First body of evidence suggesting a role of a tankyrase-binding motif (TBM) of vinculin (VCL) in epithelial cells
Background Adherens junctions (AJ) are involved in cancer, infections and neurodegeneration. Still, their composition has not been completely disclosed. Poly(ADP-ribose) polymerases (PARPs) catalyze the synthesis of poly(ADP-ribose) (PAR) as a posttranslational modification. Four PARPs synthesize PAR, namely PARP-1/2 and Tankyrase-1/2 (TNKS). In the epithelial belt, AJ are accompanied by a PAR belt and a subcortical F-actin ring. F-actin depolymerization alters the AJ and PAR belts while PARP inhibitors prevent the assembly of the AJ belt and cortical actin. We wondered which PARP synthesizes the belt and which is the PARylation target protein. Vinculin (VCL) participates in the anchorage of F-actin to the AJ, regulating its functions, and colocalized with the PAR belt. TNKS has been formerly involved in the assembly of epithelial cell junctions. Hypothesis TNKS poly(ADP-ribosylates) (PARylates) epithelial belt VCL, affecting its functions in AJ, including cell shape maintenance. Materials and Methods Tankyrase-binding motif (TBM) sequences in hVCL gene were identified and VCL sequences from various vertebrates, Drosophila melanogaster and Caenorhabditis elegans were aligned and compared. Plasma membrane-associated PAR was tested by immunocytofluorescence (ICF) and subcellular fractionation in Vero cells while TNKS role in this structure and cell junction assembly was evaluated using specific inhibitors. The identity of the PARylated proteins was tested by affinity precipitation with PAR-binding reagent followed by western blots. Finally, MCF-7 human breast cancer epithelial cells were subjected to transfection with Tol2-plasmids, carrying a dicistronic expression sequence including Gallus gallus wt VCL (Tol-2-GgVCL), or the same VCL gene with a point mutation in TBM-II (Tol2-GgVCL/*TBM) under the control of a β-actin promoter, plus green fluorescent protein following an internal ribosome entry site (IRES-GFP) to allow the identification of transfected cells without modifying the transfected protein of interest. Results and discussion In this work, some of the hypothesis predictions have been tested. We have demonstrated that: (1) VCL TBMs were conserved in vertebrate evolution while absent in C. elegans; (2) TNKS inhibitors disrupted the PAR belt synthesis, while PAR and an endogenous TNKS pool were associated to the plasma membrane; (3) a VCL pool was covalently PARylated; (4) transfection of MCF-7 cells leading to overexpression of Gg-VCL/*TBM induced mesenchymal-like cell shape changes. This last point deserves further investigation, bypassing the limits of our transient transfection and overexpression system. In fact, a 5th testable prediction would be that a single point mutation in VCL TBM-II under endogenous expression control would induce an epithelial to mesenchymal transition (EMT). To check this, a CRISPR/Cas9 substitution approach followed by migration, invasion, gene expression and chemo-resistance assays should be performed.
Vilchez Larrea et al. (2021) First body of evidence suggesting a role of a tankyrase-binding motif (TBM) of vinculin (VCL) in epithelial cells. PeerJ 9:e11442 https://doi.org/10.7717/peerj.11442
Identification of key microRNAs and the underlying molecular mechanism in spinal cord ischemia-reperfusion injury in rats
Spinal cord ischemia-reperfusion injury (SCII) is a pathological process with severe complications such as paraplegia and paralysis. Aberrant miRNA expression is involved in the development of SCII. Differences in the experimenters, filtering conditions, control selection, and sequencing platform may lead to different miRNA expression results. This study systematically analyzes the available SCII miRNA expression data to explore the key differently expressed miRNAs (DEmiRNAs) and the underlying molecular mechanism in SCII. A systematic bioinformatics analysis was performed on 23 representative rat SCII miRNA datasets from PubMed. The target genes of key DEmiRNAs were predicted on miRDB. The DAVID and TFactS databases were utilized for functional enrichment and transcription factor binding analyses. In this study, 19 key DEmiRNAs involved in SCII were identified, 9 of which were upregulated (miR-144-3p, miR-3568, miR-204, miR-30c, miR-34c-3p, miR-155-3p, miR-200b, miR-463, and miR-760-5p) and 10 downregulated (miR-28-5p, miR-21-5p, miR-702-3p, miR-291a-3p, miR-199a-3p, miR-352, miR-743b-3p, miR-125b-2-3p, miR-129-1-3p, and miR-136). KEGG enrichment analysis on the target genes of the upregulated DEmiRNAs revealed that the involved pathways were mainly the cGMP-PKG and cAMP signaling pathways. KEGG enrichment analysis on the target genes of the downregulated DEmiRNAs revealed that the involved pathways were mainly the Chemokine and MAPK signaling pathways. GO enrichment analysis indicated that the target genes of the upregulated DEmiRNAs were markedly enriched in biological processes such as brain development and the positive regulation of transcription from RNA polymerase II promoter. Target genes of the downregulated DEmiRNAs were mainly enriched in biological processes such as intracellular signal transduction and negative regulation of cell proliferation. According to the transcription factor analysis, the four transcription factors, including SP1, GLI1, GLI2, and FOXO3, had important regulatory effects on the target genes of the key DEmiRNAs. Among the upregulated DEmiRNAs, miR-3568 was especially interesting. While SCII causes severe neurological deficits of lower extremities, the anti-miRNA oligonucleotides (AMOs) of miR-3568 improve neurological function. Cleaved caspase-3 and Bax was markedly upregulated in SCII comparing to the sham group, and miR-3568 AMO reduced the upregulation. Bcl-2 expression levels showed a opposite trend as cleaved caspase-3. The expression of GATA6, GATA4, and RBPJ decreased after SCII and miR-3568 AMO attenuated this upregulation. In conclusion, 19 significant DEmiRNAs in the pathogenesis of SCII were identified, and the underlying molecular mechanisms were validated. The DEmiRNAs could serve as potential intervention targets for SCII. Moreover, inhibition of miR-3568 preserved hind limb function after SCII by reducing apoptosis, possibly through regulating GATA6, GATA4, and RBPJ in SCII.
Chen et al. (2021) Identification of key microRNAs and the underlying molecular mechanism in spinal cord ischemia-reperfusion injury in rats. PeerJ 9:e11454 https://doi.org/10.7717/peerj.11454
Identification of potential gene signatures associated with osteosarcoma by integrated bioinformatics analysis
Background Osteosarcoma (OS) is the most primary malignant bone cancer in children and adolescents with a high mortality rate. This work aims to screen novel potential gene signatures associated with OS by integrated microarray analysis of the Gene Expression Omnibus (GEO) database. Material and Methods The OS microarray datasets were searched and downloaded from GEO database to identify differentially expressed genes (DEGs) between OS and normal samples. Afterwards, the functional enrichment analysis, protein–protein interaction (PPI) network analysis and transcription factor (TF)-target gene regulatory network were applied to uncover the biological function of DEGs. Finally, two published OS datasets (GSE39262 and GSE126209) were obtained from GEO database for evaluating the expression level and diagnostic values of key genes. Results In total 1,059 DEGs (569 up-regulated DEGs and 490 down-regulated DEGs) between OS and normal samples were screened. Functional analysis showed that these DEGs were markedly enriched in 214 GO terms and 54 KEGG pathways such as pathways in cancer. Five genes (CAMP, METTL7A, TCN1, LTF and CXCL12) acted as hub genes in PPI network. Besides, METTL7A, CYP4F3, TCN1, LTF and NETO2 were key genes in TF-gene network. Moreover, Pax-6 regulated four key genes (TCN1, CYP4F3, NETO2 and CXCL12). The expression levels of four genes (METTL7A, TCN1, CXCL12 and NETO2) in GSE39262 set were consistent with our integration analysis. The expression levels of two genes (CXCL12 and NETO2) in GSE126209 set were consistent with our integration analysis. ROC analysis of GSE39262 set revealed that CYP4F3, CXCL12, METTL7A, TCN1 and NETO2 had good diagnostic values for OS patients. ROC analysis of GSE126209 set revealed that CXCL12, METTL7A, TCN1 and NETO2 had good diagnostic values for OS patients.
Jia et al. (2021) Identification of potential gene signatures associated with osteosarcoma by integrated bioinformatics analysis. PeerJ 9:e11496 https://doi.org/10.7717/peerj.11496
Bracon wasps for ecological pest control–a laboratory experiment
Biological control of pest insects by natural enemies may be an effective, cheap and environmentally friendly alternative to synthetic pesticides. The cosmopolitan parasitoid wasp species Bracon brevicornis Wesmael and B. hebetor Say (Hymenoptera: Braconidae) use lepidopteran species as hosts, including insect pests like Ephestia kuehniella or Ostrinia nubilalis. Here, we compare the reproductive success of both Bracon species on E. kuehniella in a laboratory experiment. We asked (1) how the reproductive success on a single host larva changes with temperature, (2) how it changes with temperature when more host larvae are present and (3) how temperature and availability of host larvae influence the efficacy of Bracon species as biological control agents. In general, differences between B. brevicornis and B. hebetor have been small. For rearing both Bracon species in the laboratory on one host larva, a temperature between 20–27 °C seems appropriate to obtain the highest number of offspring with a female-biased sex ratio. Rearing the braconid wasps on more than one host larva revealed a higher number of total offspring but less offspring per host larva on average. Again, highest numbers of offspring hatched at 27 °C and the sex ratio was independent from temperature. Although no parasitoids hatched at 12 °C and only few at 36 °C, host larvae were still paralyzed. The efficacy of B. brevicornis was higher than 80% at all numbers of host larvae presented at all temperatures while the efficacy of B. hebetor was less than 80% at 12 °C and 27 °C at low numbers of host larvae presented. In conclusion, practitioners can use either B. brevicornis or B. hebetor at low and high temperatures and at varying host densities to achieve high pest control efficacy.
Lettmann et al. (2021) Bracon wasps for ecological pest control–a laboratory experiment. PeerJ 9:e11540 https://doi.org/10.7717/peerj.11540
The effect of a brown-rice diets on glycemic control and metabolic parameters in prediabetes and type 2 diabetes mellitus: a meta-analysis of randomized controlled trials and controlled clinical trials
Background Brown rice is a whole-grain food that is often assumed to have a lower glycemic index compared to white rice. A few studies have objectively confirmed the effect of a brown-rice diet on glycemic control and metabolic parameters compared to a white-rice diet. The purpose of this study is to determine the effect of brown rice on improving glycemic control and metabolic parameters in prediabetes and type 2 diabetes. The researchers conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and controlled clinical trials. Methods PRISMA guidelines were used as the basis of this systematic review. Relevant studies were identified by searching the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), as well as Epistemonikos for randomized controlled trials (RCTs) and controlled clinical trials published not later than January 2021 involving adults with prediabetes and diabetes mellitus who were consuming brown rice compared to those consuming white rice. The primary outcomes measured were glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) levels. The secondary outcomes were body weight, waist circumference, systolic and diastolic blood pressure levels, LDL and HDL-cholesterol levels. The mean differences (MDs) with 95% confidence intervals (CIs) between brown and white-rice-diet groups were calculated using a random-effects model. Results Seven trials involving 417 adults with prediabetes or type 2 diabetes were included in this study. Brown-rice diet did not improve the glycemic control because it had no effect on the HbA1c level (p = 0.15) and the FBG level (p = 0.95) compared to white-rice diet. Brown-rice diet reduced body weight (p < 0.00001; MD −2.2 kg; 95% CI [−3.13 to −1.26]; I2 = 0%). However, it had no effect on the waist circumference (p = 0.09), systolic blood pressure (p = 0.60) and diastolic blood pressure level (p = 0.40). HDL-cholesterol level is increased in brown-rice diet (p = 0.01; MD 0.10, 95% CI [0.02 to 0.17]; I2 = 44%) but it had no effect on the LDL-cholesterol level (p = 0.81). Conclusions The available evidence indicated that consuming brown rice in substitute for white rice does not affect glycemic control (HbA1c and FBG levels) in pre-diabetes and type 2 diabetes patients. Brown rice, however, may be used as an alternative for white rice in such patients because it was found to reduce body weight and increase the HDL-cholesterol level. The benefits of a brown-rice diet on glycemic control may not be detected in short-term studies. The obtained evidence in this meta-analysis ranged from low to moderate quality. Thus, more high-quality trials with a larger sample size and a longer follow-up duration are needed to further investigate the effects of a brown-rice diet on diabetes glycemic control with stronger evidence. PROSPERO registration number: CRD42019143266
Abdul Rahim et al. (2021) The effect of a brown-rice diets on glycemic control and metabolic parameters in prediabetes and type 2 diabetes mellitus: a meta-analysis of randomized controlled trials and controlled clinical trials. PeerJ 9:e11291 https://doi.org/10.7717/peerj.11291
New insight into the divergent responses of plants to warming in the context of root endophytic bacterial and fungal communities
Plant adaptation under climate changes is critical to the maintenance of terrestrial ecosystem structure and function. Studying the response of the endophytic community to climate warming is a novel way to reveal the mechanism of host environmental adaptability because of the prominent role endophytes play in host nutrient acquisition and stress tolerance. However, host performance was generally neglected in previous relevant research, which limits our understanding of the relationships between the endophytic community and host responses to climate warming. The present study selected two plants with different responses to climate warming. Elymus nutans is more suitable for growing in warm environments at low altitude compared to Kobresia pygmaea. K. pygmaea and E. nutans were sampled along an altitude gradient in the natural grassland of Qinghai-Tibet Plateau, China. Root endophytic bacterial and fungal communities were analyzed using high throughput sequencing. The results revealed that hosts growing in more suitable habitats held higher endophytic fungal diversity. Elevation and host identity significantly affected the composition of the root endophytic bacterial and fungal community. 16S rRNA functional prediction demonstrated that hosts that adapted to lower temperatures recruited endophytic communities with higher abundance of genes related to cold resistance. Hosts that were more suitable for warmer and drier environments recruited endophytes with higher abundance of genes associated with nutrient absorption and oxidation resistance. We associated changes in the endophytic community with hosts adaptability to climate warming and suggested a synchronism of endophytic communities and hosts in environmental adaptation.
Wei et al. (2021) New insight into the divergent responses of plants to warming in the context of root endophytic bacterial and fungal communities. PeerJ 9:e11340 https://doi.org/10.7717/peerj.11340
Only two out of five articles by New Zealand researchers are free-to-access: a multiple API study of access, citations, cost of Article Processing Charges (APC), and the potential to increase the proportion of open access
We studied journal articles published by researchers at all eight New Zealand universities in 2017 to determine how many were freely accessible on the web. We wrote software code to harvest data from multiple sources, code that we now share to enable others to reproduce our work on their own sample set. In May 2019, we ran our code to determine which of the 2017 articles were open at that time and by what method; where those articles would have incurred an Article Processing Charge (APC) we calculated the cost if those charges had been paid. Where articles were not freely available we determined whether the policies of publishers in each case would have allowed deposit in a non-commercial repository (Green open access). We also examined citation rates for different types of access. We found that, of our 2017 sample set, about two out of every five articles were freely accessible without payment or subscription (41%). Where research was explicitly said to be funded by New Zealand’s major research funding agencies, the proportion was slightly higher at 45%. Where open articles would have incurred an APC we estimated an average cost per article of USD1,682 (for publications where all articles require an APC, that is, Gold open access) and USD2,558 (where APC payment is optional, Hybrid open access) at a total estimated cost of USD1.45m. Of the paid options, Gold is by far more common for New Zealand researchers (82% Gold, 18% Hybrid). In terms of citations, our analysis aligned with previous studies that suggest a correlation between publications being freely accessible and, on balance, slightly higher rates of citation. This is not seen across all types of open access, however, with Diamond OA achieving the lowest rates. Where articles were not freely accessible we found that a very large majority of them (88% or 3089 publications) could have been legally deposited in an institutional repository. Similarly, only in a very small number of cases had a version deposited in the repository of a New Zealand university made the difference between the publication being freely accessible or not (125 publications). Given that most New Zealand researchers support research being open, there is clearly a large gap between belief and practice in New Zealand’s research ecosystem.
White et al. (2021) Only two out of five articles by New Zealand researchers are free-to-access: a multiple API study of access, citations, cost of Article Processing Charges (APC), and the potential to increase the proportion of open access. PeerJ 9:e11417 https://doi.org/10.7717/peerj.11417
Key circular RNAs identified in male osteoporosis patients by whole transcriptome sequencing
Background Osteoporosis (OP) is a systemic disease with bone loss and microstructural deterioration. Numerous noncoding RNAs (ncRNAs) have been proved to participate in various diseases, especially circular RNAs (circRNAs). However, the expression profile and mechanisms underlying circRNAs in male osteoporosis have not yet been explored. Methods The whole transcriptome expression profile and differences in mRNAs, circRNAs, and microRNAs (miRNAs) were investigated in peripheral blood samples of patients with osteoporosis and healthy controls consisting of males ≥ 60-years-old. Results A total of 398 circRNAs, 51 miRNAs, and 642 mRNAs were significantly and differentially expressed in osteoporosis compared to healthy controls. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the host genes of significantly differentially expressed circRNAs were mainly enriched in the regulation of cell cycle process: biological process (BP), organelle part cellular components (CC), protein binding molecular function (MF), Toll-like receptor signaling pathway, tumor necrosis factor (TNF) signaling pathway, and thyroid hormone signaling pathway. circRNA-miRNA-mRNA regulatory network was constructed using the differentially expressed RNAs. Moreover, key circRNAs (hsa_circ_0042409) in osteoporosis were discovered and validated by qPCR. Conclusions The key cicrRNAs plays a major role in the pathogenesis of osteoporosis and could be used as potential biomarkers or targets in the diagnosis and treatment of osteoporosis.
Zhang et al. (2021) Key circular RNAs identified in male osteoporosis patients by whole transcriptome sequencing. PeerJ 9:e11420 https://doi.org/10.7717/peerj.11420
Integrative species delimitation based on COI, ITS, and morphological evidence illustrates a unique evolutionary history of the genus Paracercion (Odonata: Coenagrionidae)
Paracercion are common ‘blue and black’ colored damselflies. We explore the species boundaries of Paracercion (Odonata: Coenagrionidae) using ABGD, bPTP, GMYC and Distance-based clustering. We finally got the molecular data of all nine species of Paracercion. P. hieroglyphicum and P. melanotum were combined into one putative species based on cytochrome c oxidase I (COI). However, they were separated into two putative species based on the nuclear segment including ITS1-5.8S-ITS2 (ITS). This suggests the introgression of mtDNA in Paracercion. Paracercion barbatum and Paracercion melanotum can be separated into two species based on COI, whereas they were combined into one putative species based on ITS, which suggests a hybridization event between them. The lower interspecific divergence (COI: 0.49%) between P. barbatum and Paracercion v-nigrum indicates a recent speciation event in Paracercion. Paracercion sieboldii and P. v-nigrum can be separated into two putative species based on COI, while they were frequently merged into the same putative species based on ITS. This can be explained by incomplete lineage sorting in nDNA. Besides, P. pendulum and P. malayanum were synonymized as junior synonyms of P. melanotum. P. luzonicum was confirmed not to belong to Paracercion. The possibility of introgression, hybridization, recent speciation and incomplete lineage sorting makes species delimitation, based on molecular data, difficult and complicates understanding of the evolutionary history of Paracercion. The discordance in COI and ITS also indicates the value of using markers from different sources in species delimitation studies.
Zhang et al. (2021) Integrative species delimitation based on COI, ITS, and morphological evidence illustrates a unique evolutionary history of the genus Paracercion (Odonata: Coenagrionidae). PeerJ 9:e11459 https://doi.org/10.7717/peerj.11459
Autonomous Sensory Meridian Response self-reporters showed higher scores for cognitive reappraisal as an emotion regulation strategy
Background Autonomous Sensory Meridian Response (ASMR) describes the experience of a pleasant tingling sensation along the back of the head, accompanied with a feeling of well-being and relaxation, in response to specific audio-visual stimuli, such as whispers, soft sounds, and personal attention. Previous works have assessed individual variations in personality traits associated with ASMR, but no research to date has explored differences in emotion regulation associated with ASMR. This omission occurred even when ASMR, a sensory-emotional experience, has been proposed to be located in a sound sensitivity spectrum as the opposite end of misophonia, a phenomenon associated with difficulties regulating emotions. The present work aimed to assess group differences between ASMR self-reporters and non-ASMR controls associated with emotion regulation strategies. Methods We used the validated Spanish version of the Emotion Regulation Questionnaire to assess individual differences in the use of cognitive reappraisal and expressive suppression. Results Our results showed that participants who experience ASMR had higher scores in the cognitive reappraisal subscale of the emotion regulation questionnaire than the non-ASMR group. Conclusions Individuals who experience ASMR reported higher use of cognitive reevaluation of emotionally arousing situations, suggesting more effectiveness in regulating emotions. Our finding further elucidates individual differences related to this experience, supporting that ASMR is a real psychophysiological phenomenon associated with other psychological constructs and has remarkable consequences in affective/emotional dimensions and general well-being.
Morales et al. (2021) Autonomous Sensory Meridian Response self-reporters showed higher scores for cognitive reappraisal as an emotion regulation strategy. PeerJ 9:e11474 https://doi.org/10.7717/peerj.11474