Search Results (35)

Neisseria gonorrhoeae is the causative agent of the sexually transmitted infection gonorrhea. Preventative vaccines or novel treatments based on a better understanding of the molecular basis of N. gonorrhoeae infection are required as resistance to current antibiotics is widespread. Toxin–antitoxin (TA) systems modulate bacterial physiology by interfering with vital cellular processes; type II TA systems, where both toxin and antitoxin are proteins, are the best-studied. Bioinformatics analysis revealed genes encoding an uncharacterized type II HicAB TA system in the N. gonorrhoeae strain FA1090 chromosome, which were also present in >83% of the other gonococcal genome sequences examined. Gonococcal HicA overproduction inhibited bacterial growth in Escherichia coli, an effect that could be counteracted by the co-expression of HicB. Kill/rescue assays showed that this effect was bacteriostatic rather than bactericidal. The site-directed mutagenesis of key histidine and glycine residues (Gly22, His24, His29) abolished HicA-mediated growth arrest. N. gonorrhoeae FA1090∆hicAB and complemented derivatives that expressed IPTG-inducible hicA, hicB, or hicAB, respectively, grew as wild type, except for IPTG-induced FA1090∆hicAB::hicA. RT-PCR demonstrated that hicAB are transcribed in vitro under the culture conditions used. The deletion of hicAB had no effect on biofilm formation. Our study describes the first characterization of a HicAB TA system in N. gonorrhoeae. Full article

The eri silkworm Samia cynthia ricini (S. ricini) is an economically and scientifically significant lepidopteran species, though its genomic resources have remained limited. Here, we present a chromosome-level genome assembly for S. ricini generated through integrated long-read, short-read, and Hi-C sequencing data. The final 456.16 Mb assembly spans 14 chromosomes, exhibiting 98.5% BUSCO completeness and a 48.51% repetitive content. Functional annotation of the 15,729 protein-coding genes against five major databases (NR, SwissProt, Pfam, GO, and KEGG) revealed a maximum annotation rate of 92.71%, demonstrating high gene set quality. Comparative genomics with B. mori uncovered conserved syntenic blocks interspersed with chromosomal fusion/fission events and inversions. We further identified 4.27 million SNPs, 1.02 million InDels, and 53,367 SVs, establishing the first comprehensive variation map for this species. These genomic variations provide a foundation for marker-assisted breeding programs and trait association studies. All the genomic resources and interactive visualization tools were integrated into the SilkMeta database. This study establishes S. ricini as a pivotal resource for comparative lepidopteran genomics and accelerates molecular breeding programs for this agriculturally valuable insect. Full article

Side impacts tend to produce more severe injuries than frontal collisions, particularly for vulnerable occupants such as children. Despite this, there is a limited number of studies and developments focused on side impact protection systems, and existing airbag evaluations often rely on destructive and high-cost test methods. This study introduces a novel, cost-effective, and nondestructive experimental testbed designed to evaluate curtain airbags for vehicles in segments B, C, D, and E. The main objective is to develop an adjustable mechanical structure that replicates the side frame geometry of multiple vehicles, allowing the mounting and evaluation of various curtain airbags under realistic conditions. The prototype, capable of withstanding deployment forces of up to 7000 N, was tested with a 3-year-old child dummy, recording a peak head acceleration of 136.17 g, corresponding to AIS level 2. Deployment speeds reached 7.77 m/s, with inflation times between 29 and 36 ms—values that fall within the range reported in previous experimental and numerical studies. The testbed demonstrated consistency in its performance metrics and offers a valuable tool for enhancing child occupant safety in side impacts. Furthermore, it provides a measurable Head Injury Criterion (HIC) range that can be used to interpret injury severity in child occupants. This work contributes significantly to the development of flexible and safe testing methodologies for side airbag systems, reducing the reliance on full-scale crash testing. Full article

Background/Objective: Historically, immunization programs have focused on infants, children, and women of reproductive age. COVID-19 vaccination prompted countries to vaccinate adults. The objective of this manuscript is to provide a global overview of adult immunization policies post COVID-19 pandemic. Methods: We summarized WHO Strategic Advisory Group of Experts on Immunization (SAGE) recommendations by adult group and analyzed the data reported in 2024 (2023) by WHO Member States (MS) via the WHO/UNICEF electronic Joint Reporting Form on Immunization (eJRF) on national immunization schedules, and from other sources by WHO region and income group. Results: WHO policy recommendations exist for most of the licensed vaccines targeting adults; however, the inclusion in national immunization schedules is higher in high-income (HICs) and middle-income (MICs) countries. For pregnant women, 90% of MS reported vaccination against COVID-19 (65% in low-income countries [LICs]), 63% against tetanus-containing vaccines (73% in LICs), 57% against influenza (4% in LICs), and 21% against pertussis-containing vaccines (all MICs and HICs). For health workers, 91% against COVID-19 (92% in LICs), 59% against influenza (4% in LICs), and 25% against hepatitis B (10% in LICs). For adults with chronic diseases, COVID-19 vaccination data were not available, 58% against influenza, and 23% against pneumococcal disease. For older adults, more than 90% of MS across all income groups reported COVID-19 vaccination, 59% against influenza (8% of LICs versus 89% of HICs), 17% against pneumococcal, and 7% against herpes zoster (HZ). Conclusion: The disparities in adult immunization policies across income groups highlight the need to improve access and strengthen vaccination efforts. A life course approach is essential to maximize the full potential of immunization across all ages. Full article

Background: Cochlear implants (CIs) have become a widely used intervention for Deaf and hard-of-hearing (DHH) children, particularly for developing spoken language. However, parental decision-making regarding CIs is influenced by a range of factors, including socio-economic status, healthcare accessibility, cultural beliefs, and societal attitudes. While extensive research on parental perceptions of CIs exists in high-income countries (HICs), there is limited research on these perspectives in low- and middle-income countries (LMICs), like South Africa, where disparities in healthcare access significantly impact CI uptake. Objectives: This study aimed to explore the views and perceptions of South African parents regarding CIs for their DHH children, with a specific focus on how financial, cultural, and informational barriers influence decision-making. Methods: A mixed-methods approach was used, combining Q-methodology for quantitative data and thematic analysis for qualitative insights. Nine parents of DHH children participated. The Q-set survey ranked parental attitudes toward CI risks, benefits, and accessibility, while semi-structured interviews provided deeper insights into decision-making processes. Factor analysis grouped participants into clusters based on their perceptions, and qualitative data were analysed using a thematic framework approach. Results: Findings revealed two distinct parental clusters: (a) Cluster 1 parents viewed CIs as essential for speech development and strongly supported implantation, and (b) Cluster 2 parents recognized CI benefits but emphasized that outcomes vary based on individual circumstances. Three overarching themes emerged from thematic analysis: (1) financial barriers restricting CI access, (2) parental reliance on medical professionals for decision-making, and (3) persistent stigma and cultural beliefs influencing CI perceptions. Conclusions: This study highlights critical barriers to CI access in South Africa, including socio-economic inequities, limited healthcare infrastructure, and persistent stigma. While parents largely recognized the benefits of CIs, their decisions were shaped by financial constraints and concerns about Deaf identity and societal acceptance. This study calls for the expansion of publicly funded CI programmes, the development of culturally tailored parental counselling protocols, and targeted public awareness campaigns to reduce stigma surrounding hearing restoration devices. These interventions can help mitigate financial and cultural barriers to CI adoption in South Africa. Full article

Background: The African hedgehog (Atelerix albiventris) exhibits specialized skin differentiation leading to spine formation, yet its regulatory mechanisms remain unclear. Transposable elements (TEs), particularly LINEs (long interspersed nuclear elements) and SINEs (short interspersed nuclear elements), are known to influence genome organization and gene regulation. Objectives: Given the high proportion of SINEs in the hedgehog genome, this study aims to characterize the distribution, evolutionary dynamics, and potential regulatory roles of LINEs and SINEs, focusing on their associations with chromatin architecture, DNA methylation, and gene expression. Methods: We analyzed LINE and SINE distribution using HiFi sequencing and classified TE families through phylogenetic reconstruction. Hi-C data were used to explore TE interactions with chromatin architecture, while whole-genome 5mCpG methylation was inferred from PacBio HiFi reads of muscle tissue using a deep-learning-based approach. RNA-seq data from skin tissues were analyzed to assess TE expression and potential associations with genes linked to spine development. Results: SINEs form distinct genomic blocks in GC-rich and highly methylated regions, whereas LINEs are enriched in AT-rich, hypomethylated regions. LINEs and SINEs are associated differently with A/B compartments, with SINEs in euchromatin and LINEs in heterochromatin. Methylation analysis suggests that younger TEs tend to have higher methylation levels, and expression analysis indicates that some differentially expressed TEs may be linked to genes involved in epidermal and skeletal development. Conclusions: This study provides a genome-wide perspective on LINE and SINE distribution, methylation patterns, and potential regulatory roles in A. albiventris. While not establishing a direct causal link, the findings suggest that TEs may influence gene expression associated with spine development, offering a basis for future functional studies. Full article

Genome sequences contain the fundamental genetic information that largely determines the biology of a species. Over the past 20 years, advancements in high-throughput sequencing technologies and bioinformatics tools have matured, facilitating genome assembly and ushering in the telomere-to-telomere (T2T) era. Bombyx mori is renowned as a silk-producing insect and serves as an important model organism extensively studied across various fields of biology. In this study, we present the first assembled T2T genome by integrating HiFi, ultra-long ONT, NGS, and Hi-C data. This assembly comprises 450,267,439 base pairs from 28 chromosomes and includes annotations for a total of 18,253 protein-coding genes. A completeness evaluation revealed that 99.1% of conserved single-copy genes were included, as determined by a BUSCO analysis. Furthermore, the consensus quality (QV) assessed through Merqury was recorded at 59.88. The proportion of repeat sequence achieved 60.77%, marking it as the highest reported value for B. mori to date. In comparison to previously published genomes, our assembly offers a more complete and higher quality representation, particularly concerning highly homologous tandem regions such as telomeres, rDNA clusters, and Gr family regions. Furthermore, our extensive experience in genome assembly, including sample preparation experience and assembly strategies to reduce complexity, will provide valuable references for other species aiming to achieve their own T2T genome assemblies. Full article

Background: Schwann cells (SCs) and their plasticity contribute to the peripheral nervous system’s capacity for nerve regeneration after injury. The Egr2/Krox20 promoter antisense RNA (Egr2-AS) recruits chromatin remodeling complexes to inhibit Egr2 transcription following peripheral nerve injury. Methods: RNA-seq and ATAC-seq were performed on control cells, Lenti-GFP-transduced cells, and cells overexpressing Egr2-AS (Lenti-AS). Egr2 AS-RNA was cloned into the pLVX-DsRed-Express2-N1 lentiviral expression vector (Clontech, Mountain View, CA, USA), and the levels of AS-RNA expression were determined. Ezh2 and Wdr5 were immunoprecipitated from rat SCs and RT-qPCR was performed against AS-Egr2 RNA. ChIP followed by DNA purification columns was used to perform qPCR for relevant promoters. Hi-C, HiC-DC+, R, Bioconductor, and TOBIAS were used for significant and differential loop analysis, identifications of COREs and CORE-promotor loops, comparisons of TF activity at promoter sites, and identification of site-specific TF footprints. OnTAD was used to detect TADs, and Juicer was used to identify A/B compartments. Results: Here we show that a Neuregulin-ErbB2/3 signaling axis mediates binding of the Egr2-AS to YY1^Ser184 and regulates its expression. Egr2-AS modulates the chromatin accessibility of Schwann cells and interacts with two distinct histone modification complexes. It binds to EZH2 and WDR5 and enables targeting of H3K27me3 and H3K4me3 to promoters of Egr2 and C-JUN, respectively. Expression of the Egr2-AS results in reorganization of the global chromatin landscape and quantitative changes in the loop formation and contact frequency at domain boundaries exhibiting enrichment for AP-1 genes. In addition, the Egr2-AS induces changes in the hierarchical TADs and increases transcription factor binding scores on an inter-TAD loop between a super-enhancer regulatory hub and the promoter of mTOR. Conclusions: Our results show that Neuregulin-ErbB2/3-YY1 regulates the expression of Egr2-AS, which mediates remodeling of the chromatin landscape in Schwann cells. Full article

Small genetic elements known as toxin-antitoxin (TA) systems are abundant in bacterial genomes and involved in stress response, phage inhibition, mobile genetic elements maintenance and biofilm formation. Type II TA systems are the most abundant and diverse, and they are organized as bicistronic operons that code for proteins (toxin and antitoxin) able to interact through a nontoxic complex. However, HicAB is one of the type II TA systems that remains understudied. Here, we review the current knowledge of HicAB systems in different bacteria, their main characteristics and the existing evidence to associate them with some biological roles, are described. The accumulative evidence reviewed here, though modest, underscores that HicAB systems are underexplored TA systems with significant potential for future research. Full article

Adopting a plant-based diet (PBD) has been shown to reduce the risk of developing certain diseases and is linked to environmental benefits. This review synthesises the evidence on the barriers adults aged 18 to 65 living in high-income countries (HIC) may experience when adopting a PBD. A systematic literature review was conducted using four search databases: Medline, Embase, Global Health, and Web of Science. Barriers were mapped to behaviour change strategies using the COM-B model. Ten studies were included in the final review, including 1740 participants. Five were qualitative, four were cross-sectional, and one was a pre- and-post-intervention study. In total, 40 barriers were identified and synthesised into 11 themes: financial, lack of knowledge, emotional, health, convenience, social, enjoyment of meat, environmental, accessibility, personal ability, and media. Of the 40 barriers, nutritional intake/requirements (categorised into the “health” theme) had the most evidence. This barrier encompassed concerns around being able to meet nutritional needs if an individual were to adopt a PBD. Habits (in the “personal ability” theme), which included established eating habits and habitual behaviours relating to animal-source foods, had the second most evidence alongside the barrier of not knowing what to eat as part of a PBD (in the “lack of knowledge” theme). Education interventions and communication/marketing policies were the behaviour change mechanisms mapped onto these barriers. Future interventions should focus on informing individuals about what to consume as part of a nutritionally balanced PBD and facilitating habitual dietary change. Full article

Heterosis plays a significant role in enhancing variety, boosting yield, and raising economic value in crops, but the molecular mechanism is still unclear. We analyzed the transcriptomes and 3D genomes of a hybrid (F₁) and its parents (w30 and 082). The analysis of the expression revealed a total of 485 specially expressed genes (SEGs), 173 differentially expressed genes (DEGs) above the parental expression level, more actively expressed genes, and up-regulated DEGs in the F₁. Further study revealed that the DEGs detected in the F₁ and its parents were mainly involved in the response to auxin, plant hormone signal transduction, DNA metabolic process, purine metabolism, starch, and sucrose metabolism, which suggested that these biological processes may play a crucial role in the heterosis of Brassica rapa. The analysis of 3D genome data revealed that hybrid F₁ plants tend to contain more transcriptionally active A chromatin compartments after hybridization. Supplementaryly, the F₁ had a smaller TAD (topologically associated domain) genome length, but the number was the highest, and the expression change in activated TAD was higher than that of repressed TAD. More specific TAD boundaries were detected between the parents and F₁. Subsequently, 140 DEGs with genomic structural variants were selected as potential candidate genes. We found two DEGs with consistent expression changes in A/B compartments and TADs. Our findings suggested that genomic structural variants, such as TADs and A/B chromatin compartments, may affect gene expression and contribute to heterosis in Brassica rapa. This study provides further insight into the molecular mechanism of heterosis in Brassica rapa. Full article

Grifola frondosa is a valuable edible fungus with high nutritional and medicinal values. The mating systems of fungi not only offer practical strategies for breeding, but also have far-reaching effects on genetic variability. Grifola frondosa has been considered as a sexual species with a tetrapolar mating system based on little experimental data. In the present study, one group of test crosses and six groups of three-round mating experiments from two parental strains were conducted to determine the mating system in G. frondosa. A chi-squared test of the results of the test-cross mating experiments indicated that they satisfied Mendelian segregation, while a series of three-round mating experiments showed that Mendelian segregation was not satisfied, implying a segregation distortion phenomenon in G. frondosa. A genomic map of the G. frondosa strain, y59, grown from an LMCZ basidiospore, with 40.54 Mb and 12 chromosomes, was generated using genome, transcriptome and Hi-C sequencing technology. Based on the genomic annotation of G. frondosa, the mating-type loci A and B were located on chromosomes 1 and 11, respectively. The mating-type locus A coded for the β-fg protein, HD1, HD2 and MIP, in that order. The mating-type locus B consisted of six pheromone receptors (PRs) and five pheromone precursors (PPs) in a crossed order. Moreover, both HD and PR loci may have only one sublocus that determines the mating type in G. frondosa. The nonsynonymous SNP and indel mutations between the A₁B₁ and A₂B₂ mating-type strains and the reference genome of y59 only occurred on genes HD2 and PR1/2, preliminarily confirming that the mating type of the y59 strain was A₁B₂ and not A₁B₁. Based on the genetic evidence and the more reliable molecular evidence, the results reveal that the mating system of G. frondosa is tetrapolar. This study has important implications for the genetics and hybrid breeding of G. frondosa. Full article

In this paper, we present concurrent atomistic-continuum (CAC) simulations of the hydrogen (H) diffusion along a grain boundary (GB), nearby which a large population of dislocations are piled up, in a plastically deformed bi-crystalline bcc iron sample. With the microscale dislocation slip and the atomic structure evolution at the GB being simultaneously retained, our main findings are: (i) the accumulation of tens of dislocations near the H-charged GB can induce a local internal stress as high as 3 GPa; (ii) the more dislocations piled up at the GB, the slower the H diffusion ahead of the slip–GB intersection; and (iii) H atoms diffuse fast behind the pileup tip, get trapped within the GB, and diffuse slowly ahead of the pileup tip. The CAC simulation-predicted local H diffusivity, $D_{\mathrm{pileup}-\mathrm{tip}}$, and local stresses, $\sigma$, are correlated with each other. We then consolidate such correlations into a mechanics model by considering the dislocation pileup as an Eshelby inclusion. These findings will provide researchers with opportunities to: (a) characterize the interplay between plasticity, H diffusion, and crack initiation underlying H-induced cracking (HIC); (b) develop mechanism-based constitutive rules to be used in diffusion–plasticity coupling models for understanding the interplay between mechanical and mass transport in materials at the continuum level; and (c) connect the atomistic deformation physics of polycrystalline materials with their performance in aqueous environments, which is currently difficult to achieve in experiments. Full article

Three-dimensional genome organization has been increasingly recognized as an important determinant of the precise regulation of gene expression in mammalian cells, yet the relationship between gene transcriptional activity and spatial subcompartment positioning is still not fully comprehended. Here, we first utilized genome-wide Hi-C data to infer eight types of subcompartment (labeled A1, A2, A3, A4, B1, B2, B3, and B4) in mouse embryonic stem cells and four primary differentiated cell types, including thymocytes, macrophages, neural progenitor cells, and cortical neurons. Transitions of subcompartments may confer gene expression changes in different cell types. Intriguingly, we identified two subsets of subcompartments defined by higher gene density and characterized by strongly looped contact domains, named common A1 and variable A1, respectively. We revealed that common A1, which includes highly expressed genes and abundant housekeeping genes, shows a ~2-fold higher gene density than the variable A1, where cell type-specific genes are significantly enriched. Thus, our study supports a model in which both types of genomic loci with constitutive and regulatory high transcriptional activity can drive the subcompartment A1 formation. Special chromatin subcompartment arrangement and intradomain interactions may, in turn, contribute to maintaining proper levels of gene expression, especially for regulatory non-housekeeping genes. Full article

Chinese flowering cabbage (Brassica rapa var. parachinensis) is a popular and widely cultivated leaf vegetable crop in Asia. Here, we performed a high quality de novo assembly of the 384 Mb genome of 10 chromosomes of a typical cultivar of Chinese flowering cabbage with an integrated approach using PacBio, Illumina, and Hi-C technology. We modeled 47,598 protein-coding genes in this analysis and annotated 52% (205.9/384) of its genome as repetitive sequences including 17% in DNA transposons and 22% in long terminal retrotransposons (LTRs). Phylogenetic analysis reveals the genome of the Chinese flowering cabbage has a closer evolutionary relationship with the AA diploid progenitor of the allotetraploid species, Brassica juncea. Comparative genomic analysis of Brassica species with different subgenome types (A, B and C) reveals that the pericentromeric regions on chromosome 5 and 6 of the AA genome have been significantly expanded compared to the orthologous genomic regions in the BB and CC genomes, largely driven by LTR-retrotransposon amplification. Furthermore, we identified a large number of structural variations (SVs) within the B. rapa lines that could impact coding genes, suggesting the functional significance of SVs on Brassica genome evolution. Overall, our high-quality genome assembly of the Chinese flowering cabbage provides a valuable genetic resource for deciphering the genome evolution of Brassica species and it can potentially serve as the reference genome guiding the molecular breeding practice of B. rapa crops. Full article