BioEssays最新文献

Plants are in intimate association with taxonomically structured microbial communities called the plant microbiota. There is growing evidence that the plant microbiota contributes to the holistic performance and general health of plants, especially under unfavorable situations. Despite the attached benefits, surprisingly, the plant microbiota in nature also includes potentially pathogenic strains, signifying that the plant hosts have tight control over these microbes. Despite the conceivable role of plant immunity in regulating its microbiota, we lack a complete understanding of its role in governing the assembly, maintenance, and function of the plant microbiota. Here, we highlight the recent progress on the mechanistic relevance of host immunity in orchestrating plant-microbiota dialogues and discuss the pluses and perils of these microbial assemblies.

The performance of deep Neural Networks (NNs) in the text (ChatGPT) and image (DALL-E2) domains has attracted worldwide attention. Convolutional NNs (CNNs), Large Language Models (LLMs), Denoising Diffusion Probabilistic Models (DDPMs)/Noise Conditional Score Networks (NCSNs), and Graph NNs (GNNs) have impacted computer vision, language editing and translation, automated conversation, image generation, and social network management. Proteins can be viewed as texts written with the alphabet of amino acids, as images, or as graphs of interacting residues. Each of these perspectives suggests the use of tools from a different area of deep learning for protein structural biology. Here, I review how CNNs, LLMs, DDPMs/NCSNs, and GNNs have led to major advances in protein structure prediction, inverse folding, protein design, and small molecule design. This review is primarily intended as a deep learning primer for practicing experimental structural biologists. However, extensive references to the deep learning literature should also make it relevant to readers who have a background in machine learning, physics or statistics, and an interest in protein structural biology.

A recent thought-provoking theory argues that complex organisms using epigenetic information for their normal development and functioning must irreversibly age as a result of epigenetic signal loss. Importantly, the scope of this theory could be considerably expanded, with scientific benefits, by analyzing epigenetic ageing beyond the borders of the Tree of Life. Viruses that use epigenetic signals for their normal functioning may also age, that is, present an increasing risk of failing to complete their individual life cycle and to disappear with time. As viruses are ancient, abundant, and infect a considerable diversity of hosts, the ageing virus hypothesis, if verified, would have important consequences for many fields of the Life sciences. Uncovering ageing viruses would integrate the most abundant and biologically central entities on Earth into theories of ageing, enhance virology, gerontology, evolutionary biology, molecular ecology, genomics, and possibly medicine through the development of new therapies manipulating viral ageing.

Pluripotent stem cell lines derived from preimplantation mouse embryos have opened opportunities for the study of early mammalian development and generation of genetically uncompromised material for differentiation into specific cell types. Murine embryonic stem cells are highly versatile and can be engineered and introduced into host embryos, transferred to recipient females, and gestated to investigate gene function at multiple levels as well as developmental mechanisms, including lineage segregation and cell competition. In this review, we summarize the biomedical motivation driving the incremental modification to culture regimes and analyses that have advanced stem cell research to its current state. Ongoing investigation into divergent mechanisms of early developmental processes adopted by other species, such as agriculturally beneficial mammals and birds, will continue to enrich knowledge and inform strategies for future in vitro models.

The ability to initiate DNA replication is a critical step in the proliferation of all organisms. In bacteria, this process is mediated by an ATP-dependent replication initiator protein, DnaA, which recognizes and melts replication origin (oriC) elements. Despite decades of biochemical and structural work, a mechanistic understanding of how DnaA recognizes and unwinds oriC has remained enigmatic. A recent study by Pelliciari et al. provides important new structural insights into how DnaA from Bacillus subtilis recognizes and processes its cognate oriC, showing how DnaA uses sequence features encoded in the origin to engage melted DNA. Comparison of the DnaA-oriC structure with archaeal/eukaryl replication origin complexes based on Orc-family proteins reveals a high degree of similarity in origin engagement by initiators from di domains of life, despite fundamental differences in origin melting mechanisms. These findings provide valuable insights into bacterial replication initiation and highlight the intriguing evolutionary history of this fundamental biological process.

Neurodegenerative diseases encompass a spectrum of conditions characterized by the gradual deterioration of neurons in the central and peripheral nervous system. While their origins are multifaceted, emerging data underscore the pivotal role of impaired mitochondrial functions and endolysosomal homeostasis to the onset and progression of pathology. This article explores whether mitochondrial dysfunctions act as causal factors or are intricately linked to the decline in endolysosomal function. As research delves deeper into the genetics of neurodegenerative diseases, an increasing number of risk loci and genes associated with the regulation of endolysosomal and autophagy functions are being identified, arguing for a downstream impact on mitochondrial health. Our hypothesis centers on the notion that disturbances in endolysosomal processes may propagate to other organelles, including mitochondria, through disrupted inter-organellar communication. We discuss these views in the context of major neurodegenerative diseases including Alzheimer's and Parkinson's diseases, and their relevance to potential therapeutic avenues.

The LIM domain kinases (LIMKs) are important actin cytoskeleton regulators. These proteins, LIMK1 and LIMK2, are nodes downstream of Rho GTPases and are the key enzymes that phosphorylate cofilin/actin depolymerization factors to regulate filament severing. They therefore perform an essential role in cascades that control actin depolymerization. Signaling of the LIMKs is carefully regulated by numerous inter- and intra-molecular mechanisms. In this review, we discuss recent findings that improve the understanding of LIM domain kinase regulation mechanisms. We also provide an up-to-date review of the role of the LIM domain kinases, their architectural features, how activity is impacted by other proteins, and the implications of these findings for human health and disease.

The three-dimensional architecture of the bacterial chromosome is intertwined with genome processes such as transcription and replication. Conspicuously so, that the structure of the chromosome permits accurate prediction of active genome processes. Although appreciation of this interplay has developed rapidly in the past two decades, our understanding of this subject is still in its infancy, with research primarily focusing on how the process of transcription regulates and is regulated by chromosome structure. Here, we summarize the latest developments in the field with a focus on the interplay between chromosome structure and transcription in Escherichia coli (E. coli) as mediated by H-NS-a model nucleoid structuring protein. We describe how the organization of chromosomes at the global and local scales is dependent on transcription, and how transcription is regulated by chromosome structure. Finally, we take note of studies that highlight our limited knowledge of structure-function relationships in the chromosome, and we point out research tracks that will improve our insight in the topic.