Parental Generation Research Articles

An enhanced diversity indicator-based many-objective evolutionary algorithm with shape-conforming convergence metric

As the number of objectives increases, many-objective optimization problems (MaOPs) become increasingly complex. Traditional indicator-based many-objective evolutionary algorithms can often ensure the convergence of the population but tend to struggle with maintaining its diversity. In this paper, an enhanced diversity indicator-based many-objective evolutionary algorithm with shape-conforming convergence metric, namely, MaOEA-DISC, is presented to relieve this weakness. In MaOEA-DISC, firstly, we focus on the inter-individual spacing relationships within the population based on Iϵ+ Indicator, proposing a novel enhanced diversity Iϵ+ Indicator to ensure the enhancement of population diversity while converging. Secondly, we propose a new metric of individual convergence, which calculates the convergence of individuals based on the shape of Pareto front, reducing the errors caused by the shape of the Pareto front when measuring individual convergence, thereby assessing individual convergence more accurately. Finally, to further improve the convergence speed of the population, different mating strategies are employed for mating in the parental generation. MaOEA-DISC is compared with other algorithms on various benchmark MaOPs ranging from 3 to 10 objectives, as well as a real-world MaOPs. Experimental results demonstrate that when dealing with MaOPs, MaOEA-DISC not only achieves excellent population convergence and diversity but also effectively maintains a balance between them, showing promising practical value.

Diverse Origins of Near-Identical Antifreeze Proteins in Unrelated Fish Lineages Provide Insights Into Evolutionary Mechanisms of New Gene Birth and Protein Sequence Convergence.

Determining the origins of novel genes and the mechanisms driving the emergence of new functions is challenging yet crucial for understanding evolutionary innovations. Recently evolved fish antifreeze proteins (AFPs) offer a unique opportunity to explore these processes, particularly the near-identical type I AFP (AFPI) found in four phylogenetically divergent fish taxa. This study tested the hypothesis of protein sequence convergence beyond functional convergence in three unrelated AFPI-bearing fish lineages. Through comprehensive comparative analyses of newly sequenced genomes of winter flounder and grubby sculpin, along with available high-quality genomes of cunner and 14 other related species, the study revealed that near-identical AFPI proteins originated from distinct genetic precursors in each lineage. Each lineage independently evolved a de novo coding region for the novel ice-binding protein while repurposing fragments from their respective ancestors into potential regulatory regions, representing partial de novo origination-a process that bridges de novo gene formation and the neofunctionalization of duplicated genes. The study supports existing models of new gene origination and introduces new ones: the innovation-amplification-divergence model, where novel changes precede gene duplication; the newly proposed duplication-degeneration-divergence model, which describes new functions arising from degenerated pseudogenes; and the duplication-degeneration-divergence gene fission model, where each new sibling gene differentially degenerates and renovates distinct functional domains from their parental gene. These findings highlight the diverse evolutionary pathways through which a novel functional gene with convergent sequences at the protein level can evolve across divergent species, advancing our understanding of the mechanistic intricacies in new gene formation.

Identification and functional characterization of differentially expressed circRNAs in high glucose treated endothelial cells: Construction of circRNA-miRNA-mRNA network

BackgroundEndothelial dysfunction is a complication of diabetes mellitus (DM), characterized by impaired endothelial function in both microvessels and macrovessels, closely linked to atherosclerosis (AS). Endothelial dysfunction, characterized by impaired endothelial cell (EC) function, is a pivotal factor in AS and DM. Circular RNAs (circRNAs) are endogenous non-coding RNAs that can act as competing endogenous RNAs (ceRNAs) and regulate gene expression. However, the role of circRNAs in ECs dysfunction and AS under high glucose (HG) condition remains elusive. MethodsWe performed high-throughput sequencing to identify differentially expressed (DE) circRNAs in human umbilical vein endothelial cells (HUVEC) exposed to HG, one risk factors of endothelial dysfunction and AS. We then validated eight candidate circRNAs by qRT-PCR and functional analysis, directing our attention to hsa_circ_0122319. Moreover, microarray analysis identified the differential expression profiles of miRNAs and mRNAs regulated by hsa_circ_0122319. Subsequently, the construction of the ceRNAs network employed bioinformatic analysis and Cytoscape software. Furthermore, the role of the PI3K-Akt signaling pathway in regulating ceRNAs was evaluated. ResultsWe detected 917 DE circRNAs in HG treated HUVEC. The parental genes of these circRNAs were enriched in cell cycle, cellular senescence and endocytosis related pathways. The differential expression of hsa_circ_0122319 was confirmed to be most obvious at the cellular level and in clinical samples by qPCR experiments. After overexpression of hsa_circ_0122319, 49 DE miRNAs and 459 DE mRNAs were identified using microarray analysis. Subsequently, a ceRNAs network was constructed, comprising hsa_circ_0122319, 8 miRNAs, and 41 mRNAs. ConclusionIn summary, our study delves into the role of circRNAs in endothelial dysfunction associated with DM and AS. Through high-throughput sequencing and validation, we identified hsa_circ_0122319 as a pivotal regulator of ECs function under HG conditions. It also showed that hsa_circ_0123319 has the potential to serve as a biomarker for DM and its vascular complications, and provides new evidence for future exploration of the intricate molecular mechanisms of endothelial dysfunction in the progression of DM and AS.

Association of ventricular-arterial coupling with biomarkers involved in heart failure pathophysiology-the STANISLAS cohort.

Impaired left ventricular-arterial coupling (VAC) has been shown to correlate with worse prognosis in cardiac diseases and heart failure (HF). The extent of the relationship between VAC and circulating biomarkers associated with HF has been scarcely documented. We aimed to explore associations of VAC with proteins involved in HF pathophysiology within a large population-based cohort of middle-aged individuals. In the forth visit of the STANISLAS family cohort, involving 1309 participants (mean age 48 ± 14 years; 48% male) from parent and children generations, we analysed the association of 32 HF-related proteins with non-invasively assessed VAC using pulse wave velocity (PWV)/global longitudinal strain (GLS) and arterial elastance (Ea)/ventricular end-systolic elastance (Ees). Among the 32 tested proteins, fatty acid-binding protein adipocyte 4, interleukin-6, growth differentiation factor 15, matrix metalloproteinase (MMP)-1, and MMP-9 and adrenomedullin were positively associated with PWV/GLS whereas transforming growth factor beta receptor type 3, MMP-2 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were negatively associated. In multivariable models, only MMP-2 and NT-proBNP were significantly and inversely associated with PWV/GLS in the whole population and in the parent generation. Higher levels of NT-proBNP were also negatively associated with Ea/Ees in the whole cohort but this association did not persist in the parent subgroup. Elevated MMP-2 and NT-proBNP levels correlate with better VAC (lower PWV/GLS), possibly indicating a compensatory cardiovascular response to regulate left ventricular pressure amidst cardiac remodelling and overload.

Transgenerational effects of the levonorgestrel-based birth control pill in zebrafish offspring

The consumption of hormone-derived medicines, such as levonorgestrel (LNG), is increasing worldwide, and its discharge into the environment reaches non-target organisms. In our previous study, we exposed the parental generation of zebrafish to environmentally relevant concentrations of LNG during the developmental phase. Subsequently, they had grown in a tank with clean water until adulthood. Now, we allowed this parental generation to reproduce to obtain F1 progeny unexposed to LGN, in order to analyze the transgenerational effects of parental LNG exposure on the survival and hatching of unexposed F1 embryos and the stress and behavior of F1 larvae. Here, we found decreased survival rates with higher LNG concentrations, providing a transgenerational effect. This highlights the environmental impact of exposure to LNG, causing damage at the individual and population level and affecting the next generation at the beginning of development, impacting qualities in the survival of the species.

Genomic implications of the repeated shift to self-fertilization across a species' geographic distribution.

The ability to self-fertilize often varies among closely related hermaphroditic plant species, though, variation can also exist within species. In the North American Arabidopsis lyrata, the shift from self-incompatibility (SI) to selfing established in multiple regions independently, mostly since recent postglacial range expansion. This has made the species an ideal model for the investigation of the genomic underpinnings of the breakdown of SI and its population genetic consequences. By comparing nearby selfing and outcrossing populations across the entire species' geographic distribution, we investigated variation at the self-incompatibility (S-)locus and across the genome. Furthermore, a diallel crossing experiment on one mixed-mating population was performed to gain insight in the genetics of mating system variation. We confirmed that the breakdown of SI had evolved in several S-locus backgrounds. The diallel suggested the involvement of binuclearly expressed parental genes with dominance relations. Though, the population-level genome-wide association study did not single out clear-cut candidate genes but several regions with one near the S-locus. On the implication side, selfing as compared to outcrossing populations had less than half of the genomic diversity, while the number of runs of homozygosity and their length scaled with the degree of inbreeding. The results highlight that mating system shifts to selfing, its genetic underpinning and the likely negative genomic consequences for evolutionary potential can be strongly interlinked with past range dynamics.

Protein-coding circular RNA enhances antiviral immunity via JAK/STAT pathway in Drosophila.

RNA interference (RNAi) drives powerful antiviral immunity in plants and animals so that many viruses must express viral suppressor of RNAi (VSR) to establish virulent infection. However, little is known about the immune responses conferring resistance against viruses that have evolved the counter-defensive strategy to suppress antiviral RNAi. In this study, we discover that Drosophila cells infected with Drosophila C virus (DCV), a natural viral pathogen of Drosophila known to harbor a potent VSR, exhibit heightened expression of circular RNA circZfh1. circZfh1 confers virus resistance in the presence of viral suppression of antiviral RNAi. Furthermore, we validate that circZfh1 encodes a 274-amino acid protein, CRAV, essential for its antiviral activity. Notably, CRAV differs from its parental Zfh1 gene in a different reading frame, with the C-terminal 69 amino acids unique to CRAV. Our analysis also reveals the presence of CRAV in species within the melanogaster subgroup, with the C-terminal unique fragment undergoing accelerated evolution. Expression of CRAV upregulates the expression of the cytokine Upd3, which binds to its receptor, stimulating the JAK-STAT pathway and enhancing the immune response to DCV infection. Notably, CRISPR/Cas9 knockout of circZfh1 significantly enhances DCV replication in vitro and in vivo, with circZfh1-knockout adult flies displaying heightened disease susceptibility to DCV. In summary, our findings unveil a Drosophila protein-coding circular RNA that activates an innate immune signaling pathway crucial for virus resistance following the suppression of antiviral RNAi by viruses, thereby elucidating a novel counter-defensive strategy.IMPORTANCEEukaryotic hosts possess a complex, multilayered immune system that guards against pathogen invasion. In fruit flies, RNA interference (RNAi) drives robust antiviral immunity, prompting many viruses to express viral suppressors of RNAi (VSRs) to establish virulent infections. However, little is known about immune responses that confer resistance against viruses with potent VSRs. In this study, we discovered that Drosophila cells infected with Drosophila C virus (DCV), a natural viral pathogen possessing a potent VSR, upregulated the expression of circular RNA circZfh1. circZfh1 exhibits DCV-specific antiviral activity, encoding a 274-amino acid protein, CRAV, crucial for its antiviral effects. As a different reading frame from its parental Zfh1 gene, the C-terminal 69 amino acids are unique to CRAV, undergoing faster evolution. CRAV activates the JAK-STAT pathway, enhancing the immune response to DCV infection. Therefore, our work uncovers a new strategy for suppressing viral counter-defense through protein-coding circular RNA in fruit flies.

Analysis of PDE6G mutations in a patient with retinitis pigmentosa

BackgroundMutations in PDE6A and PDE6B are known to cause autosomal recessive RP in humans, On the other hand, mutations in PDE6G are rare but can lead to severe early-onset RP.Case presentationAn 8-year-old Chinese boy was referred to our hospital for poor vision issues. Refraction with cycloplegia showed high hyperopia with astigmatism both eyes. Funduscopic examination revealed typical bone spicule-type pigment deposits in the periphery and midperiphery. The patient was given glasses and a whole exome sequencing containing mitochondrial genes was performed. The results of genetic testing showed that there was a heterozygous frameshift mutation and a segment deletion in the proband’s PDE6G gene. Analysis of the parental genes showed that frameshift mutation was inherited from the proband’s mother and segment deletion from his father.ConclusionsIn this paper, we give a firsthand report that the complex heterozygous mutations of PDE6G gene can causes autosomal recessiveRP (arRP), which expands the understanding of the pathogenic genes of RP.

METTL3-mediated m6A modification of circGLIS3 promotes prostate cancer progression and represents a potential target for ARSI therapy

BackgroundCircular RNAs (circRNAs) have been shown to be involved in tumorigenesis and progression. However, the role of circGLIS3 (hsa_circ_0002874) in prostate cancer (PCa) has yet not been reported.MethodsCandidate circRNA were determined through comprehensive analysis of public datasets, PCa cell lines, and tissues data. A series of cellular functional assays, including CCK-8, colony formation, wound healing, and transwell assays were performed. Subsequently, RNA sequencing, RNA immunoprecipitation, methylated RNA immunoprecipitation, microRNA pulldown, luciferase reporter assay, and western blot were used to explore the underlying molecular mechanisms. Moreover, the xenograft tumor mouse model was established to elucidate the function of circGLIS3.ResultsCircGLIS3, derived from exon 2 of the parental GLIS3 gene, was identified as a novel oncogenic circRNA in PCa that was closely associated with the biochemical recurrence. Its expression levels were upregulated in PCa tissues and cell lines as well as enzalutamide high-resistant cells. The cellular functional assays revealed that circGLIS3 promoted PCa cell proliferation, migration, and invasion. METTL3-mediated N6-methyladenosine (m6A) modification maintained its upregulation by enhancing its stability. Mechanically, CircGLIS3 sponged miR-661 to upregulate MDM2, thus regulating the p53 signaling pathway to promote cell proliferation, migration, and invasion. Furthermore, in vitro and in vivo experiments, the knockdown of circGLIS3 improved the response of PCa cells to ARSI therapies such as enzalutamide.ConclusionsMETTL3-mediated m6A modification of circGLIS3 regulates the p53 signaling pathway via the miR-661/MDM2 axis, thereby facilitating PCa progression. Meanwhile, this study unveils a promising potential target for ARSI therapy for PCa.

Epidemic influenza virus nucleoprotein gene incorporated into vaccine influenza virus strain genome to optimize systemic and local T-cell immune response against live attenuated influenza vaccine

Introduction. Optimization of the vaccine-induced T-cell repertoire is one of the strategies to expand the spectrum of protective potential for live attenuated influenza vaccine (LAIV). LAIV cross-protective properties can be improved by introducing the nucleoprotein (NP) gene derived from epidemic parental virus into vaccine strain genome, i.e. by replacing the classical 6:2 genome formula with 5:3. The main objective of the present study was to detail evaluation for virus-specific systemic and tissue-resident memory T-cells subsets in mice immunized with seasonal H1N1 LAIV of the genome formula 6:2 and 5:3. Materials and methods. Two H1N1 LAIV strains with varying NP genes (LAIV 6:2 and LAIV 5:3) were generated using reverse genetics techniques. C57BL/6J mice were immunized intranasally with the vaccine candidates, twice, 3 weeks apart. Cells from the spleen and lung tissues were isolated 7 days after booster immunization to be stimulated with whole H1N1 influenza virus for assessing cytokine-producing memory CD44+CD62L– T-cells as well as expression of CD69 and CD103 surface markers using flow cytometry. Humoral murine serum immunity against H1N1 virus was assessed by ELISA. Results. The LAIV 5:3 vs classical 6:2 vaccine strain carrying the epidemic parental NP gene induced significantly more pronounced humoral immune response against recent influenza virus. The group of mice immunized with LAIV 5:3 demonstrated higher levels of virus-specific CD4+ and CD8+ effector memory T cells (TEM) in the spleen, including a subset of polyfunctional (IFNγ+TNFα+IL-2+) CD4+ TEM, compared to LAIV 6:2 group. Virus-specific memory T cell levels in lung tissues after immunization with LAIV 5:3 vs LAIV 6:2 also tended to increase, but no significant difference in stimulated tissue-resident CD69+CD103– and CD69+CD103+ T cells between the groups were found. Conclusion. Modification of the seasonal LAIV strain genome for updating its epitope composition allowed to enhance the virus-specific T-cell immune response both at systemic level and in lung tissues, thereby shoeing that the effectiveness of the vaccine against circulating influenza viruses can be potentially increased.

Nanoplastic at environmentally relevant concentrations induces toxicity across multiple generations associated with inhibition in germline G protein-coupled receptor CED-1 in Caenorhabditis elegans

Nanoplastics at environmentally relevant concentrations (ERCs) could cause transgenerational toxicity on organisms. Caenorhabditis elegans is an important model for the study of transgenerational toxicology of pollutants. Nevertheless, the underlying mechanisms for the control of transgenerational nanoplastic toxicity by germline signals remain largely unclear. In C. elegans, exposure to 1–100 μg/L polystyrene nanoparticle (PS-NP) decreased expression of germline ced-1 encoding a G protein-coupled receptor at parental generation (P0-G). After PS-NP exposure at P0-G, transgenerational decrease in germline ced-1 expression could be detected. Meanwhile, the susceptibility to transgenerational PS-NP toxicity was observed in ced-1(RNAi) animals. After PS-NP exposure at P0-G, germline RNAi of ced-1 increased expressions of met-2 and set-6 encoding histone methylation transferases. The susceptibility of ced-1(RNAi) to transgenerational PS-NP toxicity could be inhibited by RNAi of met-2 and set-6. Moreover, in PS-NP exposed met-2(RNAi) and set-6(RNAi) nematodes, expressions of ins-39, wrt-3, and/or efn-3 encoding secreted ligands were decreased. Therefore, our results demonstrated that inhibition in germline CED-1 mediated the toxicity induction of nanoplastics at ERCs across multiple generations in nematodes.

M6A-methylated circPOLR2B forms an R-loop and regulates the biological behavior of glioma stem cells through positive feedback loops

Glioma is the most common primary brain tumor, and targeting glioma stem cells (GSCs) has become a key aspect of glioma treatment. In this study, we discovered a molecular network in which circRNA forms an R-loop structure with its parental gene to regulate the biological behavior of GSCs. Genes with abnormal expression in GSCs were screened using RNA-seq and circRNA microarray analyses. The study results showed that high expression of YTHDC1 in GSCs promoted the transportation of N6-methyladenosine (m6A)-modified circPOLR2B from the nucleus to the cytoplasm. Decreased circPOLR2B levels in the nucleus resulted in fewer R-loop structures formed with its parental gene POLR2B. This reduction in R-loop structures relieved the inhibitory effect on POLR2B transcription and upregulated PBX1 expression through alternative polyadenylation (APA) action, thereby promoting the malignant biological behavior of GSCs. Knockdown of YTHDC1, POLR2B, and PBX1 reduced xenograft tumor volume and prolonged the survival of nude mice. The YTHDC1/circPOLR2B/POLR2B/PBX1 axis plays a regulatory role in the biological behavior of GSCs, offering potential targets and novel strategies for the treatment of glioma.

Transgenerational reproductive toxicity induced by carboxyl and amino charged microplastics at environmental concentrations in Caenorhabditis elegans: Involvement of histone methylation

Microplastics, recognized as emerging contaminants, are commonly observed to be charged in the environment, potentially exerting toxic effects on various organisms. However, the transgenerational reproductive toxicity and underlying mechanisms of polystyrene (PS), particularly carboxyl-modified PS (PS-COOH) and amino-modified PS (PS-NH2), remain largely unexplored. In this study, the parental generation (P0) of Caenorhabditis elegans was subjected to environmental concentrations (0.1–100 μg/L) of PS, PS-COOH, and PS-NH2, with subsequent generations (F1–F4) cultured under normal conditions. Exposure to PS-NH2 at concentrations of 10–100 μg/L exhibited more pronounced reproductive toxicity compared to PS or PS-COOH, resulting in decreased brood size, egg ejection rate, number of fertilized eggs, and cell corpses per gonad. Similarly, maternal exposure to 100 μg/L of PS-NH2 induced more severe transgenerational reproductive effects in C. elegans. Significant increases in H3 on lysine 4 dimethylation (H3K4me2) and H3 on lysine 9 trimethylation (H3K9me3) levels were observed in the subsequent generation, concurrent with the transgenerational upregulation of set-30 and met-2 following parental exposure to PS, PS-COOH, and PS-NH2. Correlation analyses revealed significant associations between the expression of these genes with the reproductive ability. Molecular docking studies suggested that PS-NH2 exhibited higher affinity for SET-30 and MET-2. Further analysis demonstrated that transgenerational effects on reproduction were absent in set-30(gk315) and met-2(n4256) mutants, highlighting the pivotal role of set-30 and met-2 in mediating the transgenerational effect. This study provides novel insights into the environmental risks associated with negatively and positively charged microplastics.

Identification and validation of key regulating circRNAs in Immune Thrombocytopenia by circRNAs sequencing

Dysfunction of T cells is a causative factor in Immune Thrombocytopenia (ITP), an autoimmune disorder. Circular RNAs (circRNAs), which have been associated with the pathophysiology of various immunological conditions, are of particular interest. Our study aimed to identify pivotal regulatory circRNAs within the peripheral T cells of ITP patients. We utilized circRNA sequencing to discern differences in circRNA expression between the ITP cohort and healthy controls. We identified 606 upregulated and 719 downregulated circRNAs. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to scrutinize the parent genes of these differentially expressed circRNAs, revealing their significant involvement in metabolic processes and T cell receptor signaling pathways. Following a rigorous selection process that included DEG analysis, KEGG, and GO pathways analysis, along with an assessment of the potential roles of their parent genes, five top differentially expressed circRNAs were subjected to further validation via quantitative Polymerase Chain Reaction (RT-qPCR). Specifically, in the peripheral T cells of ITP patients, hsa_circ_0008866 (TAOK1), hsa_circ_0006856 (MAP3K5), and hsa_circ_0007444 (RHOBTB3) emerged as key regulatory circRNAs. The potential miRNA targets of these circRNAs were predicted employing miRanda, RNAhybrid, and TargetScan algorithms.

Heterozygous variants in transmembrane channel-like 1 gene cause autosomal recessive nonsyndromic hearing loss.

Autosomal recessive non-syndromic hearing loss (ARNSHL) can cause severe or very severe pre-speech hearing loss. Transmembrane channel-like 1 (TMC1) gene is the sixth deafness gene discovered, but the precise extent of its protein structure and function is unknown. First, history collection, audiology examination and imaging examination were performed on the proband and his family members. Peripheral blood of proband and family members was collected, genomic DNA was extracted, exon high-throughput sequencing technology was used to detect the deafness gene mutation of the proband, and Sanger sequencing was performed to verify the TMC1 gene of the proband's parents. The proband was born with hearing impairment, normal tympanic function, inability to induce acoustic reflex in both ears (acoustic reflex threshold is 100 dBHL), and severe sensorineural deafness. One of his sisters has severe sensorineural hearing loss, and neither his parents nor his other sister is hearing impaired. High-throughput sequencing of the proband identified mutations at c.741+3_741+6delAAGT (splicing) and c.884C>T (p.A295V) of the TMC1 gene, two of which were heterozygous mutations. Sanger sequencing confirmed that the c.884C > T mutation was inherited from the mother, while the c.741+3_741+6delAAGT mutation was derived from the father. Prediction of amino acid function suggested that both mutations were pathogenic mutations. In conclusion, we found a new pathogenic complex heterozygous mutation of the TMC1 gene, which enriched the mutation spectrum of the TMC1 gene and provided a basis for genetic counseling and prenatal diagnosis of ARNSHL.

Multigenerational toxicity of microplastics derived from two types of agricultural mulching films to Folsomia candida

Degradation and fragmentation of mulching films represents an increasing source of microplastics (MPs, plastic particles 1 μm to 5 mm in size) to agricultural soils. MPs have been shown to affect many soil invertebrates, including springtails. However, these studies typically use test materials representing less environmentally relevant particle types, such as pristine uniform MPs, which do not represent the large range of particle sizes and morphologies found in the field. This study aimed at providing insight into the adverse effects of MPs originating from agricultural mulching films, by using artificially aged MPs derived from both biodegradable (starch-polybutadiene adipate terephthalate (PBAT)) blend, as well as conventional (linear low-density polyethylene (LLDPE)) plastic polymers. The soil dwelling springtail Folsomia candida was exposed to these MPs for five generations in order to elucidate population effects due to possible reproduction toxicity, endocrine disruption, mutagenesis or developmental toxicity. F. candida were exposed to 0, 0.0016, 0.008, 0.04, 0.2, 1, 2, 3, 4 and 5 % (w/w dry soil) MPs in Lufa 2.2 soil, which includes concentrations within the range of environmental relevance. Juveniles produced at each concentration were transferred to the next generation, with the parental, F2 and F4 generations being exposed for four weeks and F1 and F3 generations for five weeks. No concentration-dependent effects on F. candida survival or reproduction were observed in exposures to either of the MPs, in any of the generations. These results suggest that the particular MPs used in this study, derived from mulching films used on agricultural soils, may not be potent toxicants to F. candida, even after long-term exposure and at elevated concentrations.

Mechanisms and regulation of replication fork reversal

DNA replication is remarkably accurate with estimates of only a handful of mutations per human genome per cell division cycle. Replication stress caused by DNA lesions, transcription-replication conflicts, and other obstacles to the replication machinery must be efficiently overcome in ways that minimize errors and maximize completion of DNA synthesis. Replication fork reversal is one mechanism that helps cells tolerate replication stress. This process involves reannealing of parental template DNA strands and generation of a nascent-nascent DNA duplex. While fork reversal may be beneficial by facilitating DNA repair or template switching, it must be confined to the appropriate contexts to preserve genome stability. Many enzymes have been implicated in this process including ATP-dependent DNA translocases like SMARCAL1, ZRANB3, HLTF, and the helicase FBH1. In addition, the RAD51 recombinase is required. Many additional factors and regulatory activities also act to ensure reversal is beneficial instead of yielding undesirable outcomes. Finally, reversed forks must also be stabilized and often need to be restarted to complete DNA synthesis. Disruption or deregulation of fork reversal causes a variety of human diseases. In this review we will describe the latest models for reversal and key mechanisms of regulation.

Parental genetic effects on the offspring's phenotype without transmission of the gene itself-pathophysiology and clinical evidence.

Parental genes can influence the phenotype of their offspring through genomic-epigenomic interactions even without the direct inheritance of specific parental genotypes. Maternal genetic variations can affect the ovarian and intrauterine environments and potentially alter lactation behaviors, impacting offspring nutrition and health outcomes independently of the fetal genome. Similarly, paternal genetic changes can affect the endocrine system and vascular functions in the testes, influencing sperm quality and seminal fluid composition. These changes can initiate early epigenetic modifications in sperm, including alterations in microRNAs, tRNA-derived small RNAs (tsRNAs), and DNA methylation patterns. These epigenetic modifications might induce further changes in target organs of the offspring, leading to modified gene expression and phenotypic outcomes without transmitting the original parental genetic alterations. This review presents clinical evidence supporting this hypothesis and discusses the potential underlying molecular mechanisms. Parental gene-offspring epigenome-offspring phenotype interactions have been observed in neurocognitive disorders and cardio-renal diseases.

Boll weevils in dry bolls: is there a performance disadvantage?

BackgroundAnthonomus grandis grandis is the main cotton pest in the Americas, with the potential to become a pest in other continents. The insect uses the plant’s reproductive organs for feeding, oviposition, and survival strategies in the off-season, sheltering in dry bolls. This study aimed to know the reproductive potential, feeding, longevity, and morphometric characteristics of boll weevils from dry bolls, squares, and traps. Adults were obtained from infested squares, dry bolls, and traps installed in cotton fields and the Caatinga area. Thirty weevil pairs were maintained in the laboratory to assess the oviposition, feeding holes, longevity, and morphometric measurements of the parental and F1 generations.ResultsIn the parental generation, boll weevils from traps (the Caatinga area and cotton cultivation) showed greater reproductive potential. Boll weevils from squares and the Caatinga area showed greater feeding activity compared with those from cotton cultivation. Greater rostrum length, thorax + abdomen length, and abdomen width were observed in boll weevils from cotton cultivation and dry bolls. The origin of boll weevils parental generation did not affect progeny emergence time. The F1 generation of boll weevils showed significant differences in average longevity depending on the origin of different microhabitats. Furthermore, differences in rostrum lengths were observed, with the boll weevils coming from traps installed in cotton cultivation, the Caatinga area, and dry bolls being the largest. Regarding thorax + abdomen length and abdomen width, the highest values were observed in those from the Caatinga area and cotton cultivation.ConclusionIt was proven that dry bolls did not affect the reproductive, feeding, and longevity performance of boll weevils, enabling better insect fitness (reproduction and size) in relation to those coming from squares. The use of dry bolls as off-season shelter is an important survival strategy for the boll weevil.

Exosomal membrane proteins analysis using a silicon nanowire field effect transistor biosensor

Exosomes are of great significance in clinical diagnosis, due to their high homology with parental generation, which can reflect the pathophysiological status. However, the quantitative and classification detection of exosomes is still faced with the challenges of low sensitivity and complex operation. In this study, we develop an electrical and label-free method to directly detect exosomes with high sensitivity based on a Silicon nanowire field effect transistor biosensor (Si-NW Bio-FET). First, the impact of Debye length on Si-NW Bio-FET detection was investigated through simulation. The simulation results demonstrated that as the Debye length increased, the electrical response to Si-NW produced by charged particle at a certain distance from the surface of Si-NW was greater. A Si-NW Bio-FET modified with specific antibody CD81 on the nanowire was fabricated then used for detection of cell line-derived exosomes, which achieved a low limit of detection (LOD) of 1078 particles/mL in 0.01 × PBS. Furthermore, the Si-NW Bio-FETs modified with specific antibody CD9, CD81 and CD63 respectively, were employed to distinguish exosomes derived from human promyelocytic leukemia (HL-60) cell line in three different states (control group, lipopolysaccharide (LPS) inflammation group, and LPS + Romidepsin (FK228) drug treatment group), which was consistent with nano-flow cytometry. This study provides a highly sensitive method of directly quantifying exosomes without labeling, indicating its potential as a tool for disease surveillance and medication instruction.