The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical for clinical evaluation of the benefits and limits of helminth therapy.
- MeSH
- cizopasní červi fyziologie MeSH
- helmintoterapie * MeSH
- klinické zkoušky jako téma metody MeSH
- lidé MeSH
- samoléčba MeSH
- výzkumný projekt * trendy MeSH
- zánět MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Transfer RNAs acquire a large plethora of chemical modifications. Among those, modifications of the anticodon loop play important roles in translational fidelity and tRNA stability. Four human wobble U-containing tRNAs obtain 5-methoxycarbonylmethyluridine (mcm5U34) or 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U34), which play a role in decoding. This mark involves a cascade of enzymatic activities. The last step is mediated by alkylation repair homolog 8 (ALKBH8). In this study, we performed a transcriptome-wide analysis of the repertoire of ALKBH8 RNA targets. Using a combination of HITS-CLIP and RIP-seq analyses, we uncover ALKBH8-bound RNAs. We show that ALKBH8 targets fully processed and CCA modified tRNAs. Our analyses uncovered the previously known set of wobble U-containing tRNAs. In addition, both our approaches revealed ALKBH8 binding to several other types of noncoding RNAs, in particular C/D box snoRNAs.
Poly lactic-co-glycolic acid (PLGA) particles safely and effectively deliver pharmaceutical ingredients, with many applications approved for clinical use in humans. In fishes, PLGA particles are being considered as carriers of therapeutic drugs and vaccine antigens. However, existing studies focus mainly on vaccine antigens, the endpoint immune responses to these (e.g., improved antibody titres), without deeper understanding of whether fishes react to the carrier. To test whether or not PLGA are recognized by or interact at all with the immune system of a teleost fish, we prepared, characterized and injected PLGA microparticles intraperitoneally into common carp. The influx, phenotype of inflammatory leukocytes, and their capacity to produce reactive oxygen species and phagocytose PLGA microparticles were tested by flow cytometry, qPCR, and microscopy. PLGA microparticles were indeed recognized. However, they induced only transient recruitment of inflammatory leukocytes that was resolved 4 days later whereas only the smallest μm-sized particles were phagocytosed. The overall response resembled that described in mammals against foreign materials. Given the similarities between our findings and those described in mammals, PLGA particles can be adapted to play a dual role as both antigen and drug carriers in fishes, depending on the administered dose and their design.
In a single human gut, which is estimated to produce 1000-times more bacteria in a single day than the entire human population on Earth as of 2020, the potential for evolution is vast. In addition to the sheer volume of reproductive events, prokaryotes can transfer most genes horizontally, greatly accelerating their potential to evolve. In the face of this evolutionary potential, Westernization has led to profound changes in the ecosystem of the gut, including increased chronic inflammation in many individuals and dramatically reduced fiber consumption and decreased seasonal variation in the diet of most individuals. Experimental work using a variety of model systems has shown that bacteria will evolve within days to weeks when faced with substantial environmental changes. However, studies evaluating the effects of inflammation of the gut on the microbiota are still in their infancy and generally confounded by the effects of the microbiota on the immune system. At the same time, experimental data indicate that complete loss of fiber from the diet constitutes an extinction-level event for the gut microbiota. However, these studies evaluating diet may not apply to Westernized humans who typically have reduced but not absent levels of fiber in their diet. Thus, while it is expected that the microbiota will evolve rapidly in the face of Westernization, experimental studies that address the magnitude of that evolution are generally lacking, and it remains unknown to what extent this evolutionary process affects disease and the ability to treat the disease state.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Uridine insertion/deletion (U-indel) editing of mitochondrial mRNA, unique to the protistan class Kinetoplastea, generates canonical as well as potentially non-productive editing events. While the molecular machinery and the role of the guide (g) RNAs that provide required information for U-indel editing are well understood, little is known about the forces underlying its apparently error-prone nature. Analysis of a gRNA:mRNA pair allows the dissection of editing events in a given position of a given mitochondrial transcript. A complete gRNA dataset, paired with a fully characterized mRNA population that includes non-canonically edited transcripts, would allow such an analysis to be performed globally across the mitochondrial transcriptome. To achieve this, we have assembled 67 minicircles of the insect parasite Leptomonas pyrrhocoris, with each minicircle typically encoding one gRNA located in one of two similar-sized units of different origin. From this relatively narrow set of annotated gRNAs, we have dissected all identified mitochondrial editing events in L. pyrrhocoris, the strains of which dramatically differ in the abundance of individual minicircle classes. Our results support a model in which a multitude of editing events are driven by a limited set of gRNAs, with individual gRNAs possessing an inherent ability to guide canonical and non-canonical editing.
- MeSH
- editace RNA * MeSH
- fylogeneze MeSH
- genom protozoální * MeSH
- guide RNA, Kinetoplastida chemie metabolismus MeSH
- messenger RNA metabolismus MeSH
- RNA mitochondriální metabolismus MeSH
- transkriptom MeSH
- Trypanosomatina genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In this work, we studied the biochemical properties and evolutionary histories of catalase (CAT) and ascorbate peroxidase (APX), two central enzymes of reactive oxygen species detoxification, across the highly diverse clade Eugenozoa. This clade encompasses free-living phototrophic and heterotrophic flagellates, as well as obligate parasites of insects, vertebrates, and plants. We present evidence of several independent acquisitions of CAT by horizontal gene transfers and evolutionary novelties associated with the APX presence. We posit that Euglenozoa recruit these detoxifying enzymes for specific molecular tasks, such as photosynthesis in euglenids and membrane-bound peroxidase activity in kinetoplastids and some diplonemids.
- Publikační typ
- časopisecké články MeSH
The adaptation of eukaryotic cells to anaerobic conditions is reflected by substantial changes to mitochondrial metabolism and functional reduction. Hydrogenosomes belong among the most modified mitochondrial derivative and generate molecular hydrogen concomitant with ATP synthesis. The reduction of mitochondria is frequently associated with loss of peroxisomes, which compartmentalize pathways that generate reactive oxygen species (ROS) and thus protect against cellular damage. The biogenesis and function of peroxisomes are tightly coupled with mitochondria. These organelles share fission machinery components, oxidative metabolism pathways, ROS scavenging activities, and some metabolites. The loss of peroxisomes in eukaryotes with reduced mitochondria is thus not unexpected. Surprisingly, we identified peroxisomes in the anaerobic, hydrogenosome-bearing protist Mastigamoeba balamuthi We found a conserved set of peroxin (Pex) proteins that are required for protein import, peroxisomal growth, and division. Key membrane-associated Pexs (MbPex3, MbPex11, and MbPex14) were visualized in numerous vesicles distinct from hydrogenosomes, the endoplasmic reticulum (ER), and Golgi complex. Proteomic analysis of cellular fractions and prediction of peroxisomal targeting signals (PTS1/PTS2) identified 51 putative peroxisomal matrix proteins. Expression of selected proteins in Saccharomyces cerevisiae revealed specific targeting to peroxisomes. The matrix proteins identified included components of acyl-CoA and carbohydrate metabolism and pyrimidine and CoA biosynthesis, whereas no components related to either β-oxidation or catalase were present. In conclusion, we identified a subclass of peroxisomes, named "anaerobic" peroxisomes that shift the current paradigm and turn attention to the reductive evolution of peroxisomes in anaerobic organisms.
- MeSH
- anaerobióza MeSH
- Archamoebae genetika metabolismus MeSH
- mitochondrie genetika metabolismus MeSH
- oxidace-redukce MeSH
- peroxiny genetika metabolismus MeSH
- peroxizomy genetika metabolismus MeSH
- protozoální proteiny genetika metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We describe the monoxenous trypanosomatids parasitizing true bugs and flies on the island of Curaçao. Out of 248 examined true bugs belonging to 17 species, 93 individuals were found to be infected (overall 38% prevalence) by at least one trypanosomatid species (referred to as typing units; TUs). Out of 80 flies, six were infected. All detected trypanosomatids were compared based on their 18S rRNA sequences with TUs parasitizing bugs and flies described from mainland South America, allowing us to assess their diversity and distribution. Besides Leptomonas pyrrhocoris and Leptomonas seymouri, two known species of the subfamily Leishmaniinae, our analysis revealed six new TUs falling into the groups 'jaculum', Blastocrithidia and Herpetomonas. Moreover, two new members of the genus Phytomonas and three new TUs belonging to the monophyletic group designated as 'new clade II' sensu Mol. Phylogenet. Evol, 69, 255 (2013) were isolated. The detected trypanosomatids were characterized by moderate diversity (13 TUs) species richness. Out of nine and four TUs from the heteropteran and dipteran hosts, respectively, 11 TUs have not been encountered before. Although a sampling bias may partially affect the comparison between trypanosomatid communities on Curaçao and the mainland, the high proportion of unique TUs from the former location suggests that the prominent role of islands in increasing the global diversity of macroscopic organisms may also extend to their protistan parasites.
- MeSH
- Diptera parazitologie MeSH
- fylogeneze MeSH
- Heteroptera parazitologie MeSH
- RNA protozoální analýza MeSH
- RNA ribozomální 18S analýza MeSH
- Trypanosomatina klasifikace genetika izolace a purifikace MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Curacao MeSH
Lower termites harbor in their hindgut complex microbial communities that are involved in the digestion of cellulose. Among these are protists, which are usually associated with specific bacterial symbionts found on their surface or inside their cells. While these form the foundations of a classic system in symbiosis research, we still know little about the functional basis for most of these relationships. Here, we describe the complex functional relationship between one protist, the oxymonad Streblomastix strix, and its ectosymbiotic bacterial community using single-cell genomics. We generated partial assemblies of the host S. strix genome and Candidatus Ordinivivax streblomastigis, as well as a complex metagenome assembly of at least 8 other Bacteroidetes bacteria confirmed by ribosomal (r)RNA fluorescence in situ hybridization (FISH) to be associated with S. strix. Our data suggest that S. strix is probably not involved in the cellulose digestion, but the bacterial community on its surface secretes a complex array of glycosyl hydrolases, providing them with the ability to degrade cellulose to monomers and fueling the metabolism of S. strix In addition, some of the bacteria can fix nitrogen and can theoretically provide S. strix with essential amino acids and cofactors, which the protist cannot synthesize. On the contrary, most of the bacterial symbionts lack the essential glycolytic enzyme enolase, which may be overcome by the exchange of intermediates with S. strix This study demonstrates the value of the combined single-cell (meta)genomic and FISH approach for studies of complicated symbiotic systems.
- MeSH
- analýza jednotlivých buněk metody MeSH
- Bacteria metabolismus MeSH
- Bacteroidetes genetika MeSH
- celulosa metabolismus MeSH
- Eukaryota metabolismus MeSH
- fylogeneze MeSH
- genom MeSH
- Isoptera genetika mikrobiologie MeSH
- metagenomika metody MeSH
- Oxymonadida metabolismus MeSH
- symbióza MeSH
- trávicí systém metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Aminoacyl-tRNA synthetases (AaRSs) are enzymes that catalyze the ligation of tRNAs to amino acids. There are AaRSs specific for each amino acid in the cell. Each cellular compartment in which translation takes place (the cytosol, mitochondria, and plastids in most cases), needs the full set of AaRSs; however, individual AaRSs can function in multiple compartments due to dual (or even multiple) targeting of nuclear-encoded proteins to various destinations in the cell. We searched the genomes of the chromerids, Chromera velia and Vitrella brassicaformis, for AaRS genes: 48 genes encoding AaRSs were identified in C. velia, while only 39 AaRS genes were found in V. brassicaformis. In the latter alga, ArgRS and GluRS were each encoded by a single gene occurring in a single copy; only PheRS was found in three genes, while the remaining AaRSs were encoded by two genes. In contrast, there were nine cases for which C. velia contained three genes of a given AaRS (45% of the AaRSs), all of them representing duplicated genes, except AsnRS and PheRS, which are more likely pseudoparalogs (acquired via horizontal or endosymbiotic gene transfer). Targeting predictions indicated that AaRSs are not (or not exclusively), in most cases, used in the cellular compartment from which their gene originates. The molecular phylogenies of the AaRSs are variable between the specific types, and similar between the two investigated chromerids. While genes with eukaryotic origin are more frequently retained, there is no clear pattern of orthologous pairs between C. velia and V. brassicaformis.
