Small proteins, known as microproteins, typically consisting of fewer than 150 amino acids, have recently emerged as a previously unrecognized class of functional genes in biology. Advances in ribosome profiling, proteogenomics, and genome-wide functional screens have revealed that thousands of small open reading frames are actively translated, producing microproteins, some of which regulate essential processes in metabolism, immunity, cancer, and neurodegeneration. These discoveries have challenged long-held assumptions that gene function is confined to large, conserved proteins and have underscored microproteins as critical modulators. Dysregulation or mutation of small open reading frame-encoding microproteins contributes to a diverse range of biology, and in some cases links the noncanonical proteome to pathophysiological biology. In this review, we summarize current knowledge of microprotein discovery and function, describe key examples connecting microproteins to human disease, and discuss the opportunities and challenges that define this rapidly evolving field.

Both the levels and duration of gene expression play critical roles in many biological processes. Recent studies have further revealed that the dynamics of oscillatory versus sustained gene expression also provide essential regulatory information during cell proliferation and differentiation. Oscillatory expression, governed by intracellular negative feedback loops and intercellular coupling with appropriate delays, promotes the proliferation of stem cells, whereas sustained expression typically drives cells toward quiescence or differentiation. Over time, oscillations can result in the gradual upregulation or downregulation of downstream factors or shifts in phase relationships between distinct oscillators, thereby functioning as a timer for cell state transition. Moreover, oscillation frequency encodes critical cues for cell fate choice. Thus, oscillatory dynamics add an extra dimension to the informational landscape of gene expression. Here, we discuss recent advances in our understanding of how oscillatory gene expression is regulated and how it influences the proliferation and differentiation of stem cells.

Immune cells possess a remarkable set of complementary surface protrusions, such as microvilli, podosomes, filopodia, and lamellipodia, which play pivotal roles in the sensing of and responding to varied environmental cues. These dynamic structures maximize the surface area-to-volume ratio of immune cells, which in turn enhances cell-cell and cell-matrix interactions, while generating pulling and pushing forces, allowing immune cells to integrate biochemical and physical cues from their surroundings. This review discusses recent insights into the structures and dynamics of different protrusions, the molecular machinery behind mechanosensing, the differential role of protrusions for different subsets of immune cells, and the cutting-edge technology that has advanced our understanding of those protrusions.

Every individual animal behaves differently, even if they have the same genome and have been raised in the same environment. This diversity in behavior challenges the notion that biological variation derives solely from differences in genetics and environment, and poses the question of what biological processes generate individuality. At very small scales, the dynamics of biological matter are essentially impossible to predict with certainty, and these stochastic fluctuations can ripple out to alter the metabolism, physiology, and behavior of cells and organisms. I review major findings related to the developmental origins of stochastic individuality. These include the multivariate, dynamic organization of individual behavioral differences; control of the extent of individuality by genes, neural activity, and neuromodulation; nanoscale features of neural circuits that predict behavioral biases at the individual level; and experimental and theoretical evidence that behavioral variability may reflect an adaptive bet-hedging strategy. I conclude with a brief discussion of how large datasets like connectomes and long-term behavioral recordings will inform our understanding of the mechanisms underpinning behavioral individuality.

DNA carries genetic information, ensuring the stable transmission of genetic material through generations. However, DNA sequences can be constantly rewritten, allowing evolution and adaptation to occur at both the cellular and species levels. To facilitate this dynamic process, the genome is enriched with mobile genetic elements that can move within DNA sequences. While transposable elements are the classic example of mobile DNA, we propose that extrachromosomal circular DNA (ecDNA) represents another class of mobile genetic elements. This class can also introduce a new layer of genome dynamics, significantly shaping host biology. This review traces the historical discoveries and conceptual evolution of ecDNA, categorizing its diverse forms across organisms and highlighting its life cycle from biogenesis to maintenance and clearance. We discuss ecDNA's pivotal roles in physiological processes, including development, stress adaptation, and species evolution, and emphasize its pathological significance in cancer progression, drug resistance, and viral infections. Finally, we explore therapeutic strategies targeting ecDNA biology, offering a framework for translational advances in oncology and antiviral treatment. Together, these insights position ecDNA as a critical force in shaping genome dynamics and as a promising target for future biomedical interventions.

Science is often portrayed as the objective search for knowledge. However, science is also part of complex societies that shape science and in turn are shaped by scientific findings. In this interview, Bruce Alberts, former president of the US National Academy of Sciences, and Paul Nurse, former and future president of the Royal Society, discuss the roles of science and scientists in society. They share their passion to understand the natural world and the joy of discovery. They emphasize the importance of leadership in building institutions that support science and evidence-based decision-making. They share their frustration that current science education falls short in teaching the way science arrives at a better but incomplete understanding of the world. They urge scientists to organize and make their case to the public and fight misinformation and mistruths.

"What makes us human?" is a central question of many research fields, notably anthropology. In this review, we focus on the development of the human neocortex, the part of the brain with a key role in cognition, to gain neurobiological insight toward answering this question. We first discuss cortical stem and progenitor cells and human-specific genes that affect their behavior. We thus aim to understand the molecular foundation of the expansion of the neocortex that occurred in the course of human evolution, as this expansion is generally thought to provide a basis for our unique cognitive abilities. We then review the emerging evidence pointing to differences in the development of the neocortex between present-day humans and Neanderthals, our closest relatives. Finally, we discuss human-specific genes that have been implicated in neuronal circuitry and offer a perspective for future studies addressing the question of what makes us human.

Although most animals appear symmetric externally, they exhibit chirality within their body cavity, i.e., in terms of asymmetric organ position, directional organ looping, and lateralized organ function. Left-right (LR) asymmetry is determined genetically by intricate molecular interactions that occur during development. Key genes have been elucidated in several species. There are common mechanisms in vertebrates and invertebrates, but some appear to exhibit unique mechanisms. This review focuses on LR asymmetry formation in invertebrates, particularly Drosophila, ascidians, and mollusks. It aims to understand the role of the genes that are key to creating LR asymmetry and how chirality information is converted/transmitted across the hierarchies from molecules to cells and from cells to tissues.

Mitochondria serve as energetic and signaling hubs of the cell: This function results from the complex interplay between their structure, function, dynamics, interactions, and molecular organization. The ability to observe and quantify these properties often represents the puzzle piece critical for deciphering the mechanisms behind mitochondrial function and dysfunction. Fluorescence microscopy addresses this critical need and has become increasingly powerful with the advent of superresolution methods and context-sensitive fluorescent probes. In this review, we delve into advanced light microscopy methods and analyses for studying mitochondrial ultrastructure, dynamics, and physiology, and highlight notable discoveries they enabled.

One of the fundamental questions in developmental biology is how a cell is specified to differentiate as a specialized cell type. Traditionally, plant cell types were defined based on their function, location, morphology, and lineage. Currently, in the age of single-cell biology, researchers typically attempt to assign plant cells to cell types by clustering them based on their transcriptomes. However, because cells are dynamic entities that progress through the cell cycle and respond to signals, the transcriptome also reflects the state of the cell at a particular moment in time, raising questions about how to define a cell type. We suggest that these complexities and dynamics of cell states are of interest and further consider the roles signaling, stochasticity, cell cycle, and mechanical forces play in plant cell fate specification. Once established, cell identity must also be maintained. With the wealth of single-cell data coming out, the field is poised to elucidate both the complexity and dynamics of cell states.