Modulation of transcriptional activity in brain lower grade glioma by alternative splicing
Proteins that modify the activity of transcription factors (TFs) are often called modulators and play a vital role in gene transcriptional regulation. Alternative splicing is a critical step of gene processing, and differentially spliced isoforms may have different functions. Alternative splicing can modulate gene function by adding or removing certain protein domains and thereby influence the activity of a protein. The objective of this study is to investigate the role of alternative splicing in modulating the transcriptional regulation in brain lower grade glioma (LGG), especially transcription factor ELK1, which is closely related to various disorders, including Alzheimer’s disease and Down syndrome. The results showed that changes in the exon inclusion ratio of proteins APP and STK16 are associated with changes in the expression correlation between ELK1 and its targets. In addition, the structural features of the two modulators are strongly associated with the pathological impact of exon inclusion. The results of our analysis suggest that alternatively spliced proteins have different functions in modifying transcription factors and can thereby induce the dysregulation of multiple genes.
Li et al. (2018) Modulation of transcriptional activity in brain lower grade glioma by alternative splicing. PeerJ 6:e4686 https://doi.org/10.7717/peerj.4686
Chitin distribution in the Oithona digestive and reproductive systems revealed by fluorescence microscopy
Among copepods, which are the most abundant animals on Earth, the genus Oithona is described as one of the most numerous and plays a major role in the marine food chain and biogeochemical cycles, particularly through the excretion of chitin-coated fecal pellets. Despite the morphology of several Oithona species is well known, knowledge of its internal anatomy and chitin distribution is still limited. To answer this problem, Oithona nana and O. similis individuals were stained by Wheat Germ Agglutinin-Fluorescein IsoThioCyanate (WGA-FITC) and DiAmidino-2-PhenylIndole (DAPI) for fluorescence microscopy observations. The image analyses allowed a new description of the organization and chitin content of the digestive and reproductive systems of Oithona male and female. Chitin microfibrils were found all along the digestive system from the stomach to the hindgut with a higher concentration at the peritrophic membrane of the anterior midgut. Several midgut shrinkages were observed and proposed to be involved in faecal pellet shaping and motion. Amorphous chitin structures were also found to be a major component of the ducts and seminal vesicles and receptacles. The rapid staining protocol we proposed allowed a new insight into the Oithona internal anatomy and highlighted the role of chitin in the digestion and reproduction. This method could be applied to a wide range of copepods in order to perform comparative anatomy analyses.
Sugier et al. (2018) Chitin distribution in the Oithona digestive and reproductive systems revealed by fluorescence microscopy. PeerJ 6:e4685 https://doi.org/10.7717/peerj.4685
Testing methods to mitigate Caribbean yellow-band disease on Orbicella faveolata
Outbreaks of coral diseases continue to reduce global coral populations. In the Caribbean, yellow band is a severe and wide-spread disease that commonly affects corals of the Orbicella spp. complex, significantly impeding coral reproduction, and hindering the natural recovery of Orbicella spp. populations. Caribbean yellow-band disease (CYBD) lesions may be severe, and often result in the complete loss of coral tissue. The slow spread of CYBD, however, provides an opportunity to test methods to mitigate the disease. Here we report the results of in situ experiments, conducted within Buck Island Reef National Monument in St. Croix, USVI, to test the effectiveness of three techniques to minimize disease impact on Orbicella faveolata: (1) shading, (2) aspirating, and (3) chiseling a “firebreak” to isolate the lesion. Neither shading nor aspirating the diseased tissue significantly reduced CYBD tissue loss. However, chiseling reduced the rate and amount of tissue lost by 31%. While 30–40% of the chiseled lesions appeared to be free of disease signs 12–16 months after treatment, success significantly and steadily declined over 23 months, indicating a possible lack of long-term viability of the technique. The results of this study demonstrate that creating a “firebreak” between diseased and healthy-appearing tissue slows the spread of the disease and may prolong the life of O. faveolata colonies. The firebreak method yielded the best results of all the techniques tested, and also required the least amount of effort and resources. However, we do not recommend that this treatment alone be used for long-term disease mitigation. Rather, we propose that modifications of this and other treatment options be sought. The results also highlight the need for extended monitoring of CYBD after any treatment, due to the slow but variable rate and pattern of tissue loss in this disease.
Randall et al. (2018) Testing methods to mitigate Caribbean yellow-band disease on Orbicella faveolata. PeerJ 6:e4800 https://doi.org/10.7717/peerj.4800
‘2TM proteins’: an antigenically diverse superfamily with variable functions and export pathways
Malaria is a disease that affects millions of people annually. An intracellular habitat and lack of protein synthesizing machinery in erythrocytes pose numerous difficulties for survival of the human pathogen Plasmodium falciparum. The parasite refurbishes the infected red blood cell (iRBC) by synthesis and export of several proteins in an attempt to suffice its metabolic needs and evade the host immune response. Immune evasion is largely mediated by surface display of highly polymorphic protein families known as variable surface antigens. These include the two trans-membrane (2TM) superfamily constituted by multicopy repetitive interspersed family (RIFINs), subtelomeric variable open reading frame (STEVORs) and Plasmodium falciparum Maurer’s cleft two trans-membrane proteins present only in P. falciparum and some simian infecting Plasmodium species. Their hypervariable region flanked by 2TM domains exposed on the iRBC surface is believed to generate antigenic diversity. Though historically named “2TM superfamily,” several A-type RIFINs and some STEVORs assume one trans-membrane topology. RIFINs and STEVORs share varied functions in different parasite life cycle stages like rosetting, alteration of iRBC rigidity and immune evasion. Additionally, a member of the STEVOR family has been implicated in merozoite invasion. Differential expression of these families in laboratory strains and clinical isolates propose them to be important for host cell survival and defense. The role of RIFINs in modulation of host immune response and presence of protective antibodies against these surface exposed molecules in patient sera highlights them as attractive targets of antimalarial therapies and vaccines. 2TM proteins are Plasmodium export elements positive, and several of these are exported to the infected erythrocyte surface after exiting through the classical secretory pathway within parasites. Cleaved and modified proteins are trafficked after packaging in vesicles to reach Maurer’s clefts, while information regarding delivery to the iRBC surface is sparse. Expression and export timing of the RIFIN and Plasmodium falciparum erythrocyte membrane protein1 families correspond to each other. Here, we have compiled and comprehended detailed information regarding orthologues, domain architecture, surface topology, functions and trafficking of members of the “2TM superfamily.” Considering the large repertoire of proteins included in the 2TM superfamily and recent advances defining their function in malaria biology, a surge in research carried out on this important protein superfamily is likely.
Kaur et al. (2018) ‘2TM proteins’: an antigenically diverse superfamily with variable functions and export pathways. PeerJ 6:e4757 https://doi.org/10.7717/peerj.4757
A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants
Background Alzheimer’ disease (AD) is an ultimately fatal degenerative brain disorder that has an increasingly large burden on health and social care systems. There are only five drugs for AD on the market, and no new effective medicines have been discovered for many years. Chinese medicinal plants have been used to treat diseases for thousands of years, and screening herbal remedies is a way to develop new drugs. Methods We used molecular docking to screen 30,438 compounds from Traditional Chinese Medicine (TCM) against a comprehensive list of AD target proteins. TCM compounds in the top 0.5% of binding affinity scores for each target protein were selected as our research objects. Structural similarities between existing drugs from DrugBank database and selected TCM compounds as well as the druggability of our candidate compounds were studied. Finally, we searched the CNKI database to obtain studies on anti-AD Chinese plants from 2007 to 2017, and only clinical studies were included. Results A total of 1,476 compounds (top 0.5%) were selected as drug candidates. Most of these compounds are abundantly found in plants used for treating AD in China, especially the plants from two genera Panax and Morus. We classified the compounds by single target and multiple targets and analyzed the interactions between target proteins and compounds. Analysis of structural similarity revealed that 17 candidate anti-AD compounds were structurally identical to 14 existing approved drugs. Most of them have been reported to have a positive effect in AD. After filtering for compound druggability, we identified 11 anti-AD compounds with favorable properties, seven of which are found in anti-AD Chinese plants. Of 11 anti-AD compounds, four compounds 5,862, 5,863, 5,868, 5,869 have anti-inflammatory activity. The compound 28,814 mainly has immunoregulatory activity. The other six compounds have not yet been reported for any biology activity at present. Discussion Natural compounds from TCM provide a broad prospect for the screening of anti-AD drugs. In this work, we established networks to systematically study the connections among natural compounds, approved drugs, TCM plants and AD target proteins with the goal of identifying promising drug candidates. We hope that our study will facilitate in-depth research for the treatment of AD in Chinese medicine.
Chen et al. (2018) A strategy to find novel candidate anti-Alzheimer’s disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants. PeerJ 6:e4756 https://doi.org/10.7717/peerj.4756
The evaluation of anoxia responsive E2F DNA binding activity in the red eared slider turtle, Trachemys scripta elegans
In many cases, the DNA-binding activity of a transcription factor does not change, while its transcriptional activity is greatly influenced by the make-up of bound proteins. In this study, we assessed the protein composition and DNA-binding ability of the E2F transcription factor complex to provide insight into cell cycle control in an anoxia tolerant turtle through the use of a modified ELISA protocol. This modification also permits the use of custom DNA probes that are tailored to a specific DNA binding region, introducing the ability to design capture probes for non-model organisms. Through the use of EMSA and ELISA DNA binding assays, we have successfully determined the in vitro DNA binding activity and complex dynamics of the Rb/E2F cell cycle regulatory mechanisms in an anoxic turtle, Trachemys scripta elegans. Repressive cell cycle proteins (E2F4, Rb, HDAC4 and Suv39H1) were found to significantly increase at E2F DNA-binding sites upon anoxic exposure in anoxic turtle liver. The lack of p130 involvement in the E2F DNA-bound complex indicates that anoxic turtle liver may maintain G1 arrest for the duration of stress survival.
Biggar et al. (2018) The evaluation of anoxia responsive E2F DNA binding activity in the red eared slider turtle, Trachemys scripta elegans. PeerJ 6:e4755 https://doi.org/10.7717/peerj.4755
Plant, fungal, bacterial, and nitrogen interactions in the litter layer of a native Patagonian forest
Plant–microbial interactions in the litter layer represent one of the most relevant interactions for biogeochemical cycling as litter decomposition is a key first step in carbon and nitrogen turnover. However, our understanding of these interactions in the litter layer remains elusive. In an old-growth mixed Nothofagus forest in Patagonia, we studied the effects of single tree species identity and the mixture of three tree species on the fungal and bacterial composition in the litter layer. We also evaluated the effects of nitrogen (N) addition on these plant–microbial interactions. In addition, we compared the magnitude of stimulation of litter decomposition due to home field advantage (HFA, decomposition occurs more rapidly when litter is placed beneath the plant species from which it had been derived than beneath a different plant species) and N addition that we previously demonstrated in this same forest, and used microbial information to interpret these results. Tree species identity had a strong and significant effect on the composition of fungal communities but not on the bacterial community of the litter layer. The microbial composition of the litter layer under the tree species mixture show an averaged contribution of each single tree species. N addition did not erase the plant species footprint on the fungal community, and neither altered the bacterial community. N addition stimulated litter decomposition as much as HFA for certain tree species, but the mechanisms behind N and HFA stimulation may have differed. Our results suggest that stimulation of decomposition from N addition might have occurred due to increased microbial activity without large changes in microbial community composition, while HFA may have resulted principally from plant species’ effects on the litter fungal community. Together, our results suggest that plant–microbial interactions can be an unconsidered driver of litter decomposition in temperate forests.
Vivanco et al. (2018) Plant, fungal, bacterial, and nitrogen interactions in the litter layer of a native Patagonian forest. PeerJ 6:e4754 https://doi.org/10.7717/peerj.4754
Do running speed and shoe cushioning influence impact loading and tibial shock in basketball players?
Background Tibial stress fracture (TSF) is a common injury in basketball players. This condition has been associated with high tibial shock and impact loading, which can be affected by running speed, footwear condition, and footstrike pattern. However, these relationships were established in runners but not in basketball players, with very little research done on impact loading and speed. Hence, this study compared tibial shock, impact loading, and foot strike pattern in basketball players running at different speeds with different shoe cushioning properties/performances. Methods Eighteen male collegiate basketball players performed straight running trials with different shoe cushioning (regular-, better-, and best-cushioning) and running speed conditions (3.0 m/s vs. 6.0 m/s) on a flat instrumented runway. Tri-axial accelerometer, force plate and motion capture system were used to determine tibial accelerations, vertical ground reaction forces and footstrike patterns in each condition, respectively. Comfort perception was indicated on a 150 mm Visual Analogue Scale. A 2 (speed) × 3 (footwear) repeated measures ANOVA was used to examine the main effects of shoe cushioning and running speeds. Results Greater tibial shock (P < 0.001; η2 = 0.80) and impact loading (P < 0.001; η2 = 0.73–0.87) were experienced at faster running speeds. Interestingly, shoes with regular-cushioning or best-cushioning resulted in greater tibial shock (P = 0.03; η2 = 0.39) and impact loading (P = 0.03; η2 = 0.38–0.68) than shoes with better-cushioning. Basketball players continued using a rearfoot strike during running, regardless of running speed and footwear cushioning conditions (P > 0.14; η2 = 0.13). Discussion There may be an optimal band of shoe cushioning for better protection against TSF. These findings may provide insights to formulate rehabilitation protocols for basketball players who are recovering from TSF.
Lam et al. (2018) Do running speed and shoe cushioning influence impact loading and tibial shock in basketball players?. PeerJ 6:e4753 https://doi.org/10.7717/peerj.4753
Westwards and northwards dispersal of Triosteum himalayanum (Caprifoliaceae) from the Hengduan Mountains region based on chloroplast DNA phylogeography
The varying topography and environment that resulted from paleoorogeny and climate fluctuations of the Himalaya–Hengduan Mountains (HHM) areas had a considerable impact on the evolution of biota during the Quaternary. To understand the phylogeographic pattern and historical dynamics of Triosteum himalayanum (Caprifoliaceae), we sequenced three chloroplast DNA fragments (rbcL-accD, rps15-ycf1, and trnH-psbA) from 238 individuals representing 20 populations. Nineteen haplotypes (H1–H19) were identified based on 23 single-site mutations and eight indels. Most haplotypes were restricted to a single population or neighboring populations. Analysis of molecular variance revealed that variations among populations were much higher than that within populations for the overall gene pool, as well as for the East Himalayan group (EH group) and the North Hengduan group (NHM group), but not for the Hengduan Mountains group (HM group). Ecoregions representing relatively high genetic diversity or high frequencies of private haplotypes were discovered, suggesting that this alpine herbaceous plant underwent enhanced allopatric divergence in isolated and fragmented locations during the Quaternary glaciations. The current phylogeographic structure of T. himalayanum might be due to heterogeneous habitats and Quaternary climatic oscillations. Based on the phylogeographic structure of T. himalayanum populations, the phylogenetic relationship of identified haplotypes and palaeodistributional reconstruction, we postulated both westwards and northwards expansion from the HM group for this species. The westwards dispersal corridor could be long, narrow mountain areas and/or the Yarlung Zangbo Valley, while the northwards movement path could be south–north oriented mountains and low-elevation valleys.
Liu et al. (2018) Westwards and northwards dispersal of Triosteum himalayanum (Caprifoliaceae) from the Hengduan Mountains region based on chloroplast DNA phylogeography. PeerJ 6:e4748 https://doi.org/10.7717/peerj.4748
From the Guiana Highlands to the Brazilian Atlantic Rain Forest: four new species of Selaginella (Selaginellaceae – Lycopodiophyta: S. agioneuma, S. magnafornensis, S. ventricosa, and S. zartmanii)
We describe four new species in the genus Selaginella (i.e., S. agioneuma, S. magnafornensis, S. ventricosa, and S. zartmanii) from Brazil, all presently classified in subg. Stachygynandrum. For each of the new taxa we discuss taxonomic affinities and provide information on habitat, distribution, and conservation status. In addition, line drawings and scanning electron microscope (SEM) images of stems sections, leaves, and spores (when present) are included. Selaginella agioneuma and S. magnafornensis are from the State of Espíritu Santo where they inhabit premontane to montane Atlantic rain forests in the Reserva Biológica Augusto Ruschi and Parque Estadual Forno Grande, respectively. Selaginella ventricosa was collected in upper montane forests at Parque Nacional Serra da Mocidade, State of Roraima and S. zartmanii in premontane Amazon rain forests on upper Rio Negro at Mpio. São Gabriel da Cachoeira, Amazonas State in both Serra Curicuriari and the Morro dos Seis Lagos Biological Reserve.
Valdespino et al. (2018) From the Guiana Highlands to the Brazilian Atlantic Rain Forest: four new species of Selaginella (Selaginellaceae – Lycopodiophyta: S. agioneuma, S. magnafornensis, S. ventricosa, and S. zartmanii). PeerJ 6:e4708 https://doi.org/10.7717/peerj.4708