Highlights • During the normal waking state, the brain is in a constant state of internal exploration through the formation and dissolution of resting-state functional networks. • Based on large-scale computer models of the brain, the best fit to observed data comes when the networks are at the ‘edge of instability’. • Such a position is a distinct advantage for the efficiency and speed of network mobilization for perception and action. • We provide theoretical and empirical questions to better link resting-state networks to cognitive architectures.
How does the brain represent external reality so that it can be perceived in the form of mental images? How are the representations stored in memory so that an approximation of their original content can be re-experienced during recall? A framework introduced in the late 1980s proposed that mental images arise from neural activity in early sensory cortices both during perception and recall. Neurons in the association cortices, by contrast, would not code explicit mental content; rather, they would hold the records needed to reconstruct an approximation of the original perceptual maps in early cortices. Several neurophysiological and neuroimaging studies now lend growing support to this proposal.
Polycomb repressive complex 2 (PRC2) is a chief epigenetic regulator. In a new article, Chen . describe the crystal structure of the heterotetrameric PRC2 holo complex, which provides important mechanistic insights into the organization of its subunits and the association of PRC2 with chromatin.
The current view of the cytoplasm as a ‘bustling and well-organized metropolitan city’ raises the issue of how physicochemical forces control the macromolecular interactions and transport of metabolites and energy in the cell. Motivated by studies on bacterial osmosensors, we argue that charged cytoplasmic macromolecules are stabilized electrostatically by their ionic atmospheres. The high cytoplasmic crowding (25–50% of cell volume) shapes the remaining cell volume (50–75%) into transient networks of electrolyte pathways and pools. The predicted ‘semi-conductivity’ of the electrolyte pathways guides the flow of biochemical ions throughout the cytoplasm. This metabolic and signaling current is powered by variable electrochemical gradients between the pools. The electrochemical gradients are brought about by cellular biochemical reactions and by extracellular stimuli. The cellular metabolism is thus vectorial not only across the membrane but also throughout the cytoplasm.
The nuclear transport field has completed a decade of fast-paced research dominated by the discovery of transport signals, receptors, and regulators. What might be considered the Holy Grail of nuclear transport - the physical basis of translocation through the nuclear pore - is now under close scrutiny. Recent publications describe structural and biochemical approaches that help address key aspects of the translocation mechanism. These studies have led to the affinity gradient, Brownian affinity gate and selective phase models of translocation.
In 2010, two proteins, Piezo1 and Piezo2, were identified as the long-sought molecular carriers of an excitatory mechanically activated current found in many cells. This discovery has opened the floodgates for studying a vast number of mechanotransduction processes. Over the past 6 years, groundbreaking research has identified Piezos as ion channels that sense light touch, proprioception, and vascular blood flow, ruled out roles for Piezos in several other mechanotransduction processes, and revealed the basic structural and functional properties of the channel. Here, we review these findings and discuss the many aspects of Piezo function that remain mysterious, including how Piezos convert a variety of mechanical stimuli into channel activation and subsequent inactivation, and what molecules and mechanisms modulate Piezo function. Piezo proteins were identified in 2010 as the pore-forming subunits of excitatory mechanosensitive ion channels. Piezo ion channels play essential roles in diverse physiological processes ranging from regulation of red blood cell volume to sensation of gentle touch, and are associated with a number of diseases. A recent medium-resolution structure gives insight into the overall architecture of Piezo1, but does not give straight answers as to how the channel transduces mechanical force into pore opening. The function of Piezos, including the inactivation mechanism, can be modulated by many factors both intrinsic and extrinsic to the channel.
Neural oscillations are ubiquitously observed in the mammalian brain, but it has proven difficult to tie oscillatory patterns to specific cognitive operations. Notably, the coupling between neural oscillations at different timescales has recently received much attention, both from experimentalists and theoreticians. We review the mechanisms underlying various forms of this cross-frequency coupling. We show that different types of neural oscillators and cross-frequency interactions yield distinct signatures in neural dynamics. Finally, we associate these mechanisms with several putative functions of cross-frequency coupling, including neural representations of multiple environmental items, communication over distant areas, internal clocking of neural processes, and modulation of neural processing based on temporal predictions.
Computer Methods for Architects deals with the use of computers in the architecture profession. The text explores where and how computers can and cannot help. The book begins with an explanation of how the majority of the architects around the world were once reluctant to use a computer. It then discusses how some architects improved and advanced the use of computers in the profession. The next part of the book discusses the advantages that a computer can offer an architect, as well as some disadvantages. The next chapter talks about how a computer can handle the files of an entire office. Discussions on the computer's database, proper selection of programs, and simulation techniques are also included in the book. The text finally talks about what the future may hold for computers and architects. This book caters to architects, as it talks about what a person in the field could encounter while using computers..
Reelin controls the migration of neurons and layer formation during brain development. However, recent studies have shown that disrupting Reelin function in the adult hippocampus induces repositioning of fully differentiated neurons, suggesting a stabilizing effect of Reelin on mature neuronal circuitry. Indeed, Reelin was recently found to stabilize the actin cytoskeleton by inducing cofilin phosphorylation. When unphosphorylated, cofilin acts as an actin-depolymerizing protein that promotes the disassembly of F-actin. Here, a novel hypothesis is proposed whereby decreased Reelin expression in the mature brain causes destabilization of neurons and their processes, leading to aberrant plasticity and aberrant wiring of brain circuitry. This has implications for brain disorders, such as epilepsy and schizophrenia, in which deficiencies in Reelin expression occur.
Chemical topology has emerged as one intriguing feature in protein engineering. Nature demonstrates the elegance and power of protein topology engineering in the unique biofunctions and exceptional stabilities of cyclotides and lasso peptides. With entangling protein motifs and genetically encoded peptide–protein chemistry, artificial proteins with complex topologies, including cyclic proteins, star proteins, and protein catenanes, have become accessible. Among them, proteins with mechanical bonds (‘mechanoproteins’) are of special interest, owing to their potential functional benefits such as structure stabilization, quaternary structure control, synergistic multivalency effect, and dynamic mechanical sliding/switching properties. In this review article, we summarize recent progress in the field of protein topology engineering as well as the challenges and opportunities that it holds. Chemical topology of the protein backbone has become an important dimension in protein engineering for tuning the stability and dynamic properties of proteins. Natural proteins with nonlinear backbones or nontrivial topologies exist largely in places where exceptional stability is desired. Mechanoproteins are proteins containing one or more mechanical bonds. The dynamic nature of mechanical bonds in proteins has been demonstrated in lasso peptides exhibiting thermally switchable properties. As a powerful toolset, genetically encoded peptide–protein chemistry has facilitated the design and synthesis of artificial proteins with complex topologies including cyclic, branched, tadpole, lasso, rotaxane, and catenane architectures.