The dinosaurs that weren’t: osteohistology supports giant ichthyosaur affinity of enigmatic large bone segments from the European Rhaetian
Very large unidentified elongate and rounded fossil bone segments of uncertain origin recovered from different Rhaetian (Late Triassic) fossil localities across Europe have been puzzling the paleontological community since the second half of the 19th century. Different hypotheses have been proposed regarding the nature of these fossils: (1) giant amphibian bones, (2) dinosaurian or other archosaurian long bone shafts, and (3) giant ichthyosaurian jaw bone segments. We call the latter proposal the ‘Giant Ichthyosaur Hypothesis’ and test it using bone histology. In presumable ichthyosaur specimens from SW England (Lilstock), France (Autun), and indeterminate cortical fragments from Germany (Bonenburg), we found a combination of shared histological features in the periosteal cortex: an unusual woven-parallel complex of strictly longitudinal primary osteons set in a novel woven-fibered matrix type with intrinsic coarse collagen fibers (IFM), and a distinctive pattern of Haversian substitution in which secondary osteons often form within primary ones. The splenial and surangular of the holotype of the giant ichthyosaur Shastasaurus sikanniensis from Canada were sampled for comparison. The results of the sampling indicate a common osteohistology with the European specimens. A broad histological comparison is provided to reject alternative taxonomic affinities aside from ichthyosaurs of the very large bone segment. Most importantly, we highlight the occurrence of shared peculiar osteogenic processes in Late Triassic giant ichthyosaurs, reflecting special ossification strategies enabling fast growth and achievement of giant size and/or related to biomechanical properties akin to ossified tendons.
Perillo et al. (2024) The dinosaurs that weren’t: osteohistology supports giant ichthyosaur affinity of enigmatic large bone segments from the European Rhaetian. PeerJ 12:e17060 https://doi.org/10.7717/peerj.17060
Integration of temporal & spatial properties of dynamic functional connectivity based on two-directional two-dimensional principal component analysis for disease analysis
Dynamic functional connectivity, derived from resting-state functional magnetic resonance imaging (rs-fMRI), has emerged as a crucial instrument for investigating and supporting the diagnosis of neurological disorders. However, prevalent features of dynamic functional connectivity predominantly capture either temporal or spatial properties, such as mean and global efficiency, neglecting the significant information embedded in the fusion of spatial and temporal attributes. In addition, dynamic functional connectivity suffers from the problem of temporal mismatch, i.e., the functional connectivity of different subjects at the same time point cannot be matched. To address these problems, this article introduces a novel feature extraction framework grounded in two-directional two-dimensional principal component analysis. This framework is designed to extract features that integrate both spatial and temporal properties of dynamic functional connectivity. Additionally, we propose to use Fourier transform to extract temporal-invariance properties contained in dynamic functional connectivity. Experimental findings underscore the superior performance of features extracted by this framework in classification experiments compared to features capturing individual properties.
Zhao et al. (2024) Integration of temporal & spatial properties of dynamic functional connectivity based on two-directional two-dimensional principal component analysis for disease analysis. PeerJ 12:e17078 https://doi.org/10.7717/peerj.17078
Reappraisal of sauropod dinosaur diversity in the Upper Cretaceous Winton Formation of Queensland, Australia, through 3D digitisation and description of new specimens
Skeletal remains of sauropod dinosaurs have been known from Australia for over 100 years. Unfortunately, the classification of the majority of these specimens to species level has historically been impeded by their incompleteness. This has begun to change in the last 15 years, primarily through the discovery and description of several partial skeletons from the Cenomanian–lower Turonian (lower Upper Cretaceous) Winton Formation in central Queensland, with four species erected to date: Australotitan cooperensis, Diamantinasaurus matildae, Savannasaurus elliottorum, and Wintonotitan wattsi. The first three of these appear to form a clade (Diamantinasauria) of early diverging titanosaurs (or close relatives of titanosaurs), whereas Wintonotitan wattsi is typically recovered as a distantly related non-titanosaurian somphospondylan. Through the use of 3D scanning, we digitised numerous specimens of Winton Formation sauropods, facilitating enhanced comparison between type and referred specimens, and heretofore undescribed specimens. We present new anatomical information on the holotype specimen of Diamantinasaurus matildae, and describe new remains pertaining to twelve sauropod individuals. Firsthand observations and digital analysis enabled previously proposed autapomorphic features of all four named Winton Formation sauropod species to be identified in the newly described specimens, with some specimens exhibiting putative autapomorphies of more than one species, prompting a reassessment of their taxonomic validity. Supported by a specimen-level phylogenetic analysis, we suggest that Australotitan cooperensis is probably a junior synonym of Diamantinasaurus matildae, but conservatively regard it herein as an indeterminate diamantinasaurian, meaning that the Winton Formation sauropod fauna now comprises three (rather than four) valid diamantinasaurian species: Diamantinasaurus matildae, Savannasaurus elliottorum, and Wintonotitan wattsi, with the latter robustly supported as a member of the clade for the first time. We refer some of the newly described specimens to these three species and provide revised diagnoses, with some previously proposed autapomorphies now regarded as diamantinasaurian synapomorphies. Our newly presented anatomical data and critical reappraisal of the Winton Formation sauropods facilitates a more comprehensive understanding of the mid-Cretaceous sauropod palaeobiota of central Queensland.
Beeston et al. (2024) Reappraisal of sauropod dinosaur diversity in the Upper Cretaceous Winton Formation of Queensland, Australia, through 3D digitisation and description of new specimens. PeerJ 12:e17180 https://doi.org/10.7717/peerj.17180
IGF-1 rs6218 polymorphisms modulate the susceptibility to age-related cataract
Background Single nucleotide polymorphisms (SNPs), as the most abundant form of DNA variation in the human genome, contribute to age-related cataracts (ARC) development. Apoptosis of lens epithelial cells (LECs) is closely related to ARC formation. Insulin-like growth factor 1 (IGF1) contributes to cell apoptosis regulation. Moreover, IGF1 was indicated to exhibit a close association with cataract formation. Afterward, an investigation was conducted to examine the correlation between polymorphisms in IGF1 and the susceptibility to ARC. Methods The present investigation was a case-control study. Venous blood draws were collected from the participants for DNA genotyping. Lens capsule samples were collected to detect mRNA and apoptosis. TaqMan RT-PCR was used to detect IGF1 polymorphism genotypes and qRT PCR was used to detect IGF1 mRNA levels in LECs. LEC apoptosis was evaluated through flow cytometry. The chi-square test was used to compare differences between ARCs and controls of each SNP. Results We found that the G allele frequency in the IGF1-rs6218 was higher in the ARCs than in the controls. Furthermore, it was observed that the rs6218 GG genotype exhibited a positive correlation to elevated levels of IGF1 mRNA in LECs. The IGF1 mRNA in the LECs and the apoptosis of LECs in nuclear type of ARCs (ARNC) was higher than the controls. Conclusion The susceptibility to ARC was related to IGF1-rs6218 polymorphism, and this polymorphism is associated with IGF1 expression at the mRNA level. Moreover, apoptosis in LECs of ARNCs was found to be increased.
Zou et al. (2024) IGF-1 rs6218 polymorphisms modulate the susceptibility to age-related cataract. PeerJ 12:e17220 https://doi.org/10.7717/peerj.17220
The role of echinacoside-based cross-linker nanoparticles in the treatment of osteoporosis
Background Current drugs for treating osteoporosis may lead to toxic side effects. Echinacoside (ECH) is a natural small molecule drug. This study examined and compared the therapeutic effects of cross-linker (CL)-ECH and ECH-free nanoparticles on osteoporosis. Methods Echinocandin-based CL-ECH nanoparticles were prepared, and the nanoparticle size and drug loading were optimized and characterized by adjusting the ratio. The antioxidant effect of CL-ECH nanoparticles on bone marrow-derived macrophages (BMDMs) was analyzed using flow cytometry, immunofluorescence staining and quantitative real-time polymerase chain reaction (qRT-PCR). Bone marrow stromal cells (BMSCs)-based detection of bone-producing effects was conducted using alkaline phosphatase (ALP), Alizarin Red S (ARS) and qRT-PCR. TRAP, phalloidin staining, and qRT-PCR was performed to detect osteogenesis-inhibiting effect on BMDMs. CL-ECH nanoparticles were applied to treat an ovariectomized (OVX) mouse model at low doses. Results Compared to ECH, CL-ECH nanoparticles suppressed oxidative stress in BMDMs by promoting NRF-2 nuclear translocation, which inhibited the production of both reactive oxygen species (ROS) and osteoclast production through downregulating NF-κB expression, with limited effect on the osteogenesis of BMSCs. In vivo studies showed that low-dose CL-ECH nanoparticles markedly improved bone trabecular loss compared to ECH administration in the treatment of osteoporosis. Conclusions The current discoveries provided a solid theoretical foundation for the development of a new generation of anti-bone resorption drugs and antiosteoporosis drugs.
Hu et al. (2024) The role of echinacoside-based cross-linker nanoparticles in the treatment of osteoporosis. PeerJ 12:e17229 https://doi.org/10.7717/peerj.17229
Heterogeneity of the effect of the COVID-19 pandemic on the incidence of Metabolic Syndrome onset at a Japanese campus
Background The coronavirus disease 2019 (COVID-19) outbreak began in China in December 2019, with the World Health Organization declaring a state of emergency in January 2020. Worldwide implementation of lockdown measures to slow the spread of the virus led to reduced physical activity, disrupted eating habits, mental health issues, and sleep disturbances, which increased the risk of lifestyle-related diseases such as metabolic syndrome (MetS). During the COVID-19 pandemic, healthcare workers, especially intensive care workers, experienced longer working hours and burnout, which further increased the risk of lifestyle-related diseases. Accordingly, it is important to identify individuals at a risk of new-onset MetS during a pandemic, which could direct preventive interventions. This study aimed to assess the heterogeneous impact of the COVID-19 pandemic on the incidence of new-onset MetS based on the conditional average treatment effect (CATE) and to identify at-risk populations. Methods This study analyzed health checkup data obtained from Okayama University Shikata Campus workers using paired baseline and follow-up years. Baseline data encompassed 2017 to 2019, with respective follow-up data from 2018 to 2020. Furthermore, as the COVID-19 pandemic in Japan began in January 2020, workers who underwent follow-up health checkups in 2018 to 2019 and 2020 were considered as “unexposed” and “exposed,” respectively. As the Shikata campus has several departments, comparisons among departments were made. The primary outcome was new-onset MetS at follow-up. Predictor variables included baseline health checkup results, sex, age, and department (administrative, research, medical, or intensive care department). X-learner was used to calculate the CATE. Results This study included 3,572 eligible individuals (unexposed, n = 2,181; exposed, n = 1,391). Among them, 1,544 (70.8%) and 866 (62.3%) participants in the unexposed and exposed groups, respectively, were females. The mean age (±standard deviation) of the unexposed and exposed groups was 48.2 ± 8.2 and 47.8 ± 8.3 years, respectively. The COVID-19 pandemic increased the average probability of new-onset MetS by 4.4% in the overall population. According to the department, the intensive care department showed the highest CATE, with a 15.4% increase. Moreover, there was large heterogeneity according to the department. The high-CATE group was characterized by older age, urinary protein, elevated liver enzymes, higher triglyceride levels, and a history of hyperlipidemia treatment. Conclusions This study demonstrated that the COVID-19 pandemic increased the incidence of new-onset MetS, with this effect showing heterogeneity at a single Japanese campus. Regarding specific populations, workers in the intensive care department showed an increased risk of new-onset MetS. At-risk populations require specific preventive interventions in case the current COVID-19 pandemic persists or a new pandemic occurs.
Mitsuhashi (2024) Heterogeneity of the effect of the COVID-19 pandemic on the incidence of Metabolic Syndrome onset at a Japanese campus. PeerJ 12:e17013 https://doi.org/10.7717/peerj.17013
HSP90B1 regulates autophagy via PI3K/AKT/mTOR signaling, mediating HNSC biological behaviors
Background Autophagy, a crucial cellular mechanism, facilitates the degradation and removal of misfolded proteins and impaired organelles. Recent research has increasingly highlighted the intimate connection between autophagy and heat shock proteins (HSPs) in the context of tumor development. However, the specific role and underlying mechanisms of heat shock protein 90 beta family member 1 (HSP90B1) in modulating autophagy within head and neck squamous cell carcinoma (HNSCC) remain elusive. Methods Quantitative real-time PCR (qRT-PCR), Western blot (WB), immunohistochemistry (IHC) were used to detect the expression in HNSC cell lines and tissues. The relationship between HSP90B1 and clinicopathologic features was explored based on TCGA (The Cancer Genome Atlas) data and IHC results. The biological functions of HSP90B1 were analyzed through in vitro and in vivo models to evaluate proliferation, migration, invasion, and autophagy. The mechanisms of HSP90B1 were studied using bioinformatics and WB. Results HSP90B1 was upregulated in HNSC cells and tissues. High HSP90B1 levels were associated with T-stage, M-stage, clinical stage, and poor prognosis in HNSC patients. Functionally, HSP90B1 promotes HNSC cell proliferation, migration, invasion and inhibits apoptosis. We discovered that HSP90B1 obstructs autophagy and advances HNSC progression through the PI3K/Akt/mTOR pathway. Conclusion Our study demonstrates that HSP90B1 is highly expressed in HNSC. Furthermore, HSP90B1 may regulate autophagy through the PI3K/Akt/mTOR pathway, mediating HNSC cell biological behaviors. These provide new insights into potential biomarkers and targets for HNSC therapy.
Li et al. (2024) HSP90B1 regulates autophagy via PI3K/AKT/mTOR signaling, mediating HNSC biological behaviors. PeerJ 12:e17028 https://doi.org/10.7717/peerj.17028
Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model
Background Acute pulmonary embolism (APE) is classified as a subset of diseases that are characterized by lung obstruction due to various types of emboli. Current clinical APE treatment using anticoagulants is frequently accompanied by high risk of bleeding complications. Recombinant hirudin (R-hirudin) has been found to have antithrombotic properties. However, the specific impact of R-hirudin on APE remains unknown. Methods Sprague-Dawley (SD) rats were randomly assigned to five groups, with thrombi injections to establish APE models. Control and APE group rats were subcutaneously injected with equal amounts of dimethyl sulfoxide (DMSO). The APE+R-hirudin low-dose, middle-dose, and high-dose groups received subcutaneous injections of hirudin at doses of 0.25 mg/kg, 0.5 mg/kg, and 1.0 mg/kg, respectively. Each group was subdivided into time points of 2 h, 6 h, 1 d, and 4 d, with five animals per point. Subsequently, all rats were euthanized, and serum and lung tissues were collected. Following the assessment of right ventricular pressure (RVP) and mean pulmonary artery pressure (mPAP), blood gas analysis, enzyme-linked immunosorbnent assay (ELISA), pulmonary artery vascular testing, hematoxylin-eosin (HE) staining, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, immunohistochemistry, and Western blot experiments were conducted. Results R-hirudin treatment caused a significant reduction of mPAP, RVP, and Malondialdehyde (MDA) content, as well as H2O2 and myeloperoxidase (MPO) activity, while increasing pressure of oxygen (PaO2) and Superoxide Dismutase (SOD) activity. R-hirudin also decreased wall area ratio and wall thickness to diameter ratio in APE rat pulmonary arteries. Serum levels of endothelin-1 (ET-1) and thromboxaneB2 (TXB2) decreased, while prostaglandin (6-K-PGF1α) and NO levels increased. Moreover, R-hirudin ameliorated histopathological injuries and reduced apoptotic cells and Matrix metalloproteinase-9 (MMP9), vascular cell adhesion molecule-1 (VCAM-1), p-Extracellular signal-regulated kinase (ERK)1/2/ERK1/2, and p-P65/P65 expression in lung tissues. Conclusion R-hirudin attenuated pulmonary hypertension and thrombosis in APE rats, suggesting its potential as a novel treatment strategy for APE.
Wei et al. (2024) Recombinant hirudin attenuates pulmonary hypertension and thrombosis in acute pulmonary embolism rat model. PeerJ 12:e17039 https://doi.org/10.7717/peerj.17039
Self-reported side effects of COVID-19 vaccines among health professions students in India
Studies focusing on the safety and common side effects of vaccines play a crucial role in enhancing public acceptance of vaccination. Research is scarce regarding the usage of COVID-19 vaccines and the side effects experienced by health professions students in India and other countries. This study aimed to document self-reported side effects associated with COVID-19 vaccination among medical and dental students of six medical and dental colleges and teaching hospitals in four states (Tamil Nadu, Madhya Pradesh, Gujarat, and West Bengal) of India. A cross-sectional survey using purposive sampling of medical and dental students was conducted from 26 April to 26 May 2021. Data was collected using a Google Forms questionnaire capturing information regarding receiving COVID-19 vaccines, side effects and symptoms, onset and duration of symptoms, use of treatment to alleviate symptoms, awareness of haematologic risks associated with vaccination, and side effects from previous (non-COVID-19) vaccinations. The majority (94.5%) of participants received both doses of the Covishield/AstraZeneca COVID-19 vaccine. Among participants (n = 492), 45.3% (n = 223) reported one or more side effects. The most frequently reported side effects were soreness of the injected arm (80.3%), tiredness (78.5%), fever (71.3%), headache (64.1%), and hypersomnia (58.7%). The two most common severe symptoms were fever (14.8%) and headache (13%). Most side effects appeared on the day of vaccination: soreness of the injection site (57%), fever (43.1%), and tiredness (42.6%). Most reported symptoms persisted for one to three days–soreness of the injection site (53%), fever (47.1%), and headache (42.6%). Logistic regression showed that women were almost 85% less likely to report side effects. The study’s findings corroborate the safety of the Covishield/AstraZeneca vaccine’s first dose, evidenced by the relatively minor and transient nature of the side effects. However, the study underscores the necessity for ongoing research to assess the long-term impacts of COVID-19 vaccines, especially in the context of booster doses, thereby contributing to the global understanding of vaccine safety and efficacy.
Majumder et al. (2024) Self-reported side effects of COVID-19 vaccines among health professions students in India. PeerJ 12:e17083 https://doi.org/10.7717/peerj.17083
Exogenous melatonin improves germination rate in buckwheat under high temperature stress by regulating seed physiological and biochemical characteristics
The germinations of three common buckwheat (Fagopyrum esculentum) varieties and two Tartary buckwheat (Fagopyrum tataricum) varieties seeds are known to be affected by high temperature. However, little is known about the physiological mechanism affecting germination and the effect of melatonin (MT) on buckwheat seed germination under high temperature. This work studied the effects of exogenous MT on buckwheat seed germination under high temperature. MT was sprayed. The parameters, including growth, and physiological factors, were examined. The results showed that exogenous MT significantly increased the germination rate (GR), germination potential (GP), radicle length (RL), and fresh weight (FW) of these buckwheat seeds under high-temperature stress and enhanced the content of osmotic adjustment substances and enzyme activity. Comprehensive analysis revealed that under high-temperature stress during germination, antioxidant enzymes play a predominant role, while osmotic adjustment substances work synergistically to reduce the extent of damage to the membrane structure, serving as the primary key indicators for studying high-temperature resistance. Consequently, our results showed that MT had a positive protective effect on buckwheat seeds exposed to high temperature stress, providing a theoretical basis for improving the ability to adapt to high temperature environments.
Tian et al. (2024) Exogenous melatonin improves germination rate in buckwheat under high temperature stress by regulating seed physiological and biochemical characteristics. PeerJ 12:e17136 https://doi.org/10.7717/peerj.17136