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
Comparison of hoop-net trapping and visual surveys to monitor abundance of the Rio Grande cooter (Pseudemys gorzugi)
Abundance estimates play an important part in the regulatory and conservation decision-making process. It is important to correct monitoring data for imperfect detection when using these data to track spatial and temporal variation in abundance, especially in the case of rare and elusive species. This paper presents the first attempt to estimate abundance of the Rio Grande cooter (Pseudemys gorzugi) while explicitly considering the detection process. Specifically, in 2016 we monitored this rare species at two sites along the Black River, New Mexico via traditional baited hoop-net traps and less invasive visual surveys to evaluate the efficacy of these two sampling designs. We fitted the Huggins closed-capture estimator to estimate capture probabilities using the trap data and distance sampling models to estimate detection probabilities using the visual survey data. We found that only the visual survey with the highest number of observed turtles resulted in similar abundance estimates to those estimated using the trap data. However, the estimates of abundance from the remaining visual survey data were highly variable and often underestimated abundance relative to the estimates from the trap data. We suspect this pattern is related to changes in the basking behavior of the species and, thus, the availability of turtles to be detected even though all visual surveys were conducted when environmental conditions were similar. Regardless, we found that riverine habitat conditions limited our ability to properly conduct visual surveys at one site. Collectively, this suggests visual surveys may not be an effective sample design for this species in this river system. When analyzing the trap data, we found capture probabilities to be highly variable across sites and between age classes and that recapture probabilities were much lower than initial capture probabilities, highlighting the importance of accounting for detectability when monitoring this species. Although baited hoop-net traps seem to be an effective sampling design, it is important to note that this method required a relatively high trap effort to reliably estimate abundance. This information will be useful when developing a larger-scale, long-term monitoring program for this species of concern.
Mali et al. (2018) Comparison of hoop-net trapping and visual surveys to monitor abundance of the Rio Grande cooter (Pseudemys gorzugi). PeerJ 6:e4677 https://doi.org/10.7717/peerj.4677
Lighten up the dark: metazoan parasites as indicators for the ecology of Antarctic crocodile icefish (Channichthyidae) from the north-west Antarctic Peninsula
Due to its remote and isolated location, Antarctica is home to a unique diversity of species. The harsh conditions have shaped a primarily highly adapted endemic fauna. This includes the notothenioid family Channichthyidae. Their exceptional physiological adaptations have made this family of icefish the focus of many studies. However, studies on their ecology, especially on their parasite fauna, are comparatively rare. Parasites, directly linked to the food chain, can function as biological indicators and provide valuable information on host ecology (e.g., trophic interactions) even in remote habitats with limited accessibility, such as the Southern Ocean. In the present study, channichthyid fish (Champsocephalus gunnari: n = 25, Chaenodraco wilsoni: n = 33, Neopagetopsis ionah: n = 3, Pagetopsis macropterus: n = 4, Pseudochaenichthys georgianus: n = 15) were collected off South Shetland Island, Elephant Island, and the tip of the Antarctic Peninsula (CCAML statistical subarea 48.1). The parasite fauna consisted of 14 genera and 15 species, belonging to the six taxonomic groups including Digenea (four species), Nematoda (four), Cestoda (two), Acanthocephala (one), Hirudinea (three), and Copepoda (one). The stomach contents were less diverse with only Crustacea (Euphausiacea, Amphipoda) recovered from all examined fishes. Overall, 15 new parasite-host records could be established, and possibly a undescribed genotype or even species might exist among the nematodes.
Kuhn et al. (2018) Lighten up the dark: metazoan parasites as indicators for the ecology of Antarctic crocodile icefish (Channichthyidae) from the north-west Antarctic Peninsula. PeerJ 6:e4638 https://doi.org/10.7717/peerj.4638
Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications
The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogram human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy. However, fundamental questions have been raised regarding the molecular mechanism of iPSCs generation, a process still poorly understood by scientists. The efficiency of reprogramming of iPSCs remains low due to the effect of various barriers to reprogramming. There is also the risk of chromosomal instability and oncogenic transformation associated with the use of viral vectors, such as retrovirus and lentivirus, which deliver the reprogramming transcription factors by integration in the host cell genome. These challenges can hinder the therapeutic prospects and promise of iPSCs and their clinical applications. Consequently, extensive studies have been done to elucidate the molecular mechanism of reprogramming and novel strategies have been identified which help to improve the efficiency of reprogramming methods and overcome the safety concerns linked with iPSC generation. Distinct barriers and enhancers of reprogramming have been elucidated, and non-integrating reprogramming methods have been reported. Here, we summarize the progress and the recent advances that have been made over the last 10 years in the iPSC field, with emphasis on the molecular mechanism of reprogramming, strategies to improve the efficiency of reprogramming, characteristics and limitations of iPSCs, and the progress made in the applications of iPSCs in the field of disease modelling, drug discovery and regenerative medicine. Additionally, this study appraises the role of genomic editing technology in the generation of healthy iPSCs.
Omole et al. (2018) Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications. PeerJ 6:e4370 https://doi.org/10.7717/peerj.4370
Glycosylceramide modifies the flavor and metabolic characteristics of sake yeast
In the manufacture of sake, Japanese traditional rice wine, sake yeast is fermented with koji, which is steamed rice fermented with the non-pathogenic fungus Aspergillus oryzae. During fermentation, sake yeast requires lipids, such as unsaturated fatty acids and sterols, in addition to substances provided by koji enzymes for fermentation. However, the role of sphingolipids on the brewing characteristics of sake yeast has not been studied. In this study, we revealed that glycosylceramide, one of the sphingolipids abundant in koji, affects yeast fermentation. The addition of soy, A. oryzae, and Grifola frondosa glycosylceramide conferred a similar effect on the flavor profiles of sake yeast. In particular, the addition of A. oryzae and G. frondosa glycosylceramide were very similar in terms of the decreases in ethyl caprylate and ethyl 9-decenoate. The addition of soy glycosylceramide induced metabolic changes to sake yeast such as a decrease in glucose, increases in ethanol and glycerol and changes in several amino acids and organic acids concentrations. Tricarboxylic acid (TCA) cycle, pyruvate metabolism, starch and sucrose metabolism, and glycerolipid metabolism were overrepresented in the cultures incubated with sake yeast and soy glycosylceramide. This is the first study of the effect of glycosylceramide on the flavor and metabolic profile of sake yeast.
Ferdouse et al. (2018) Glycosylceramide modifies the flavor and metabolic characteristics of sake yeast. PeerJ 6:e4768 https://doi.org/10.7717/peerj.4768