Cold Spring Harbor perspectives in biology最新文献

Lipids are characterized by extremely high structural diversity translated into a wide range of physicochemical properties. As such, lipids are vital for many different functions including organization of cellular and organelle membranes, control of cellular and organismal energy metabolism, as well as mediating multiple signaling pathways. To maintain the lipid chemical diversity and to achieve rapid lipid remodeling required for the responsiveness and adaptability of cellular membranes, living systems make use of a network of chemical modifications of already existing lipids that complement the rather slow biosynthetic pathways. Similarly to biopolymers, which can be modified epigenetically and posttranscriptionally (for nucleic acids) or posttranslationally (for proteins), lipids can also undergo chemical alterations through oxygenation, nitration, phosphorylation, glycosylation, etc. In this way, an expanded collective of modified lipids that we term the "epilipidome," provides the ultimate level of complexity to biological membranes and delivers a battery of active small-molecule compounds for numerous regulatory processes. As many lipid modifications are tightly controlled and often occur in response to extra- and intracellular stimuli at defined locations, the emergence of the epilipidome greatly contributes to the spatial and temporal compartmentalization of diverse cellular processes. Accordingly, epilipid modifications are observed in all living organisms and are among the most consistent prerequisites for complex life.

The blastocyst forms during the first days of mammalian development. The structure of the blastocyst is conserved among placental mammals and is paramount to the establishment of the first mammalian lineages. The blastocyst is composed of an extraembryonic epithelium, the trophectoderm (TE), that envelopes a fluid-filled lumen and the inner cell mass (ICM). To shape the blastocyst, embryos transit through three stages driven by forces that have been characterized in the mouse embryo over the past decade. The morphogenetically quiescent cleavage stages mask dynamic cytoskeletal remodeling. Then, during the formation of the morula, cells pull themselves together and the strongest ones internalize. Finally, the blastocyst forms after the pressurized lumen breaks the radial symmetry of the embryo before expanding in cycles of collapses and regrowth. In this review, we delineate the force patterns sculpting the blastocyst, based on our knowledge on the mouse and, to some extent, human embryos.

The importance of physical forces in the morphogenesis, homeostatic function, and pathological dysfunction of multicellular tissues is being increasingly characterized, both theoretically and experimentally. Analogies between biological systems and inert materials such as foams, gels, and liquid crystals have provided striking insights into the core design principles underlying multicellular organization. However, these connections can seem surprising given that a key feature of multicellular systems is their ability to constantly consume energy, providing an active origin for the forces that they produce. Key emerging questions are, therefore, to understand whether and how this activity grants tissues novel properties that do not have counterparts in classical materials, as well as their consequences for biological function. Here, we review recent discoveries at the intersection of active matter and tissue biology, with an emphasis on how modeling and experiments can be combined to understand the dynamics of multicellular systems. These approaches suggest that a number of key biological tissue-scale phenomena, such as morphogenetic shape changes, collective migration, or fate decisions, share unifying design principles that can be described by physical models of tissue active matter.

Interactions between alleles and across environments play an important role in the fitness of hybrids and are at the heart of the speciation process. Fitness landscapes capture these interactions and can be used to model hybrid fitness, helping us to interpret empirical observations and clarify verbal models. Here, we review recent progress in understanding hybridization outcomes through Fisher's geometric model, an intuitive and analytically tractable fitness landscape that captures many fitness patterns observed across taxa. We use case studies to show how the model parameters can be estimated from different types of data and discuss how these estimates can be used to make inferences about the divergence history and genetic architecture. We also highlight some areas where the model's predictions differ from alternative incompatibility-based models, such as the snowball effect and outlier patterns in genome scans.

How tissue architecture and function emerge during development and what facilitates their resilience and homeostatic dynamics during adulthood is a fundamental question in biology. Biological tissue barriers such as the skin epidermis have evolved strategies that integrate dynamic cellular turnover with high resilience against mechanical and chemical stresses. Interestingly, both dynamic and resilient functions are generated by a defined set of molecular and cell-scale processes, including adhesion and cytoskeletal remodeling, cell shape changes, cell division, and cell movement. These traits are coordinated in space and time with dynamic changes in cell fates and cell mechanics that are generated by contractile and adhesive forces. In this review, we discuss how studies on epidermal morphogenesis and homeostasis have contributed to our understanding of the dynamic interplay between biochemical and mechanical signals during tissue morphogenesis and homeostasis, and how the material properties of tissues dictate how cells respond to these active stresses, thereby linking cell-scale behaviors to tissue- and organismal-scale changes.

Transcription factors play crucial roles in cancer, and oncogenic counterparts of cellular transcription factors are present in a number of tumor viruses. It was studies in the early 1980s that first showed tumor viruses could encode nuclear as well as cytoplasmic oncoproteins. Subsequent work provided detailed insight into their mechanisms of action, as well as potential therapeutic avenues. In this excerpt from his forthcoming book on the history of cancer research, Joe Lipsick looks back at early work on nuclear oncogenes, including the discovery of MYC, MYB, FOS and JUN, Rel/NF-κB, and nuclear receptors such as the retinoic acid receptor and thyroid hormone receptor.

Peripheral nerves exist in a stable state in adulthood providing a rapid bidirectional signaling system to control tissue structure and function. However, following injury, peripheral nerves can regenerate much more effectively than those of the central nervous system (CNS). This multicellular process is coordinated by peripheral glia, in particular Schwann cells, which have multiple roles in stimulating and nurturing the regrowth of damaged axons back to their targets. Aside from the repair of damaged nerves themselves, nerve regenerative processes have been linked to the repair of other tissues and de novo innervation appears important in establishing an environment conducive for the development and spread of tumors. In contrast, defects in these processes are linked to neuropathies, aging, and pain. In this review, we focus on the role of peripheral glia, especially Schwann cells, in multiple aspects of nerve regeneration and discuss how these findings may be relevant for pathologies associated with these processes.

Accurate predictions are commonly taken as a hallmark of strong scientific understanding. Yet, we do not seem capable today of making many accurate predictions about biological speciation. Why? What limits predictability in general, what exactly is the function and value of predictions, and how might we go about predicting new species? Inspired by an orrery used to explain solar eclipses, we address these questions with a thought experiment in which we conceive an evolutionary speciation machine generating new species. This experiment highlights complexity, chance, and speciation pluralism as the three fundamental challenges for predicting speciation. It also illustrates the methodological value of predictions in testing and improving conceptual models. We then outline how we might move from the hypothetical speciation machine to a predictive standard model of speciation. Operationalizing, testing, and refining this model will require a concerted shift to large-scale, integrative, and interdisciplinary efforts across the tree of life. This endeavor, paired with technological advances, may reveal apparently stochastic processes to be deterministic, and promises to expand the breadth and depth of our understanding of speciation and more generally, of evolution.

Plants take up carbon dioxide, and lose water, through pores on their leaf surfaces called stomata. We have a good understanding of the biochemical signals that control the production of stomata, and over the past decade, these have been manipulated to produce crops with fewer stomata. Crops with abnormally low stomatal densities require less water to produce the same yield and have enhanced drought tolerance. These "water-saver" crops also have improved salinity tolerance and are expected to have increased resistance to some diseases. We calculate that the widespread adoption of water-saver crops could lead to reductions in greenhouse gas emissions equivalent to a maximum of 0.5 GtCO₂/yr and thus could help to mitigate the impacts of climate change on agriculture and food security through protecting yields in stressful environments and requiring fewer inputs.

The ability to regenerate after the loss of a part is a hallmark of living systems and occurs at both the tissue and organ scales, but also within individual cells. Regeneration entails many processes that are physical and mechanical in nature, including the closure of wounds, the repositioning of material from one place to another, and the restoration of symmetry following perturbations. However, we currently know far more about the genetics and molecular signaling pathways involved in regeneration, and there is a need to investigate the role of physical forces in the process. Here, we will provide an overview of how physical forces may play a role in wound healing and regeneration, in which we compare and contrast regenerative processes at the tissue and cell scales.