Cold Spring Harbor perspectives in biology最新文献

Gene editing and genetic modification hold enormous potential to deliver solutions to multiple climate change challenges. The most important rate-limiting obstacles impeding their development and deployment are not technical, but rather counterproductive policies and regulations. These are driven in part by the mistaken apprehension of widespread public opposition. These obstacles are described and solutions to overcoming them are presented.

The endoplasmic reticulum (ER) is the key organelle for membrane biogenesis. Most lipids are synthesized in the ER, and most membrane proteins are first inserted into the ER membrane before they are transported to their target organelle. The composition and properties of the ER membrane must be carefully controlled to provide a suitable environment for the insertion and folding of membrane proteins. The unfolded protein response (UPR) is a powerful signaling pathway that balances protein and lipid production in the ER. Here, we summarize our current knowledge of how aberrant compositions of the ER membrane, referred to as lipid bilayer stress, trigger the UPR.

Facioscapulohumeral dystrophy (FSHD) is caused by misexpression of the early embryonic transcription factor Double Homeobox Protein 4 (DUX4) in skeletal muscle. DUX4 is normally expressed at the 4-cell stage of the human embryo and initiates a portion of the first wave of embryonic gene expression that establishes the totipotent cells of the embryo. Following brief expression, the DUX4 locus is suppressed by epigenetic silencing and remains silenced in nearly all somatic cells. Mutations that cause FSHD decrease the efficiency of epigenetic silencing of the DUX4 locus and result in aberrant expression of this transcription factor in skeletal muscles. DUX4 expression in these skeletal muscles reactivates part of the early totipotent program and suppresses the muscle program-resulting in a progressive muscular dystrophy that affects some muscles earlier than others. These advances in understanding the cause of FSHD have led to multiple therapeutic strategies that are now entering clinical trials.

Neural development must construct neural circuits that can perform the computations necessary for survival. However, many theoretical models of development do not explicitly address the computational goals of the resulting networks, or computations that evolve in time. Recurrent neural networks (RNNs) have recently come to prominence as both models of neural circuit computation and building blocks of powerful artificial intelligence systems. Here, we review progress in using RNNs for understanding how developmental processes lead to effective computations, and how abnormal development disrupts these computations.

The rapid pace of climate change has created great urgency for short-term mitigation strategies. Appropriately, the long-term target for intervening in global warming is CO₂, but experts suggest that methane should be a key short-term target. Methane has a warming impact 34 times greater than CO₂ on a 100-year timescale, and 86 times greater on a 20-year timescale, and its short half-life in the atmosphere provides the opportunity for near-term positive climate impacts. One approach to removing methane is the use of bacteria for which methane is their sole carbon and energy source (methanotrophs). Such bacteria convert methane to CO₂ and biomass, a potentially value-added product and co-benefit. If air above emissions sites with elevated methane is targeted, technology harnessing the aerobic methanotrophs has the potential to become economically viable and environmentally sound. This article discusses challenges and opportunities for using aerobic methanotrophs for methane removal from air, including the avoidance of increased N₂O emissions.

Blood vessels are critical to deliver oxygen and nutrients to tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier (BBB), which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and protects the neural tissue from toxins and pathogens, and alterations of this barrier are important components of the pathogenesis and progression of various neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the brain endothelial cells (ECs) that form the walls of the blood vessels. These properties are regulated by interactions between different vascular, perivascular, immune, and neural cells. Understanding how these cell populations interact to regulate barrier properties is essential for understanding how the brain functions in both health and disease contexts.

In addition to their many functions in the healthy central nervous system (CNS), astrocytes respond to CNS damage and disease through a process called "reactivity." Recent evidence reveals that astrocyte reactivity is a heterogeneous spectrum of potential changes that occur in a context-specific manner. These changes are determined by diverse signaling events and vary not only with the nature and severity of different CNS insults but also with location in the CNS, genetic predispositions, age, and potentially also with "molecular memory" of previous reactivity events. Astrocyte reactivity can be associated with both essential beneficial functions as well as with harmful effects. The available information is rapidly expanding and much has been learned about molecular diversity of astrocyte reactivity. Emerging functional associations point toward central roles for astrocyte reactivity in determining the outcome in CNS disorders.

Enteric glia are a unique type of peripheral neuroglia that accompany neurons in the enteric nervous system (ENS) of the digestive tract. The ENS displays integrative neural circuits that are capable of governing moment-to-moment gut functions independent of input from the central nervous system. Enteric glia are interspersed with neurons throughout these intrinsic gut neural circuits and are thought to fulfill complex roles directed at maintaining homeostasis in the neuronal microenvironment and at neuroeffector junctions in the gut. Changes to glial functions contribute to a wide range of gastrointestinal diseases, but the precise roles of enteric glia in gut physiology and pathophysiology are still under examination. This review summarizes current concepts regarding enteric glial development, diversity, and functions in health and disease.

Neuronal circuits represent the functional units of the brain. Understanding how the circuits are generated to perform computations will help us understand how the brain functions. Nevertheless, neuronal circuits are not engineered, but have formed through millions of years of animal evolution. We posit that it is necessary to study neuronal circuit evolution to comprehensively understand circuit function. Here, we review our current knowledge regarding the mechanisms that underlie circuit evolution. First, we describe the possible genetic and developmental mechanisms that have contributed to circuit evolution. Then, we discuss the structural changes of circuits during evolution and how these changes affected circuit function. Finally, we try to put circuit evolution in an ecological context and assess the adaptive significance of specific examples. We argue that, thanks to the advent of new tools and technologies, evolutionary neurobiology now allows us to address questions regarding the evolution of circuitry and behavior that were unimaginable until very recently.