reported that Caenorhabditis elegans harbors only one tars-1, generating cytoplasmic and mitochondrial ThrRSs via translational reinitiation. Mitochondrial tars-1 knockdown decreased mitochondrial tRNA charging and translation and caused pleotropic phenotypes of delayed development, decreased motor ability and prolonged lifespan, which could be rescued by replenishing mitochondrial tars-1. Mitochondrial tars-1 deficiency leads to compromised mitochondrial functions including the decrease in oxygen consumption rate, complex Ⅰ activity and the activation of the mitochondrial unfolded protein response (UPR), which contributes to longevity. Furthermore, deficiency of other eight mitochondrial aaRSs in C. elegans and five in mammal also caused activation of the UPR. In summary, we deciphered the mechanism of one tars-1, generating two aaRSs, and elucidated the biochemical features and physiological function of C. elegans tars-1. We further uncovered a conserved connection between mitochondrial translation deficiency and UPR.
Topics: Animals; Caenorhabditis elegans; Longevity; Caenorhabditis elegans Proteins; Unfolded Protein Response; Amino Acyl-tRNA Synthetases; Tars; RNA, Transfer; Mammals
PubMed: 37167879
DOI: 10.1016/j.redox.2023.102722 -
Acta Crystallographica. Section D,... Nov 2023DHX9 is a DExH-box RNA helicase with versatile functions in transcription, translation, RNA processing and regulation of DNA replication. DHX9 has recently emerged as a...
DHX9 is a DExH-box RNA helicase with versatile functions in transcription, translation, RNA processing and regulation of DNA replication. DHX9 has recently emerged as a promising target for oncology, but to date no mammalian structures have been published. Here, crystal structures of human, dog and cat DHX9 bound to ADP are reported. The three mammalian DHX9 structures share identical structural folds. Additionally, the overall architecture and the individual domain structures of DHX9 are highly conserved with those of MLE, the Drosophila orthologue of DHX9 previously solved in complex with RNA and a transition-state analogue of ATP. Due to differences in the bound substrates and global domain orientations, the localized loop conformations and occupancy of dsRNA-binding domain 2 (dsRBD2) differ between the mammalian DHX9 and MLE structures. The combined effects of the structural changes considerably alter the RNA-binding channel, providing an opportunity to compare active and inactive states of the helicase. Finally, the mammalian DHX9 structures provide a potential tool for structure-based drug-design efforts.
Topics: Humans; Animals; Cats; Dogs; RNA; DEAD-box RNA Helicases; Cat Diseases; Dog Diseases; DNA Replication; RNA Helicases; Mammals; Neoplasm Proteins
PubMed: 37860960
DOI: 10.1107/S2059798323007611 -
Trends in Neurosciences Nov 2023Circulation of highly pathogenic avian influenza (HPAI) H5Nx viruses of the A/Goose/Guangdong/1/96 lineage in birds regularly causes infections of mammals, including... (Review)
Review
Circulation of highly pathogenic avian influenza (HPAI) H5Nx viruses of the A/Goose/Guangdong/1/96 lineage in birds regularly causes infections of mammals, including humans. In many mammalian species, infections are associated with severe neurological disease, a unique feature of HPAI H5Nx viruses compared with other influenza A viruses. Here, we provide an overview of the neuropathogenesis of HPAI H5Nx virus infection in mammals, centered on three aspects: neuroinvasion, neurotropism, and neurovirulence. We focus on in vitro studies, as well as studies on naturally or experimentally infected mammals. Additionally, we discuss the contribution of viral factors to the neuropathogenesis of HPAI H5Nx virus infections and the efficacy of intervention strategies to prevent neuroinvasion or the development of neurological disease.
Topics: Animals; Humans; Influenza in Birds; Influenza A virus; Birds; Mammals
PubMed: 37684136
DOI: 10.1016/j.tins.2023.08.002