Comprehensive analysis based on DNA methylation and RNA-seq reveals hypermethylation of the up-regulated WT1 gene with potential mechanisms in PAM50 subtypes of breast cancer
Background Breast cancer (BC), one of the most widespread cancers worldwide, caused the deaths of more than 600,000 women in 2018, accounting for about 15% of all cancer-associated deaths in women that year. In this study, we aimed to discover potential prognostic biomarkers and explore their molecular mechanisms in different BC subtypes using DNA methylation and RNA-seq. Methods We downloaded the DNA methylation datasets and the RNA expression profiles of primary tissues of the four BC molecular subtypes (luminal A, luminal B, basal-like, and HER2-enriched), as well as the survival information from The Cancer Genome Atlas (TCGA). The highly expressed and hypermethylated genes across all the four subtypes were screened. We examined the methylation sites and the downstream co-expressed genes of the selected genes and validated their prognostic value using a different dataset (GSE20685). For selected transcription factors, the downstream genes were predicted based on the Gene Transcription Regulation Database (GTRD). The tumor microenvironment was also evaluated based on the TCGA dataset. Results We found that Wilms tumor gene 1 (WT1), a transcription factor, was highly expressed and hypermethylated in all the four BC subtypes. All the WT1 methylation sites exhibited hypermethylation. The methylation levels of the TSS200 and 1stExon regions were negatively correlated with WT1 expression in two BC subtypes, while that of the gene body region was positively associated with WT1 expression in three BC subtypes. Patients with low WT1 expression had better overall survival (OS). Five genes including COL11A1, GFAP, FGF5, CD300LG, and IGFL2 were predicted as the downstream genes of WT1. Those five genes were dysregulated in the four BC subtypes. Patients with a favorable 6-gene signature (low expression of WT1 and its five predicted downstream genes) exhibited better OS than that with an unfavorable 6-gene signature. We also found a correlation between WT1 and tamoxifen using STITCH. Higher infiltration rates of CD8 T cells, plasma cells, and monocytes were found in the lower quartile WT1 group and the favorable 6-gene signature group. In conclusion, we demonstrated that WT1 is hypermethylated and up-regulated in the four BC molecular subtypes and a 6-gene signature may predict BC prognosis.
Ren et al. (2021) Comprehensive analysis based on DNA methylation and RNA-seq reveals hypermethylation of the up-regulated WT1 gene with potential mechanisms in PAM50 subtypes of breast cancer. PeerJ 9:e11377 https://doi.org/10.7717/peerj.11377
Bootstrap methods can help evaluate monitoring program performance to inform restoration as part of an adaptive management program
The objective of many fish and wildlife restoration programs is to utilize management actions to change the state of a system. Because restoration programs are often expensive, iteratively assessing whether the restoration is having the desired outcome is a critical aspect of learning how to inform ongoing and sampling designs to evaluate proposed restoration programs. We provide an example of how we are using data resampling as part of an adaptive restoration process to test the effectiveness of a restoration action and associated monitoring program to restore the degraded Lone Cabbage oyster reef in Suwannee Sound, Florida in the northeast Gulf of Mexico. We use a resampling framework through simulations to inform the progress of the restoration efforts by examining the direction and magnitude of the differences in live oyster counts between restored and unrestored (wild) reefs over time. In addition, we evaluated the effort (number of sites sampled) needed to determine the effect of restoration to understand how many surveys should be conducted in subsequent sampling seasons. These efforts allow us to provide timely insight into the effectiveness of both our monitoring efforts and restoration strategy which is of critical importance not only to the restoration of Lone Cabbage Reef but to larger restoration efforts within the Gulf of Mexico as part of the consolidated Deepwater Horizon settlements and funded restoration efforts.
Moore et al. (2021) Bootstrap methods can help evaluate monitoring program performance to inform restoration as part of an adaptive management program. PeerJ 9:e11378 https://doi.org/10.7717/peerj.11378
The autistic-like behaviors development during weaning and sexual maturation in VPA-induced autistic-like rats is accompanied by gut microbiota dysbiosis
Researches on gut microbiota in autism have mostly focused on children, but the dynamic changes of gut microbiota from weaning to adulthood were still not clear because of the difficulty of diagnosing autism. In this study, autistic-like rats indued by valproate (VPA) were tracked from weaning (end of breastfeeding; four weeks old) to sexual maturation (food; eight weeks old). Autistic-like rats were found to show obvious developmental disorders. During weaning, autistic-like rats only exhibited obvious repetitive stereotyped behaviors, but the autistic-like behaviors were fully apparent upon sexual maturation. Significant differences were observed between the gut microbiota of autistic-like and healthy rats across both age groups. The correlation analysis results revealed that the correlation between behaviors and some microbiota, especially Helicobacter, did not vary with age or diet. The total amount of short-chain fatty acids (SCFAs) decreased, butyric acid metabolism decreased, and propionic acid metabolism increased in the feces of autistic-like rats. The correlation between autistic-like behaviors and the butyric acid and propionic acid levels did not vary with diet or age. Inositol phosphate metabolism, amino acid metabolism, and lipopolysaccharide biosynthesis were significantly associated with autistic-like behaviors. Our results showed that although the microbiota and SCFAs related to autism were affected by age and diet, some remained consistent irrespective of age and diet, and they could be considered two of the factors related to autistic-like behaviors development.
Kong et al. (2021) The autistic-like behaviors development during weaning and sexual maturation in VPA-induced autistic-like rats is accompanied by gut microbiota dysbiosis. PeerJ 9:e11103 https://doi.org/10.7717/peerj.11103
A new phylogenetic hypothesis of Tanystropheidae (Diapsida, Archosauromorpha) and other “protorosaurs”, and its implications for the early evolution of stem archosaurs
The historical clade “Protorosauria” represents an important group of archosauromorph reptiles that had a wide geographic distribution between the Late Permian and Late Triassic. “Protorosaurs” are characterized by their long necks, which are epitomized in the genus Tanystropheus and in Dinocephalosaurus orientalis. Recent phylogenetic analyses have indicated that “Protorosauria” is a polyphyletic clade, but the exact relationships of the various “protorosaur” taxa within the archosauromorph lineage is currently uncertain. Several taxa, although represented by relatively complete material, have previously not been assessed phylogenetically. We present a new phylogenetic hypothesis that comprises a wide range of archosauromorphs, including the most exhaustive sample of “protorosaurs” to date and several “protorosaur” taxa from the eastern Tethys margin that have not been included in any previous analysis. The polyphyly of “Protorosauria” is confirmed and therefore we suggest the usage of this term should be abandoned. Tanystropheidae is recovered as a monophyletic group and the Chinese taxa Dinocephalosaurus orientalis and Pectodens zhenyuensis form a new archosauromorph clade, Dinocephalosauridae, which is closely related to Tanystropheidae. The well-known crocopod and former “protorosaur” Prolacerta broomi is considerably less closely related to Archosauriformes than was previously considered.
Spiekman et al. (2021) A new phylogenetic hypothesis of Tanystropheidae (Diapsida, Archosauromorpha) and other “protorosaurs”, and its implications for the early evolution of stem archosaurs. PeerJ 9:e11143 https://doi.org/10.7717/peerj.11143
Predictors of work-related musculoskeletal symptoms in shoulders among nursing assistants working in nursing homes
Nursing assistants (NAs) working in nursing homes (NHs) are at higher risk for work-related musculoskeletal symptoms (WRMSs) than their counterparts working in other health care settings. Worldwide, NAs have ranked shoulders in the top three body parts at risk of WRMSs. However, factors associated with their shoulder WRMSs are currently unknown. The aim of this study was to identify these associated risk factors among NAs working in NHs. 440 NAs from 47 nursing homes (with 60–90% response rate from each nursing home), recruited by convenience sampling, participated in this cross-sectional study in 2014–2015. A validated and reliable questionnaire was used for data collection. Information on demographic, job content questionnaire (JCQ), perceived physical exertion (PE), workstyle, ergonomic and manual handling knowledge and other work-related factors was collected using a self-administered questionnaire. 53% of the participants reported experiencing with WRMSs in their shoulders. Nine associated factors of shoulder WRMSs were identified using bivariate analysis. With the adjustment of age and gender using multivariable logistic regression, body mass index (OR = .931, 95% CI [.874–.991]), job title of health workers (OR = 2.72, 95% CI [1.18–6.25]) and workstyle-working through pain (OR = 1.06, 95% CI [1.01–1.11]) remained as predictors. Effort should be directed at integrating “workstyle intervention” into lifestyle physical activity training for NAs.
Cheung et al. (2021) Predictors of work-related musculoskeletal symptoms in shoulders among nursing assistants working in nursing homes. PeerJ 9:e11152 https://doi.org/10.7717/peerj.11152
Intact tactile anisotropy despite altered hand perception in complex regional pain syndrome: rethinking the role of the primary sensory cortex in tactile and perceptual dysfunction
Complex Regional Pain Syndrome (CRPS) is characterised by pain, autonomic, sensory and motor abnormalities. It is associated with changes in the primary somatosensory cortex (S1 representation), reductions in tactile sensitivity (tested by two-point discrimination), and alterations in perceived hand size or shape (hand perception). The frequent co-occurrence of these three phenomena has led to the assumption that S1 changes underlie tactile sensitivity and perceptual disturbances. However, studies underpinning such a presumed relationship use tactile sensitivity paradigms that involve the processing of both non-spatial and spatial cues. Here, we used a task that evaluates anisotropy (i.e., orientation-dependency; a feature of peripheral and S1 representation) to interrogate spatial processing of tactile input in CRPS and its relation to hand perception. People with upper limb CRPS (n = 14) and controls with (n = 15) or without pain (n = 19) judged tactile distances between stimuli-pairs applied across and along the back of either hand to provide measures of tactile anisotropy. Hand perception was evaluated using a visual scaling task and questionnaires. Data were analysed with generalised estimating equations. Contrary to our hypotheses, tactile anisotropy was bilaterally preserved in CRPS, and the magnitude of anisotropic perception bias was comparable between groups. Hand perception was distorted in CRPS but not related to the magnitude of anisotropy or bias. Our results suggest against impairments in spatial processing of tactile input, and by implication S1 representation, as the cause of distorted hand perception in CRPS. Further work is warranted to elucidate the mechanisms of somatosensory dysfunction and distorted hand perception in CRPS.
Reinersmann et al. (2021) Intact tactile anisotropy despite altered hand perception in complex regional pain syndrome: rethinking the role of the primary sensory cortex in tactile and perceptual dysfunction. PeerJ 9:e11156 https://doi.org/10.7717/peerj.11156
Coverage and quality of DNA barcode references for Central and Northern European Odonata
Background Dragonflies and damselflies (Odonata) are important components in biomonitoring due to their amphibiotic lifecycle and specific habitat requirements. They are charismatic and popular insects, but can be challenging to identify despite large size and often distinct coloration, especially the immature stages. DNA-based assessment tools rely on validated DNA barcode reference libraries evaluated in a supraregional context to minimize taxonomic incongruence and identification mismatches. Methods This study reports on findings from the analysis of the most comprehensive DNA barcode dataset for Central European Odonata to date, with 103 out of 145 recorded European species included and publicly deposited in the Barcode of Life Data System (BOLD). The complete dataset includes 697 specimens (548 adults, 108 larvae) from 274 localities in 16 countries with a geographic emphasis on Central Europe. We used BOLD to generate sequence divergence metrics and to examine the taxonomic composition of the DNA barcode clusters within the dataset and in comparison with all data on BOLD. Results Over 88% of the species included can be readily identified using their DNA barcodes and the reference dataset provided. Considering the complete European dataset, unambiguous identification is hampered in 12 species due to weak mitochondrial differentiation and partial haplotype sharing. However, considering the known species distributions only two groups of five species possibly co-occur, leading to an unambiguous identification of more than 95% of the analysed Odonata via DNA barcoding in real applications. The cases of small interspecific genetic distances and the observed deep intraspecific variation in Cordulia aenea (Linnaeus, 1758) are discussed in detail and the corresponding taxa in the public reference database are highlighted. They should be considered in future applications of DNA barcoding and metabarcoding and represent interesting evolutionary biological questions, which call for in depth analyses of the involved taxa throughout their distribution ranges.
Geiger et al. (2021) Coverage and quality of DNA barcode references for Central and Northern European Odonata. PeerJ 9:e11192 https://doi.org/10.7717/peerj.11192
Self-compassion, ego-resiliency, coping with stress and the quality of life of parents of children with autism spectrum disorder
Background The literature shows a fairly coherent picture of the types of difficulties parents face. Adaptive both coping styles and resources, such as self-compassion and ego-resiliency, indicated as important predictors of the quality of life among parents of children with autism spectrum disorder. The aim of the study was to determine the links between self-compassion and ego-resiliency, coping with stress and quality of life among parents of children with autism spectrum disorder in a Polish sample (N = 76). Methods A cross-sectional study was conducted. The CISS, Self-Compassion Scale-Short, Ego-Resiliency Scale, and Quality of Life Questionnaire were used. Results Regression analysis was carried out to address the research question. It was confirmed that both resources studied exhibited negative relations with emotion-oriented coping, while ego-resiliency was also positively correlated with task- and avoidance-oriented strategies. The hierarchical multiple regression conducted in three steps indicated that ego-resiliency (18%) and emotion-oriented (14%) were the strongest predictors of quality of life among parents of children with ASD. Conclusions The obtained results proved that ego-resiliency and a task-oriented coping strategy were important indicators of the quality of life of parents of children with ASD.
Pyszkowska et al. (2021) Self-compassion, ego-resiliency, coping with stress and the quality of life of parents of children with autism spectrum disorder. PeerJ 9:e11198 https://doi.org/10.7717/peerj.11198
Lactobacillus reuteri TSR332 and Lactobacillus fermentum TSF331 stabilize serum uric acid levels and prevent hyperuricemia in rats
Background Uric acid (UA) is the end product of purine metabolism in the liver and is excreted by the kidneys. When purine metabolism is impaired, the serum UA level will be elevated (hyperuricemia) and eventually lead to gout. During evolution, humans and some primates have lost the gene encoding uricase, which is vital in UA metabolism. With the advances of human society, the prevalence of hyperuricemia has dramatically increased because of the refined food culture. Hyperuricemia can be controlled by drugs, such as allopurinol and probenecid. However, these drugs have no preventive effect and are associated with unpleasant side effects. An increasing number of probiotic strains, which are able to regulate host metabolism and prevent chronic diseases without harmful side effects, have been characterized. The identification of probiotic strains, which are able to exert beneficial effects on UA metabolism, will provide an alternative healthcare strategy for patients with hyperuricemia, especially for those who are allergic to anti-hyperuricemia drugs. Methods To elicit hyperuricemia, rats in the symptom control group (HP) were injected with potassium oxonate and fed a high-purine diet. Rats in the probiotic groups received the high-purine diet, oxonate injection, and supplements of probiotic strains TSR332, TSF331, or La322. Rats in the blank control group (C) received a standard diet (AIN-93G) and oxonate injection. Results Purine-utilizing strains of probiotics were screened using high-pressure liquid chromatography (HPLC) in vitro, and the lowering effect on serum UA levels was analyzed in hyperuricemia rats in vivo. We found that Lactobacillus reuteri strain TSR332 and Lactobacillus fermentum strain TSF331 displayed significantly strong assimilation of inosine (90%; p = 0.00003 and 59%; p = 0.00545, respectively) and guanosine (78%; p = 0.00012 and 51%; p = 0.00062, respectively) within 30 min in vitro. Further animal studies revealed that serum UA levels were significantly reduced by 60% (p = 0.00169) and 30% (p = 0.00912), respectively, in hyperuricemic rats treated with TSR332 and TSF331 for 8 days. Remarkably, TSR332 ameliorated the occurrence of hyperuricemia, and no evident side effects were observed. Overall, our study indicates that TSR332 and TSF331 are potential functional probiotic strains for controlling the development of hyperuricemia.
Kuo et al. (2021) Lactobacillus reuteri TSR332 and Lactobacillus fermentum TSF331 stabilize serum uric acid levels and prevent hyperuricemia in rats. PeerJ 9:e11209 https://doi.org/10.7717/peerj.11209
Molecular evidence for cross boundary spread of Salmonella spp. in meat sold at retail markets in the middle Mekong basin area
Background The surrounding areas of the middle Mekong basin, particularly along the border between Thailand and Lao People’s Democratic Republic (Lao PDR), are high-risk areas for many livestock-associated foodborne illnesses, especially salmonellosis. This study aimed to determine the prevalence and characteristics of Salmonella spp. contamination in pork, beef and chicken meats sold at retail markets in the Thailand-Laos border area surrounding the Thai-Lao Friendship Bridge I from January to May 2019. We focused on the prevalent serotypes, antimicrobial susceptibility profiles and the multilocus sequence type (MLST) genotypes of the collected Salmonella strains. Results From a total of 370 meat samples collected, 63% were positive for Salmonella, with the prevalence of 73%, 60% and 56% from pork, beef and chicken meat samples, respectively. Of all the positive samples, 53 serotypes were identified. Of these, Salmonella enterica serovar London accounted for the majority (27%), followed by serovars Corvallis (14%), and Rissen (6%). Resistance against tetracycline was found at the highest frequency (50%), followed by ampicillin (35%) and sulfamethoxazole-trimethoprim (28%). MLST revealed no evidence of shared genetic relatedness of Salmonella at retail sites among Thailand-Laos border zone. However, a diverse range of Salmonella genotypes were spread over the area. Besides, the persistence of the residential pathogen and sharing of the supply route within-country can be inferred. Conclusions Given the high levels of contamination of retail meats, regular disinfecting of all working areas and quality control checking at pre-retail stage must be applied to reduce the transmission of Salmonella and other foodborne pathogens to consumers. The findings of this study will make a significant contribution to the current understanding of Salmonella epidemiology to enhance food security in the region.
Meunsene et al. (2021) Molecular evidence for cross boundary spread of Salmonella spp. in meat sold at retail markets in the middle Mekong basin area. PeerJ 9:e11255 https://doi.org/10.7717/peerj.11255