93 research outputs found
Epigenetics in paediatric gastroenterology, hepatology, and nutrition: Present trends and future perspectives
No full textEpigenetics can be defined as stable, potentially heritable changes in the cellular phenotype caused by mechanisms other than alterations to the underlying DNA sequence. As such, any observed phenotypic changes including organ development, aging, and the occurrence of disease could be driven by epigenetic mechanisms in the presence of stable cellular DNA sequences. Indeed, with the exception of rare mutations, the human genome-sequence has remained remarkably stable over the past centuries. In contrast, substantial changes to our environment as part of our modern life style have not only led to a significant reduction of certain infectious diseases but also seen the exponential increase in complex traits including obesity and multifactorial diseases such as autoimmune disorders. It is becoming increasingly clear that epigenetic mechanisms operate at the interface between the genetic code and our environment, and a large body of existing evidence supports the importance of environmental factors such as diet and nutrition, infections, and exposure to toxins on human health. This seems to be particularly the case during vulnerable periods of human development such as pregnancy and early life. Importantly, as the first point of contact for many of such environmental factors including nutrition, the digestive system is being increasingly linked to a number of "modern" pathologies. In this review article, we aim to give a brief introduction to the basic molecular principals of epigenetics and provide a concise summary of the existing evidence for the role of epigenetic mechanisms in gastrointestinal health and disease, hepatology, and nutrition
Investigating the effects of management practice on mammalian co-occurrence along the West Coast of South Africa
No full textCITATION: Winterton, D. J., Van Wilgen, N. J. & Venter, J. A. 2020. Investigating the effects of management practice on mammalian co-occurrence along the West Coast of South Africa. PeerJ 8, e8184, 27 pages. DOI: 10.7717/peerj.8184.ENGLISH ABSTRACT: The subtle and cascading effects (e.g., altered interspecific interactions) that anthropogenic stressors have on local ecological assemblages often go unnoticed but are concerning given their importance in ecosystem function. For example, elimination of buffalo from the Serengeti National Park is suggested to have driven increased abundance of smaller antelope as a result of release from competition. The perceived low abundance of small antelope in the contractual Postberg section of the West Coast National Park (the park) has been an ongoing management concern which has been anecdotally attributed to predation by a mesopredator (the caracal, Caracal caracal). However, we hypothesized that the historical overstocking, and consequent overgrazing by larger-bodied managed ungulates would influence small antelope abundance. Using camera traps, we investigated species co-occurrence and temporal activity between small antelope, managed ungulates and caracals in Postberg as well as another part of the park (Langebaan) and a farm outside of the park. Results suggest that small antelope and managed ungulates have a high degree of temporal overlap (Delta = 0.74, 0.79 and 0.86 for the farm, Langebaan and Postberg respectively), while temporal partitioning between small antelope and caracal is apparent (Delta = 0.59). Further, small antelope and managed ungulates appear to occur independently of one another (SIF = 0.91-1 across areas). Managed ungulates were detected almost three times more frequently on fallow lands when compared to the more vegetated sites within the park suggesting that segregated food/cover resources allow for independent occurrence. Small antelope had a much higher probability of occurrence outside of the protected area (e.g., psi = 0.192 and 0.486 for steenbok at Postberg, Langebaan compared to 0.841 on the farm), likely due to less variable (more intact) habitat outside of the protected area. There is not sufficient evidence to currently warrant management intervention for predators. The small size of the protected area provides limited scope for spatial replication thus reducing possibilities to infer the cause and effect for complex interactions (which would historically have taken place over much larger areas) with negative implications for adaptive management. We recommend continued monitoring over multiple seasons and a wider area to determine the spatial information requirements to inform management of small protected areas.Publisher's versio
Evolutionary origin of the cell nucleus and its functional architecture
No full textUnderstanding the evolutionary origin of the nucleus and its compartmentalized architecture provides a huge but, as expected, greatly rewarding challenge in the post-genomic era. We start this chapter with a survey of current hypotheses on the evolutionary origin of the cell nucleus. Thereafter, we provide an overview of evolutionarily conserved features of chromatin organization and arrangements, as well as topographical aspects of DNA replication and transcription, followed by a brief introduction of current models of nuclear architecture. In addition to features which may possibly apply to all eukaryotes, the evolutionary plasticity of higher-order nuclear organization is reflected by cell-type- and species-specific features, by the ability of nuclear architecture to adapt to specific environmental demands, as well as by the impact of aberrant nuclear organization on senescence and human disease. We conclude this chapter with a reflection on the necessity of interdisciplinary research strategies to map epigenomes in space and time.</jats:p
Biogenesis of Developmental Master Regulatory 27nt-RNAs in Stylonychia—Can Coding RNA Turn into Non-Coding?
No full textIn the ciliate Stylonychia, somatic macronuclei differentiate from germline micronuclei during sexual reproduction, accompanied by developmental sequence reduction. Concomitantly, over 95% of micronuclear sequences adopt a heterochromatin structure characterized by the histone variant H3.4 and H3K27me3. RNAi-related genes and histone variants dominate the list of developmentally expressed genes. Simultaneously, 27nt-ncRNAs that match sequences retained in new macronuclei are synthesized and bound by PIWI1. Recently, we proposed a mechanistic model for ‘RNA-induced DNA replication interference’ (RIRI): during polytene chromosome formation PIWI1/27nt-RNA-complexes target macronucleus-destined sequences (MDS) by base-pairing and temporarily cause locally stalled replication. At polytene chromosomal segments with ongoing replication, H3.4K27me3-nucleosomes become selectively deposited, thus dictating the prospective heterochromatin structure of these areas. Consequently, these micronucleus-specific sequences become degraded, whereas 27nt-RNA-covered sites remain protected. However, the biogenesis of the 27nt-RNAs remains unclear. It was proposed earlier that in stichotrichous ciliates 27nt-RNA precursors could derive from telomere-primed bidirectional transcription of nanochromosomes and subsequent Dicer-like (DCL) activity. As a minimalistic explanation, we propose here that the 27nt-RNA precursor could rather be mRNA or pre-mRNA and that the transition of coding RNA from parental macronuclei to non-coding RNAs, which act in premature developing macronuclei, could involve RNA-dependent RNA polymerase (RDRP) activity creating dsRNA intermediates prior to a DCL-dependent pathway. Interestingly, by such mechanism the partition of a parental somatic genome and possibly also the specific nanochromosome copy numbers could be vertically transmitted to the differentiating nuclei of the offspring
The evolutionary history of histone H3 suggests a deep eukaryotic root of chromatin modifying mechanisms
No full textAbstract Background The phenotype of an organism is an outcome of both its genotype, encoding the primary sequence of proteins, and the developmental orchestration of gene expression. The substrate of gene expression in eukaryotes is the chromatin, whose fundamental units are nucleosomes composed of DNA wrapped around each two of the core histone types H2A, H2B, H3 and H4. Key regulatory steps involved in the determination of chromatin conformations are posttranslational modifications (PTM) at histone tails as well as the assembly of histone variants into nucleosomal arrays. Although the mechanistic background is fragmentary understood, it appears that the chromatin signature of metazoan cell types is inheritable over generations. Even less understood is the conservation of epigenetic mechanisms among eukaryotes and their origins. Results In the light of recent progress in understanding the tree of eukaryotic life we discovered the origin of histone H3 by phylogenetic analyses of variants from all supergroups, which allowed the reconstruction of ancestral states. We found that H3 variants evolved frequently but independently within related species of almost all eukaryotic supergroups. Interestingly, we found all core histone types encoded in the genome of a basal dinoflagellate and H3 variants in two other species, although is was reported that dinoflagellate chromatin is not organized into nucleosomes. Most probably one or more animal/nuclearid H3.3-like variants gave rise to H3 variants of all opisthokonts (animals, choanozoa, fungi, nuclearids, Amoebozoa). H3.2 and H3.1 as well as H3.1t are derivatives of H3.3, whereas H3.2 evolved already in early branching animals, such as Trichoplax. H3.1 and H3.1t are probably restricted to mammals. We deduced a model for protoH3 of the last eukaryotic common ancestor (LECA) confirming a remarkable degree of sequence conservation in comparison to canonical human H3.1. We found evidence that multiple PTMs are conserved even in putatively early branching eukaryotic taxa (Euglenozoa/Excavata). Conclusions At least a basal repertoire of chromatin modifying mechanisms appears to share old common ancestry and may thus be inherent to all eukaryotes. We speculate that epigenetic principles responsive to environmental triggers may have had influenced phenotypic variation and concomitantly may potentially have had impact on eukaryotic diversification.</p
Probing telomeric G-quadruplex DNA structures in cells with in vitro generated single-chain antibody fragments
No full textGuanine-rich sequences have been shown to readily form parallel or antiparallel G-quadruplex DNA structures in vitro. All telomeric repeat sequences contain stretches of guanine residues that can form quadruplex structures. In order to demonstrate the occurrence of the quadruplex structure in vivo, we generated by ribosome display, scFv antibodies specific for quadruplex DNA structures formed by the telomeric sequence of the ciliate Stylonychia. The macronucleus of this hypotrichous ciliate contains 10(8) telomere-capped nanochromosomes and was stained with the antibody recognizing the antiparallel G-quadruplex DNA in indirect immuno-fluorescence assays. This antibody was also used as a specific probe to study the interaction of the telomere end-binding proteins with the G-quadruplex during different stages of the cell cycle.</p
The Draft Assembly of the Radically Organized Stylonychia lemnae Macronuclear Genome.
No full textStylonychia lemnae is a classical model single-celled eukaryote, and a quintessential ciliate typified by dimorphic nuclei: A small, germline micronucleus and a massive, vegetative macronucleus. The genome within Stylonychia's macronucleus has a very unusual architecture, comprised variably and highly amplified "nanochromosomes," each usually encoding a single gene with a minimal amount of surrounding noncoding DNA. As only a tiny fraction of the Stylonychia genes has been sequenced, and to promote research using this organism, we sequenced its macronuclear genome. We report the analysis of the 50.2-Mb draft S. lemnae macronuclear genome assembly, containing in excess of 16,000 complete nanochromosomes, assembled as less than 20,000 contigs. We found considerable conservation of fundamental genomic properties between S. lemnae and its close relative, Oxytricha trifallax, including nanochromosomal gene synteny, alternative fragmentation, and copy number. Protein domain searches in Stylonychia revealed two new telomere-binding protein homologs and the presence of linker histones. Among the diverse histone variants of S. lemnae and O. trifallax, we found divergent, coexpressed variants corresponding to four of the five core nucleosomal proteins (H1.2, H2A.6, H2B.4, and H3.7) suggesting that these ciliates may possess specialized nucleosomes involved in genome processing during nuclear differentiation. The assembly of the S. lemnae macronuclear genome demonstrates that largely complete, well-assembled highly fragmented genomes of similar size and complexity may be produced from one library and lane of Illumina HiSeq 2000 shotgun sequencing. The provision of the S. lemnae macronuclear genome sets the stage for future detailed experimental studies of chromatin-mediated, RNA-guided developmental genome rearrangements
Experimental simulation and assessment of the geysers of icy moons in the laboratory
No full textThe Cassini spacecraft, observing the Saturnian system for over 13 years, discovered aspects of the planetary system that were previously unseen. One such discovery is the eruption of geysers (plumes) from the Tiger Stripes on the surface of the icy moon Enceladus. An unexpected liquid water ocean exists underneath Enceladus’ icy crust (Postberg et al. 2018). A consequence of this finding was the complete revision of the habitability of the Solar System. This liquid ocean is propagated through conduits within the crust, and forms plumes when it reaches the surface. The plume material is believed to accelerate supersonically through nozzle-like channels (Schmidt et al. 2008) before being ejected at high speeds from the plume vents. This thesis aims to improve the physical understanding of the interaction between the ocean, icy crust, and the plumes of Enceladus, by experimentally simulating such a plume in the wind tunnel laboratories of TU Delft, and monitoring and analyzing the dynamic physical processes taking place across the experimental setup. A physical analog, separated into regions simulating the ocean, crevasse, and vent of the plume mechanism, is monitored with pressure and temperature sensors, while plume particles are detected with optical tracingtechniques. These observations lead to estimations of the vapor mass flow rate, the outflow Mach number, and the fraction of the plume mass that is condensed. It is found that the ocean conditions can be easily controlled through an adjustable heating power supply. The vapor flow generated by the boiling ocean becomes choked in the crevasse and can attain supersonic velocities. The thermodynamic conditions at the vent of the plume exhibit a greatly varying behavior suggesting that the combined effect of the crevasse geometry and thenucleation of vapor into liquid and icy particles results in considerable diversity in the plume characteristics. Thus, an isentropic description of the plume flow is found to be inadequate, while a Rayleigh flow is found to be feasible. Heat exchange phenomena appear to dominate locally the plume flow, as strong evidence of thermal choking in the crevasse is found. Particles with speeds of up to 426 ± 5 m/s are detected being ejected from the vent of the crevasse, and the maximum fraction of condensed plume mass is found to be 2.94% ± 0.15%. Finally, the possibility of a supersonic plume generated on Enceladus by a crevasse of constant cross-sectional area and cold walls is examined and found to be feasible.Aerospace Engineerin
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