KSFinder—a knowledge graph model for link prediction of novel phosphorylated substrates of kinases
Background Aberrant protein kinase regulation leading to abnormal substrate phosphorylation is associated with several human diseases. Despite the promise of therapies targeting kinases, many human kinases remain understudied. Most existing computational tools predicting phosphorylation cover less than 50% of known human kinases. They utilize local feature selection based on protein sequences, motifs, domains, structures, and/or functions, and do not consider the heterogeneous relationships of the proteins. In this work, we present KSFinder, a tool that predicts kinase-substrate links by capturing the inherent association of proteins in a network comprising 85% of the known human kinases. We also postulate the potential role of two understudied kinases based on their substrate predictions from KSFinder. Methods KSFinder learns the semantic relationships in a phosphoproteome knowledge graph using a knowledge graph embedding algorithm and represents the nodes in low-dimensional vectors. A multilayer perceptron (MLP) classifier is trained to discern kinase-substrate links using the embedded vectors. KSFinder uses a strategic negative generation approach that eliminates biases in entity representation and combines data from experimentally validated non-interacting protein pairs, proteins from different subcellular locations, and random sampling. We assess KSFinder’s generalization capability on four different datasets and compare its performance with other state-of-the-art prediction models. We employ KSFinder to predict substrates of 68 “dark” kinases considered understudied by the Illuminating the Druggable Genome program and use our text-mining tool, RLIMS-P along with manual curation, to search for literature evidence for the predictions. In a case study, we performed functional enrichment analysis for two dark kinases - HIPK3 and CAMKK1 using their predicted substrates. Results KSFinder shows improved performance over other kinase-substrate prediction models and generalized prediction ability on different datasets. We identified literature evidence for 17 novel predictions involving an understudied kinase. All of these 17 predictions had a probability score ≥0.7 (nine at >0.9, six at 0.8–0.9, and two at 0.7–0.8). The evaluation of 93,593 negative predictions (probability ≤0.3) identified four false negatives. The top enriched biological processes of HIPK3 substrates relate to the regulation of extracellular matrix and epigenetic gene expression, while CAMKK1 substrates include lipid storage regulation and glucose homeostasis. Conclusions KSFinder outperforms the current kinase-substrate prediction tools with higher kinase coverage. The strategically developed negatives provide a superior generalization ability for KSFinder. We predicted substrates of 432 kinases, 68 of which are understudied, and hypothesized the potential functions of two dark kinases using their predicted substrates.
Anandakrishnan et al. (2023) KSFinder—a knowledge graph model for link prediction of novel phosphorylated substrates of kinases. PeerJ 11:e16164 https://doi.org/10.7717/peerj.16164
Factors influencing recurrent emergency department visits for mild acute respiratory tract infections caused by the influenza virus
Background Seasonal viral outbreaks, exemplified by influenza A and B viruses, lead to spikes in emergency department (ED) visits, straining healthcare facilities. Addressing ED overcrowding has become paramount due to its implications for patient care and healthcare operations. Recurrent visits among influenza patients remain an underexplored aspect, necessitating investigation into factors influencing such revisits. Methods Conducted within a tertiary care university hospital, this study adopts an observational retrospective cohort design. The study included adult patients with acute respiratory symptoms diagnosed with influenza using rapid antigen testing. The cohort was divided into single and recurrent ED visitors based on revisits within 10 days of initial discharge. A comparative analysis was performed, evaluating demographics, laboratory parameters, and clinical process data between recurrent visitors and single visitors. Results Among 218 patients, 36.2% (n = 139) experienced recurrent ED visits. Age and gender disparities were not significant. Antibiotics were prescribed for 55.5% (n = 121) and antivirals for 92.7% (n = 202) of patients, with no notable influence on recurrence. Recurrent visitors exhibited lower monocyte counts, hemoglobin levels, higher PDW and P-LCR percentages, and increased anemia prevalence (p = 0.036, p = 0.01, p = 0.004, p = 0.029, p = 0.017, respectively). C-reactive protein (CRP) levels did not significantly affect recurrence. Conclusion This study highlights the pressing concern of recurrent ED visits among mild influenza patients, magnifying the challenges of ED overcrowding. The observed notable prescription rates of antibiotics and antivirals underscore the intricate landscape of influenza management. Diminished monocyte counts, hemoglobin levels, and altered platelet parameters signify potential markers for identifying patients at risk of recurrent visits.
Tatlıparmak et al. (2023) Factors influencing recurrent emergency department visits for mild acute respiratory tract infections caused by the influenza virus. PeerJ 11:e16198 https://doi.org/10.7717/peerj.16198
Global change impacts on bird biodiversity in South Asia: potential effects of future land-use and climate change on avian species richness in Pakistan
Evaluating the impact of future changes in land-use and climate on species communities, especially species richness, is one of the most important challenges of current research in ecology and conservation. The impact of environmental changes on species richness depends on its sensitivity (i.e., how strongly a given level of change influences the ecological community) and its exposure (i.e., the amount of change that occurs). To examine the sensitivity, exposure, and potential impact of future environmental conditions on bird communities, we compiled data on bird species richness for Pakistan—a neglected region in macro- or country-scale studies. Since bird species richness strongly varies across seasons due to the seasonal occurrence of migratory species in winter, we compared both wintering (migratory plus resident species) and breeding (resident species only) bird richness. We found breeding and wintering species richness to be sensitive to temperature, precipitation and rainfed cropland by being positively related to these factors. Exposure varied regionally, with projected temperature changes being most profound in northern regions while the strongest projected precipitation changes occurred in central and southern regions. The projected impact of future environmental change were highly heterogeneous across the country and differed between the wintering and breeding communities. Overall, the most negatively impacted region was projected to be the Khyber Pakhtunkha province in the North of Pakistan, due to reductions in precipitation and rainfed cropland, resulting in a projected negative impact, especially on wintering species richness. By highlighting the regional and seasonal bird communities most at risk, our findings provide useful information for policy makers to help devise new policies for mitigating negative impacts of future environmental changes on birds within Pakistan.
Khaliq et al. (2023) Global change impacts on bird biodiversity in South Asia: potential effects of future land-use and climate change on avian species richness in Pakistan. PeerJ 11:e16212 https://doi.org/10.7717/peerj.16212
Neural drive and motor unit characteristics after anterior cruciate ligament reconstruction: implications for quadriceps weakness
Purpose The purpose of this investigation was to compare the quality of neural drive and recruited quadriceps motor units’ (MU) action potential amplitude (MUAPAMP) and discharge rate (mean firing rate (MFR)) relative to recruitment threshold (RT) between individuals with anterior cruciate ligament reconstruction (ACLR) and controls. Methods Fourteen individuals with ACLR and 13 matched controls performed trapezoidal knee extensor contractions at 30%, 50%, 70%, and 100% of their maximal voluntary isometric contraction (MVIC). Decomposition electromyography (dEMG) and torque were recorded concurrently. The Hoffmann reflex (H-reflex) and central activation ratio (CAR) were acquired bilaterally to detail the proportion of MU pool available and volitionally activated. We examined MUAPAMP-RT and MFR-RT relationships with linear regression and extracted the regression line slope, y-intercept, and RT range for each contraction. Linear mixed effect modelling used to analyze the effect of group and limb on regression line slope and RT range. Results Individuals with ACLR demonstrated lower MVIC torque in the involved limb compared to uninvolved limb. There were no differences in H-reflex or CAR between groups or limbs. The ACLR involved limb demonstrated smaller mass-normalized RT range and slower MU firing rates at high contraction intensities (70% and 100% MVIC) compared to uninvolved and control limbs. The ACLR involved limb also demonstrated larger MU action potentials in the VM compared to the contralateral limb. These differences were largely attenuated with relative RT normalization. Conclusions These results suggest that persistent strength deficits following ACLR may be attributable to a diminished quadriceps motor neuron pool and inability to upregulate the firing rate of recruited MUs.
Sherman et al. (2023) Neural drive and motor unit characteristics after anterior cruciate ligament reconstruction: implications for quadriceps weakness. PeerJ 11:e16261 https://doi.org/10.7717/peerj.16261
Study on soil hydraulic properties of slope farmlands with different degrees of erosion degradation in a typical black soil region
In order to explore the impact of soil erosion degradation on soil hydraulic properties of slope farmland in a typical black soil region, typical black soils with three degrees of erosion degradation (light, moderate and heavy) were selected as the research objects. The saturated hydraulic conductivity, water holding capacity and water supply capacity of the soils were analyzed, as well as their correlations with soil physicochemical properties. The results showed that the saturated hydraulic conductivity of black soils in slope farmlands decreased with erosion degradation degree, which was higher in 0–10 cm soil layer than in 10–20 cm soil layer. The water holding capacity and water supplying capacity of typical black soils also decreased with the increase of erosion degradation degree, and both of them were stronger in the upper soil than in the lower soil. With the aggravation of erosion degradation of black soils, soil organic matter content decreased while soil bulk density increased, leading to the decline of soil hydraulic conductivity. The increase of soil bulk density and the decrease of contents of organic matter and >0.25 mm water stable aggregates were the main factors leading to the decrease of soil water holding capacity. These findings provide scientific basis and basic data for rational utilization of soil water, improvement of land productivity and prevention of soil erosion.
Mai et al. (2023) Study on soil hydraulic properties of slope farmlands with different degrees of erosion degradation in a typical black soil region. PeerJ 11:e15930 https://doi.org/10.7717/peerj.15930
Impact of forest disturbance on microarthropod communities depends on underlying ecological gradients and species traits
Windstorms and salvage logging lead to huge soil disturbance in alpine spruce forests, potentially affecting soil-living arthropods. However, the impacts of forest loss and possible interactions with underlying ecological gradients on soil microarthropod communities remain little known, especially across different environmental conditions. Here we used DNA metabarcoding approach to study wind-induced disturbances on forest communities of springtails and soil mites. In particular, we aimed to test the effect of forest soil disturbance on the abundance, richness, species composition, and functional guilds of microarthropods. We sampled 29 pairs of windfall-forest sites across gradients of elevation, precipitation, aspect and slope, 2 years after a massive windstorm, named Vaia, which hit North-Eastern Italy in October 2018. Our results showed that wind-induced disturbances led to detrimental impacts on soil-living communities. Abundance of microarthropods decreased in windfalls, but with interacting effects with precipitation gradients. Operative Taxonomic Units (OTU) richness strongly decreased in post-disturbance sites, particularly affecting plant-feeder trophic guilds. Furthermore, species composition analyses revealed that communities occurring in post-disturbance sites were different to those in undisturbed forests (i.e., stands without wind damage). However, variables at different spatial scales played different roles depending on the considered taxon. Our study contributes to shed light on the impacts on important, but often neglected arthropod communities after windstorm in spruce forests. Effects of forest disturbance are often mediated by underlying large scale ecological gradients, such as precipitation and topography. Massive impacts of stronger and more frequent windstorms are expected to hit forests in the future; given the response we recorded, mediated by environmental features, forest managers need to take site-specific conservation measures.
Nardi et al. (2023) Impact of forest disturbance on microarthropod communities depends on underlying ecological gradients and species traits. PeerJ 11:e15959 https://doi.org/10.7717/peerj.15959
Biodiversity of symbiotic microalgae associated with meiofaunal marine acoels in Southern Japan
Acoels in the family Convolutidae are commonly found with microalgal symbionts. Convolutids can host green algal Tetraselmis and dinoflagellates within the family Symbiodiniaceae and the genus Amphidinium. The diversity of these microalgae has not been well surveyed. In this study, we used PCR and culture techniques to demonstrate the biodiversity of Tetraselmis and dinoflagellates in symbiosis with meiofaunal acoels. Here, 66 acoels were collected from seven localities around Okinawa, Ishigaki, and Kochi, Japan. While convolutids were heavily represented in this sampling, some acoels formed a clade outside Convolutidae and are potentially a new family of acoels harboring symbiotic microalgae. From the acoels collected, a total of 32 Tetraselmis and 26 Symbiodiniaceae cultures were established. Molecular phylogenies were constructed from cultured material (and from total host DNA) using the 18S rRNA gene (Tetraselmis) and 28S rRNA gene (dinoflagellates). The majority of Tetraselmis sequences grouped within the T. astigmatica clade but strains closely related to T. convolutae, T. marina, and T. gracilis were also observed. This is the first report of Tetraselmis species, other than T. convolutae, naturally associating with acoels. For dinoflagellates, members of Cladocopium and Miliolidium were observed, but most Symbiodiniaceae sequences formed clusters within Symbiodinium, grouping with S. natans, or sister to S. tridacnidorum. Several new Symbiodinium sequences from this study may represent novel species. This is the first molecular record of Miliolidium and Symbiodinium from acoels. Microalgal strains from this study will provide a necessary framework for future taxonomic studies and research on symbiotic relationships between acoels and microalgae.
Riewluang et al. (2023) Biodiversity of symbiotic microalgae associated with meiofaunal marine acoels in Southern Japan. PeerJ 11:e16078 https://doi.org/10.7717/peerj.16078
Tilapia lake virus causes mitochondrial damage: a proposed mechanism that leads to extensive death in fish cells
Background Tilapia lake virus (TiLV), also known as Tilapinevirus tilapiae, poses a significant threat to tilapia aquaculture, causing extensive mortality and economic losses. Understanding the mechanisms and pathogenesis of TiLV is crucial to mitigate its impact on this valuable fish species. Methodology In this study, we utilized transmission electron microscopy to investigate the ultrastructural changes in E-11 cells following TiLV infection. We also examined the presence of TiLV particles within the cells. Cellular viability and mitochondrial functions were assessed using MTT and ATP measurement assays and mitochondrial probes including JC-1 staining and MitoTracker™ Red. Results Our findings provide novel evidence demonstrating that TiLV causes cytotoxicity through the destruction of mitochondria. Transmission electron micrographs showed that TiLV particles were present in the cytoplasm of E-11 cells as early as 1 h after infection. Progressive swelling of mitochondria and ultrastructural damage to the cells were observed at 1, 3 and 6 days post-infection. Furthermore, losses of mitochondrial mass and membrane potential (MMP) were detected at 1 day after TiLV inoculation, as determined by mitochondrial probes. The results of the MTT assay also supported the hypothesis that the cell deaths in E-11 cells during TiLV infection may be caused by the disruption of mitochondrial structure and function. Conclusions Our study reveals the significant role of mitochondrial disruption in contributing to cellular death during the early stages of TiLV infection. These findings advance the understanding of TiLV pathogenesis and further enhance our knowledge of viral diseases in fish.
Raksaseri et al. (2023) Tilapia lake virus causes mitochondrial damage: a proposed mechanism that leads to extensive death in fish cells. PeerJ 11:e16190 https://doi.org/10.7717/peerj.16190
Calcareous dinoflagellate blooms during the Late Cretaceous ‘greenhouse’ world—a case study from western Ukraine
The Late Cretaceous was a unique period in the history of the Earth characterized by elevated sea levels, reduced land area, and significantly high concentrations of atmospheric CO2 resulting in increased temperatures across the globe—a ‘Greenhouse World’. During this period, calcareous dinoflagellate cysts (c-dinocysts) flourished and became a ubiquitous constituent of calcifying plankton around the world. An acme in calcareous dinocysts during the Albian to the Turonian coincided with the highest recorded seawater surface temperatures and was possibly linked to conditions that favored calcification and a highly oligotrophic system in European shelf seas. This study examines the potential applicability of c-dinocysts as a proxy for paleoenvironmental conditions based on their assemblage changes plotted against foraminiferal occurrences and microfacies analysis. The material was extracted from the upper Turonian chalk of the Dubivtsi region in western Ukraine. An inverse correlation was observed between species diversity and the number of c-dinocyst specimens. Nutrient availability gradients apparently determined important changes in the calcareous dinocysts distribution. These trophic changes were likely caused by the interplay of eustatic sea-level fluctuations and Subhercynian tectonic activity leading to changeable nutrient inputs from the nearby land.
Ciurej et al. (2023) Calcareous dinoflagellate blooms during the Late Cretaceous ‘greenhouse’ world—a case study from western Ukraine. PeerJ 11:e16201 https://doi.org/10.7717/peerj.16201
Genome sequence analysis of Malayan pangolin (Manis javanica) forensic samples reveals the presence of Paraburkholderia fungorum sequences
Background The Malayan pangolin (Manis javanica) is a placental mammal and is listed as Critically Endangered on the IUCN Red List of Threatened Species. Most previous attempts to breed pangolins in captivity have met with little success because of dietary issues, infections, and other complications, although a previous study reported breeding pangolins in captivity to the third generation. In our previous pangolin genome sequencing data analysis, we obtained a considerable amount of bacterial DNA from a pregnant female Malayan pangolin (named “UM3”), which was likely infected by Paraburkholderia fungorum—an agent of biodegradation and bioremediation in agriculture. Methodology Here, we further confirmed and characterized this bacterial species using PCR, histological staining, whole-genome sequencing, and bioinformatics approaches. PCR assays with in-house designed primer sets and 16S universal primers showed clear positive bands in the cerebrum, cerebellum, lung, and blood of UM3 suggesting that UM3 might have developed septicaemia. Histological staining showed the presence of Gram-negative rod-shaped bacteria in the pangolin brain and lungs, indicating the colonization of the bacteria in these two organs. In addition, PCR screening of UM3’s fetal tissues revealed the presence of P. fungorum in the gastrocnemius muscle, but not in other tissues that we examined. We also sequenced and reconstructed the genome of pangolin P. fungorum, which has a genome size of 7.7 Mbps. Conclusion Our study is the first to present detailed evidence of the presence of P. fungorum in a pangolin and her fetus (although preliminary results were presented in our previous article). Here, we raise the concern that P. fungorum may potentially infect humans, especially YOPI (young, old, pregnant, and immunocompromised) people. Therefore, caution should be exercised when using this bacterial species as biodegradation or bioremediation agents in agriculture.
Tan et al. (2023) Genome sequence analysis of Malayan pangolin (Manis javanica) forensic samples reveals the presence of Paraburkholderia fungorum sequences. PeerJ 11:e16002 https://doi.org/10.7717/peerj.16002