Frontiers In Biology Research Articles

Distribution Patterns of tfdI and tfdII Gene Clusters and New Insights into the Formation of the Architecture of pJP4, a Canonical 2,4-dichlorophenoxyacetic Acid (2,4-D) Degradation Plasmid

Currently, pJP4 is one of the best-known plasmids for the biodegradation of xenobiotics that mediate the degradation of 2,4-dichlorophenoxyacetic acid (2,4-D), which is associated with serious health and environmental risks. Although the sequencing and proposed theory of pJP4 formation occurred almost 20 years ago (2004), pJP4 is still the model object of many studies focused on the biodegradation of 2,4-D. The uniqueness of this plasmid is due to the presence of two evolutionarily distinct gene clusters, tfdI and tfdII, controlling the degradation of 2,4-D. Recent advances in plasmid biology, especially those concerning the characterization of new IncP-1 plasmids and the systematization of tfd gene cluster findings, serve as a basis for proposing new insights into the formation of the clusters’ architecture of the canonical plasmid, pJP4, and their distribution among other plasmids. In the present work, a comparative genomic and phylogenetic in silico study of plasmids with tfdI and tfdII clusters was carried out. The possible initial distribution patterns of tfdI clusters among plasmids of different incompatibility groups (non-IncP-1) and tfdII clusters among IncP-1 plasmids using the IS1071-based composite transposon were revealed. A new theory on the formation of the architecture of the tfdI and tfdII clusters of pJP4 through sequential internal rearrangements, recombination, and ISJP4 insertion, is proposed. In addition, small gene clusters resulting from internal rearrangements of pJP4 (tfdIISA and ORF31/32) served as fingerprints for exploring the distribution of tfdI and tfdII clusters. The revealed patterns and formulated theory extend the frontiers of plasmid biology and will be beneficial for understanding the role of plasmids in bacterial adaptation to xenobiotic-contaminated environments.

Exploring The Protease Diversity of Psychrophilic Yeast, Glaciozyma antarctica Through Genome Mining Analysis

Proteases are one of the most significant classes of enzymes, holding immense physiological relevance and extensive industrial applications. The genome of Glaciozyma antarctica was fully sequenced, showing 7,857 open reading frames that offer an intriguing opportunity to investigate its proteolytic repertoire. This study aims to unveil the protease landscape of G. antarctica, a psychrophilic yeast that produces cold-active enzymes that offer remarkable benefits, particularly in the food and pharmaceutical industries. In this work, we performed a comprehensive analysis to identify the diverse families of proteases encoded within the G. antarctica genome and compare them with proteases from other mesophilic and thermophilic fungi in the MEROPS database. The sequence similarity searches resulted in the identification of 195 open reading frames predicted to encode for proteases in G. antarctica with a high number of intracellular proteases. These findings suggest an evolved system for protein quality control and turnover, essential for cell viability and adaptation to environmental stressors. The MEROPS classification analysis showed an abundance of metalloproteases, constituting 38% of the total protease genes, a proportion surpassing that found in other yeast and fungal genomes studied. This reflects the vital role of metalloproteases in the cold adaptation of microbes in the Antarctic region. This unique profile not only sheds light on the adaptive mechanisms of psychrophilic organisms but also presents a rich reservoir of potential cold-active proteases for various applications. The findings of this study provide a foundation for targeted enzyme discovery and engineering, unlocking new frontiers in industrial biotechnology and extremophile biology.

Bile Acids and Liver Cancer: Molecular Mechanism and Therapeutic Prospects.

Hepatocellular carcinoma (HCC) is a highly aggressive liver malignancy and one of the most lethal cancers globally, with limited effective therapeutic options. Bile acids (BAs), as primary metabolites of hepatic cholesterol, undergo enterohepatic circulation involving secretion into the intestine and reabsorption into the liver, and their composition is modulated in this process. Recent clinical observations have revealed a correlation between alteration in the BAs profile and HCC incidence, and the effect of various species of BAs on HCC development has been investigated. The regulatory effect of different BA species on cell proliferation, migration, and apoptosis in tumor cells, as well as their interaction with gut microbiota, inflammation, and immunity have been identified to be involved in HCC progression. In this review, we summarize the current understanding of the diverse functions of BAs in HCC pathogenesis and therapy, from elucidating the fundamental mechanisms underlying both tumor-promoting and tumor-suppressive consequences of various BA species to exploring potential strategies for leveraging BAs for HCC therapy. We also discuss ongoing efforts to target specific BA species in HCC treatment while highlighting new frontiers in BA biology that may inspire further exploration regarding their connection to HCC.

Nanoscale single-vesicle analysis: High-throughput approaches through AI-enhanced super-resolution image analysis

The analysis of membrane vesicles at the nanoscale level is crucial for advancing the understanding of intercellular communication and its implications for health and disease. Despite their significance, the nanoscale analysis of vesicles at the single particle level faces challenges owing to their small size and the complexity of biological fluids. This new vesicle analysis tool leverages the single-molecule sensitivity of super-resolution microscopy (SRM) and the high-throughput analysis capability of deep-learning algorithms. By comparing classical clustering methods (k-means, DBSCAN, and SR-Tesseler) with deep-learning-based approaches (YOLO, DETR, Deformable DETR, and Faster R–CNN) for the analysis of super-resolution fluorescence images of exosomes, we identified the deep-learning algorithm, Deformable DETR, as the most effective. It showed superior accuracy and a reduced processing time for detecting individual vesicles from SRM images. Our findings demonstrate that image-based deep-learning-enhanced methods from SRM images significantly outperform traditional coordinate-based clustering techniques in identifying individual vesicles and resolving the challenges related to misidentification and computational demands. Moreover, the application of the combined Deformable DETR and ConvNeXt-S algorithms to differently labeled exosomes revealed its capability to differentiate between them, indicating its potential to dissect the heterogeneity of vesicle populations. This breakthrough in vesicle analysis suggests a paradigm shift towards the integration of AI into super-resolution imaging, which is promising for unlocking new frontiers in vesicle biology, disease diagnostics, and the development of vesicle-based therapeutics.

Zooming into lipid droplet biology through the lens of electron microscopy.

Electron microscopy (EM), in its various flavors, has significantly contributed to our understanding of lipid droplets (LD) as central organelles in cellular metabolism. For example, EM has illuminated that LDs, in contrast to all other cellular organelles, are uniquely enclosed by a single phospholipid monolayer, revealed the architecture of LD contact sites with different organelles, and provided near-atomic resolution maps of key enzymes that regulate neutral lipid biosynthesis and LD biogenesis. In this review, we first provide a brief history of pivotal findings in LD biology unveiled through the lens of an electron microscope. We describe the main EM techniques used in the context of LD research and discuss their current capabilities and limitations, thereby providing a foundation for utilizing suitable EM methodology to address LD-related questions with sufficient level of structural preservation, detail, and resolution. Finally, we highlight examples where EM has recently been and is expected to be instrumental in expanding the frontiers of LD biology.

Observing A Protein In Its Natural Habitat

Much of our knowledge about proteins inside biological cells comes from ex situ methods, where cellular proteins are extracted from their native environment. This approach has yielded basic information on each protein's structure and function averaged across distinct subcellular compartments, cell states, and, sometimes, cell types. However, the functional demands from different (sub)cellular environments vary. To probe the structural and functional adaptation of proteins in distinct subcellular environments, in situ single-protein characterization has emerged as an important approach. Here we comment on emerging in situ approaches by light and electron microscopy that begin to raise new questions about the distribution, structure, and function of individual protein copies in specific subcellular environments. The advent of in situ single-protein characterization is a key frontier of spatial biology to elucidate the architecture of a single cell.

WTAP-mediated abnormal m6A modification promotes cancer progression by remodeling the tumor microenvironment: bibliometric and database analyses.

Wilms' tumor 1 associated protein (WTAP) is an essential component of the m6A methyltransferase complex. The research on WTAP has been continuously developed and promoted in recent years. It is needed to make systematic specific bibliometric and database analyses on WTAP, to identify the cooperation and impact of authors, countries, institutions and journals, to evaluate the knowledge base and find the hotspot trends, and to detect the emerging topics regarding WTAP research. The related articles and reviews of WTAP in the Web of Science Core Collection from January 1999 to June 2022 were retrieved, and CiteSpace and VOSviewer were used to perform bibliometric and knowledge-map analyses. Multiple databases were used to explore the expression level of WTAP in pan-cancers and its correlation with prognosis and immune infiltration. In recent years, the number of publications on WTAP research has increased rapidly. Among the journals publishing WTAP research, Frontiers in Cell and Developmental Biology had the most papers, while Nature papers were most cited. The country with the highest number of publications on WTAP was China, and China Medical University was the institution with the most publications. The most prominent author was Haruo Sugiyama from Japan. Four main aspects of WTAP research included m6A modification, tumor association, cancer therapy, and regulatory mechanisms. The research frontiers and hotspots were m6A modification, methyltransferase, demethylation, tumor microenvironment (TME), and immunotherapy. Bioinformatics analysis showed that the expression of WTAP was up-regulated in a variety of tumors and closely related to TME and survival prognosis. From the bibliometric and database analyses on the researches on WTAP, it is suggested that up-regulated WTAP in cancers may promote cancer progression by mediating abnormal m6A modifications to reshape the TME, thereby affecting the survival prognosis of the patients. The information would provide helpful references for scholars focusing on WTAP and provide new insights for WTAP as a prognostic evaluation and immunotherapy for tumors in the future.

Pituitary stem cells: past, present and future perspectives.

Pituitary cells that express the transcription factor SOX2 are stem cells because they can self-renew and differentiate into multiple pituitary hormone-producing cell types as organoids. Wounding and physiological challenges can activate pituitary stem cells, but cell numbers are not fully restored, and the ability to mobilize stem cells decreases with increasing age. The basis of these limitations is still unknown. The regulation of stem cell quiescence and activation involves many different signalling pathways, including those mediated by WNT, Hippo and several cytokines; more research is needed to understand the interactions between these pathways. Pituitary organoids can be formed from human or mouse embryonic stem cells, or from human induced pluripotent stem cells. Human pituitary organoid transplantation is sufficient to induce corticosterone release in hypophysectomized mice, raising the possibility of therapeutic applications. Today, pituitary organoids have the potential to assess the role of individual genes and genetic variants on hormone production ex vivo, providing an important tool for the advancement of exciting frontiers in pituitary stem cell biology and pituitary organogenesis. In this article, we provide an overview of notable discoveries in pituitary stem cell function and highlight important areas for future research.

Revolutionizing Biological Science: The Synergy of Genomics in Health, Bioinformatics, Agriculture, and Artificial Intelligence.

With climate emergency, COVID-19, and the rise of planetary health scholarship, the binary of human and ecosystem health has been deeply challenged. The interdependence of human and nonhuman animal health is increasingly acknowledged and paving the way for new frontiers in integrative biology. The convergence of genomics in health, bioinformatics, agriculture, and artificial intelligence (AI) has ushered in a new era of possibilities and applications. However, the sheer volume of genomic/multiomics big data generated also presents formidable sociotechnical challenges in extracting meaningful biological, planetary health and ecological insights. Over the past few years, AI-guided bioinformatics has emerged as a powerful tool for managing, analyzing, and interpreting complex biological datasets. The advances in AI, particularly in machine learning and deep learning, have been transforming the fields of genomics, planetary health, and agriculture. This article aims to unpack and explore the formidable range of possibilities and challenges that result from such transdisciplinary integration, and emphasizes its radically transformative potential for human and ecosystem health. The integration of these disciplines is also driving significant advancements in precision medicine and personalized health care. This presents an unprecedented opportunity to deepen our understanding of complex biological systems and advance the well-being of all life in planetary ecosystems. Notwithstanding in mind its sociotechnical, ethical, and critical policy challenges, the integration of genomics, multiomics, planetary health, and agriculture with AI-guided bioinformatics opens up vast opportunities for transnational collaborative efforts, data sharing, analysis, valorization, and interdisciplinary innovations in life sciences and integrative biology.

Growth and opportunities for drone surveillance in pinniped research

AbstractPinniped species undergo uniquely amphibious life histories that make them valuable subjects for many domains of research. Pinniped research has often progressed hand‐in‐hand with technological frontiers of wildlife biology, and drones represent a leap forward for methods of aerial remote sensing, enabling data collection, and integration at new scales of biological importance. Drone methods and data types provide four key opportunities for wildlife surveillance that are already advancing pinniped research and management: 1) repeat and on‐demand surveillance, 2) high‐resolution coverage at large extents, 3) morphometric photogrammetry, and 4) computer vision and deep learning applications. Drone methods for pinniped research represent early stages of technological adoption and can reshape the field as they scale towards the full potential of their techniques.

A research program at the frontier of lipid and membrane biology.

A research program at the frontier of lipid and membrane biology.

A deep learning method for replicate-based analysis of chromosome conformation contacts using Siamese neural networks

The organisation of the genome in nuclear space is an important frontier of biology. Chromosome conformation capture methods such as Hi-C and Micro-C produce genome-wide chromatin contact maps that provide rich data containing quantitative and qualitative information about genome architecture. Most conventional approaches to genome-wide chromosome conformation capture data are limited to the analysis of pre-defined features, and may therefore miss important biological information. One constraint is that biologically important features can be masked by high levels of technical noise in the data. Here we introduce a replicate-based method for deep learning from chromatin conformation contact maps. Using a Siamese network configuration our approach learns to distinguish technical noise from biological variation and outperforms image similarity metrics across a range of biological systems. The features extracted from Hi-C maps after perturbation of cohesin and CTCF reflect the distinct biological functions of cohesin and CTCF in the formation of domains and boundaries, respectively. The learnt distance metrics are biologically meaningful, as they mirror the density of cohesin and CTCF binding. These properties make our method a powerful tool for the exploration of chromosome conformation capture data, such as Hi-C capture Hi-C, and Micro-C.

Plant synthetic biology: exploring the frontiers of sustainable agriculture and fundamental plant biology.

Plant synthetic biology: exploring the frontiers of sustainable agriculture and fundamental plant biology.

RNAs as Sensors of Oxidative Stress in Bacteria.

Oxidative stress is an important and pervasive physical stress encountered by all kingdoms of life, including bacteria. In this review, we briefly describe the nature of oxidative stress, highlight well-characterized protein-based sensors (transcription factors) of reactive oxygen species that serve as standards for molecular sensors in oxidative stress, and describe molecular studies that have explored the potential of direct RNA sensitivity to oxidative stress. Finally, we describe the gaps in knowledge of RNA sensors-particularly regarding the chemical modification of RNA nucleobases. RNA sensors are poised to emerge as an essential layer of understanding and regulating dynamic biological pathways in oxidative stress responses in bacteria and, thus, also represent an important frontier of synthetic biology.

Could the tumor-associated microbiota be the new multi-faceted player in the tumor microenvironment?

Microorganisms have been identified in tumor specimens for over a century. It is only in recent years that tumor-associated microbiota has become a rapidly expanding field. Assessment techniques encompass methods at the frontiers of molecular biology, microbiology, and histology, requiring a transdisciplinary process to carefully decipher this new component of the tumor microenvironment. Due to the low biomass, the study of tumor-associated microbiota poses technical, analytical, biological, and clinical challenges and must be approached as a whole. To date, several studies have begun to shed light on the composition, functions, and clinical relevance of the tumor-associated microbiota. This new piece of the tumor microenvironment puzzle could potentially change the way we think about and treat patients with cancer.

Discovering Nature’s Fingerprints: Isotope Ratio Analysis on Bioanalytical Mass Spectrometers

For a generation or more, the mass spectrometry that developed at the frontier of molecular biology was worlds apart from isotope ratio mass spectrometry, a label-free approach done on optimized gas-source magnetic sector instruments. Recent studies show that electrospray-ionization Orbitraps and other mass spectrometers widely used in the life sciences can be fine-tuned for high-precision isotope ratio analysis. Since isotope patterns form everywhere in nature based on well-understood principles, intramolecular isotope measurements allow unique insights into a fascinating range of research topics. This Perspective introduces a wider readership to current topics in stable isotope research with the aim of discussing how soft-ionization mass spectrometry coupled with ultrahigh mass resolution can enable long-envisioned progress. We highlight novel prospects of observing isotopes in intact polar compounds and speculate on future directions of this adventure into the overlapping realms of biology, chemistry, and geology.

Nanobionics: A Sustainable Agricultural Approach towards Understanding Plant Response to Heavy Metals, Drought, and Salt Stress.

In the current scenario, the rising concentration of heavy metals (HMs) due to anthropogenic activities is a severe problem. Plants are very much affected by HM pollution as well as other abiotic stress such as salinity and drought. It is very important to fulfil the nutritional demands of an ever-growing population in these adverse environmental conditions and/or stresses. Remediation of HM in contaminated soil is executed through physical and chemical processes which are costly, time-consuming, and non-sustainable. The application of nanobionics in crop resilience with enhanced stress tolerance may be the safe and sustainable strategy to increase crop yield. Thus, this review emphasizes the impact of nanobionics on the physiological traits and growth indices of plants. Major concerns and stress tolerance associated with the use of nanobionics are also deliberated concisely. The nanobionic approach to plant physiological traits and stress tolerance would lead to an epoch of plant research at the frontier of nanotechnology and plant biology.

Remembering the Work of Phillip L. Geissler: A Coda to His Scientific Trajectory.

Phillip L. Geissler made important contributions to the statistical mechanics of biological polymers, heterogeneous materials, and chemical dynamics in aqueous environments. He devised analytical and computational methods that revealed the underlying organization of complex systems at the frontiers of biology, chemistry, and materials science. In this retrospective we celebrate his work at these frontiers.

Multiomics Integration at Single-Cell Resolution Using Bayesian Networks: A Case Study in Hepatocellular Carcinoma.

Multiomics data integration is one of the leading frontiers of complex disease research and integrative biology. The advances in single-cell sequencing technologies offer yet another crucial dimension in multiomics research. The single-cell studies enable the study and integration of multiomics data simultaneously in the same cell. We report in this study multiomics data integration in single-cell resolution using Bayesian networks (BNs) in a case study of hepatocellular carcinoma (HCC). A BN encodes the conditional dependencies/independencies of variables using a graphical model with an accompanying joint probability. RNA-seq and Reduced Representation Bisulfite Sequencing data were analyzed separately, and copy number variations were estimated by the hidden Markov model method. Several BN models were constructed to reveal omics' causal and associational relationships. These methods were subjected to a validation study using an independent data set. We show the heterogeneity of the multiple cellular layers of HCC at single-cell omics resolution by identifying best-fitted BN models of 295 genes. We also provide novel insights into the multiomics mechanistic relationships in the human lymphocyte antigen class I genes in HCC. To the best of our knowledge, this is the first study to focus on integrating omics data using a machine learning algorithm, BNs, at the single-cell resolution using a case study of HCC.

Phylogenetics and the Cenozoic radiation of lampreys

The development of a movable jaw is one of the most important transitions in the evolutionary history of animals.1 Jawed vertebrates rapidly diversified after appearing approximately 470 million years ago. Today, only lampreys and hagfishes represent the once dominant jawless grade2,3,4 and comprise less than 1% of living vertebrate species. Their relationship to other vertebrates ranks among the more contentious problems in animal phylogenetics.5,6,7,8,9,10,11,12 Further, the phylogenetic relationships within lampreys and hagfishes remain unclear,13,14,15 and the ages of their living lineages are largely unexplored.16,17 Because of their importance for the genomic and developmental changes that prefigured jawed vertebrate diversity,18,19,20,21 the evolutionary history of lampreys and hagfishes is a major frontier of organismal biology. Of these two clades, lampreys22 are more ecologically diverse, exhibiting freshwater, anadromous, and fully marine forms, as well as parasitic and nonparasitic species.23,24 Here, we present a new phylogeny and historical biogeographic reconstruction of all living lampreys. Whereas the early diversification of this clade tracks Pangaean fragmentation, lampreys also rapidly radiated in the northern hemisphere during the mid-Cretaceous and directly after the Cretaceous-Paleogene extinction. These radiations mirrored concurrent ones in other animals and plants and coincided with changes to lamprey ecology and feeding behavior. Our results suggest that 80% of living lamprey clades appeared in the last 20 million years of Earth history. Rather than gradually accumulating since the oldest stem-group forms appeared in the early Paleozoic, living lamprey biodiversity results from diversifications extending from the Cretaceous to present.