At first glance, the U.S. decision to escalate the war in Vietnam in the mid-1960s, China's position on North Korea's nuclear program in the late 1990s and early 2000s, and the EU resolution to lift ...what remained of the arms embargo against Libya in the mid-2000s would appear to share little in common. Yet each of these seemingly unconnected and far-reaching foreign policy decisions resulted at least in part from the exercise of a unique kind of coercion, one predicated on the intentional creation, manipulation, and exploitation of real or threatened mass population movements.
InWeapons of Mass Migration, Kelly M. Greenhill offers the first systematic examination of this widely deployed but largely unrecognized instrument of state influence. She shows both how often this unorthodox brand of coercion has been attempted (more than fifty times in the last half century) and how successful it has been (well over half the time). She also tackles the questions of who employs this policy tool, to what ends, and how and why it ever works. Coercers aim to affect target states' behavior by exploiting the existence of competing political interests and groups, Greenhill argues, and by manipulating the costs or risks imposed on target state populations.
This "coercion by punishment" strategy can be effected in two ways: the first relies on straightforward threats to overwhelm a target's capacity to accommodate a refugee or migrant influx; the second, on a kind of norms-enhanced political blackmail that exploits the existence of legal and normative commitments to those fleeing violence, persecution, or privation. The theory is further illustrated and tested in a variety of case studies from Europe, East Asia, and North America. To help potential targets better respond to-and protect themselves against-this kind of unconventional predation,Weapons of Mass Migrationalso offers practicable policy recommendations for scholars, government officials, and anyone concerned about the true victims of this kind of coercion-the displaced themselves.
Burrowers and borers are ecosystem engineers that alter their physical environments through bioturbation, bioirrigation and bioerosion. The mechanisms of moving through solid substrata by burrowing ...or boring depend on the mechanical properties of the medium and the size and morphology of the organism. For burrowing animals, mud differs mechanically from sand; in mud, sediment grains are suspended in an organic matrix that fails by fracture. Macrofauna extend burrows through this elastic mud by fracture. Sand is granular and non-cohesive, enabling grains to more easily move relative to each other, and macrofaunal burrowers use fluidization or plastic rearrangement of grains. In both sand and mud, peristaltic movements apply normal forces and reduce shear. Excavation and localized grain compaction are mechanisms that plastically deform sediments and are effective in both mud and sand, with bulk excavation being used by larger organisms and localized compaction by smaller organisms. Mechanical boring of hard substrata is an extreme form of excavation in which no compaction of burrow walls occurs and grains are abraded with rigid, hard structures. Chemical boring involves secretion to dissolve or soften generally carbonate substrata. Despite substantial differences in the mechanics of the media, similar burrowing behaviors are effective in mud and sand.
Pathophysiology of Eosinophilic Esophagitis O’Shea, Kelly M.; Aceves, Seema S.; Dellon, Evan S. ...
Gastroenterology (New York, N.Y. 1943),
01/2018, Letnik:
154, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Eosinophilic esophagitis is an emerging disease that is distinguished from gastroesophageal reflux disease by the expression of a unique esophageal transcriptome and the interplay of early life ...environmental factors with distinct genetic susceptibility elements at 5q22 (TSLP) and 2p23 (CAPN14). Rare genetic syndromes have uncovered the contribution of barrier disruption, mediated in part by defective desmosomes and dysregulated transforming growth factor beta production and signaling, to eosinophilic esophagitis pathophysiology. Experimental modeling has defined a cooperative role of activated eosinophils, mast cells, and the cytokines IL-5 and IL-13, mediated by allergic sensitization to multiple foods. Understanding these processes is opening the way to better treatment based on disrupting allergic inflammatory and type 2 cytokine–mediated responses, including anti-cytokine therapeutics and dietary therapy.
To mitigate transmission of COVID-19, rapid changes in instructional delivery moved from in-person to remote instruction. Although literature from before the crisis suggests that online language ...learners fare at least as well as their face-to-face counterparts, the abrupt shift from face-to-face contexts to remote learning is fundamentally different from planned online learning. Understanding the nature of this shift can inform future online and remote teaching. This national survey study was guided by research questions that explore any substantive change in the practices and perceptions of PreK-12 and post-secondary language teachers’ instruction during COVID-19. It explores any change as related to classroom setting (PreK-12 vs post-secondary) and prior experience with distance education. Data suggest that few language educators reported experiences with or positive perceptions toward teaching online before COVID-19. However, they made numerous adjustments to their typical procedures/policies and expectations while engaged in remote teaching. Educators expressed concerns about student outcomes. PreK-12 teachers and those without prior experience with online teaching were least confident that instructional goals were met despite having reported well-designed courses. Implications for effective remote language teaching are presented for consideration.
Background and Purpose
Cannabidiol has been reported to act as an antagonist at cannabinoid CB1 receptors. We hypothesized that cannabidiol would inhibit cannabinoid agonist activity through negative ...allosteric modulation of CB1 receptors.
Experimental Approach
Internalization of CB1 receptors, arrestin2 recruitment, and PLCβ3 and ERK1/2 phosphorylation, were quantified in HEK 293A cells heterologously expressing CB1 receptors and in the STHdhQ7/Q7 cell model of striatal neurons endogenously expressing CB1 receptors. Cells were treated with 2‐arachidonylglycerol or Δ9‐tetrahydrocannabinol alone and in combination with different concentrations of cannabidiol.
Key Results
Cannabidiol reduced the efficacy and potency of 2‐arachidonylglycerol and Δ9‐tetrahydrocannabinol on PLCβ3‐ and ERK1/2‐dependent signalling in cells heterologously (HEK 293A) or endogenously (STHdhQ7/Q7) expressing CB1 receptors. By reducing arrestin2 recruitment to CB1 receptors, cannabidiol treatment prevented internalization of these receptors. The allosteric activity of cannabidiol depended upon polar residues being present at positions 98 and 107 in the extracellular amino terminus of the CB1 receptor.
Conclusions and Implications
Cannabidiol behaved as a non‐competitive negative allosteric modulator of CB1 receptors. Allosteric modulation, in conjunction with effects not mediated by CB1 receptors, may explain the in vivo effects of cannabidiol. Allosteric modulators of CB1 receptors have the potential to treat CNS and peripheral disorders while avoiding the adverse effects associated with orthosteric agonism or antagonism of these receptors.
Functional micropeptides can be concealed within RNAs that appear to be noncoding. We discovered a conserved micropeptide, which we named myoregulin (MLN), encoded by a skeletal muscle-specific RNA ...annotated as a putative long noncoding RNA. MLN shares structural and functional similarity with phospholamban (PLN) and sarcolipin (SLN), which inhibit SERCA, the membrane pump that controls muscle relaxation by regulating Ca2+ uptake into the sarcoplasmic reticulum (SR). MLN interacts directly with SERCA and impedes Ca2+ uptake into the SR. In contrast to PLN and SLN, which are expressed in cardiac and slow skeletal muscle in mice, MLN is robustly expressed in all skeletal muscle. Genetic deletion of MLN in mice enhances Ca2+ handling in skeletal muscle and improves exercise performance. These findings identify MLN as an important regulator of skeletal muscle physiology and highlight the possibility that additional micropeptides are encoded in the many RNAs currently annotated as noncoding.
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•Myoregulin is a micropeptide encoded by an annotated long noncoding RNA•Myoregulin is a transmembrane alpha helix expressed only in skeletal muscle•Myoregulin regulates Ca2+ handling by inhibiting the pump activity of SERCA•Myoregulin KO mice show improved exercise performance and Ca2+ handling in muscle
Myoregulin is a skeletal muscle-specific micropeptide that regulates muscle performance by modulating intracellular calcium handling.
Black Americans are systematically undertreated for pain relative to white Americans. We examine whether this racial bias is related to false beliefs about biological differences between blacks and ...whites (e.g., “black people’s skin is thicker than white people’s skin”). Study 1 documented these beliefs among white laypersons and revealed that participants who more strongly endorsed false beliefs about biological differences reported lower pain ratings for a black (vs. white) target. Study 2 extended these findings to the medical context and found that half of a sample of white medical students and residents endorsed these beliefs. Moreover, participants who endorsed these beliefs rated the black (vs. white) patient’s pain as lower and made less accurate treatment recommendations. Participants who did not endorse these beliefs rated the black (vs. white) patient’s pain as higher, but showed no bias in treatment recommendations. These findings suggest that individuals with at least some medical training hold and may use false beliefs about biological differences between blacks and whites to inform medical judgments, which may contribute to racial disparities in pain assessment and treatment.
Macrophage polarization involves a coordinated metabolic and transcriptional rewiring that is only partially understood. By using an integrated high-throughput transcriptional-metabolic profiling and ...analysis pipeline, we characterized systemic changes during murine macrophage M1 and M2 polarization. M2 polarization was found to activate glutamine catabolism and UDP-GlcNAc-associated modules. Correspondingly, glutamine deprivation or inhibition of N-glycosylation decreased M2 polarization and production of chemokine CCL22. In M1 macrophages, we identified a metabolic break at Idh, the enzyme that converts isocitrate to alpha-ketoglutarate, providing mechanistic explanation for TCA cycle fragmentation. 13C-tracer studies suggested the presence of an active variant of the aspartate-arginosuccinate shunt that compensated for this break. Consistently, inhibition of aspartate-aminotransferase, a key enzyme of the shunt, inhibited nitric oxide and interleukin-6 production in M1 macrophages, while promoting mitochondrial respiration. This systems approach provides a highly integrated picture of the physiological modules supporting macrophage polarization, identifying potential pharmacologic control points for both macrophage phenotypes.
•Glutamine deprivation affects M2 polarization but not M1 polarization•UDP-GlcNAc biosynthesis and N-glycosylation are important for M2 polarization•There is no reverse or direct flow through Idh or malic enzyme in M1 macrophages•Aspartate-arginosuccinate shunt connects the NO and TCA cycles in M1 polarization
Polarization of macrophages involves a metabolic and transcriptional rewiring that is only partially understood. Artyomov and colleagues used an integrated high-throughput transcriptional-metabolic profiling and analysis pipeline to identify metabolic modules that support macrophage polarization and function.
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