In the nuclear pore complex, intrinsically disordered nuclear pore proteins (FG Nups) form a selective barrier for transport into and out of the cell nucleus, in a way that remains poorly understood. The collective FG Nup behavior has long been conceptualized either as a polymer brush, dominated by entropic and excluded-volume (repulsive) interactions, or as a hydrogel, dominated by cohesive (attractive) interactions between FG Nups. Here we compare mesoscale computational simulations with a wide range of experimental data to demonstrate that FG Nups are at the crossover point between these two regimes. https://www.selleckchem.com/products/tubastatin-a.html Specifically, we find that repulsive and attractive interactions are balanced, resulting in morphologies and dynamics that are close to those of ideal polymer chains. We demonstrate that this property of FG Nups yields sufficient cohesion to seal the transport barrier, and yet maintains fast dynamics at the molecular scale, permitting the rapid polymer rearrangements needed for transport events.Green algae of the Volvocine lineage, spanning from unicellular Chlamydomonas to vastly larger Volvox, are models for the study of the evolution of multicellularity, flagellar dynamics, and developmental processes. Phototactic steering in these organisms occurs without a central nervous system, driven solely by the response of individual cells. All such algae spin about a body-fixed axis as they swim; directional photosensors on each cell thus receive periodic signals when that axis is not aligned with the light. The flagella of Chlamydomonas and Volvox both exhibit an adaptive response to such signals in a manner that allows for accurate phototaxis, but in the former the two flagella have distinct responses, while the thousands of flagella on the surface of spherical Volvox colonies have essentially identical behavior. The planar 16-cell species Gonium pectorale thus presents a conundrum, for its central 4 cells have a Chlamydomonas-like beat that provide propulsion normal to the plane, while its 12 peripheral cells generate rotation around the normal through a Volvox-like beat. Here we combine experiment, theory, and computations to reveal how Gonium, perhaps the simplest differentiated colonial organism, achieves phototaxis. High-resolution cell tracking, particle image velocimetry of flagellar driven flows, and high-speed imaging of flagella on micropipette-held colonies show how, in the context of a recently introduced model for Chlamydomonas phototaxis, an adaptive response of the peripheral cells alone leads to photoreorientation of the entire colony. The analysis also highlights the importance of local variations in flagellar beat dynamics within a given colony, which can lead to enhanced reorientation dynamics.Preferential attachment drives the evolution of many complex networks. Its analytical studies mostly consider the simplest case of a network that grows uniformly in time despite the accelerating growth of many real networks. Motivated by the observation that the average degree growth of nodes is time invariant in empirical network data, we study the degree dynamics in the relevant class of network models where preferential attachment is combined with heterogeneous node fitness and aging. We propose an analytical framework based on the time invariance of the studied systems and show that it is self-consistent only for two special network growth forms the uniform and the exponential network growth. Conversely, the breaking of such time invariance explains the winner-takes-all effect in some model settings, revealing the connection between the Bose-Einstein condensation in the Bianconi-Barabási model and similar gelation in superlinear preferential attachment. Aging is necessary to reproduce realistic node degree growth curves and can prevent the winner-takes-all effect under weak conditions. Our results are verified by extensive numerical simulations.We theoretically design a kind of diffusion bistability (and even multistability) in the macroscopic scale, which has a similar phenomenon but different underlying mechanism from its microscopic counterpart [Phys. Rev. Lett. 101, 267203 (2008)10.1103/PhysRevLett.101.267203]; the latter has been extensively investigated in literature, e.g., for building nanometer-scale memory components. By introducing second- and third-order nonlinear terms (that opposite in sign) into diffusion coefficient matrices, a bistable energy or mass diffusion occurs with two different steady states identified as "0" and "1." In particular, we study heat conduction in a two-terminal three-body system and show that this bistable system exhibits a macroscale thermal memory effect with tailored nonlinear thermal conductivities. The theoretical analysis is confirmed by finite-element simulations. Also, we suggest experiments with metamaterials based on shape memory alloys. This theoretical framework blazes a trail on constructing intrinsic bistability or multistability in diffusive systems for macroscopic energy or mass management.Prediction in complex systems at criticality is believed to be very difficult, if not impossible. Of particular interest is whether earthquakes, whose distribution follows a power-law (Gutenberg-Richter) distribution, are in principle unpredictable. We study the predictability of event sizes in the Olmai-Feder-Christensen model at different proximities to criticality using a convolutional neural network. The distribution of event sizes satisfies a power law with a cutoff for large events. We find that predictability decreases as criticality is approached and that prediction is possible only for large, nonscaling events. Our results suggest that earthquake faults that satisfy Gutenberg-Richter scaling are difficult to forecast.Multiple organs in a living system respond to environmental changes, and the signals from the organs regulate the physiological environment. Inspired by this biological feedback, we propose a simple autonomous system of active rotators to explain how multiple units are synchronized under a fluctuating environment. We find that the feedback via an environment can entrain rotators to have synchronous phases for specific conditions. This mechanism is markedly different from the simple entrainment by a common oscillatory external stimulus that is not interacting with systems. We theoretically examine how the phase synchronization depends on the interaction strength between rotators and environment. Furthermore, we successfully demonstrate the proposed model by realizing an analog electric circuit with microelectronic devices. This bioinspired platform can be used as a sensor for monitoring varying environments and as a controller for amplifying signals by their feedback-induced synchronization.

Although intramuscular (i.m.) administration is the most commonly used route for licensed vaccines, subcutaneous (s.c.) delivery is being explored for several new vaccines under development. Here, we use rhesus macaques, physiologically relevant to humans, to identify the anatomical compartments and early immune processes engaged in the response to immunization via the two routes. Administration of fluorescently labeled HIV-1 envelope glycoprotein trimers displayed on liposomes enables visualization of targeted cells and tissues. Both s.c. and i.m. routes induce efficient immune cell infiltration, activation, and antigen uptake, functions that are tightly restricted to the skin and muscle, respectively. Antigen is also transported to different lymph nodes depending on route. However, these early differences do not translate into significant differences in the magnitude or quality of antigen-specific cellular and humoral responses over time. Thus, although some distinct immunological differences are noted, the choice of route may instead be motivated by clinical practicality. Rationally designing drugs that last longer in the face of biological evolution is a critical objective of drug discovery. However, this goal is thwarted by the diversity and stochasticity of evolutionary trajectories that drive uncertainty in the clinic. Although biophysical models can qualitatively predict whether a mutation causes resistance, they cannot quantitatively predict the relative abundance of resistance mutations in patient populations. We present stochastic, first-principle models that are parameterized on a large in vitro dataset and that accurately predict the epidemiological abundance of resistance mutations across multiple leukemia clinical trials. The ability to forecast resistance variants requires an understanding of their underlying mutation biases. Beyond leukemia, a meta-analysis across prostate cancer, breast cancer, and gastrointestinal stromal tumors suggests that resistance evolution in the adjuvant setting is influenced by mutational bias. Our analysis establishes a principle for rational drug design when evolution favors the most probable mutant, so should drug design. In this issue of Cell Reports, Oemer et al. (2020) define the acyl chain composition of cardiolipin and other lipid classes in murine tissues. They then employ artificial neural networks to predict mechanisms that govern cardiolipin tissue specificity, with implications for understanding cellular pathogenesis in human disease. Preeclampsia is a dangerous hypertensive disorder of pregnancy with known links to negative child health outcomes. Here, we review epidemiological and basic neuroscience work from the past several decades linking prenatal preeclampsia to altered neurodevelopment. This work demonstrates increased rates of neuropsychiatric disorders [e.g., increased autism spectrum disorder, attention deficit hyperactivity disorder (ADHD)] in children of preeclamptic pregnancies, as well as increased rates of cognitive impairments [e.g., decreased intelligence quotient (IQ), academic performance] and neurological disease (e.g., stroke and epilepsy). We also review findings from multiple animal models of preeclampsia. Manipulation of key clinical preeclampsia processes in these models (e.g., placental hypoxia, immune dysfunction, angiogenesis, oxidative stress) causes various disruptions in offspring, including ones in white matter/glia, glucocorticoid receptors, neuroimmune outcomes, cerebrovascular structure, and cognition/behavior. This animal work implicates potentially high-yield targets that may be leveraged in the future for clinical application. Some patients who are considered cortically blind due to the loss of their primary visual cortex (V1) show a remarkable ability to act upon or discriminate between visual stimuli presented to their blind field, without any awareness of those stimuli. This phenomenon is often referred to as blindsight. Despite the range of spared visual abilities, the identification of the pathways mediating blindsight remains an active and contentious topic in the field. In this review, we discuss recent findings of the candidate pathways and their relative contributions to different forms of blindsight across the lifespan to illustrate the varied nature of unconscious visual processing. Genes that are mutated in Autism Spectrum Disorders (ASD) can be classified broadly as either synaptic or developmental. But what if this is a false distinction? A recent spate of publications has provided evidence for developmental mechanisms that rely on neural activity for proper cortical development. Conversely, a growing body of evidence indicates a role for developmental mechanisms, particularly chromatin remodeling, during learning or in response to neural activity. Here, we review these recent publications and propose a model in which genes that confer ASD risk operate in signal transduction networks critical for both cortical development and synaptic homeostasis. Neural stem cells (NSCs) are multipotent progenitors that are responsible for producing all of the neurons and macroglia in the nervous system. In adult mammals, NSCs reside predominantly in a mitotically dormant, quiescent state, but they can proliferate in response to environmental inputs such as feeding or exercise. It is hoped that quiescent NSCs could be activated therapeutically to contribute towards repair in humans. This will require an understanding of quiescent NSC heterogeneities and regulation during normal physiology and following brain injury. Non-mammalian vertebrates (zebrafish and salamanders) and invertebrates (Drosophila) offer insights into brain repair and quiescence regulation that are difficult to obtain using rodent models alone. We review conceptual progress from these various models, a first step towards harnessing quiescent NSCs for therapeutic purposes. Childhood maltreatment increases the likelihood of developing anxiety disorders in humans. https://www.selleckchem.com/products/e7766-diammonium-salt.html Early life adversity (ELA) paradigms in rodents produce lasting increases in avoidant and inhibitory responses to both immediate and nonspecific threats, collectively referred to as defensive behaviors. This approach provides an opportunity to thoroughly investigate the underlying mechanisms, an effort that is currently under way. In this review, we consider the growing literature indicating that ELA alters the rhythmic firing of neurons in brain regions associated with defensive behavior, as well as potential neuronal, glial, and extracellular matrix contributions to functional changes in this circuitry. We also consider how ELA studies in rodents may inform us about both susceptible and resilient outcomes in humans.