BAG3 regulates bone marrow mesenchymal stem cell proliferation by targeting INTS7
Background BAG3 is an essential regulator of cell survival and has been investigated in the context of heart disease and cancer. Our previous study used immunoprecipitation-liquid chromatography-tandem mass spectrometry to show that BAG3 might directly interact with INTS7 and regulate bone marrow mesenchymal stem cell (BMMSCs) proliferation. However, whether BAG3 bound INTS7 directly and how it regulated BMMSCs expansion was unclear. Methods BAG3 expression was detected by quantitative real-time PCR in BMMSCs after siRNA-mediated BAG3 knockdown. BMMSC proliferation was determined using the CCK-8 and colony formation assays. The transwell migration, flow cytometry and TUNEL assays were performed to measure BMMSC migration, cell cycle and apoptosis, respectively. Moreover, co-immunoprecipitation, protein half-life assay and western blotting analyses were used to determine the regulatory mechanism underlying the BAG3-mediated increase in BMMSC proliferation. Results The results showed that knocking down BAG3 in BMMSCs markedly decreased their proliferative activity, colony formation and migratory capacity, and induced cell apoptosis as well as cell cycle arrest. Meanwhile, overexpression of BAG3 had the opposite effect. Bioinformatics and BAG3-INTS7 co-immunoprecipitation analyses revealed that BAG3 directly interacted with INTS7. Moreover, the downregulation of BAG3 inhibited the expression of INTS7 and promoted its ubiquitination. We also observed that BAG3 knockdown increased the levels of reactive oxygen species and the extent of DNA damage in BMMSCs. Notably, the upregulation of INTS7 or the addition of an antioxidant scavenger could rescue the BMMSC phenotype induced by BAG3 downregulation. Conclusions BAG3 directly interacts with INTS7 and promotes BMMSC expansion by reducing oxidative stress.
Liu et al. (2023) BAG3 regulates bone marrow mesenchymal stem cell proliferation by targeting INTS7. PeerJ 11:e15828 https://doi.org/10.7717/peerj.15828
Constructing a prognostic tool for predicting the risk of non-adherence to antiplatelet therapy in discharged patients with coronary heart disease: a retrospective cohort study
Objective To investigate the incidence and influencing factors affecting the non-adherence behavior of patients with coronary heart disease (CHD) to antiplatelet therapy after discharge and to construct a personalized predictive tool. Methods In this retrospective cohort study, 289 patients with CHD who were admitted to the Department of Cardiology of The First Affiliated Hospital of the University of Science and Technology of China between June 2021 and September 2021 were enrolled. The clinical data of all patients were retrospectively collected from the hospital information system, and patients were followed up for 1 year after discharge to evaluate their adherence level to antiplatelet therapy, analyze their present situation and influencing factors for post-discharge adherence to antiplatelet therapy, and construct a nomogram model to predict the risk of non-adherence. Results Based on the adherence level to antiplatelet therapy within 1 year after discharge, the patients were divided into the adherence (n = 216) and non-adherence (n = 73) groups. Univariate analysis revealed statistically significant differences between the two groups in terms of variable distribution, including age, education level, medical payment method, number of combined risk factors, percutaneous coronary intervention, duration of antiplatelet medication, types of drugs taken at discharge, and CHD type (P < 0.05). Furthermore, multivariate logistic regression analysis revealed that, except for the medical payment method, all the seven abovementioned variables were independent risk factors for non-adherence to antiplatelet therapy (P < 0.05). The areas under the receiver operating characteristic curve before and after the internal validation of the predictive tool based on the seven independent risk factors and the nomogram were 0.899 (95% confidence interval [CI]: 0.858–0.941) and 0.89 (95% CI: 0.847–0.933), respectively; this indicates that the tool has good discrimination ability. The calibration curve and Hosmer–Lemeshow goodness of fit test revealed that the tool exhibited good calibration and prediction consistency (χ2 = 5.17, P = 0.739). Conclusion In this retrospective cohort study, we investigated the incidence and influencing factors affecting the non-adherence behavior of patients with CHD after discharge to antiplatelet therapy. For this, we constructed a personalized predictive tool based on seven independent risk factors affecting non-adherence behavior. The predictive tool exhibited good discrimination ability, calibration, and clinical applicability. Overall, our constructed tool is useful for predicting the risk of non-adherence behavior to antiplatelet therapy in discharged patients with CHD and can be used in personalized intervention strategies to improve patient outcomes.
Cao et al. (2023) Constructing a prognostic tool for predicting the risk of non-adherence to antiplatelet therapy in discharged patients with coronary heart disease: a retrospective cohort study. PeerJ 11:e15876 https://doi.org/10.7717/peerj.15876
Bighorn sheep associations: understanding tradeoffs of sociality and implications for disease transmission
Sociality directly influences mating success, survival rates, and disease, but ultimately likely evolved for its fitness benefits in a challenging environment. The tradeoffs between the costs and benefits of sociality can operate at multiple scales, resulting in different interpretations of animal behavior. We investigated the influence of intrinsic (e.g., relatedness, age) and extrinsic factors (e.g., land cover type, season) on direct contact (simultaneous GPS locations ≤ 25 m) rates of bighorn sheep (Ovis canadensis) at multiple scales near the Waterton-Glacier International Peace Park. During 2002–2012, male and female bighorn were equipped with GPS collars. Indirect contact (GPS locations ≤ 25 m regardless of time) networks identified two major breaks whereas direct contact networks identified an additional barrier in the population, all of which corresponded with prior disease exposure metrics. More direct contacts occurred between same-sex dyads than female-male dyads and between bighorn groups with overlapping summer home ranges. Direct contacts occurred most often during the winter-spring season when bighorn traveled at low speeds and when an adequate number of bighorn were collared in the area. Direct contact probabilities for all dyad types were inversely related to habitat quality, and differences in contact probability were driven by variables related to survival such as terrain ruggedness, distance to escape terrain, and canopy cover. We provide evidence that probabilities of association are higher when there is greater predation risk and that contact analysis provides valuable information for understanding fitness tradeoffs of sociality and disease transmission potential.
Tosa et al. (2023) Bighorn sheep associations: understanding tradeoffs of sociality and implications for disease transmission. PeerJ 11:e15625 https://doi.org/10.7717/peerj.15625
Data-specific substitution models improve protein-based phylogenetics
Calculating amino-acid substitution models that are specific for individual protein data sets is often difficult due to the computational burden of estimating large numbers of rate parameters. In this study, we tested the computational efficiency and accuracy of five methods used to estimate substitution models, namely Codeml, FastMG, IQ-TREE, P4 (maximum likelihood), and P4 (Bayesian inference). Data-specific substitution models were estimated from simulated alignments (with different lengths) that were generated from a known simulation model and simulation tree. Each of the resulting data-specific substitution models was used to calculate the maximum likelihood score of the simulation tree and simulated data that was used to calculate the model, and compared with the maximum likelihood scores of the known simulation model and simulation tree on the same simulated data. Additionally, the commonly-used empirical models, cpREV and WAG, were assessed similarly. Data-specific models performed better than the empirical models, which under-fitted the simulated alignments, had the highest difference to the simulation model maximum-likelihood score, clustered further from the simulation model in principal component analysis ordination, and inferred less accurate trees. Data-specific models and the simulation model shared statistically indistinguishable maximum-likelihood scores, indicating that the five methods were reasonably accurate at estimating substitution models by this measure. Nevertheless, tree statistics showed differences between optimal maximum likelihood trees. Unlike other model estimating methods, trees inferred using data-specific models generated with IQ-TREE and P4 (maximum likelihood) were not significantly different from the trees derived from the simulation model in each analysis, indicating that these two methods alone were the most accurate at estimating data-specific models. To show the benefits of using data-specific protein models several published data sets were reanalysed using IQ-TREE-estimated models. These newly estimated models were a better fit to the data than the empirical models that were used by the original authors, often inferred longer trees, and resulted in different tree topologies in more than half of the re-analysed data sets. The results of this study show that software availability and high computation burden are not limitations to generating better-fitting data-specific amino-acid substitution models for phylogenetic analyses.
Brazão et al. (2023) Data-specific substitution models improve protein-based phylogenetics. PeerJ 11:e15716 https://doi.org/10.7717/peerj.15716
Impact of ocean warming on a coral reef fish learning and memory
Tropical ectotherms are highly sensitive to environmental warming, especially coral reef fishes, which are negatively impacted by an increase of a few degrees in ocean temperature. However, much of our understanding on the thermal sensitivity of reef fish is focused on a few traits (e.g., metabolism, reproduction) and we currently lack knowledge on warming effects on cognition, which may endanger decision-making and survival. Here, we investigated the effects of warming on learning and memory in a damselfish species, Acanthochromis polyacanthus. Fish were held at 28–28.5 °C (control group), 30–30.5 °C (moderate warming group) or 31.5–32 °C (high warming group) for 2 weeks, and then trained to associate a blue tag (cue) to the presence of a conspecific (reward). Following 20 training trials (5 days), fish were tested for associative learning (on the following day) and memory storage (after a 5-days interval). The control group A. polyacanthus showed learning of the task and memory retention after five days, but increasing water temperature impaired learning and memory. A thorough understanding of the effects of heat stress, cognition, and fitness is urgently required because cognition may be a key factor determining animals’ performance in the predicted scenario of climate changes. Knowing how different species respond to warming can lead to better predictions of future community dynamics, and because it is species specific, it could pinpoint vulnerable/resilience species.
Silveira et al. (2023) Impact of ocean warming on a coral reef fish learning and memory. PeerJ 11:e15729 https://doi.org/10.7717/peerj.15729
Implementation of artificial intelligence for the detection of cutaneous melanoma within a primary care setting: prevalence and types of skin cancer in outdoor enthusiasts
Background There is enthusiasm for implementing artificial intelligence (AI) to assist clinicians detect skin cancer. Performance metrics of AI from dermoscopic images have been promising, with studies documenting sensitivity and specificity values equal to or superior to specialists for the detection of malignant melanomas (MM). Early detection rates would particularly benefit Australia, which has the worlds highest incidence of MM per capita. The detection of skin cancer may be delayed due to late screening or the inherent difficulty in diagnosing early skin cancers which often have a paucity of clinical features and may blend into sun damaged skin. Individuals who participate in outdoor sports and recreation experience high levels of intermittent ultraviolet radiation (UVR), which is associated with the development of skin cancer, including MM. This research aimed to assess the prevalence of skin cancer in individuals who regularly participate in activities outdoors and to report the performance parameters of a commercially available AI-powered software to assess the predictive risk of MM development. Methods Cross-sectional study design incorporating a survey, total body skin cancer screening and AI-embedded software capable of predictive scoring of queried MM. Results A total of 423 participants consisting of surfers (n = 108), swimmers (n = 60) and walkers/runners (n = 255) participated. Point prevalence for MM was highest for surfers (6.48%), followed by walkers/runners (4.3%) and swimmers (3.33%) respectively. When compared to the general Australian population, surfers had the highest odds ratio (OR) for MM (OR 119.8), followed by walkers/runners (OR 79.74), and swimmers (OR 61.61) rounded out the populations. Surfers and swimmers reported comparatively lower lifetime hours of sun exposure (5,594 and 5,686, respectively) but more significant amounts of activity within peak ultraviolet index compared with walkers/runners (9,554 h). A total of 48 suspicious pigmented lesions made up of histopathology-confirmed MM (n = 15) and benign lesions (n = 33) were identified. The performance of the AI from this clinical population was found to have a sensitivity of 53.33%, specificity of 54.44% and accuracy of 54.17%. Conclusions Rates of both keratinocyte carcinomas and MM were notably higher in aquatic and land-based enthusiasts compared to the general Australian population. These findings further highlight the clinical importance of sun-safe protection measures and regular skin screening in individuals who spend significant time outdoors. The use of AI in the early identification of MM is promising. However, the lower-than-expected performance metrics of the AI software used in this study indicated reservations should be held before recommending this particular version of this AI software as a reliable adjunct for clinicians in skin imaging diagnostics in patients with potentially sun damaged skin.
Miller et al. (2023) Implementation of artificial intelligence for the detection of cutaneous melanoma within a primary care setting: prevalence and types of skin cancer in outdoor enthusiasts. PeerJ 11:e15737 https://doi.org/10.7717/peerj.15737
Recognition of emotion and pain by owners benefits the welfare of donkeys in a challenging working environment
Working donkeys (Equus asinus) support human living standards globally. However, there is little information on the effect of human perceptions of emotion and pain on the welfare of working donkeys. We interviewed donkey owners (n = 332) in Pakistan to determine the relationship between human perspectives on donkey sentience: emotions and the ability to feel pain, and the routine working practices that could impact donkey welfare. The majority of donkey owners used padding under the saddle (n = 211; 63.6%; 95% CI (58.3%–68.9%)) and provided access to food (n = 213; 64.2%; 95% CI (58.9%–69.3%)) and water (n = 195; 58.7%; 95% CI (53.4%–64.1%)) during the working day. Owners reported that at some point in their donkey’s life, 65.3% (95% CI (60.2%–70.5%)) had load-associated injuries, of which 27.7% (n = 92; 95% CI (22.8%–32.5%)) were wounds, 20.5% (n = 68; 95% CI (16.1%–24.8%)) were lameness and 7.2% (n = 24; 95% CI 4.4%–10.0%) were back pain. In total, 81.3% (95% CI 77.1%–85.5%; n = 270) of owners believed that their donkeys felt pain, and 70.2% (95% CI (65.2%–75.1%; n = 233) of owners believed that their donkeys had emotions. Multiple correspondence analysis (MCA) was used to understand the relationship between owners’ recognition of emotions and pain in donkeys and their working practices. The MCA factor map revealed two clusters, named positive and negative clusters. The positive cluster included owner’s recognition of donkey pain and emotions, the availability of food and water, use of padding under the saddle, absence of injuries along with the willingness to follow loading guidelines. The negative cluster represented practices that did not benefit donkey welfare, such as using saddles without padding and a lack of food and water during work. The presence of injuries, owners not recognizing that donkeys feel pain and emotion along with an unwillingness to follow loading guidelines were also found in the negative cluster. We show that the owners who recognized sentience in their donkeys were more likely to use practices that are good for donkey welfare. The ability of owners to identify sentience in donkeys, along with their willingness to follow welfare guidelines, are important factors in improving the lives of working donkeys.
Bukhari et al. (2023) Recognition of emotion and pain by owners benefits the welfare of donkeys in a challenging working environment. PeerJ 11:e15747 https://doi.org/10.7717/peerj.15747
Genetic and morphological diversity in populations of Annona senegalensis Pers. occurring in Western (Benin) and Southern (Mozambique) Africa
Background Understanding morpho-genetic diversity and differentiation of species with relatively large distributions is crucial for the conservation and sustainable management of their genetic resources. The present study focused on Annona senegalensis Pers., an important multipurpose wild plant, distributed exclusively in natural ecosystems but facing several threats. The study assessed the genetic and morphological diversity, structure, and differentiation of the species in populations from Western (Benin) and Southern (Mozambique) Africa. The material was evaluated to ascertain the environmental (climatic) determinants of the variation within this species. Methods Four sub-populations comprised of 154 individuals were phenotyped based on nineteen plant, fruit, and leaf morphological traits and further genotyped using ten polymorphic nuclear microsatellite (nSSR) markers. Results The results indicated strong differences in plant, fruit, and leaf morphological traits between Western and Southern populations. Furthermore, the studied populations were characterized by high genetic diversity, with an average genetic diversity index of 1.02. Western populations showed higher heterozygosity values (0.61–0.71) than Southern populations (0.41–0.49). Western and Southern populations were clearly differentiated into two different genetic groups, with further genetic subdivisions reflecting four sub-populations. Genetic variation between regions (populations) was higher (69.1%) than among (21.3%) and within (9.6%) sub-populations. Four distinct morphological clusters were obtained, which were strongly associated with the four genetic groups representing each sub-population. Climate, mainly precipitation and temperature indexes, explained the relatively higher variation found in morphological traits from Western (40.47%) in relation to Southern (27.98%) populations. Our study suggests that both environmental and genetic dynamics play an important role in the development of morphological variation in A. senegalensis.
Donhouedé et al. (2023) Genetic and morphological diversity in populations of Annona senegalensis Pers. occurring in Western (Benin) and Southern (Mozambique) Africa. PeerJ 11:e15767 https://doi.org/10.7717/peerj.15767
I feel addicted to watching TV series: association between binge-watching and mental health
Background Binge-watching (BW) is the consecutive viewing of three or more episodes of the same series in one sitting. Although some negative effects on mental health were evidenced, the continuum of BW from leisure activity to problematic behavior is still unclear. This study aimed to analyze mental health (depression, trait anxiety, social anxiety, impulsivity, alexithymia) of people involved in different expressions of BW. Methods A cross-sectional survey collected data from 482 respondents. According to a validated BW questionnaire, participants were divided into Problematic BW, Moderate BW, Non-BW, and No-viewer, and differences between groups were tested on psychological dimensions assessed via standardized questionnaires evaluating: trait and social anxiety, depression, impulsivity, and emotional dysregulation. Results An association between problematic BW and worse mental health conditions was evidenced, and a positive effect of non-problematic BW was supported. A negative linear trend from the BW as a leisure activity to problematic BW was marked, indicating how a possible maladaptive behavior orientation of BW in specific mental health conditions could be figured out as a behavioral addiction.
Favieri et al. (2023) I feel addicted to watching TV series: association between binge-watching and mental health. PeerJ 11:e15796 https://doi.org/10.7717/peerj.15796
Potential factors promoting the natural regeneration of Larix principis-rupprechtii in North China
Natural regeneration plays an important role in species diversity and evolution. Exploring the causes of variation in regeneration dynamics can provide key insights into the factors affecting regeneration. However, the relationship between the regeneration of Larix principis-rupprechtii and environmental factors in North China has remained unexplored. In this study, 14 plots were established based on the three extents of regenerated plant numbers in Shanxi Province. Redundancy analysis determined that environmental factors (topography, stand structure, soil property, and litter) affected natural regeneration. Structural equation modeling identified the most important direct and indirect factors that affected L. principis-rupprechtii natural regeneration. Litter thickness, canopy density, and adult tree diameter at breast height were positively correlated with natural regeneration. Aspect and total nitrogen volume were negatively associated with natural regeneration. Additionally, there was no significant correlation between natural regeneration and other environmental factors (altitude, slope, adult tree height, stand density, soil water content, SOC, total P, available N, available P, or soil enzyme). Further artificial intervention measures should be considered to promote plantation regeneration. These findings provide an effective basis for future forest restorations and sustainable management.
Zhao et al. (2023) Potential factors promoting the natural regeneration of Larix principis-rupprechtii in North China. PeerJ 11:e15809 https://doi.org/10.7717/peerj.15809