Non-canonical (non-B) DNA structures-e.g. bent DNA, hairpins, G-quadruplexes (G4s), Z-DNA, etc.-which form at certain sequence motifs (e.g. A-phased repeats, inverted repeats, etc.), have emerged as important regulators of cellular processes and drivers of genome evolution. Yet, they have been understudied due to their repetitive nature and potentially inaccurate sequences generated with short-read technologies. Here we comprehensively characterize such motifs in the long-read telomere-to-telomere (T2T) genomes of human, bonobo, chimpanzee, gorilla, Bornean orangutan, Sumatran orangutan, and siamang. Non-B DNA motifs are enriched at the genomic regions added to T2T assemblies and occupy 9%-15%, 9%-11%, and 12%-38% of autosomes and chromosomes X and Y, respectively. G4s and Z-DNA are enriched at promoters and enhancers, as well as at origins of replication. Repetitive sequences harbor more non-B DNA motifs than non-repetitive sequences, especially in the short arms of acrocentric chromosomes. Most centromeres and/or their flanking regions are enriched in at least one non-B DNA motif type, consistent with a potential role of non-B structures in determining centromeres. Our results highlight the uneven distribution of predicted non-B DNA structures across ape genomes and suggest their novel functions in previously inaccessible genomic regions.
- MeSH
- DNA * chemie genetika MeSH
- G-kvadruplexy MeSH
- genom lidský MeSH
- genom * MeSH
- Hominidae * genetika MeSH
- lidé MeSH
- nukleotidové motivy MeSH
- Pan troglodytes genetika MeSH
- repetitivní sekvence nukleových kyselin MeSH
- telomery * genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- DNA * MeSH
Wild chimpanzees consume a variety of plants to meet their dietary needs and maintain wellbeing. While some plants have obvious value, others are nutritionally poor and/or contain bioactive toxins which make ingestion costly. In some cases, these nutrient-poor resources are speculated to be medicinal, thought to help individuals combat illness. In this study, we observed two habituated chimpanzee communities living in the Budongo Forest, Uganda, and collected 17 botanical samples associated with putative self-medication behaviors (e.g., bark feeding, dead wood eating, and pith-stripping) or events (e.g., when consumer had elevated parasite load, abnormal urinalysis, or injury). In total, we selected plant parts from 13 species (nine trees and four herbaceous plants). Three extracts of different polarities were produced from each sample using n-hexane, ethyl acetate, and methanol/water (9/1, v/v) and introduced to antibacterial and anti-inflammatory in vitro models. Extracts were evaluated for growth inhibition against a panel of multidrug-resistant clinical isolates of bacteria, including ESKAPE strains and cyclooxygenase-2 (COX-2) inhibition activity. Pharmacological results suggest that Budongo chimpanzees consume several species with potent medicinal properties. In the antibacterial library screen, 45 out of 53 extracts (88%) exhibited ≥40% inhibition at a concentration of 256 μg/mL. Of these active extracts, 41 (91%) showed activity at ≤256μg/mL in subsequent dose-response antibacterial experiments. The strongest antibacterial activity was achieved by the n-hexane extract of Alstonia boonei dead wood against Staphylococcus aureus (IC50: 16 μg/mL; MIC: 32 μg/mL) and Enterococcus faecium (IC50: 16 μg/mL; MIC: >256 μg/mL) and by the methanol-water extract of Khaya anthotheca bark and resin against E. faecium (IC50: 16 μg/mL; MIC: 32 μg/mL) and pathogenic Escherichia coli (IC50: 16 μg/mL; MIC: 256 μg/mL). We observed ingestion of both these species by highly parasitized individuals. K. anthotheca bark and resin were also targeted by individuals with indicators of infection and injuries. All plant species negatively affected growth of E. coli. In the anti-inflammatory COX-2 inhibition library screen, 17 out of 51 tested extracts (33%) showed ≥50% COX-2 inhibition at a concentration of 5 μg/mL. Several extracts also exhibited anti-inflammatory effects in COX-2 dose-response experiments. The K. anthotheca bark and resin methanol-water extract showed the most potent effects (IC50: 0.55 μg/mL), followed by the fern Christella parasitica methanol-water extract (IC50: 0.81 μg/mL). This fern species was consumed by an injured individual, a feeding behavior documented only once before in this population. These results, integrated with associated observations from eight months of behavioral data, provide further evidence for the presence of self-medicative resources in wild chimpanzee diets. This study addresses the challenge of distinguishing preventative medicinal food consumption from therapeutic self-medication by integrating pharmacological, observational, and health monitoring data-an essential interdisciplinary approach for advancing the field of zoopharmacognosy.
- MeSH
- antibakteriální látky farmakologie MeSH
- chování zvířat účinky léků MeSH
- dieta veterinární MeSH
- léčivé rostliny chemie MeSH
- Pan troglodytes * MeSH
- rostlinné extrakty * farmakologie chemie MeSH
- stravovací zvyklosti účinky léků MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Uganda MeSH
- Názvy látek
- antibakteriální látky MeSH
- rostlinné extrakty * MeSH
Rapid increases in human populations and environmental changes of past decades have led to changes in rates of contact and spatial overlap with wildlife. Together with other historical, social and environmental processes, this has significantly contributed to pathogen transmission in both directions, especially between humans and non-human primates, whose close phylogenetic relationship facilitates cross-infections. Using high-throughput amplicon sequencing, we studied strongylid communities in sympatric western lowland gorillas, central chimpanzees and humans co-occurring in an unprotected area in the northern periphery of the Dja Faunal Reserve, Cameroon. At the genus level, we classified 65 strongylid ITS-2 amplicon sequencing variants (ASVs) in humans and great apes. Great apes exhibited higher strongylid diversity than humans. Necator and Oesophagostomum were the most prevalent genera, and we commonly observed mixed infections of more than one strongylid species. Human strongylid communities were dominated by the human hookworm N. americanus, while great apes were mainly infected with N. gorillae, O. stephanostomum and trichostrongylids. We were also able to detect rare strongylid taxa (such as Ancylostoma and Ternidens). We detected eight ASVs shared between humans and great apes (four N. americanus variants, two N. gorillae variants, one O. stephanostomum type I and one Trichostrongylus sp. type II variant). Our results show that knowledge of strongylid communities in primates, including humans, is still limited. Sharing the same habitat, especially outside protected areas (where access to the forest is not restricted), can enable mutual parasite exchange and can even override host phylogeny or conserved patterns. Such studies are critical for assessing the threats posed to all hosts by increasing human-wildlife spatial overlap. In this study, the term "contact" refers to physical contact, while "spatial overlap" refers to environmental contact.
- MeSH
- Ancylostoma * MeSH
- divoká zvířata MeSH
- fylogeneze MeSH
- lidé MeSH
- Pan troglodytes * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Kamerun epidemiologie MeSH
The exact signaling leading to neurological dysfunction in neurodegenerative diseases is currently unknown. We hypothesize that the c-Jun N-terminal kinase (JNK) signaling pathway is a potential therapeutic target for neurodegenerative diseases. This postulate rests on extensive data from cell and animal experimental studies, demonstrating that JNK signaling plays a crucial role in the pathogenesis of neurodegenerative diseases. The sustained activation of JNK leads to synaptic dysfunction and even neuronal apoptosis, ultimately resulting in memory deficits and neurodegeneration. JNK phosphorylates the amyloid precursor protein and tau, ultimately resulting in the formation of extraneuronal senile plaques and intraneuronal neurofibrillary tangles. Our hypothesis could be validated by investigating the cerebral cortex of elderly chimpanzees injected with phosphorylated JNK or transgenic pig and chimpanzee models established using gene editing technology including CRISPR. This hypothesis provides clues for further understanding the molecular mechanisms of neurodegenerative diseases and the development of potential target therapeutic drugs.
- Klíčová slova
- Alzheimer's disease, JNK, amyloid beta, neurodegenerative diseases, tau,
- MeSH
- Alzheimerova nemoc genetika MeSH
- amyloidní beta-protein * metabolismus MeSH
- amyloidový prekurzorový protein beta * genetika metabolismus MeSH
- fosforylace MeSH
- genový targeting * MeSH
- JNK mitogenem aktivované proteinkinasy metabolismus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- mozková kůra metabolismus patologie MeSH
- neurodegenerativní nemoci patologie MeSH
- neurony metabolismus MeSH
- Pan troglodytes MeSH
- prasata MeSH
- proteiny tau metabolismus MeSH
- signální transdukce * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- amyloidní beta-protein * MeSH
- amyloidový prekurzorový protein beta * MeSH
- JNK mitogenem aktivované proteinkinasy MeSH
- proteiny tau MeSH
The gut microbiome exhibits extreme compositional variation between hominid hosts. However, it is unclear how this variation impacts host physiology across species and whether this effect can be mediated through microbial regulation of host gene expression in interacting epithelial cells. Here, we characterize the transcriptional response of human colonic epithelial cells in vitro to live microbial communities extracted from humans, chimpanzees, gorillas, and orangutans. We find that most host genes exhibit a conserved response, whereby they respond similarly to the four hominid microbiomes. However, hundreds of host genes exhibit a divergent response, whereby they respond only to microbiomes from specific host species. Such genes are associated with intestinal diseases in humans, including inflammatory bowel disease and Crohn's disease. Last, we find that inflammation-associated microbial species regulate the expression of host genes previously associated with inflammatory bowel disease, suggesting health-related consequences for species-specific host-microbiome interactions across hominids.
- Klíčová slova
- Gut microbiome, Primates, Hominids, Gene regulation,
- MeSH
- Bacteria genetika MeSH
- druhová specificita MeSH
- epitelové buňky metabolismus MeSH
- exprese genu genetika MeSH
- feces mikrobiologie MeSH
- fylogeneze MeSH
- Gorilla gorilla mikrobiologie MeSH
- Hominidae genetika mikrobiologie MeSH
- idiopatické střevní záněty genetika MeSH
- lidé MeSH
- mikrobiota genetika MeSH
- Pan troglodytes mikrobiologie MeSH
- Pongo mikrobiologie MeSH
- regulace genové exprese genetika MeSH
- RNA ribozomální 16S genetika MeSH
- střevní mikroflóra genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- RNA ribozomální 16S MeSH
The oral microbiome plays key roles in human biology, health, and disease, but little is known about the global diversity, variation, or evolution of this microbial community. To better understand the evolution and changing ecology of the human oral microbiome, we analyzed 124 dental biofilm metagenomes from humans, including Neanderthals and Late Pleistocene to present-day modern humans, chimpanzees, and gorillas, as well as New World howler monkeys for comparison. We find that a core microbiome of primarily biofilm structural taxa has been maintained throughout African hominid evolution, and these microbial groups are also shared with howler monkeys, suggesting that they have been important oral members since before the catarrhine-platyrrhine split ca. 40 Mya. However, community structure and individual microbial phylogenies do not closely reflect host relationships, and the dental biofilms of Homo and chimpanzees are distinguished by major taxonomic and functional differences. Reconstructing oral metagenomes from up to 100 thousand years ago, we show that the microbial profiles of both Neanderthals and modern humans are highly similar, sharing functional adaptations in nutrient metabolism. These include an apparent Homo-specific acquisition of salivary amylase-binding capability by oral streptococci, suggesting microbial coadaptation with host diet. We additionally find evidence of shared genetic diversity in the oral bacteria of Neanderthal and Upper Paleolithic modern humans that is not observed in later modern human populations. Differences in the oral microbiomes of African hominids provide insights into human evolution, the ancestral state of the human microbiome, and a temporal framework for understanding microbial health and disease.
- Klíčová slova
- Neanderthal, dental calculus, microbiome, primate, salivary amylase,
- MeSH
- Bacteria klasifikace genetika MeSH
- biofilmy MeSH
- biologická evoluce * MeSH
- ekologie metody MeSH
- fylogeneze MeSH
- Gorilla gorilla mikrobiologie MeSH
- Hominidae klasifikace mikrobiologie MeSH
- lidé MeSH
- metagenom genetika MeSH
- mikrobiota genetika MeSH
- Pan troglodytes mikrobiologie MeSH
- ústa mikrobiologie MeSH
- zeměpis MeSH
- zubní plak mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Afrika MeSH
We investigated intestinal trichomonads in western lowland gorillas, central chimpanzees and humans cohabiting the forest ecosystem of Dzanga-Sangha Protected Area in Central African Republic, using the internal transcribed spacer (ITS) region and SSU rRNA gene sequences. Trichomonads belonging to the genus Tetratrichomonas were detected in 23% of the faecal samples and in all host species. Different hosts were infected with different genotypes of Tetratrichomonas. In chimpanzees, we detected tetratrichomonads from 'novel lineage 2', which was previously reported mostly in captive and wild chimpanzees. In gorillas, we found two different genotypes of Tetratrichomonas. The ITS region sequences of the more frequent genotype were identical to the sequence found in a faecal sample of a wild western lowland gorilla from Cameroon. Sequences of the second genotype from gorillas were almost identical to sequences previously obtained from an anorexic French woman. We provide the first report of the presence of intestinal tetratrichomonads in asymptomatic, apparently healthy humans. Human tetratrichomonads belonged to the lineage 7, which was previously reported in domestic and wild pigs and a domestic horse. Our findings suggest that the ecology and spatial overlap among hominids in the tropical forest ecosystem has not resulted in exchange of intestinal trichomonads among these hosts.
- Klíčová slova
- Chimpanzee, Parabasalia, Tetratrichomonas, gorilla, human, transmission, trichomonads,
- MeSH
- feces parazitologie MeSH
- fylogeneze MeSH
- Gorilla gorilla parazitologie MeSH
- hostitelská specificita MeSH
- lidé MeSH
- nemoci lidoopů epidemiologie parazitologie MeSH
- Pan troglodytes parazitologie MeSH
- protozoální infekce zvířat epidemiologie parazitologie MeSH
- protozoální infekce epidemiologie parazitologie MeSH
- Trichomonadida klasifikace MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Středoafrická republika epidemiologie MeSH
G-Quadruplexes are noncanonical nucleic acid structures made up of stacked guanosine tetrads connected by short loops. They are frequently used building blocks in synthetic biology and thought to play widespread biological roles. Multimerization can change the functional properties of G-quadruplexes, and understanding the factors that modulate this process remains an important goal. Here, we report the discovery of a novel mechanism by which the formation of multimeric G-quadruplexes can be controlled using GTP. We show that GTP likely inhibits multimer formation by becoming incorporated into a tetrad in the monomeric form of the structure and define the sequence requirements of G-quadruplexes that form GTP-dependent structures. These experiments provide new insights into the small molecule control of G-quadruplex multimerization. They also suggest possible roles for GTP-dependent multimeric G-quadruplexes in both synthetic and natural biological systems.
- MeSH
- biochemické jevy MeSH
- DNA genetika metabolismus MeSH
- G-kvadruplexy * MeSH
- guanosintrifosfát metabolismus MeSH
- lidé MeSH
- mutace MeSH
- Pan troglodytes MeSH
- Pongo MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA MeSH
- guanosintrifosfát MeSH
Human parvovirus 4 (PARV4, family Parvoviridae, genus Tetraparvovirus) displays puzzling features, such as uncertain clinical importance/significance, unclear routes of transmission, and discontinuous geographical distribution. The origin, or the general reservoir, of human PARV4 infection is unknown. We aimed to detect and characterize PARV4 virus in faecal samples collected from two wild chimpanzee populations and 19 species of captive non-human primates. We aimed to investigate these species as a potential reservoir and alternate route of transmission on the African continent. From almost 500 samples screened, a single wild Pan troglodytes schweinfurthii sample tested positive. Full genome analysis, as well as single ORF phylogenies, confirmed species-specific PARV4 infection.
- MeSH
- divoká zvířata virologie MeSH
- feces virologie MeSH
- fylogeneze MeSH
- genom virový MeSH
- infekce viry z čeledi Parvoviridae přenos veterinární virologie MeSH
- nemoci primátů přenos virologie MeSH
- otevřené čtecí rámce MeSH
- Pan troglodytes MeSH
- Parvovirinae klasifikace genetika izolace a purifikace MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Understanding the complex Entamoeba communities in the mammalian intestine has been, to date, complicated by the lack of a suitable approach for molecular detection of multiple variants co-occurring in mixed infections. Here, we report on the application of a high throughput sequencing approach based on partial 18S rDNA using the Illumina MiSeq platform. We describe, to our knowledge, for the first time, the Entamoeba communities in humans, free-ranging western lowland gorillas and central chimpanzees living in the Dja Faunal Reserve in Cameroon. We detected 36 Entamoeba haplotypes belonging to six haplotype clusters, containing haplotypes possessing high and low host specificity. Most of the detected haplotypes belonged to commensal Entamoeba, however, the pathogenic species (Entamoeba histolytica and Entamoeba nuttalli) were also detected. We observed that some Entamoeba haplotypes are shared between humans and other hosts, indicating their zoonotic potential. The findings are important not only for understanding the epidemiology of amoebiasis in humans in rural African localities, but also in the context of wild great ape conservation.
- Klíčová slova
- Central chimpanzee, Diversity, Entamoeba, Entamoeba histolytica, Humans, Metabarcoding, Mixed infections, Western lowland gorilla,
- MeSH
- entamébóza epidemiologie parazitologie veterinární MeSH
- Entamoeba * MeSH
- Gorilla gorilla parazitologie MeSH
- lidé MeSH
- nemoci lidoopů epidemiologie parazitologie MeSH
- Pan troglodytes parazitologie MeSH
- parazitární nemoci střev epidemiologie parazitologie veterinární MeSH
- vysoce účinné nukleotidové sekvenování * MeSH
- zachování přírodních zdrojů MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Afrika epidemiologie MeSH