BioEssays最新文献

Organismal death has long been considered the irreversible ending of an organism's integrated functioning as a whole. However, the persistence of functionality in organs, tissues, and cells postmortem, as seen in organ donation, raises questions about the mechanisms underlying this resilience. Recent research reveals that various factors, such as environmental conditions, metabolic activity, and inherent survival mechanisms, influence postmortem cellular functionality and transformation. These findings challenge our understanding of life and death, highlighting the potential for certain cells to grow and form new multicellular entities. This opens new avenues in biology and medicine, expanding our comprehension of life's complexity.

Daily rhythms in the rate and specificity of protein synthesis occur in most mammalian cells through an interaction between cell-autonomous circadian regulation and daily cycles of systemic cues. However, the overall protein content of a typical cell changes little over 24 h. For most proteins, translation appears to be coordinated with protein degradation, producing phases of proteomic renewal that maximize energy efficiency while broadly maintaining proteostasis across the solar cycle. We propose that a major function of this temporal compartmentalization-and of circadian rhythmicity in general-is to optimize the energy efficiency of protein synthesis and associated processes such as complex assembly. We further propose that much of this temporal compartmentalization is achieved at the level of translational initiation, such that the translational machinery alternates between distinct translational mechanisms, each using a distinct toolkit of phosphoproteins to preferentially recognize and translate different classes of mRNA.

Several recently discovered small proteins of less than 100 amino acids control important, but sometimes surprising, steps in the metabolism of cyanobacteria. There is mounting evidence that a large number of small protein genes have also been overlooked in the genome annotation of many other microorganisms. Although too short for enzymatic activity, their functional characterization has frequently revealed the involvement in processes such as signaling and sensing, interspecies communication, stress responses, metabolism, regulation of transcription and translation, and in the formation of multisubunit protein complexes. Cyanobacteria are the only prokaryotes that perform oxygenic photosynthesis. They thrive under a wide variety of conditions as long as there is light and must cope with dynamic changes in the environment. To acclimate to these fluctuations, frequently small regulatory proteins become expressed that target key enzymes and metabolic processes. The consequences of their actions are profound and can even impact the surrounding microbiome. This review highlights the diverse functions of recently discovered small proteins that control cyanobacterial metabolism. It also addresses why many of these proteins have been overlooked so far and explores the potential for implementing metabolic engineering strategies to improve the use of cyanobacteria in biotechnological applications.

The retinal pigment epithelium (RPE) is a specialized epithelium at the back of the eye that carries out a variety of functions essential for visual health. Recent studies have advanced our molecular understanding of one of the major functions of the RPE; phagocytosis of spent photoreceptor outer segments (POS). Notably, a mechanical link, formed between apical integrins bound to extracellular POS and the intracellular actomyosin cytoskeleton, is proposed to drive the internalization of POS. The process may involve a “nibbling” action, as an initial step, to sever outer segment tips. These insights have led us to hypothesize an “integrin adhesome-like” network, atypically assembled at apical membrane RPE-POS contacts. I propose that this hypothetical network orchestrates the complex membrane remodeling events required for particle internalization. Therefore, its analysis and characterization will likely lead to a more comprehensive understanding of the molecular mechanisms that control POS phagocytosis.

In cancer research, the term epigenetics was used in the 1970s in its modern sense encompassing non-genetic events modifying the chromatin state, mainly to oppose the emerging oncogene paradigm. However, starting from the establishment of this prominent concept, the importance of these epigenetic phenomena in cancer rarely led to questioning the causal role of genetic alterations. Only in the last 10 years, the accumulation of problematic data, better experimental technologies, and some ambitious models pushed the idea that epigenetics could be at least as important as genetics in early oncogenesis. Until this year, a direct demonstration of epigenetic oncogenesis was still lacking. Now, Parreno, Cavalli and colleagues, using a refined experimental model in the fruit fly Drosophila melanogaster, enforced the initiation of tumors solely by imposing a transient loss of Polycomb repression, leading to a purely epigenetic oncogenesis phenomenon. Despite a few caveats that we discuss, this pioneering work represents a major breakpoint in cancer research. We are led to consider the theoretical and conceptual implications on oncogenesis and to search for links between this artificial experimental model and naturally occurring processes, while revisiting cancer theories that were previously proposed as alternatives to the oncogene-centered paradigm.

We explore the potential of using magnetic cues as a novel approach to modulating ion channel expression, which could provide an alternative to traditional pharmacological interventions. Ion channels are crucial targets for pharmacological therapies, and ongoing research in this field continues to introduce new methods for treating various diseases. However, the efficacy of ion channel drugs is often compromised by issues such as target selectivity, leading to side effects, toxicity, and complex drug interactions. These challenges, along with problems like drug resistance and difficulties in crossing biological barriers, highlight the need for innovative strategies. In this context, the proposed use of magnetic cues to modulate ion channel expression may offer a promising solution to address these limitations, potentially improving the safety and effectiveness of treatments, particularly for long-term use. Key developments in this area are reviewed, the relationships between changes in ion channel expression and magnetic fields are summarized, knowledge gaps are identified, and central issues relevant to future research are discussed.

The dominant paradigm in biomedicine focuses on genetically-specified components of cells and their biochemical dynamics, emphasizing bottom-up emergence of complexity. Here, I explore the biomedical implications of a complementary emerging field: diverse intelligence. Using tools from behavioral science and multiscale neuroscience, we can study development, regenerative repair, and cancer suppression as behaviors of a collective intelligence of cells navigating the spaces of possible morphologies and transcriptional and physiological states. A focus on the competencies of living material-from molecular to organismal scales-reveals a new landscape for interventions. Such top-down approaches take advantage of the memories and homeodynamic goal-seeking behavior of cells and tissues, offering the same massive advantages in biomedicine and bioengineering that reprogrammable hardware has provided information technologies. The bioelectric networks that bind individual cells toward large-scale anatomical goals are an especially tractable interface to organ-level plasticity, and tools to modulate them already exist. This suggests a research program to understand and tame the software of life for therapeutic gain by understanding the many examples of basal cognition that operate throughout living bodies.

Human pluripotent stem cells can differentiate to all cells of the body, including those of the heart. The heart contains multiple cell types but the contractile cells are called cardiomyocytes. In article 2400078, Christine Mummery describes her serendipitous finding on how to induce differentiation of human embryonic stem cells into cardiomyocytes by co-culture with visceral endoderm. This was later reproduced in human induced pluripotent stem cells using growth factors. The contractile apparatus of cardiomyocytes, which consists of structures called sarcomeres, is clearly evident in these cells after antibody staining. hiPSC can be derived from patients with different cardiac diseases. Cardiomyocytes from these hiPSC often capture patient phenotypes. This has led both to new insights into mechanisms underlying genetic cardiac diseases, like myopathies or arrhythmias, and created opportunities for discovering new drugs to treat these conditions and to assess their cardiac safety, without using animal models.

The image shows immunofluorescent staining of sarcomeres, the contractile units of the human heart, in cardiomycytes derived from human induced pluripotent stem cells. Staining is for cardiac Troponin T (green) and α-sarcomeric actinin (red). Nuclei are stained blue with Hoechst. Credit to Viviana Meraviglia.