Biological Research Research Articles

Ecological perspectives on female and male reproductive success with competition in two Serapias species.

The deceptive strategies by which orchids are pollinated and how these are capable of attracting pollinators remain understudied with regard to their implications on plant fitness. Despite its ecological importance, limited investigations have been conducted on sexual deception and shelter mimicry in orchid species, making it a compelling avenue in orchid biology research. To expand the knowledge of these reproductive mechanisms, we studied the pollination of Serapias lingua and S. parviflora, in co-occurring and isolated sites in Balearic Islands (Spain), further accentuated by the presence of a hybrid, indicating shared pollinators. We employed bagging and hand pollination experiments to examine their reproductive biology. Furthermore, we evaluated the influence of phenotypical and ecological factors on reproductive success, including biometric measurements, reproductive performance and neighborhood diversity (co-flowering and pollinator communities). Reproductive mechanisms between these two orchid species exhibit substantial disparities. Serapias lingua relies primarily on insect-mediated pollination, while S. parviflora demonstrates self-reproduction capacity. Although events of open pollination are rare, hybridization occurs predominantly when S. lingua is the pollen donor. Fruit set in S. parviflora was positively correlated with plant height, while in S. lingua it was negatively associated with flower size. The coexistence of both species positively affected pollinia removal in S. parviflora, but did not exert an influence on reproductive traits in S. lingua. Overall, biometric parameters were diminished in isolated compared to co-occurring sites. At the community level, the increased diversity of co-flowering species in the vicinity exhibited an inhibitory effect on pollinia removal in S. parviflora. Under a context of pollinator loss or phenological mismatch between pollinator presence and flowering, the selfing capacity of S. parviflora would guarantee reproduction whereas S. lingua survival would be compromised. Furthers studies are needed to assess the effects of phenotypical and ecological factors on reproductive success of S. lingua in pollinator-decline scenarios.

From synthesis to applications of biomolecule-protected luminescent gold nanoclusters.

Gold nanoclusters (AuNCs) are a class of novel luminescent nanomaterials that exhibit unique properties of ultra-small size, featuring strong anti-photo-bleaching ability, substantial Stokes shift, good biocompatibility, and low toxicity. Various biomolecules have been developed as templates or ligands to protect AuNCs with enhanced stability and luminescent properties for biomedical applications. In this review, the synthesis of AuNCs based on biomolecules including amino acids, peptides, proteins and DNA are summarized. Owing to the advantages of biomolecule-protected AuNCs, they have been employed extensively for diverse applications. The biological applications, particularly in bioimaging, biosensing, disease therapy and biocatalysis have been described in detail herein. Finally, current challenges and future potential prospects of bio-templated AuNCs in biological research are briefly discussed.

User-Friendly Multifunctional Red-Emissive Carbon Dots for Rapid Cell Nucleus Staining via Targeting Nuclear Proteins.

Cytoarchitectural staining is of great importance in disease diagnosis and cell biology research. This study developed user-friendly multifunctional red-emissive carbon dots (R-CDs) for rapid cell nucleus staining via targeting nuclear proteins. R-CDs, simply prepared by electrochemical treatment of 1,2,4-benzenetriamine, exhibit strong emission at 635 nm when excited at 507 nm. The R-CDs can rapidly stain the nucleus of human SH-SY5Y, HepG2, and HUH-7 cells with a high signal-to-noise ratio owing to fluorescence enhancement after entering the nucleus. Compared to conventional cytosolic dyes such as Hoechst and DAPI, R-CDs are cheaper, more highly dispersed in water, and more stable (requiring no stringent storage conditions). The R-CDs show stable optical properties with insignificant photobleaching over 7 days and salt resistance up to 2 M of NaCl. More importantly, R-CDs, possessing a positive charge, allow rapid staining of live cells (3 min) and dead cells (10 s) in saline. According to kinetic variation, R-CDs can distinguish live cells from dead cells. Staining exhibits high efficiency in onion epidermal cells, Aspergillus niger, Caenorhabditis elegans, and human spermatozoa. The mechanism for efficient staining is based on their fast accumulation in the nucleus due to their small size and positive charge and strong interaction with nuclear proteins at amino acid residues of histidine and arginine, resulting in fluorescence enhancement by dozens of times. The developed R-CDs do not bind to DNA and would not cause genetic damage and will find various safe applications in biological and medical fields.

Pangenome and multi-tissue gene atlas provide new insights into the domestication and highland adaptation of yaks

BackgroundThe genetic diversity of yak, a key domestic animal on the Qinghai-Tibetan Plateau (QTP), is a vital resource for domestication and breeding efforts. This study presents the first yak pangenome obtained through the de novo assembly of 16 yak genomes.ResultsWe discovered 290 Mb of nonreference sequences and 504 new genes. Our pangenome-wide presence and absence variation (PAV) analysis revealed 5,120 PAV-related genes, highlighting a wide range of variety-specific genes and genes with varying frequencies across yak populations. Principal component analysis (PCA) based on binary gene PAV data classified yaks into three new groups: wild, domestic, and Jinchuan. Moreover, we proposed a ‘two-haplotype genomic hybridization model’ for understanding the hybridization patterns among breeds by integrating gene frequency, heterozygosity, and gene PAV data. A gene PAV-GWAS identified a novel gene (BosGru3G009179) that may be associated with the multirib trait in Jinchuan yaks. Furthermore, an integrated transcriptome and pangenome analysis highlighted the significant differences in the expression of core genes and the mutational burden of differentially expressed genes between yaks from high and low altitudes. Transcriptome analysis across multiple species revealed that yaks have the most unique differentially expressed mRNAs and lncRNAs (between high- and low-altitude regions), especially in the heart and lungs, when comparing high- and low-altitude adaptations.ConclusionsThe yak pangenome offers a comprehensive resource and new insights for functional genomic studies, supporting future biological research and breeding strategies.

Academia Molecular Biology and Genomics: A repository of information for all areas of Genomics and Molecular Biology Research

Academia Molecular Biology and Genomics: A repository of information for all areas of Genomics and Molecular Biology Research

Modular Approach to Highly Substituted 3-Methylpyridones.

A method has been developed for the rapid synthesis of highly substituted 3-methylpyridones via the condensation of Baylis-Hillman amines and ketones under benzoic acid catalysis. The process features readily available starting materials, broad substrate scope, high functional group tolerance, excellent regioselectivity, and gram-scale synthesis. We envision that this on-demand construction of 3-methylpyridones will provide exciting opportunities in biological research, therapeutics, and material sciences.

The age and growth information of a ctenoid scale fossil from the Upper Cretaceous Nenjiang Formation in Songliao Basin, China.

The study of morphological characteristics and growth information in fish scales is a crucial component of modern fishery biological research, while it has been less studied in fossil materials. This paper presents a detailed morphological description and growth analysis of a fossil ctenoid scale obtained from the Upper Cretaceous Campanian lacustrine deposits in northeastern China. The morphological features of this fossil scale are well-preserved and consistent with the structures found in ctenoid scales of extant fish species and display prominent ring ornamentation radiating outward from the central focus, with grooves intersecting the rings. A comparative analysis of the morphological characteristics between the fossil ctenoid scale and those well-studied extant fish Mugilidae allows us to explore the applicability of modern fishery biological research methods to the field of fossil scales. The scale length, scale width, the vertical distance from the focus to the apex of the scale, and the total number of radii have been measured. The age of the fish that possessed this ctenoid scale has been estimated by carefully counting the annuli, suggesting an age equal to or more than seven years. The distribution of growth rings on the scale potentially reflects the warm paleoclimatic condition and fish-friendly paleoenvironment prevalent during that period. This paper, moreover, serves as a notable application of fishery biological methods in the examination of fossil materials.

Improved Optics for Super-Resolution Time-Lapse Observations of Biological Phenomenon Using Speckle Interferometry

This study proposes a new optical system with the potential for time-lapse observation of living cellular tissue beyond the diffraction limit through speckle interferometry to facilitate biological research. The spatial resolution of this optical system was investigated and improved upon. This study also experimentally verified a finding from an earlier simulation study that the new super-resolution technology could be realised by analysing the phase distribution related to the shape of the measured object, preserved in the light reflected from the object. Additionally, a method was presented to confirm the positions of microstructures, based on the extracted characteristics of the structure.

The importance of basic and translational research in caring for children with malignant solid tumors in Latin America.

Basic and translational research in pediatric cancer are essential to improve patient care. To critically assess the developments achieved in these areas in Latin America, we systematically reviewed information published between 2013 and 2023. Studies of basic and translational research performed by investigators in Latin America evaluating pediatric malignant solid and central nervous system tumors were retrieved from PubMed. Original articles published in English between 2013 and 2023 were included. Collaborations among Latin American authors or among Latin American authors working with researchers from other continents were also included. Studies were excluded if they focused only on adults or on basic research in tumor biology not specifically related to the tumor types analyzed in this review. A total of 550 articles were retrieved, but after removal of duplicates, 514 articles were included in the analysis, the majority of which were authored by researchers affiliated with institutions in Argentina, Brazil and Mexico. These countries also had the highest number of collaborations on original articles published with authors from Europe and North America. Argentina had the highest number of collaborations on original publications, with coauthors from Brazil and Uruguay. The median impact factor of the 244 journals in which articles were published was 3.5. The most commonly studied tumors were osteosarcomas, neuroblastomas and medulloblastomas; the most commonly studied areas were molecular analysis, tumor cell biology and biomarkers. In Latin America, research in pediatric oncology is on the agenda, despite a notable disparity in publication rates and frequency of collaboration between countries. There is a need to strengthen scientific collaboration within Latin America and with countries from other continents to promote research and to develop novel treatment strategies that reflect the local needs of children in Latin America who have solid tumors and brain cancer.

Revealing isochoric water nucleation: a visual study

The phenomena of water freezing at constant volume, or isochoric, is becoming more and more fascinating. However, because the system is subjected to extremely high pressures, it is exceedingly challenging to investigate it visually. Fewer properties have been found visually up till now, but many have been found through other means. Nevertheless, we were able to design a reactor so that it could be observed through a microscope as water was frozen and thawed at constant volume, reaching temperatures as low as − 12 °C and pressures up to 129 MPa. In this study, we observed critical characteristics visually, focusing on the location of the ice nucleus, its shape, and dynamics. Phase transitions from liquid to solid state are essential mechanisms in the physical sciences. The creation of ice stands as the quintessential and pervasive example of nucleation, playing a central role in diverse disciplines such as geology, biology, aviation, and climate research.

A new suite of reporter vectors and a novel landing site survey system to study cis-regulatory elements in diverse insect species

Comparative analyses between traditional model organisms, such as the fruit fly Drosophila melanogaster, and more recent model organisms, such as the red flour beetle Tribolium castaneum, have provided a wealth of insight into conserved and diverged aspects of gene regulation. While the study of trans-regulatory components is relatively straightforward, the study of cis-regulatory elements (CREs, or enhancers) remains challenging outside of Drosophila. A central component of this challenge has been finding a core promoter suitable for enhancer-reporter assays in diverse insect species. Previously, we demonstrated that a Drosophila Synthetic Core Promoter (DSCP) functions in a cross-species manner in Drosophila and Tribolium. Given the over 300 million years of divergence between the Diptera and Coleoptera, we reasoned that DSCP-based reporter constructs will be useful when studying cis-regulation in a variety of insect models across the holometabola and possibly beyond. To this end, we sought to create a suite of new DSCP-based reporter vectors, leveraging dual compatibility with piggyBac and PhiC31-integration, the 3xP3 universal eye marker, GATEWAY cloning, different colors of reporters and markers, as well as Gal4-UAS binary expression. While all constructs functioned properly with a Tc-nub enhancer in Drosophila, complications arose with tissue-specific Gal4-UAS binary expression in Tribolium. Nevertheless, the functionality of these constructs across multiple holometabolous orders suggests a high potential compatibility with a variety of other insects. In addition, we present the piggyLANDR (piggyBac-LoxP AttP Neutralizable Destination Reporter) platform for the establishment of proper PhiC31 landing sites free from position effects. As a proof-of-principle, we demonstrated the workflow for piggyLANDR in Drosophila. The potential utility of these tools ranges from molecular biology research to pest and disease-vector management, and will help advance the study of gene regulation beyond traditional insect models.

The Role of the MYL4 Gene in Porcine Muscle Development and Its Molecular Regulatory Mechanisms

Muscle growth stands as a pivotal economic trait within pig production, governed by a complex interplay of multiple genes, each playing a role in its quantitative manifestation. Understanding the intricate regulatory mechanisms of porcine muscle development is crucial for enhancing both pork yield and quality. This study used the GSE99749 dataset downloaded from the GEO database, conducting a detailed analysis of the RNA-seq results from the longissimus dorsi muscle (LD) of Tibetan pigs (TP), Wujin pigs (WJ) and large white pigs (LW) at 60 days of gestation, representing diverse body sizes and growth rates. Comparative analyses between TPvsWJ and TPvsLW, along with differential gene expression (DEG) analysis, functional enrichment analysis, and protein–protein interaction (PPI) network analysis, revealed 1048 and 1157 significantly differentially expressed genes (p < 0.001) in TPvsWJ and TPvsLW, respectively. With stricter screening criteria, 37 DEGs were found to overlap between the 2 groups. PPI analysis identified MYL5, MYL4, and ACTC1 as the three core genes. This article focuses on exploring the MYL4 gene. Molecular-level experimental validation, through overexpression and interference of the MYL4 gene combined with EDU staining experiments, demonstrated that overexpression of MYL4 significantly promoted the proliferation of porcine skeletal muscle satellite cells (PSMSC), while interference with MYL4 inhibited their proliferation. Furthermore, by examining the effects of overexpressing and interfering with the MYL4 gene on the muscle hypertrophy marker Fst gene and the muscle degradation marker FOXO3 gene, the pivotal role of the MYL4 gene in promoting muscle growth and preventing muscle degradation was further confirmed. These findings offer a new perspective on the molecular mechanisms behind porcine muscle growth and development, furnishing valuable data and insights for muscle biology research.

Triple Sensing Modes for Triggered β-Galactosidase Activity Assays Based on Kaempferol-Deduced Silicon Nanoparticles and Biological Imaging of MCF-7 Breast Cancer Cells.

β-Galactosidase (β-Gala) is an essential biomarker enzyme for early detection of breast tumors and cellular senescence. Creating an accurate way to monitor β-Gala activity is critical for biological research and early cancer detection. This work used fluorometric, colorimetric, and paper-based color sensing approaches to determine β-Gala activity effectively. Via the sensing performance, the catalytic activity of β-Gala resulted in silicon nanoparticles (SiNPs), fluorescent indicators obtained via a one-pot hydrothermal process. As a standard enzymatic hydrolysis product of the substrate, kaempferol 3-O-β-d-galactopyranoside (KOβDG) caused the fluorometric signal to be attenuated on kaempferol-silicon nanoparticles (K-SiNPs). The sensing methods demonstrated a satisfactory linear response in sensing β-Gala and a low detection limit. The findings showed the low limit of detection (LOD) as 0.00057 and 0.098 U/mL for fluorometric and colorimetric, respectively. The designed probe was then used to evaluate the catalytic activity of β-Gala in yogurt and human serum, with recoveries ranging from 98.33 to 107.9%. The designed sensing approach was also applied to biological sample analysis. In contrast, breast cancer cells (MCF-7) were used as a model to test the in vitro toxicity and molecular fluorescence imaging potential of K-SiNPs. Hence, our fluorescent K-SiNPs can be used in the clinic to diagnose breast cellular carcinoma, since they can accurately measure the presence of invasive ductal carcinoma in serologic tests.

Return of the organism? The concept in plant biology, now and then

AbstractThis essay argues for the importance of an organismic perspective in plant biology and considers some of its implications. These include an increased attention to plant-environment interaction and an emphasis on integrated approaches. Furthermore, this essay contextualizes the increased emphasis on the concept of organism in recent years and places the concept in a longer history. Recent developments in biology and worsening environmental crises have led researchers to study plant responses to changing environments with whole plant approaches that situate plants in their environments, emphasizing the intricate and dynamic interaction between them. This renewed attention to the organism recalls the debates of the early twentieth century, when organicism was one of the three main frameworks in biology (along with vitalism and mechanism). Some scholars see this renewed importance today as a “return” of this earlier period. This essay argues that including insights from plant biology will benefit philosophy of biology research that examines the concept of organism and organicism now and in earlier periods. A comprehensive account of the concept of organism should involve a botanical conception of the organism as well as a zoological one (which is more frequently considered). Although this essay does not aim to present a conceptual analysis, it presents examples of how an organismic perspective can be useful for understanding concepts (such as phenotype, stress, etc.) and research processes (such as experiment set-ups, data processes, etc.) in plant biology. Philosophy of biology investigations that aim at a comprehensive understanding of the concept of organism can benefit greatly from examinations of cases in plant biology, both now and in the past.

Abstract PO3-10-09: The allocation of US $2.6 billion in global funding for breast cancer research between 2016 – 2020: are we investing wisely for breast cancer patients?

Abstract Background: Breast cancer is a global health challenge and the highest incident cancer globally, with over 2 million new cases and 685,000 deaths in 2020, making it the highest incident cancer globally. Furthermore, it is the most prevalent cancer, resulting in the loss of more disability-adjusted life years than any other malignancy. Research is thus crucial to improving outcomes and reducing suffering for breast cancer patients worldwide. This study aimed to analyse global patterns of funding for breast cancer research. Methods: We have previously created a comprehensive database of awards for human cancer research in this period using publicly available data on research funding awards. From this database we extracted all awards relating to breast cancer research, and categorised these by cancer type, cross-cutting research theme and phase of research. Findings: We identified 7051 awards with a total investment of $2.6 billion in 2016-2020, representing 11.2% of all global public and philanthropic cancer research funding during this period. Breast cancer research funding fell year on year, from $773.4 million in 2016 to $243.8 million in 2020. The majority of the investment was in pre-clinical research ($1.9 billion, 73.9%), with clinical trials ($276 million, 10.7%) and public health ($269.2 million, 10.5%) receiving roughly equivalent amounts of funding. The USA accounted for 66.9% of all global breast cancer research investment, with China ($110.4 million, 4.3%) and the UK ($96.6 million, 3.8%) the next largest funders. By research theme, cancer biology research received most funding ($926.2 million, 37.5% of investment), with drug treatment the next best funded research area ($600.5 million, 23.4%), and diagnosis, screening and monitoring third ($396 million, 15.4%). Surgery ($65.2 million, 2.5%) and radiotherapy ($35.3 million, 1.4%) accounted for only a small proportion of research investment. There was minimal investment into breast cancer as a global health issue ($8.1 million, 0.3%). Research into metastatic disease received a greater proportion of investment in breast cancer than in the overall cancer portfolio (23.2% in breast cancer, $597.4 million, compared with 11.7% across all cancers). Conclusions: Breast cancer public and philanthropic research funding is largely invested in pre-clinical research in high-income countries, with the main areas of investment being cancer biology research and drug treatment. The direct benefit to patients from such research is likely to be low and only apparent after a substantial time lag (if at all). Despite their pivotal role in the treatment of the majority of breast cancer patients, surgery and radiotherapy research received a tiny proportion of the overall research investment. Furthermore, relatively little investment is directed towards cancer prevention and early detection, despite their acknowledged key role in cancer control globally. Finally, more equitable research funding is required to align with the global burden of breast cancer, with increased funding for low- and middle-income countries, which account for an increasing proportion of this burden. These data should be considered by funders and policymakers in the allocation of finite resources, which must be invested wisely. Citation Format: Stuart McIntosh, Ellen Copson, Ramsey Cutress, Michael Head. The allocation of US $2.6 billion in global funding for breast cancer research between 2016 – 2020: are we investing wisely for breast cancer patients? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-10-09.

OpenCell: A low-cost, open-source, 3-in-1 device for DNA extraction.

High-cost DNA extraction procedures pose significant challenges for budget-constrained laboratories. To address this, we introduce OpenCell, an economical, open-source, 3-in-1 laboratory device that combines the functionalities of a bead homogenizer, a microcentrifuge, and a vortex mixer. OpenCell utilizes modular attachments that magnetically connect to a central rotating brushless motor. This motor couples to an epicyclic gearing mechanism, enabling efficient bead homogenization, vortex mixing, and centrifugation within one compact unit. OpenCell's design incorporates multiple redundant safety features, ensuring both the device's and operator's safety. Additional features such as RPM measurement, programmable timers, battery operation, and optional speed control make OpenCell a reliable and reproducible laboratory instrument. In our study, OpenCell successfully isolated DNA from Spinacia oleracea (spinach), with an average yield of 2.3 μg and an A260/A280 ratio of 1.77, demonstrating its effectiveness for downstream applications such as Polymerase Chain Reaction (PCR) amplification. With its compact size (20 cm x 28 cm x 6.7 cm) and lightweight design (0.8 kg), comparable to the size and weight of a laptop, OpenCell is portable, making it an attractive component of a 'lab-in-a-backpack' for resource-constrained environments in low-and-middle-income countries and synthetic biology in remote field stations. Leveraging the accessibility of 3D printing and off-the-shelf components, OpenCell can be manufactured and assembled at a low unit cost of less than $50, providing an affordable alternative to expensive laboratory equipment costing over $4000. OpenCell aims to overcome the barriers to entry in synthetic biology research and contribute to the growing collection of frugal and open hardware.

Fostering biodiversity research in post-fire biology

The impacts of wildfire on vegetation and soil erosion have been studied for decades aiming to bring back ecosystems after fire perturbance. However, the influence of fires on above and belowground biodiversity remains far less understood. Biodiversity is critical for supporting ecosystem function, and this data scarcity is hampering managers in adopting effective practices for a proper restoration of burned ecosystems. This limitation could be overcome by future research that should focus post-fire diversity of plants and soil biota, by (i) analysing the environmental factors driving post-fire evolutionary trends; (ii) exploring their interrelations across different spatial and temporal scales; (iii) identifying the variability across fires of different severities and frequency; (iv) ascertaining the post-fire response of individual plant species and soil taxa to fire with or without application of post-fire restoration actions.

Global transmission of extended-spectrum cephalosporin resistance in Escherichia coli driven by epidemic plasmids

Extended-spectrum cephalosporins (ESCs) are third and fourth generation cephalosporin antimicrobials used in humans and animals to treat infections due to multidrug-resistant (MDR) bacteria. Resistance to ESCs (ESC-R) in Enterobacterales is predominantly due to the production of extended-spectrum β-lactamases (ESBLs) and plasmid-mediated AmpC β-lactamases (AmpCs). The dynamics of ESBLs and AmpCs are changing across countries and host species, the result of global transmission of ESC-R genes. Plasmids are known to play a key role in this dissemination, but the relative importance of different types of plasmids is not fully understood. In this study, Escherichia coli with the major ESC-R genes blaCTX-M-1, blaCTX-M-15, blaCTX-M-14 (ESBLs) and blaCMY-2 (AmpC), were selected from diverse host species and other sources across Canada, France and Germany, collected between 2003 and 2017. To examine in detail the vehicles of transmission of the ESC-R genes, long- and short-read sequences were generated to obtain complete contiguous chromosome and plasmid sequences (n=192 ESC-R E.coli). The types, gene composition and genetic relatedness of these plasmids were investigated, along with association with isolate year, source and geographical origin, and put in context with publicly available plasmid sequences. We identified five epidemic resistance plasmid subtypes with distinct genetic properties that are associated with the global dissemination of ESC-R genes across multiple E.coli lineages and host species. The IncI1 pST3 blaCTX-M-1 plasmid subtype was found in more diverse sources than the other main plasmid subtypes, whereas IncI1 pST12 blaCMY-2 was more frequent in Canadian and German human and chicken isolates. Clonal expansion also contributed to the dissemination of the IncI1 pST12 blaCMY-2 plasmid in ST131 and ST117 E.coli harbouring this plasmid. The IncI1 pST2 blaCMY-2 subtype was predominant in isolates from humans in France, while the IncF F31:A4:B1 blaCTX-M-15 and F2:A-:B- blaCTX-M-14 plasmid subtypes were frequent in human and cattle isolates across multiple countries. Beyond their epidemic nature with respect to ESC-R genes, in our collection almost all IncI1 pST3 blaCTX-M-1 and IncF F31:A4:B1 blaCTX-M-15 epidemic plasmids also carried multiple antimicrobial resistance (AMR) genes conferring resistance to other antimicrobial classes. Finally, we found genetic signatures in the regions surrounding specific ESC-R genes, identifying the predominant mechanisms of ESC-R gene movement, and using publicly available databases, we identified these epidemic plasmids from widespread bacterial species, host species, countries and continents. We provide evidence that epidemic resistance plasmid subtypes contribute to the global dissemination of ESC-R genes, and in addition, some of these epidemic plasmids confer resistance to multiple other antimicrobial classes. The success of these plasmids suggests that they may have a fitness advantage over other plasmid types and subtypes. Identification and understanding of the vehicles of AMR transmission are crucial to develop and target strategies and interventions to reduce the spread of AMR. This project was supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), through the Medical Research Council (MRC, MR/R000948/1), the Canadian Institutes of Health Research (CFC-150770), and the Genomics Research and Development Initiative (Government of Canada), the German Federal Ministry of Education and Research (BMBF) grant no. 01KI1709, the French Agency for food environmental and occupational health & safety (Anses), and the French National Reference Center (CNR) for antimicrobial resistance. Support was also provided by the Biotechnology and Biological Sciences Research Council (BBSRC) through the BBSRC Institute Strategic Programme Microbes in the Food ChainBB/R012504/1 and its constituent project BBS/E/F/000PR10348 (Theme 1, Epidemiology and Evolution of Pathogens in the Food Chain).

Predicting Associations between CircRNA and Diseases through Structure-Aware Graph Transformer and Path-Integral Convolution.

A series of biological experiments has demonstrated that circular RNAs play a crucial regulatory role in cellular processes and may be potentially associated with diseases. Uncovering these connections helps in understanding potential disease mechanisms and advancing the development of treatment strategies. However, in biology, traditional experiments face limitations in terms of efficiency and cost, especially when enumerating possible associations. To address these limitations, several computational methods have been proposed, but existing methods only measure from a nodal perspective and cannot capture structural similarities between edges. In this study, we introduce an advanced computational method called SATPIC2CD for analyzing potential associations between circular RNAs and diseases. Specifically, we first employ an Structure-Aware Graph Transformer (SAT), which extracts five predefined metapath representations before calculating attention. This adaptive network integrates structural information into the original self-attention by aggregating information within and between paths. Subsequently, we use Path Integral Convolutional Networks (PACN) to integrate feature information for all path weights between two nodes. Afterward, we complement the network node features with feature loss and feature smoothing using Gated Recurrent Units (GRU) and node centrality. Finally, a Multi-Layer Perceptron (MLP) is employed to obtain the ultimate prediction scores for each circular RNA-disease pair. SATPIC2CD performs remarkably well, with an accuracy of up to 0.9715 measured by the Area Under the Curve (AUC) in a 5-fold cross-validation, surpassing other comparative models. Case studies further emphasize the high precision of our method in identifying circular RNA-disease associations, laying a solid foundation for guiding future biological research efforts.

Factors Influencing Effects of Low-dose Radiation Exposure.

It is now well accepted that the mechanisms induced by low-dose exposures to ionizing radiation (LDR) are different from those occurring after high-dose exposures. However, the downstream effects of these mechanisms are unclear as are the quantitative relationships between exposure, effect, harm, and risk. In this paper, we will discuss the mechanisms known to be important with an overall emphasis on how so-called "non-targeted effects" (NTE) communicate and coordinate responses to LDR. Targeted deposition of ionizing radiation energy in cells causing DNA damage is still regarded as the dominant trigger leading to all downstream events whether targeted or non-targeted. We regard this as an over-simplification dating back to formal target theory. It ignores that last 100 y of biological research into stress responses and signaling mechanisms in organisms exposed to toxic substances, including ionizing radiation. We will provide evidence for situations where energy deposition in cellular targets alone cannot be plausible as a mechanism for LDR effects. An example is where the energy deposition takes place in an organism not receiving the radiation dose. We will also discuss how effects after LDR depend more on dose rate and radiation quality rather than actual dose, which appears rather irrelevant. Finally, we will use recent evidence from studies of cataract and melanoma induction to suggest that after LDR, post-translational effects, such as protein misfolding or defects in energy metabolism or mitochondrial function, may dominate the etiology and progression of the disease. A focus on such novel pathways may open the way to successful prophylaxis and development of new biomarkers for better risk assessment after low dose exposures.