BioEssays最新文献

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.

Due to various intracellular and external cues, cellular organelles are frequently stressed in both physiological and pathological conditions. Sensing these stresses initiates various signaling pathways which may lead to adaptation of the stressed cells or trigger its their death. At the unicellular level, this stress signaling involves a crosstalk between different organelles. At the multicellular level, such pathways can contribute to indicate the presence of a stressed cell to its neighboring cells. Here, we highlight the crucial and diverse roles played by Ubiquitin and Ubiquitin-like modification in organelle stress signaling.

Human pluripotent stem cells acquire mutations in culture. The resulting genetically variant cells that possess advantageous phenotypes are selected in culture over time, eventually leading to their overtake. In article 2400062, John Vales and Ivana Barbaric highlight a collection of genetic variations that are recurrently found in stem cell culture. The authors also recollect how our understanding of genetically variant human pluripotent stem cells has grown over the past 20 years since the discovery of these aberrant cells in 2004, particularly bringing attention to the phenotypes associated with specific recurrent variants, how these are similar to those found in cancer cells, and how they might affect the applications of human pluripotent stem cells in both clinical and research settings.

At the end of the year, we would like once again to express our deep thanks to the members of our Editorial Board listed below for their valuable input. We are grateful for their involvement in various aspects of the journal.

After 10 years of service, we say goodbye to Matt Kaeberlein, Bernd Schierwater, Michael Shen, and Reiner Veitia, and wish them all the best for their research.

Targeted protein degradation (TPD) has emerged as a highly promising approach for eliminating disease-associated proteins in the field of drug discovery. Among the most advanced TPD technologies, PROteolysis TArgeting Chimera (PROTAC), functions by bringing a protein of interest (POI) into proximity with an E3 ubiquitin ligase, leading to ubiquitin (Ub)-dependent proteasomal degradation. However, the designs of most PROTACs are based on the utilization of a limited number of available E3 ligases, which significantly restricts their potential. Recent studies have shown that phytoplasmas, a group of bacterial plant pathogens, have developed several E3- and ubiquitin-independent proteasomal degradation (UbInPD) mechanisms for breaking down host targets. This suggests an alternative approach for substrate recruitment and TPD. Here, we present existing evidence that supports the feasibility of UbInPD in eukaryotic cells and propose candidate proteins that can serve as docking sites for the development of E3-independent PROTACs.

Transfer RNA (tRNA) modifications play an important role in regulating mRNA translation at the codon level. tRNA modifications can influence codon selection and optimality, thus shifting translation toward specific sets of mRNAs in a dynamic manner. Queuosine (Q) is a tRNA modification occurring at the wobble position. In eukaryotes, queuosine is synthesized by the tRNA-guanine trans-glycosylase (TGT) complex, which incorporates the nucleobase queuine (or Qbase) into guanine of the GUN anticodons. Queuine is sourced from gut bacteria and dietary intake. Q was recently shown to be critical for cellular responses to oxidative and mitochondrial stresses, as well as its potential role in neurodegenerative diseases and brain health. These unique features of Q provide an interesting insight into the regulation of mRNA translation by gut bacteria, and the potential health implications. In this review, Q biology is examined in the light of recent literature and nearly 4 decades of research. Q's role in neuropsychiatric diseases and cancer is highlighted and discussed. Given the recent interest in Q, and the new findings, more research is needed to fully comprehend its biological function and disease relevance, especially in neurobiology.