“Science, like most forms of human activity, is occasionally liable to lose sight of its ultimate ends under a flood of controversy, the strugglings of personal ambition, or the fight for pecuniary ...rewards or less physical honors … Celebrated across the world as a major turning point in the young science of genetics, the paper formally reconciled mendelian and biometric approaches to inheritance by introducing the concepts of variance and polygenicity and laying the groundwork for the complex trait liability threshold model, which remains highly relevant to modern human genetics 2. Through years of painstaking data collection and analysis, the team eventually began to realize that anthropometric traits that distinguished different crab species also varied greatly within species. ...upon the collection of enough data, even “dimorphic” traits appeared continuous. ...they came to believe that the most likely mechanism to explain evolution was slow and gradual natural selection.
Fragile X syndrome (FXS), a heritable intellectual and autism spectrum disorder (ASD), results from the loss of Fragile X mental retardation protein (FMRP). This neurodevelopmental disease state ...exhibits neural circuit hyperconnectivity and hyperexcitability. Canonically, FMRP functions as an mRNA-binding translation suppressor, but recent findings have enormously expanded its proposed roles. Although connections between burgeoning FMRP functions remain unknown, recent advances have extended understanding of its involvement in RNA, channel, and protein binding that modulate calcium signaling, activity-dependent critical period development, and the excitation–inhibition (E/I) neural circuitry balance. In this review, we contextualize 3 years of FXS model research. Future directions extrapolated from recent advances focus on discovering links between FMRP roles to determine whether FMRP has a multitude of unrelated functions or whether combinatorial mechanisms can explain its multifaceted existence.
FXS, a leading heritable autism, is caused by a 5′ untranslated region (UTR) trinucleotide repeat expansion in the gene encoding FMRP.
The disease presents with stereotypical hyperexcitability and synaptic overelaboration, which are well replicated across a range of neural circuits in genetic models.
Canonically, FMRP is a mRNA-binding translational suppressor, but genetic roles range from chromatin binding to mRNA splicing and/or editing to other forms of translation control.
Additional FMRP roles include direct ion channel binding to regulate neural excitability, which may be an independent function or linked to activity-dependent translation control.
FXS cell type-specific defects in neurons and glia include altered calcium signaling, critical period synapse refinement, and E/I imbalance in neural circuitry.
The concept of epistemic communities – professional networks with authoritative and policy-relevant expertise – is well-known thanks to a 1992 special issue of International Organization. Over the ...past twenty years, the idea has gained some traction in International Relations scholarship, but has not evolved much beyond its original conceptualisation. Much of the research on epistemic communities has been limited to single case studies in articles, rather than broader comparative works, and has focused narrowly on groups of scientists. As a result, it is often assumed, erroneously, that epistemic communities are only comprised of scientists, and that the utility of the concept for understanding International Relations is quite narrow. Consequently, an otherwise promising approach to transnational networks has become somewhat marginalised over the years. This article revisits the concept of epistemic communities twenty years later and proposes specific innovations to the framework. In an increasingly globalising world, transnational actors are becoming progressively more numerous and influential. Epistemic communities are certainly at the forefront of these trends, and a better understanding of how they form and operate can give us a clear demonstration of how knowledge translates into power.
Inflammasome activation leads to caspase-1 activation, which causes the maturation and secretion of pro-IL-1β and pro-IL-18 among other substrates. A subgroup of the NLR (nucleotide-binding domain, ...leucine-rich repeat containing) proteins are key mediators of the inflammasome. Studies of gene-deficient mice and cells have implicated NLR inflammasomes in a host of responses to a wide range of microbial pathogens, inflammatory diseases, cancer, and metabolic and autoimmune disorders. Determining exactly how the inflammasome is activated in these diseases and disease models remains a challenge. This review presents and integrates recent progress in the field.
At a time when many observers question the EU's ability to achieve integration of any significance, and indeed Europeans themselves appear disillusioned, Mai'a K. Davis Cross argues that the EU has ...made remarkable advances in security integration, in both its external and internal dimensions. Moreover, internal security integration-such as dealing with terrorism, immigration, cross-border crime, and drug and human trafficking-has made even greater progress with dismantling certain barriers that previously stood at the core of traditional state sovereignty.
Such unprecedented collaboration has become possible thanks to knowledge-based transnational networks, or "epistemic communities," of ambassadors, military generals, scientists, and other experts who supersede national governments in the diplomacy of security decision making and are making headway at remarkable speed by virtue of their shared expertise, common culture, professional norms, and frequent meetings. Cross brings together nearly 80 personal interviews and a host of recent government documents over the course of five separate case studies to provide a microsociological account of how governance really works in today's EU and what future role it is likely to play in the international environment.
"This is an ambitious work which deals not only with European security and defense but also has much to say about the policy-making process of the EU in general."-Ezra Suleiman, Princeton University
Deserts are commonly imagined as barren, defiled, worthless places, wastelands in need of development. This understanding has fueled extensive anti-desertification efforts -- a multimillion-dollar ...global campaign driven by perceptions of a looming crisis. In this book, Diana Davis argues that estimates of desertification have been significantly exaggerated and that deserts and drylands -- which constitute about 41% of the earth's landmass -- are actually resilient and biodiverse environments in which a great many indigenous people have long lived sustainably. Meanwhile, contemporary arid lands development programs and anti-desertification efforts have met with little success. As Davis explains, these environments are not governed by the equilibrium ecological dynamics that apply in most other regions. Davis shows that our notion of the arid lands as wastelands derives largely from politically motivated Anglo-European colonial assumptions that these regions had been laid waste by "traditional" uses of the land. Unfortunately, such assumptions still frequently inform policy. Drawing on political ecology and environmental history, Davis traces changes in our understanding of deserts, from the benign views of the classical era to Christian associations of the desert with sinful activities to later (neo)colonial assumptions of destruction. She further explains how our thinking about deserts is problematically related to our conceptions of forests and desiccation. Davis concludes that a new understanding of the arid lands as healthy, natural, but variable ecosystems that do not necessarily need improvement or development will facilitate a more sustainable future for the world's magnificent drylands.
We investigate the relation between corporate tax payments and corporate social responsibility. Because existing theory and empirical studies find inconsistent evidence on the relation between these ...constructs, we investigate whether the two activities act as complements or substitutes. We estimate the relation between measures of corporate social responsibility and (1) the amount of corporate taxes paid, and (2) the amount invested in tax lobbying activities using both ordinary least squares and a system of simultaneous equations. We find consistent evidence that corporate social responsibility is negatively related to five-year cash effective tax rates and positively related to tax lobbying expenditures. Our evidence suggests that, on average, corporate social responsibility and tax payments act as substitutes.
Oxidative stress plays a crucial role in traumatic brain injury (TBI) pathogenesis. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) formed in excess after TBI synergistically ...contribute to secondary brain damage together with lipid peroxidation products (reactive aldehydes) and inflammatory mediators. Furthermore, oxidative stress, endoplasmic reticulum stress and inflammation potentiate each other. Following TBI, excessive oxidative stress overloads the endogenous cellular antioxidant system leading to cell death. To combat oxidative stress, several antioxidant therapies were tested in preclinical animal models of TBI. These include free radical scavengers, activators of antioxidant systems, Inhibitors of free radical generating enzymes and antioxidant enzymes. Many of these therapies showed promising outcomes including reduced edema, blood-brain barrier (BBB) protection, smaller contusion volume, and less inflammation. In addition, many antioxidant therapies also promoted better sensory, motor, and cognitive functional recovery after TBI. Overall, preventing oxidative stress is a viable therapeutic option to minimize the secondary damage and to improve the quality of life after TBI.
•Oxidative stress is one of the proponents of TBI pathophysiology.•Post-TBI antioxidant therapies include those that prevent the formation and those that promote the disposal of free radicals.•Antioxidant therapies decreased edema and lesion volume after TBI.•Efficacy of antioxidant therapies after TBI depends on dose, time of administration and type of injury.
Today's debates about transgender inclusion and public restrooms may seem unmistakably contemporary, but they have a surprisingly long and storied history in the United States-one that concerns more ...than mere "potty politics." Alexander K. Davis takes readers behind the scenes of two hundred years' worth of conflicts over the existence, separation, and equity of gendered public restrooms, documenting at each step how bathrooms have been entangled with bigger cultural matters: the importance of the public good, the reach of institutional inclusion, the nature of gender difference, and, above all, the myriad privileges of social status. Chronicling the debut of nineteenth-century "comfort stations," twentieth-century mandates requiring equal-but-separate men's and women's rooms, and twenty-first-century uproar over laws like North Carolina's "bathroom bill," Davis reveals how public restrooms are far from marginal or unimportant social spaces. Instead, they are-and always have been-consequential sites in which ideology, institutions, and inequality collide.
Naturally occurring and psychedelic drug-occasioned experiences interpreted as personal encounters with God are well described but have not been systematically compared. In this study, five groups of ...individuals participated in an online survey with detailed questions characterizing the subjective phenomena, interpretation, and persisting changes attributed to their single most memorable God encounter experience (n = 809 Non-Drug, 1184 psilocybin, 1251 lysergic acid diethylamide (LSD), 435 ayahuasca, and 606 N,N-dimethyltryptamine (DMT)). Analyses of differences in experiences were adjusted statistically for demographic differences between groups. The Non-Drug Group was most likely to choose "God" as the best descriptor of that which was encountered while the psychedelic groups were most likely to choose "Ultimate Reality." Although there were some other differences between non-drug and the combined psychedelic group, as well as between the four psychedelic groups, the similarities among these groups were most striking. Most participants reported vivid memories of the encounter experience, which frequently involved communication with something having the attributes of being conscious, benevolent, intelligent, sacred, eternal, and all-knowing. The encounter experience fulfilled a priori criteria for being a complete mystical experience in approximately half of the participants. More than two-thirds of those who identified as atheist before the experience no longer identified as atheist afterwards. These experiences were rated as among the most personally meaningful and spiritually significant lifetime experiences, with moderate to strong persisting positive changes in life satisfaction, purpose, and meaning attributed to these experiences. Among the four groups of psychedelic users, the psilocybin and LSD groups were most similar and the ayahuasca group tended to have the highest rates of endorsing positive features and enduring consequences of the experience. Future exploration of predisposing factors and phenomenological and neural correlates of such experiences may provide new insights into religious and spiritual beliefs that have been integral to shaping human culture since time immemorial.
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