Search Results (44)

This paper examines the extended evolutionary synthesis’s critique of the modern synthesis, and introduces the “survival of the luckiest” framework as a mediating perspective. This framework preserves the core principles of the modern synthesis, while incorporating an additional element of randomness arising from the interplay of natural and sexual selection. Although the extended synthesis emphasizes developmental processes, niche construction, epigenetic inheritance, and horizontal gene transfer, it also neglects the critical role of this additional randomness. By critically analyzing the evidence provided by proponents of the extended synthesis, we show that the survival of the luckiest framework offers compelling alternative explanations. In doing so, it bridges the modern synthesis with principles of self-organization and emergence, addressing key gaps while maintaining its foundational tenets. Full article

Identifying major blast resistance genes in Oryza sativa L. genotypes is key to enhancing and maintaining the resistance. Observing rice varieties with durable resistance to blast has become a potential target in rice breeding programs. In this study, an evaluation was conducted during 2020 and 2021 on ten Egyptian and introduced varieties. First, a field experiment was conducted in a randomized complete block design with three replications, and it was found that the Egyptian cultivar Sakha 101 had the highest crop grain yields (53.27 g). The Spanish varieties Hispagrán and Puebla were the earliest (110 and 108 days, respectively) as well as the highest in 1000-grain yield, giving them priority as donors for these traits; however, they had the lowest mean values in the number of panicles. Second, these cultivars were subjected to eighteen isolates from five strains of Pyricularia oryzae (IH, IC, ID, IE, and II). The Egyptian varieties Giza 177, Giza 179, Sakha 106, Giza 182, GZ1368-5-5-4, and GZ6296 were 100% resistant, while Hispagrán’s resistance was 16.6%, followed by Sakha 101 with 27.8%. To gain insight into the ten varieties, we used STS, SCAR, and CAPS markers to detect and mine alleles for major blast broad-spectrum resistance genes Pi2, Pi9, and Pita2. In the context of considering gene pyramiding as an effective strategy for achieving broad durable spectrum resistance to blast, molecular profiling was also conducted on eighteen F2 single plants obtained from the hybridization of Giza 177 (resistant) × Puebla (susceptible) varieties. Also, eighteen F2 single plants were obtained from Giza 177 × Hispagrán (highly susceptible) varieties. Conducting a molecular scan with STS dominant marker YL153/YL154 was performed on ten cultivars to detect the presence of the Pita2 gene, which conferred a unique band in Puebla. By doing a scan of the 18 second-generation plants derived from Giza 177 × Puebla, 11 individual plants of the 18 plants obtained a band, which was transferred from Puebla. F2 plants obtained from Giza 177 × Puebla amplified with CAPS marker RG64-431/RG64-432 had higher numbers of Pi2 alleles, while F2 plants of Giza 177 × Hispagrán cross-amplified with SCAR marker linked to Pi9 exceeded their parents more. Our results have revealed that molecular markers played an essential role in determining the direction of evolution for blast resistance traits. Full article

NLR genes are crucial components of the effector-triggered immunity (ETI) system, responsible for recognizing pathogens and initiating immune responses. Although NLR genes in many plant species have been extensively studied, the diversity of NLR genes in citrus remains largely unknown. Our analysis revealed significant variations in the copy numbers of NLR genes among these species. Gene duplication and recombination were identified as the major driving forces behind this diversity. Additionally, horizontal gene transfer (HGT) emerged as the principal mechanism responsible for the increase in NLR gene copy number in A. buxifolia. The citrus NLR genes were classified into four categories: TIR-NBS-LRR (TNL), CC-NBS-LRR (CNL), RPW8-NBS-LRR (RNL), and NL. Our findings indicate that TNL, RNL, and CNL genes originated from NL genes through the acquisition of TIR and RPW8 domains, along with CC motifs, followed by the random loss of corresponding domains. Phylogenetic analysis suggested that citrus NLR genes originated alongside the species and underwent adaptive evolution, potentially playing crucial roles in the global colonization of citrus. This study provides important insights into the diversity of citrus NLR genes and serves as a foundational dataset for future research aimed at breeding disease-resistant citrus varieties. Full article

Background: This study aimed to examine the differential variations in the metabolic composition of follicular fluid (FF) among normal-weight patients with polycystic ovary syndrome (PCOS) and controls and to identify potential biomarkers that may offer insights into the early identification and management of these patients. Methods: We collected FF samples from 45 normal-weight women with PCOS and 36 normal-weight controls without PCOS who were undergoing in vitro fertilization–embryo transfer. An untargeted metabolomic study of collected FF from infertile women was performed using high-performance liquid chromatography–tandem spectrometry (LC-MS). The tendency of the two groups to separate was demonstrated through multivariate analysis. Univariate analysis and variable importance in projection were used to screen out differential metabolites. Metabolic pathway analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG), and a diagnostic model was established using the random forest algorithm. Results: The metabolomics analysis revealed an increase in the expression of 23 metabolites and a decrease in that of 10 metabolites in the FF of normal-weight women with PCOS. According to the KEGG pathway analysis, these differential metabolites primarily participated in the metabolism of glycerophospholipids and the biosynthesis of steroid hormones. Based on the biomarker combination of the top 10 metabolites, the area under the curve value was 0.805. The concentrations of prostaglandin E2 in the FF of individuals with PCOS exhibited an inverse association with the proportion of high-quality embryos (p < 0.05). Conclusions: Our research identified a distinct metabolic profile of the FF from normal-weight women with PCOS. The results offer a broader comprehension of the pathogenesis and advancement of PCOS, and the detected differential metabolites could be potential biomarkers and targets for the treatment of PCOS. Full article

The expansion of animal husbandry for food production has necessitated effective management of livestock waste, including cattle manure and poultry litter. Using these byproducts as organic fertilizers in agriculture represents a sustainable approach to their disposal. While these residues offer known benefits for soil health and crop productivity, further studies are needed to explore the effect of different manure microbiota on soil composition. The objective of this study was to address this gap and contribute to the advancement of this area. A randomized block design experiment was set up in the field with three replications per treatment, including the application of cattle manure, poultry litter, and a control treatment without fertilizer. After a 60 day period, the chemical characteristics and bacterial population composition of the soil were analyzed using 16S rRNA gene sequencing. Organic carbon, phosphorus (P), aluminum (Al), and the pH level played pivotal roles in changing the structure of the soil’s bacterial community. Notably, the incorporation of poultry litter induced more pronounced changes in both the chemical properties and bacterial community composition compared with cattle manure. Bacterial groups were enriched in the soils treated with poultry litter, which may indicate enhanced soil fertility. This association may stem from both the chemical alterations resulting from poultry litter application and the direct transfer of microorganisms from this organic fertilizer to the soil. Full article

Although statins have served as the cornerstone for pharmacological lowering of lipid levels in atherosclerotic cardiovascular disease (ASCVD) risk reduction, many patients are unable to achieve target doses of statin medication due to side effects or target levels of cholesterol reduction on statin monotherapy. The landscape of lipid-lowering strategies has expanded in recent years, with the emergence of therapies that make use of small interfering RNA (siRNA) and antisense oligonucleotides, in addition to traditional small-molecule agents. Non-statin therapies that have shown promising results in randomized controlled trials include adenosine triphosphate-citrate lyase inhibitors, proprotein convertase subtilisin/kexin 9 (PCSK9)-inhibiting antibodies and siRNA, omega-3 polyunsaturated fatty acids, and lipoprotein(a) gene-inhibiting siRNA and ASOs, in addition to older therapies such as ezetimibe. In contrast, cholesteryl ester transfer protein (CETP) inhibitors have shown less promising results in randomized trials. The purpose of this narrative review is to summarize the evidence for these medications, with a focus on phase III randomized trials. Full article

During the period of ‘Feizixiao’ litchi fruit pericarp’s full coloring, there is a phenomenon of “sugar withdrawal” in the pulp, and the mixed foliar nutrients of calcium and magnesium (Ca+Mg) can effectively overcome this phenomenon. One of the reasons for this may be that it is related to the influence of the mixed nutrients of Ca+Mg on the bypass respiratory pathways of the pulp. The major fruit quality indicators, the rates of cytochrome and cyanide-resistant respiratory pathways (CP and AP) in the pulp and the activities of their key enzymes, were observed continuously in 2021 and 2022, and the deferentially expressed genes (DEGs) related to the two bypass respiratory pathways in the pulp were screened by RNA-seq analysis, with a qPCR of the random genes performed to verify the results. Ca+Mg treatment kept the content of the total soluble sugar in the pulp stable and higher than that the control in the ripening stage; Ca+Mg treatment increased the activities of electron-transferring enzymes in the electron transport chain, such as NADH dehydrogenase (ND), succinate dehydrogenase (SDH), cytochrome bc1 complex, and cytochrome c (Cyt c) through up-regulating their gene expression. In terms of the rate-limiting enzymes in the pulp, Ca+Mg treatment increased the activity of cytochrome oxidase (COX) in the CP pathway by up-regulating the expression of COX genes, then increased the CP respiratory rate and inhibited the CP respiratory rate decrease; meanwhile, it also inhibited the activity of AOX (alternate oxidase) in the pulp in the AP pathway by down-regulating the expression of AOX genes, then inhibited the increase in the AP respiration rate. The qPCR validation of randomly selected DEGs showed a significant unitary linear correlation between their expression levels and the results of the RNA-seq analysis. Therefore, one of the physiological mechanisms on the mixed foliar nutrients of Ca and Mg overcoming the phenomenon of “sugar withdrawal” in the ‘Feizixiao’ litchi pulp could be to promote CP and to inhibit AP, and then to delay the ripening and senescence of the pulp. Full article

Despite the increasing availability of genomic data and enhanced data analysis procedures, predicting the severity of associated diseases remains elusive in the absence of clinical descriptors. To address this challenge, we have focused on the K_V7.2 voltage-gated potassium channel gene (KCNQ2), known for its link to developmental delays and various epilepsies, including self-limited benign familial neonatal epilepsy and epileptic encephalopathy. Genome-wide tools often exhibit a tendency to overestimate deleterious mutations, frequently overlooking tolerated variants, and lack the capacity to discriminate variant severity. This study introduces a novel approach by evaluating multiple machine learning (ML) protocols and descriptors. The combination of genomic information with a novel Variant Frequency Index (VFI) builds a robust foundation for constructing reliable gene-specific ML models. The ensemble model, MLe-KCNQ2, formed through logistic regression, support vector machine, random forest and gradient boosting algorithms, achieves specificity and sensitivity values surpassing 0.95 (AUC-ROC > 0.98). The ensemble MLe-KCNQ2 model also categorizes pathogenic mutations as benign or severe, with an area under the receiver operating characteristic curve (AUC-ROC) above 0.67. This study not only presents a transferable methodology for accurately classifying KCNQ2 missense variants, but also provides valuable insights for clinical counseling and aids in the determination of variant severity. The research context emphasizes the necessity of precise variant classification, especially for genes like KCNQ2, contributing to the broader understanding of gene-specific challenges in the field of genomic research. The MLe-KCNQ2 model stands as a promising tool for enhancing clinical decision making and prognosis in the realm of KCNQ2-related pathologies. Full article

Cancer is a leading cause of morbidity and mortality worldwide. While numerous factors have been identified as contributing to the development of malignancy, our understanding of the mechanisms involved remains limited. Early cancer detection and the development of effective treatments are therefore critical areas of research. One class of molecules that play a crucial role in the transmission of genetic information are transfer RNAs (tRNAs), which are the most abundant RNA molecules in the human transcriptome. Dysregulated synthesis of tRNAs directly results in translation disorders and diseases, including cancer. Moreover, various types of tRNA modifications and the enzymes responsible for these modifications have been implicated in tumor biology. Furthermore, alterations in tRNA modification can impact tRNA stability, and impaired stability can prompt the cleavage of tRNAs into smaller fragments known as tRNA fragments (tRFs). Initially believed to be random byproducts lacking any physiological function, tRFs have now been redefined as non-coding RNA molecules with distinct roles in regulating RNA stability, translation, target gene expression, and other biological processes. In this review, we present recent findings on translational regulatory models centered around tRNAs in tumors, providing a deeper understanding of tumorigenesis and suggesting new directions for cancer treatment. Full article

Omnipresent microplastics (MPs) in marine ecosystems are ingested at all trophic levels and may be a vector for the transfer of persistent organic pollutants (POPs) through the food web. We fed rotifers polyethylene MPs (1–4 µm) spiked with seven congeners of polychlorinated biphenyls (PCBs) and two congeners of polybrominated diphenyl ethers (PBDEs). In turn, these rotifers were fed to cod larvae from 2–30 days post-hatching (dph), while the control groups were fed rotifers without MPs. After 30 dph, all the groups were fed the same feed without MPs. Whole-body larvae were sampled at 30 and 60 dph, and four months later the skin of 10 g juveniles was sampled. The PCBs and PBDEs concentrations were significantly higher in MP larvae compared to the control larvae at 30 dph, but the significance dissipated at 60 dph. Expression of stress-related genes in cod larvae at 30 and 60 dph showed inconclusive minor random effects. The skin of MP juveniles showed disrupted epithelial integrity, fewer club cells and downregulation of a suite of genes involved in immunity, metabolism and the development of skin. Our study showed that POPs were transferred through the food web and accumulated in the larvae, but that the level of pollutants decreased once the exposure was ceased, possibly related to growth dilution. Considering the transcriptomic and histological findings, POPs spiked to MPs and/or MPs themselves may have long-term effects in the skin barrier defense system, immune response and epithelium integrity, which may potentially reduce the robustness and overall fitness of the fish. Full article

The consumption of fresh produce and fruits has increased over the last few years as a result of increasing consumer awareness of healthy lifestyles. Several studies have shown that fresh produces and fruits could be potential sources of human pathogens and antibiotic-resistant bacteria. In this study, 248 strains were isolated from lettuce and surrounding soil samples, and 202 single isolates selected by the random amplified polymorphic DNA (RAPD) fingerprinting method were further characterized. From 202 strains, 184 (91.2%) could be identified based on 16S rRNA gene sequencing, while 18 isolates (8.9%) could not be unequivocally identified. A total of 133 (69.3%) and 105 (54.7%) strains showed a resistance phenotype to ampicillin and cefoxitin, respectively, while resistance to gentamicin, tobramycin, ciprofloxacin, and tetracycline occurred only at low incidences. A closer investigation of selected strains by whole genome sequencing showed that seven of the fifteen sequenced strains did not possess any genes related to acquired antibiotic resistance. In addition, only one strain possessed potentially transferable antibiotic resistance genes together with plasmid-related sequences. Therefore, this study indicates that there is a low possibility of transferring antibiotic resistance by potential pathogenic enterobacteria via fresh produce in Korea. However, with regards to public health and consumer safety, fresh produce should nevertheless be continuously monitored to detect the occurrence of foodborne pathogens and to hinder the transfer of antibiotic resistance genes potentially present in these bacteria. Full article

Window of implantation (WOI) genes have been comprehensively identified at the single cell level. DNA methylation changes in cervical secretions are associated with in vitro fertilization embryo transfer (IVF-ET) outcomes. Using a machine learning (ML) approach, we aimed to determine which methylation changes in WOI genes from cervical secretions best predict ongoing pregnancy during embryo transfer. A total of 2708 promoter probes were extracted from mid-secretory phase cervical secretion methylomic profiles for 158 WOI genes, and 152 differentially methylated probes (DMPs) were selected. Fifteen DMPs in 14 genes (BMP2, CTSA, DEFB1, GRN, MTF1, SERPINE1, SERPINE2, SFRP1, STAT3, TAGLN2, TCF4, THBS1, ZBTB20, ZNF292) were identified as the most relevant to ongoing pregnancy status. These 15 DMPs yielded accuracy rates of 83.53%, 85.26%, 85.78%, and 76.44%, and areas under the receiver operating characteristic curves (AUCs) of 0.90, 0.91, 0.89, and 0.86 for prediction by random forest (RF), naïve Bayes (NB), support vector machine (SVM), and k-nearest neighbors (KNN), respectively. SERPINE1, SERPINE2, and TAGLN2 maintained their methylation difference trends in an independent set of cervical secretion samples, resulting in accuracy rates of 71.46%, 80.06%, 80.72%, and 80.68%, and AUCs of 0.79, 0.84, 0.83, and 0.82 for prediction by RF, NB, SVM, and KNN, respectively. Our findings demonstrate that methylation changes in WOI genes detected noninvasively from cervical secretions are potential markers for predicting IVF-ET outcomes. Further studies of cervical secretion of DNA methylation markers may provide a novel approach for precision embryo transfer. Full article

We studied the reproductive behaviour associated with mate choice by size in three species of White Sea molluscs of the genus Littorina—L. saxatilis, L. obtusata and L. fabalis. Three behavioural patterns were revealed after a comparative analysis of the behaviour of the male snails. The males of L. obtusata, regardless of their size, could mate with all females but preferred to mate with larger ones. The males of L. fabalis chose females of their own size or larger. The males of L. saxatilis mated with females of approximately their own size. In the first case (L. obtusata), there is a free exchange of genes between all the size groups in the population. In the second case (L. fabalis), the gene transfer from small males to females of any size is free but the gene transfer from large males to small females is limited. In the third case (L. saxatilis), the gene flow is limited between groups of individuals of dramatically different size. Thus, in the case of L. saxatilis and L. fabalis, to varying degrees restriction of random mating associated with size assortativity in choosing a mating partner was expressed, which under certain circumstances (divergence of individuals in different econiches, the presence of ecotypes differing in size, lack of stronger natural selection in the other direction) can favour sympatric speciation. The males of all the three periwinkles’ species preferred larger females but sexual selection in favour of larger females was found only in L. obtusata. In the other two species, there were no statistically significant size differences between copulating and non-copulating females. This appears to be due to the occurrence of size-assortative mating in these species, which limits the ability of males to choose larger female partners. Full article

(1) Background: C-X-C Motif Chemokine Receptor 4 (CXCR4) and Fibroblast Activation Protein Alpha (FAP) are promising theranostic targets. However, it is unclear whether CXCR4 and FAP positivity mark distinct microenvironments, especially in solid tumors. (2) Methods: Using Random Forest (RF) analysis, we searched for entity-independent mRNA and microRNA signatures related to CXCR4 and FAP overexpression in our pan-cancer cohort from The Cancer Genome Atlas (TCGA) database—representing n = 9242 specimens from 29 tumor entities. CXCR4- and FAP-positive samples were assessed via StringDB cluster analysis, EnrichR, Metascape, and Gene Set Enrichment Analysis (GSEA). Findings were validated via correlation analyses in n = 1541 tumor samples. TIMER2.0 analyzed the association of CXCR4 / FAP expression and infiltration levels of immune-related cells. (3) Results: We identified entity-independent CXCR4 and FAP gene signatures representative for the majority of solid cancers. While CXCR4 positivity marked an immune-related microenvironment, FAP overexpression highlighted an angiogenesis-associated niche. TIMER2.0 analysis confirmed characteristic infiltration levels of CD8+ cells for CXCR4-positive tumors and endothelial cells for FAP-positive tumors. (4) Conclusions: CXCR4- and FAP-directed PET imaging could provide a non-invasive decision aid for entity-agnostic treatment of microenvironment in solid malignancies. Moreover, this machine learning workflow can easily be transferred towards other theranostic targets. Full article

Alterations in the gut microbiome have been linked to obesity and type 2 diabetes, in epidemiologic studies and studies of fecal transfer effects in germ-free mice. Here, we aimed to identify the effects of specific gut microbes on the phenotype of mice fed a high-fat diet (HFD). After eight weeks of HFD feeding, male C57BL/6J mice in the HFD group ranking in the upper and lower quartiles for body weight gain were considered obese prone and obese resistant, respectively. 16S rRNA gene sequencing was used to determine the composition of the intestinal microbiota, and fecal transplantation (FMT) was conducted to determine whether the microbiota plays a causal role in phenotypic variation. Ruminococcaceae_UCG-013 was more abundant in the gut microbes of mice with a lean phenotype than in those with an obese phenotype. Ruminococcaceae_UCG-013 was identified as the most significant biomarker for alleviating obesity by random forest analysis. In a correlation analysis of serum parameters and body weight, Ruminococcaceae_UCG-013 was positively associated with serum HDL-C levels and negatively associated with serum TC, TG, and LDL-C levels. To conclude, Ruminococcaceae_UCG-013 was identified as a novel microbiome biomarker for obesity resistance, which may serve as a basis for understanding the critical gut microbes responsible for obesity resistance. Ruminococcaceae_UCG-013 may serve as a target for microbiome-based diagnoses and treatments in the future. Full article