Search Results (90)

With 493 taxa and 63 sections, Astragalus L. is the largest genus in Türkiye. Most of these are narrow endemics and usually found in marginal habitats or require edaphic specializations (about 42% of the species are endemic). Due to the genus’s extensive diversity of species and common economic use, numerous scientific studies have concentrated on specific species. Taxonomic categorization based on morphological characteristics is insufficient to distinguish certain taxonomic groups. However, there is no systematic molecular phylogenetic analysis of Turkish species that deals with speciation in this genus. To concentrate on molecular-level speciation, fresh leaves from 152 samples representing 30 species across six sections native to Türkiye were collected over several months of comprehensive field studies and analyzed with regard to the internal transcribed spacer (ITS) of nrDNA and the trn L5′-L3′ + L3′-F(GAA) + mat K of cpDNA regions. Additionally, molecular clock estimations and biogeographical histories were analyzed to clearly understand the species’ divergence. Based on all studied regions, the Poterion section was found to be the newest and most divergent section, while the Megalocystis Bunge and Halicacabus Bunge sections were the closest and older ones. Furthermore, A. vaginans from section Hymenocoleus Bunge were included not only in this section but also in several other lineages. It is noteworthy that A. dipodurus and A. oleaefolius species from the section Macrophyllium Bunge are usually put together in a distinct sub-branch from other species members of the section in phylogenetic trees generated using both researched cpDNA and nrDNA regions. Moreover, some of the species are divided by the Anatolian diagonal, and the speciation of a significant number of species began during the Pleistocene geological time period. Geographical isolations or other weak isolation mechanisms preceded speciation in Astragalus, which requires more research in the future. Full article

The nocturnal, flightless camel crickets (Rhaphidophoridae) have a global distribution and are believed to have originated prior to the breakup of Pangea. We investigated the phylogeny and the timing of the radiation of East Asian species with mitogenomic data. Initially we analyzed a large taxon dataset (n = 117) using available partial mitochondrial and nuclear DNA sequences to confirm the monophyly of subfamilies and current taxonomy. Our findings support the monophyly of each genus within the subfamily Aemodogryllinae, with a minor inconsistency between taxonomy and phylogeny resolved by resurrection of the genus Gymnaeta Adelung. Fossil-calibrated molecular clock analysis used 11,124 bp alignment of 13 complete mitochondrial protein-coding genes for 20 species of Rhaphidophoridae, with a focus on the neglected Rhaphidophorinae and Aemodogryllinae lineages. Divergence time estimates suggest that the most recent common ancestor of the family lived during the Early Jurassic (189 Mya ± 23 Mya) before Pangea broke into the supercontinents or possibly during the early stage of breakup when Gondwana and Laurasia were still connected by land. The two subfamilies, Rhaphidophorinae and Aemodogryllinae, that overlap in Asia are estimated to have diverged 138 Mya ± 17 Mya, well before the Late Cretaceous northern connection between America and Asia (the Bering Land Bridge). Thus, our extended sampling of species from East Asia and Oceania refutes the importance of continental drift in the evolution of this wingless orthopteran family. Full article

A new method of macroevolutionary analysis—high-resolution phylogenetics, integrating both morphological and molecular traits—has revealed well-supported evidence of complexity-based processes generating and controlling biodiversity. A novel technique of using evolutionary rates following a strict morphological clock, at least approximately, may allow detailed information on speciation and extinction events across geologic time. Branching series of minimally monophyletic genera are used to characterize in detail the branching lineage of the widely distributed moss family Streptotrichaceae. A strict morphological clock is calibrated by timing of genera new to recently exposed islands, molecular scaling against fossil taxa, and fossil evidence of the origin of the modern bryoflora. The numbers of genera generated in each 22-million-year interval are similar, while only one genus is inferred as extinct. The general outline of the phylogeny is tadpole-shaped because cumulative extinction is less than cumulative speciation, thus sustaining the family over vast time spans. Extant species per genus increase significantly over time, not through the proliferation of secondary descendants (i.e., more than four species per ancestral node), but through the selective preservation of lineages via extinction. Ancient traits are preserved throughout the lineage. It is hypothesized that descendant species are protected from coeval competition through bursts of speciation. This study supports a complexity-based explanation of the interaction of major evolutionary processes resulting in sustainability. Full article

Significant deviations between chronological and biological age can signal the early risk of chronic diseases, driving the need for tools that accurately determine biological age. While DNA methylation-based clocks have demonstrated strong predictive power for biological aging determination, their clinical application is limited by several barriers including high costs, the need to analyze hundreds of methylation sites using sophisticated platforms and the lack of standardized measurement tools and protocols. In this study, we developed a multivariate linear model using the analysis of eight CpGs within the promoter region of the very long chain fatty acid elongase 2 gene (ELOVL2). The model generated predicts biological age with a mean absolute error (MAE) of 5.04, providing a simplified, cost-effective alternative to more complex methylation-based clocks. Additionally, we identified sex-specific biological clocks, achieving MAEs of 4.37 for males and 5.38 for females, highlighting sex-related molecular differences in the methylation of this gene during aging. Our minimal CpG-based clock offers a practical solution for estimating biological age, with potential applications in clinical practice for assessing age-related disease risks and providing personalized healthcare interventions. Full article

This study examined the genetic and evolutionary features of influenza A/H3N2 viruses in Hangzhou (2010–2022) by analyzing 28,651 influenza-like illness samples from two sentinel hospitals. Influenza A/H3N2 coexisted with other subtypes, dominating seasonal peaks (notably summer). Whole-genome sequencing of 367 strains was performed on GridION platforms. Phylogenetic analysis showed they fell into 16 genetic groups, with multiple clades circulating simultaneously. Shannon entropy indicated HA, NA, and NS gene segments exhibited significantly higher variability than other genomic segments, with HA glycoprotein mutations concentrated in antigenic epitopes A–E. Antiviral resistance showed no inhibitor resistance mutations in PA, PB1, or PB2, but NA mutations were detected in some strains, and most strains harbored M2 mutations. A Bayesian molecular clock showed the HA segment exhibited the highest nucleotide substitution rate (3.96 × 10⁻³ substitutions/site/year), followed by NA (3.77 × 10⁻³) and NS (3.65 × 10⁻³). Selective pressure showed A/H3N2 strains were predominantly under purifying selection, with only sporadic positive selection at specific sites. The Pepitope model demonstrated that antigenic epitope mismatches between circulating H3N2 variants and vaccine strains led to a significant decline in influenza vaccine effectiveness (VE), particularly in 2022. Overall, the study underscores the complex circulation patterns of influenza in Hangzhou and the global importance of timely vaccine strain updates. Full article

The circadian clock, an intrinsic 24 h cellular timekeeping system, regulates fundamental biological processes, including tumor physiology and metabolism. Cancer stem cells (CSCs), a subpopulation of cancer cells with self-renewal and tumorigenic capacities, are implicated in tumor initiation, recurrence, and metastasis. Despite growing evidence for the circadian clock’s involvement in regulating CSC functions, its precise regulatory mechanisms remain largely unknown. Here, using a human osteosarcoma (OS) model (143B), we have shown that core molecular clock factors are critical for OS stem cell survival and behavior via direct modulation of CSC and lipid metabolic pathways. In single-cell-derived spheroid formation assays, 143B OS cells exhibited robust spheroid-forming capacity under 3D culture conditions. Furthermore, siRNA-mediated depletion of core clock components (i.e., BMAL1, CLOCK, CRY1/2, PER1/2)—essential positive and negative elements of the circadian clock feedback loop—significantly reduced spheroid formation in 143B CSCs isolated from in vivo OS xenografts. In contrast, knockdown of the secondary clock-stabilizing factor genes NR1D1 and NR1D2 had little effect. We also found that knockdown of BMAL1, CLOCK, or CRY1/2 markedly impaired the migration and invasion capacities of 143B CSCs. At the molecular level, silencing of BMAL1, CLOCK, or CRY1/2 distinctly altered the expression of genes associated with stem cell properties and the epithelial–mesenchymal transition (EMT) in 143B CSCs. In addition, disruption of BMAL1, CLOCK, or CRY1/2 expression significantly reduced lipid droplet formation by downregulating the expression of genes involved in lipogenesis (e.g., DGAT1, FASN, ACSL4, PKM2, CHKA, SREBP1), which are closely linked to CSC/EMT processes. Furthermore, transcriptomic analysis of human OS patient samples revealed that compared with other core clock genes, CRY1 was highly expressed in OS tumors relative to controls, and its expression exhibited strong positive correlations with patient prognosis, survival, and LD biogenesis gene expression. These findings highlight the critical role of the molecular circadian clock in regulating CSC properties and metabolism, underscoring the therapeutic potential of targeting the core clock machinery to enhance OS treatment outcomes. Full article

The genus Cyprinus encompasses economically vital freshwater fish species; yet the phylogenetic relationships and evolutionary history of many taxa within this genus remain unresolved. To address this knowledge gap, we reconstructed the molecular phylogenetic and estimated divergence times using complete mitochondrial cytochrome b (CYTB) sequences of 76 Cyprinidae specimens, within Cyprinidae, including 4 outgroup species. Phylogenetic trees were reconstructed using maximum likelihood (ML) and Bayesian inference (BI) methods, while divergence times were estimated using a Bayesian relaxed molecular clock approach. The results confirmed the monophyly of the genus Cyprinus. The relationships among C. (Cyprinus) multitaeniata, C. (C.) pellegrini, C. (C.) acutidorsalis, and three Erhai Lake species (C. (C.) longipectoralis, C. (C.) barbatus, and C. (C.) chilia) were resolved with strong support. Cyprinus (C.) multitaeniata is basal. The species in Erhai Lake form a monophyletic group, and C. (C.) acutidorsalis is at the top of the phylogenetic tree. The taxonomic delineation within the genus Cyprinus remains controversial, particularly regarding the proposed division into two subgenera (Cyprinus and Mesocyprinus), which has been historically constrained by limited specimen availability for Mesocyprinus. Our comprehensive phylogenetic analysis reveals significant evolutionary divergence patterns: The genus Cyprinus diverged from Carassius during the 56.9 Mya. Notably, the Erhai Lake radiation species (C. (C.) longipectoralis, C. (C.) barbatus, and C. (C.) chilia) originated during 2.03 Mya, while the Lake Biwa endemic C. (C.) haematopterus demonstrates 8.7 Mya. We identified a late Pleistocene speciation event (0.75 Mya) in C. (C.) acutidorsalis, coinciding with its adaptation to brackish water ecosystems. The native C. (C.) pellegrini of Xingyun Lake and Chilu Lake may have originated 4.8 Mya, when the ancient lake that its ancestral population inhabited became isolated. These findings provide robust molecular evidence supporting the recognition of two evolutionary distinct subgenera within Cyprinus. Full article

Acute Hemorrhagic Conjunctivitis (AHC) is primarily caused by viral infections, with Coxsackievirus A-24v (CV-A24v) being a significant culprit. Enteroviruses, including CV-A24v, are responsible for global AHC outbreaks. Over time, CV-A24v has evolved, and genotype IV (GIV) has become the dominant strain. This study focused on examining the genetic features and evolutionary trends of CV-A24v responsible for the recent AHC outbreak of 2023 in India. Researchers isolated viral strains from ocular swabs and confirmed the presence of CV-A24v using reverse transcriptase quantitative PCR (RT-qPCR) and whole-genome sequencing. Genomic comparisons between isolates of 2023 and those from a previous outbreak in 2009 were conducted. Phylogenetic analysis revealed that the 2023 isolates formed a distinct cluster within GIV-5 and were related to recent strains from China and Pakistan. The older Indian isolates from 2009 grouped with GIV-3. New subclades, GIV-6 and GIV-7, were also identified in this study, indicating the diversification of CV-A24. Molecular clock and phylogeographic analysis traced the virus’s circulation back to the 1960s, with the common ancestor likely to have originated in Singapore in 1968. The 2023 Indian strains probably originated from Thailand around 2014, with subsequent spread to China and Pakistan. This study concluded that the 2023 outbreak was caused by a genetically distinct CV-A24v strain with nine mutations, underlining the virus’s ongoing evolution and adaptations and offering valuable insights for future outbreak control. Full article

The paramount objectives of this study were to analyze the beneficial role of the circadian clock in alleviating drought stress in an essential green leafy horticultural crop, spinach (Spinacia oleracea), and to attain knowledge on drought-stress adaptation for crop productivity. From dawn to dusk, a circadian core oscillator-based defense mechanism was noticed in relation to the strength of the chloroplast proteome and transcriptome, and the defense hormone fused it along with the molecular physiology using genotypes “Malav Jyoti” and “Delhi Green”. A photo-periodic rhythmicity containing a 4 h time interval (morning–evening loop) for 12 h in spinach was exhibited under drought-stressed (day-5) and drought re-irrigated (day-10) conditions. The circadian oscillator controlled 70% of the major part of growth and physiological measures such as the biomass, plant height, leaf-relative water content, and the shoot–root ratio under drought stress. Contrarily, drought stress resulted in the upregulation of antioxidative activities and stress markers, whereas it was diversified and maintained in the case of the re-irrigated state at certain rhythmic time intervals of the circadian clock. The physiological parameters we examined, such as net photosynthesis, transpiration, stomatal conductance, and antioxidative enzymes, exhibited the role of the circadian clock in drought stress by showing 80–90% improvements found in plants when they were re-watered after drought stress based on their circadian oscillations. Based on the physiological results, 10 a.m. and 2 p.m. were disclosed to be the rhythmic times for controlling drought stress. Moreover, an extensive study on a gene expression analysis of circadian clock-based genes (CCA1, LHY, TOC1, PRR3, PRR5, PRR7, PRR9, and RVE8) and drought-responsive genes (DREB1, DREB2, and PIP1) depicted the necessity of a circadian oscillator in alleviating drought stress. Hence, the findings of our study allowed for an intense understanding of photo-periodic rhythms in terms of the morning–evening loop, which is in line with the survival rate of spinach plants and occurs by altering cellular ROS-scavenging mechanisms, chloroplast protein profiles, gene regulation, and metabolite concentrations. Full article

The Kunlun, Arjin, and Qilian mountain ranges mark the northern edge of the Qinghai–Tibet Plateau (QTP), where rapid uplift and Quaternary glacial cycles have shaped a unique cold desert ecosystem and species distribution. Despite sampling challenges, phylogeographic studies are crucial for understanding reptile populations such as the Qinghai toad-headed agama (Phrynocephalus vlangalii), a viviparous lizard with limited dispersal and multiple subspecies in the northeastern QTP. Our fieldwork identified populations of P. vlangalii on the northern slope of the Kunlun–Arjin Mountains, similar to the controversial subspecies P. v. lidskii. We analyzed 130 individuals from the northern slope of the Kunlun–Arjin–Qilian Mountains and 253 individuals from GenBank, using three mitochondrial genes and two nuclear genes to assess intraspecific differentiation and demographic history. We found high haplotype diversity and low nucleotide diversity in P. vlangalii, with phylogenetic analyses revealing six distinct clades. Clade VI, confirmed as P. v. lidskii, and Clade IV, a new genetic lineage, were identified alongside three recognized subspecies. Genetic variation was largely attributed to clade splitting, indicating significant divergence. The Mantel test indicated that geographical and environmental factors drove population differentiation. Bayesian molecular clock analysis suggested that the most recent common ancestor of P. vlangalii lived 2.55 million years ago, influenced by the Qinghai–Tibet Movement and glacial cycles. Demographic history and ecological niche modeling (ENM) indicated no population decline during the Last Glacial Maximum, supporting the glacial maximum expansion model, with ENM predicting future habitat expansion for P. vlangalii. In addition, morphological data from 13 meristic and 15 metric characters confirmed clade differences. Our findings significantly advance our understanding of P. vlangalii diversification, population dynamics and response to geological and climatic changes in the QTP. Full article

Clock genes regulate physiological and metabolic processes by responding to changes in environmental light and temperature, and genetic variations in these genes may facilitate environmental adaptation, offering opportunities for resilience to climate change. However, the genetic and molecular mechanisms remain unclear in marine organisms. In this study, we investigated the role of a key clock gene, the circadian locomotor output cycles kaput (Clock), in thermal adaptation using DNA affinity purification sequencing (DAP-Seq) and RNA interference (RNAi)-based transcriptome analysis. In cold-adapted Crassostrea gigas and warm-adapted Crassostrea angulata, Clock was subject to environmental selection and exhibited contrasting expression patterns. The transcriptome analysis revealed 2054 differentially expressed genes (DEGs) following the knockdown of the Clock expression, while DAP-Seq identified 150,807 genes regulated by Clock, including 5273 genes located in promoter regions. The combined analyses identified 201 overlapping genes between the two datasets, of which 98 were annotated in public databases. These 98 genes displayed distinct expression patterns in C. gigas and C. angulata under heat stress, which were potentially regulated by Clock, indicating its role in a molecular regulatory network that responds to heat stress. Notably, a heat-shock protein 70 family gene (Hsp12b) and a tripartite motif-containing protein (Trim3) were significantly upregulated in C. angulata but showed no significant changes in C. gigas, further highlighting their critical roles in thermal adaptation. This study preliminarily constructs a thermal regulatory network involving Clock, providing insights into the molecular mechanisms of clock genes in thermal adaptation. Full article

This paper provides a critical analysis of the molecular mechanisms presently used to explain transcriptional strand asymmetries of single base substitution (SBS) signatures observed in cancer genomes curated at the Catalogue of Somatic Mutations in Cancer (COSMIC) database (Wellcome Trust Sanger Institute). The analysis is based on a deaminase-driven reverse transcriptase (DRT) mutagenesis model of cancer oncogenesis involving both the cytosine (AID/APOBEC) and adenosine (ADAR) mutagenic deaminases. In this analysis we apply what is known, or can reasonably be inferred, of the immunoglobulin somatic hypermutation (Ig SHM) mechanism to the analysis of the transcriptional stand asymmetries of the COSMIC SBS signatures that are observed in cancer genomes. The underlying assumption is that somatic mutations arising in cancer genomes are driven by dysregulated off-target Ig SHM-like mutagenic processes at non-Ig loci. It is reasoned that most SBS signatures whether of “unknown etiology” or assigned-molecular causation, can be readily understood in terms of the DRT-paradigm. These include the major age-related “clock-like” SBS5 signature observed in all cancer genomes sequenced and many other common subset signatures including SBS1, SBS3, SBS2/13, SBS6, SBS12, SBS16, SBS17a/17b, SBS19, SBS21, as well as signatures clearly arising from exogenous causation. We conclude that the DRT-model provides a plausible molecular framework that augments our current understanding of immunogenetic mechanisms driving oncogenesis. It accommodates both what is known about AID/APOBEC and ADAR somatic mutation strand asymmetries and provides a fully integrated understanding into the molecular origins of common COSMIC SBS signatures. The DRT-paradigm thus provides scientists and clinicians with additional molecular insights into the causal links between deaminase-associated genomic signatures and oncogenic processes. Full article

The Cordycipitaceae family of insecticidal fungi is widely distributed in nature, is the most complex in the order Hypocreales (Ascomycota), with members displaying a diversity of morphological characteristics and insect host ranges. Based on Bayesian evolutionary analysis of five genomic loci(the small subunit of ribosomal RNA (SSU) gene, the large subunit of ribosomal RNA (LSU) gene, the translation elongation factor 1-α (tef1-α) gene, the largest subunit of RNA polymerase II (rpb1), and the second largest subunit of RNA polymerase II (rpb2), we inferred the divergence times for members of the Cordycipitaceae, improving the internal phylogeny of this fungal family. Molecular clock analyses indicate that the ancestor of Akanthomyces sensu lato occurred in the Paleogene period (34.57 Mya, 95% HPD: 31.41–37.67 Mya), and that most species appeared in the Neogene period. The historical biogeography of Akanthomyces sensu lato was reconstructed using reconstructing ancestral state in phylogenies (RASP) analysis, indicating that it most likely originated in Asia. Combined morphological characterization and phylogenetic analyses were used to identify and taxonomically place five species within Cordycipitaceae. These include the following: (i) two new species, namely Akanthomyces baishanensis sp. nov. and Samsoniella sanmingense sp. nov., (ii) a new record species isolated from infected Lepidopteran host, Blackwellomyces lateris, (iii) a new record species in the genus Niveomyces, with sporothrix-like asexual morphs, namely N. multisynnematus, isolated from dipteran insects (flies), and (iv) a known species of the (hyper-) mycoparasite, Liangia sinensis, isolated from the fungus Ophiocordyceps globiceps (Ophiocordycipitaceae) growing on a dipteran host. Our data provide a significant addition to the diversity, ecology, and evolutionary aspects of the Cordycipitaceae. Full article

Background: Chronobiology has gained attention in the context of paediatric neurological and neuropsychiatric disorders, including migraine, epilepsy, autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD). Disruptions in circadian rhythms are associated with key symptoms such as sleep disturbances, mood dysregulation, and cognitive impairments, suggesting a potential for chronobiology-based therapeutic approaches. Methods: This narrative review employs a systematic approach to identify relevant studies through searches of three major scientific databases, NCBI/PubMed, ScienceDirect, and Scopus, up to July 2024. We used a combination of broad and condition-specific keywords, such as “chronobiology”, “biorhythm”, “pediatric”, “epilepsy”, “ADHD”, and “ASD”, among others. Articles in English that focused on clinical features, treatments, or outcomes related to circadian rhythms in paediatric populations were included, while non-peer-reviewed articles and studies lacking original data were excluded. Rayyan software was used for article screening, removing duplicates, and facilitating consensus among independent reviewers. Results: A total of 87 studies were included in the analysis. Findings reveal a consistent pattern of circadian rhythm disruptions across the disorders examined. Specifically, dysregulation of melatonin and cortisol secretion is observed in children with ASD, ADHD, and PTSD, with altered circadian timing contributing to sleep disturbances and mood swings. Alterations in core clock genes (CLOCK, BMAL1, PER, and CRY) were also noted in children with epilepsy, which was linked to seizure frequency and timing. Chronotherapy approaches showed promise in managing these disruptions: melatonin supplementation improved sleep quality and reduced ADHD symptoms in some children, while light therapy proved effective in stabilizing sleep–wake cycles in ASD and ADHD patients. Additionally, behaviour-based interventions, such as the Early Start Denver Model, showed success in improving circadian alignment in children with ASD. Conclusions: This review highlights the significant role of circadian rhythm disruptions in paediatric neurological and neuropsychiatric disorders, with direct implications for treatment. Chronobiology-based interventions, such as melatonin therapy, light exposure, and individualized behavioural therapies, offer potential for improving symptomatology and overall functioning. The integration of chronotherapy into clinical practice could provide a paradigm shift from symptom management to more targeted, rhythm-based treatments. Future research should focus on understanding the molecular mechanisms behind circadian disruptions in these disorders and exploring personalized chronotherapeutic approaches tailored to individual circadian patterns. Full article

While TGF-β3 promoted defect healing in a primate baboon skull defect model and patients, it remains unclear whether TGF-β3 affects the formation of osteoclasts and bone resorption between osteogenesis and osteolysis. Analysis of the full transcriptome of hPDLSCs (human periodontal ligament stem cells) revealed that the expression of RANKL was significantly up-regulated after TGF-β3 treatment during osteogenesis, which suggests its involvement in clock-controlled autophagy in bone metabolism. TRAP staining and bone resorption lacunae were used to assess the osteoclasts formed from RANKL-induced differentiated BMMs. During osteoclast differentiation, the characteristics of autophagy regulated by TGF-β3 were observed in BMMs through MDC staining, transmission electron microscopy, and LC3 immunofluorescence. The expression of related genes and proteins were detected on the sixth day in mCherry-EGFP-LC3B lentivirus-transfected BMMs using RT-qPCR and WB. Finally, a trans-well co-culture system was used to evaluate the effects of osteogenic differentiated hPDLSCs treated with TGF-β3 on the osteoclastic differentiation of BMMs. The results showed 10 ng/mL of TGF-β3 significantly suppressed osteoclastic differentiation and bone resorption in BMMs (p < 0.05 vs. RANKL). In particular, TGF-β3 augments the expression of LC3-II to stimulate autophagy, consequently restraining osteoclastic resorption. These findings provide a molecular basis and are beneficial to illustrate the potential druggability of TGF-β3 in osteoporotic diseases. Full article