In the face of the most perilous challenges of our time-climate change, terrorism, poverty, and trafficking of drugs, guns, and people-the nations of the world seem paralyzed. The problems are too ...big, too interdependent, too divisive for the nation-state. Is the nation-state, once democracy's best hope, today democratically dysfunctional? Obsolete? The answer, says Benjamin Barber in this highly provocative and original book, is yes. Cities and the mayors who run them can do and are doing a better job.
Barber cites the unique qualities cities worldwide share: pragmatism, civic trust, participation, indifference to borders and sovereignty, and a democratic penchant for networking, creativity, innovation, and cooperation. He demonstrates how city mayors, singly and jointly, are responding to transnational problems more effectively than nation-states mired in ideological infighting and sovereign rivalries. Featuring profiles of a dozen mayors around the world-courageous, eccentric, or both at once-If Mayors Ruled the Worldpresents a compelling new vision of governance for the coming century. Barber makes a persuasive case that the city is democracy's best hope in a globalizing world, and great mayors are already proving that this is so.
Muscle contraction depends on release of Ca²⁺ from the sarcoplasmic reticulum (SR) and reuptake by the Ca²⁺ adenosine triphosphatase SERCA. We discovered a putative muscle-specific long noncoding RNA ...that encodes a peptide of 34 amino acids and that we named dwarf open reading frame (DWORF). DWORF localizes to the SR membrane, where it enhances SERCA activity by displacing the SERCA inhibitors, phospholamban, sarcolipin, and myoregulin. In mice, overexpression of DWORF in cardiomyocytes increases peak Ca²⁺ transient amplitude and SR Ca²⁺ load while reducing the time constant of cytosolic Ca²⁺ decay during each cycle of contraction-relaxation. Conversely, slow skeletal muscle lacking DWORF exhibits delayed Ca²⁺ clearance and relaxation and reduced SERCA activity. DWORF is the only endogenous peptide known to activate the SERCA pump by physical interaction and provides a means for enhancing muscle contractility.
This paper investigates consumer inertia in health insurance markets, where adverse selection is a potential concern. We leverage a major change to insurance provision that occurred at a large firm ...to identify substantial inertia, and develop and estimate a choice model that also quantifies risk preferences and ex ante health risk. We use these estimates to study the impact of policies that nudge consumers toward better decisions by reducing inertia. When aggregated, these improved individual-level choices substantially exacerbate adverse selection in our setting, leading to an overall reduction in welfare that doubles the existing welfare loss from adverse selection.
The ways that couples form and manage their intimate relationships at higher and lower levels of socioeconomic status (SES) have been diverging steadily over the past several decades. At higher SES ...levels, couples postpone marriage and childbirth to invest in education and careers, but they eventually marry at high rates and have relatively low risk for divorce. At lower SES levels, couples are more likely to cohabit and give birth prior to marriage and less likely to marry at all. This review examines how SES comes to be associated with the formation, development, and dissolution of intimate relationships. Overall, research has highlighted how a couple's socioeconomic context facilitates some choices and constrains others, resulting in different capacities for relationship maintenance and different adaptive mating strategies for more and less advantaged couples. A generalizable relationship science requires research that acknowledges these differences and one that recruits, describes, and attends to socioeconomic diversity across couples.
When ultralight axion dark matter encounters a static magnetic field, it sources an effective electric current that follows the magnetic field lines and oscillates at the axion Compton frequency. We ...propose a new experiment to detect this axion effective current. In the presence of axion dark matter, a large toroidal magnet will act like an oscillating current ring, whose induced magnetic flux can be measured by an external pickup loop inductively coupled to a SQUID magnetometer. We consider both resonant and broadband readout circuits and show that a broadband approach has advantages at small axion masses. We estimate the reach of this design, taking into account the irreducible sources of noise, and demonstrate potential sensitivity to axionlike dark matter with masses in the range of 10^{-14}-10^{-6} eV. In particular, both the broadband and resonant strategies can probe the QCD axion with a GUT-scale decay constant.
Self-replicating genetic material presumably provided the architecture necessary for generating the last universal ancestor of all nucleic-acid-based life. As biological complexity increased in the ...billions of years that followed, the same genetic material also morphed into a wide spectrum of viruses and other parasitic genetic elements. The resulting struggle for existence drove the evolution of host defenses, giving rise to a perpetual arms race. This Perspective summarizes the antiviral mechanisms evident across the tree of life, discussing each in their evolutionary context to postulate how the coevolution of host and pathogen shaped the cellular antiviral defenses we know today.
In this Perspective, tenOever summarizes the antiviral mechanisms evident across the tree of life, discussing each in their evolutionary context to postulate how the coevolution of host and pathogen shaped the cellular antiviral defenses we know today.
Ultracompact dark matter (DM) minihalos at masses at and below 10^{-12} M_{⊙} arise in axion DM models where the Peccei-Quinn (PQ) symmetry is broken after inflation. The minihalos arise from ...density perturbations that are generated from the nontrivial axion self-interactions during and shortly after the collapse of the axion-string and domain-wall network. We perform high-resolution simulations of this scenario starting at the epoch before the PQ phase transition and ending at matter-radiation equality. We characterize the spectrum of primordial perturbations that are generated and comment on implications for efforts to detect axion DM. We also measure the DM density at different simulated masses and argue that the correct DM density is obtained for m_{a}=25.2±11.0 μeV.
Eight types of short-chain Lys acylations have recently been identified on histones: propionylation, butyrylation, 2-hydroxyisobutyrylation, succinylation, malonylation, glutarylation, crotonylation ...and β-hydroxybutyrylation. Emerging evidence suggests that these histone modifications affect gene expression and are structurally and functionally different from the widely studied histone Lys acetylation. In this Review, we discuss the regulation of non-acetyl histone acylation by enzymatic and metabolic mechanisms, the acylation 'reader' proteins that mediate the effects of different acylations and their physiological functions, which include signal-dependent gene activation, spermatogenesis, tissue injury and metabolic stress. We propose a model to explain our present understanding of how differential histone acylation is regulated by the metabolism of the different acyl-CoA forms, which in turn modulates the regulation of gene expression.
Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host ...response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.
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•SARS-CoV-2 infection induces low IFN-I and -III levels with a moderate ISG response•Strong chemokine expression is consistent across in vitro, ex vivo, and in vivo models•Low innate antiviral defenses and high pro-inflammatory cues contribute to COVID-19
In comparison to other respiratory viruses, SARS-CoV-2 infection drives a lower antiviral transcriptional response that is marked by low IFN-I and IFN-III levels and elevated chemokine expression, which could explain the pro-inflammatory disease state associated with COVID-19.
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