In 2014, we proposed that orexin signaling transformed motivationally relevant states into adaptive behavior directed toward exploiting an opportunity or managing a threat, a process we referred to ...as motivational activation. Advancements in animal models since then have permitted higher-resolution measurements of motivational states; in particular, the behavioral economics approach for studying drug demand characterizes conditions that lead to the enhanced motivation that underlies addiction. This motivational plasticity is paralleled by persistently increased orexin expression in a topographically specific manner—a finding confirmed across species, including in humans. Normalization of orexin levels also reduces drug motivation in addiction models. These new advancements lead us to update our proposed framework for the orexin function. We now propose that the capacity of orexin neurons to exhibit dynamic shifts in peptide production contributes to their role in adaptive motivational regulation and that this is achieved via a pool of reserve orexin neurons. This reserve is normally bidirectionally recruited to permit motivational plasticity that promotes flexible, adaptive behavior. In pathological states such as addiction, however, we propose that the orexin system loses capacity to adaptively adjust peptide production, resulting in focused hypermotivation for drug, driven by aberrantly and persistently high expression in the orexin reserve pool. This mechanistic framework has implications for the understanding and treatment of several psychiatric disorders beyond addiction, particularly those characterized by motivational dysfunction.
Quantum light–matter interactions of bound electron systems have been studied extensively. By contrast, quantum interactions of free electrons with light have only become accessible in recent years, ...following the discovery of photon-induced near-field electron microscopy (PINEM). So far, the fundamental free electron–light interaction in all PINEM experiments has remained weak due to its localized near-field nature, which imposes an energy–momentum mismatch between electrons and light. Here, we demonstrate a strong interaction between free-electron waves and light waves, resulting from precise energy–momentum phase-matching with the extended propagating light field. By exchanging hundreds of photons with the field, each electron simultaneously accelerates and decelerates in a coherent manner. Consequently, each electron’s quantum wavefunction evolves into a quantized energy comb, spanning a bandwidth of over 1,700 eV, requiring us to extend the PINEM theory. Our observation of coherent electron phase-matching with a propagating wave is a type of inverse-Cherenkov interaction that occurs with a quantum electron wavefunction, demonstrating how the extended nature of the electron wavefunction can alter stimulated electron–light interactions.Energy–momentum phase-matching enables strong interactions between free electrons and light waves. As a result, the wavefunction of the electron exhibits a comb structure, which was observed using photon-induced near-field electron microscopy.
Global Estimate of Human Brucellosis Incidence Laine, Christopher G; Johnson, Valen E; Scott, H. Morgan ...
Emerging infectious diseases,
09/2023, Letnik:
29, Številka:
9
Journal Article
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Brucellosis is a major public health concern worldwide, especially for persons living in resource-limited settings. Historically, an evidence-based estimate of the global annual incidence of human ...cases has been elusive. We used international public health data to fill this information gap through application of risk metrics to worldwide and regional at-risk populations. We performed estimations using 3 statistical models (weighted average interpolation, bootstrap resampling, and Bayesian inference) and considered missing information. An evidence-based conservative estimate of the annual global incidence is 2.1 million, significantly higher than was previously assumed. Our models indicate Africa and Asia sustain most of the global risk and cases, although areas within the Americas and Europe remain of concern. This study reveals that disease risk and incidence are higher than previously suggested and lie mainly within resource-limited settings. Clarification of both misdiagnosis and underdiagnosis is required because those factors will amplify case estimates.
Antimicrobial resistance (AMR) is a significant threat to both human and animal health. The spread of AMR bacteria and genes across systems can occur through a myriad of pathways, both related and ...unrelated to agriculture, including via wastewater, soils, manure applications, direct exchange between humans and animals, and food exposure. Tracing origins and drivers of AMR bacteria and genes is challenging due to the array of contexts and the complexity of interactions overlapping health practice, microbiology, genetics, applied science and engineering, as well as social and human factors. Critically assessing the diverse and sometimes contradictory AMR literature is a valuable step in identifying tractable mitigation options to stem AMR spread. In this article we review research on the nonfoodborne spread of AMR, with a focus on domesticated animals and the environment and possible exposures to humans. Attention is especially placed on delineating possible sources and causes of AMR bacterial phenotypes, including underpinning the genetics important to human and animal health.
Antimicrobial resistance (AMR) is a significant threat to both human and animal health. Our article reviews research on the nonfoodborne spread of AMR with a focus on domesticated animals and the environment, and possible exposure risks to humans. Attention is especially placed on delineating possible sources and causes of AMR bacterial phenotypes, including underpinning genetics important to human and animal health.
In 2010, the international community, under the auspices of the Convention on Biological Diversity, agreed on 20 biodiversity-related “Aichi Targets” to be achieved within a decade. We provide a ...comprehensive mid-term assessment of progress toward these global targets using 55 indicator data sets. We projected indicator trends to 2020 using an adaptive statistical framework that incorporated the specific properties of individual time series. On current trajectories, results suggest that despite accelerating policy and management responses to the biodiversity crisis, the impacts of these efforts are unlikely to be reflected in improved trends in the state of biodiversity by 2020. We highlight areas of societal endeavor requiring additional efforts to achieve the Aichi Targets, and provide a baseline against which to assess future progress.
The orexin (hypocretin) system is important for reward-driven motivation but has not been implicated in the expression of a multiphenotype addicted state.
Rats were assessed for economic demand for ...cocaine before and after 14 days of short access, long access, or intermittent access (IntA) to cocaine. Rats were also assessed for a number of other DSM-5–relevant addiction criteria following differential access conditions. Orexin system function was assessed by quantification of numbers and activity of orexin cells, pharmacological blockade of the orexin-1 receptor, and subregion-specific knockdown of orexin cell populations.
IntA produced a cluster of addiction-like behaviors that closely recapitulate key diagnostic criteria for addiction to a greater extent than long access or short access. IntA was accompanied by an increase in number and activity of orexin-expressing neurons within the lateral hypothalamic subregion. This increase in orexin cell number and activity persisted during protracted withdrawal from cocaine for at least 150 days and was accompanied by enhanced incubation of craving in the same rats. Selective knockdown of lateral hypothalamic orexin neurons reduced motivation for cocaine, and orexin-1 receptor signaling played a larger role in drug seeking after IntA.
We provide the first evidence that lateral hypothalamic orexin system function extends beyond general reward seeking to play a critical role in expression of a multiphenotype addiction-like state. Thus, the orexin system is a potential novel target for pharmacotherapies designed to treat cocaine addiction. In addition, these data point to the IntA model as a preferred approach to modeling addiction-like behavior in rats.
1. Large digestive organs increase rates of energy gain when food is plentiful but are costly to maintain and increase rates of energy loss when food is scarce. The physiological adaptations to this ...trade-off differ depending on the scale and predictability of variation in food abundance. 2. Currently, there is little understanding of how animals balance trade-offs between the cost and capacity of the digestive system in response to resource pulses: rare, ephemeral periods of resource superabundance. We investigated the physiological and behavioural tactics of the fish Dolly Varden (Salvelinus malma) that rear in watersheds with low in situ productivity, but experience annual resource pulses from the spawning migrations of Pacific salmon. The eggs of Pacific salmon provide high-energy food for Dolly Varden. 3. Dolly Varden sampled 6 weeks prior to the resource pulse exhibited atrophy of the stomach, pyloric caeca, intestine and liver. Throughout the portion of the growing season prior to the resource pulse, fish exhibited empty stomachs, low indices of energy condition and muscle isotope signatures reflecting the previous resource pulse. 4. During the resource pulse, Dolly Varden exhibited large digestive machinery, gorged on salmon eggs and rapidly stored energy in fat reserves, somatic growth and gonad development. Dolly Varden appeared to achieve nearly their entire annual energy surplus during the ∼5-week period when sockeye salmon spawn. 5. Digestive flexibility provides Dolly Varden the energy efficiency required to survive and reproduce when resource abundance is concentrated into an annual pulse that is predictable, yet highly ephemeral. Although fish are known to incur extremely variable energy budgets, our study is one of the first to document digestive flexibility in wild fish. Our study emphasize that fish can rely heavily on rare, high-magnitude foraging opportunities. Human actions that attenuate spikes in food abundance may have stronger than anticipated effects on consumer energy budgets.
Prestige-biased social learning (henceforth “prestige-bias”) occurs when individuals predominantly choose to learn from a prestigious member of their group, i.e. someone who has gained attention, ...respect and admiration for their success in some domain. Prestige-bias is proposed as an adaptive social-learning strategy as it provides a short-cut to identifying successful group members, without having to assess each person’s success individually. Previous work has documented prestige-bias and verified that it is used adaptively. However, the domain-specificity and generality of prestige-bias has not yet been explicitly addressed experimentally. By domain-specific prestige-bias we mean that individuals choose to learn from a prestigious model only within the domain of expertise in which the model acquired their prestige. By domain-general prestige-bias we mean that individuals choose to learn from prestigious models in general, regardless of the domain in which their prestige was earned. To distinguish between domain specific and domain general prestige we ran an online experiment (n = 397) in which participants could copy each other to score points on a general-knowledge quiz with varying topics (domains). Prestige in our task was an emergent property of participants’ copying behaviour. We found participants overwhelmingly preferred domain-specific (same topic) prestige cues to domain-general (across topic) prestige cues. However, when only domain-general or cross-domain (different topic) cues were available, participants overwhelmingly favoured domain-general cues. Finally, when given the choice between cross-domain prestige cues and randomly generated Player IDs, participants favoured cross-domain prestige cues. These results suggest participants were sensitive to the source of prestige, and that they preferred domain-specific cues even though these cues were based on fewer samples (being calculated from one topic) than the domain-general cues (being calculated from all topics). We suggest that the extent to which people employ a domain-specific or domain-general prestige-bias may depend on their experience and understanding of the relationships between domains.
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