Centrifugal terms in the WKB approximation and semiclassical quantization of hydrogen

A systematic semiclassical expansion of the hydrogen problem about the classical Kepler problem is shown to yield remarkably accurate results. Ad hoc changes of the centrifugal term, such as the standard Langer modification where the factor l(l+1) is replaced by (l+1/2)^2, are avoided. The semiclassical energy levels are shown to be exact to first order in $\hbar$ with all higher order contributions vanishing. The wave functions and dipole matrix elements are also discussed.Comment: 5 pages, to appear in Phys. Rev.

Parvovirus-derived endogenous viral elements in two South American rodent genomes

We describe endogenous viral elements (EVEs) derived from parvoviruses (family <i>Parvoviridae</i>) in the long-tailed chinchilla (<i>Chinchilla lanigera</i>) and degu (<i>Octodon degus</i>) genomes. The novel EVEs include Dependovirus-related elements, and representatives of a clearly distinct parvovirus lineage that also has endogenous representatives in marsupial genomes. In the degu, one dependovirus-derived EVEs was found to encode an intact reading frame, and was differentially expressed <i>in vivo</i>, with increased expression in the liver

The Role of Inhibitory Receptors in Monosodium Urate Crystal-Induced Inflammation

Inhibitory receptors are key regulators of immune responses. Aberrant inhibitory receptor function can either lead to an exacerbated or defective immune response. Several regulatory mechanisms involved in the inflammatory reaction induced by monosodium urate crystals (MSU) during acute gout have been identified. One of these mechanisms involves inhibitory receptors. The engagement of the inhibitory receptors Clec12A and SIRL-1 has opposing effects on the responses of neutrophils to MSU. We review the general concepts of inhibitory receptor biology and apply them to understand and compare the modulation of MSU-induced inflammation by Clec12A and SIRL-1. We also discuss gaps in our knowledge of the contribution of inhibitory receptors to the pathogenesis of gout and propose future avenues of research

Helminth resistance is mediated by differential activation of recruited monocyte-derived alveolar macrophages and arginine depletion

Macrophages are known to mediate anti-helminth responses, but it remains uncertain which subsets are involved or how macrophages actually kill helminths. Here, we show rapid monocyte recruitment to the lung after infection with the nematode parasite Nippostrongylus brasiliensis. In this inflamed tissue microenvironment, these monocytes differentiate into an alveolar macrophage (AM)-like phenotype, expressing both SiglecF and CD11c, surround invading parasitic larvae, and preferentially kill parasites in vitro. Monocyte-derived AMs (Mo-AMs) express type 2-associated markers and show a distinct remodeling of the chromatin landscape relative to tissue-derived AMs (TD-AMs). In particular, they express high amounts of arginase-1 (Arg1), which we demonstrate mediates helminth killing through L-arginine depletion. These studies indicate that recruited monocytes are selectively programmed in the pulmonary environment to express AM markers and an anti-helminth phenotype

Whole brain modelling for simulating pharmacological interventions on patients with disorders of consciousness

Disorders of consciousness (DoC) represent a challenging and complex group of neurological conditions characterised by profound disturbances in consciousness. The current range of treatments for DoC is limited. This has sparked growing interest in developing new treatments, including the use of psychedelic drugs. Nevertheless, clinical investigations and the mechanisms behind them are methodologically and ethically constrained. To tackle these limitations, we combined biologically plausible whole-brain models with deep learning techniques to characterise the low-dimensional space of DoC patients. We investigated the effects of model pharmacological interventions by including the whole-brain dynamical consequences of the enhanced neuromodulatory level of different neurotransmitters, and providing geometrical interpretation in the low-dimensional space. Our findings show that serotonergic and opioid receptors effectively shifted the DoC models towards a dynamical behaviour associated with a healthier state, and that these improvements correlated with the mean density of the activated receptors throughout the brain. These findings mark an important step towards the development of treatments not only for DoC but also for a broader spectrum of brain diseases. Our method offers a promising avenue for exploring the therapeutic potential of pharmacological interventions within the ethical and methodological confines of clinical research

Human neutrophil phosphodiesterase

Extracts of human neutrophils were examined for phosphodiesterase activity using a radiochemical assay. As reported by other investigators, both high- and low- K m forms of the enzyme were found. Although calmodulin could be measured in these extracts, human neutrophil phosphodiesterase proved not to be calmodulin dependent. Activity of the neutrophil phosphodiesterase was also not altered by physiologic concentrations of indomethacin, p -bromophenacyl bromide, eicosatetraenoic acid, or eicosatetraynoic acid, all inhibitors of arachidonic acid metabolism. These results are relevant to stimulus-secretion coupling in neutrophils, wherein calmodulin-dependent reactions play a vital role.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44535/1/10753_2004_Article_BF00916094.pd

The Flexibility of Nonconsciously Deployed Cognitive Processes: Evidence from Masked Congruence Priming

Background: It is well accepted in the subliminal priming literature that task-level properties modulate nonconscious processes. For example, in tasks with a limited number of targets, subliminal priming effects are limited to primes that are physically similar to the targets. In contrast, when a large number of targets are used, subliminal priming effects are observed for primes that share a semantic (but not necessarily physical) relationship with the target. Findings such as these have led researchers to conclude that task-level properties can direct nonconscious processes to be deployed exclusively over central (semantic) or peripheral (physically specified) representations. Principal Findings: We find distinct patterns of masked priming for "novel" and "repeated" primes within a single task context. Novel primes never appear as targets and thus are not seen consciously in the experiment. Repeated primes do appear as targets, thereby lending themselves to the establishment of peripheral stimulus-response mappings. If the source of the masked priming effect were exclusively central or peripheral, then both novel and repeated primes should yield similar patterns of priming. In contrast, we find that both novel and repeated primes produce robust, yet distinct, patterns of priming. Conclusions: Our findings indicate that nonconsciously elicited cognitive processes can be flexibly deployed over both central and peripheral representations within a single task context. While we agree that task-level properties can influence nonconscious processes, our findings sharply constrain the extent of this influence. Specifically, our findings are inconsistent with extant accounts which hold that the influence of task-level properties is strong enough to restrict the deployment of nonconsciously elicited cognitive processes to a single type of representation (i.e. central or peripheral).13 page(s

The Inhibitory Receptor CLEC12A Regulates PI3K-Akt Signaling to Inhibit Neutrophil Activation and Cytokine Release

The myeloid inhibitory C-type lectin receptor CLEC12A limits neutrophil activation, pro-inflammatory pathways and disease in mouse models of inflammatory arthritis by a molecular mechanism that remains poorly understood. We addressed how CLEC12A-mediated inhibitory signaling counteracts activating signaling by cross-linking CLEC12A in human neutrophils. CLEC12A cross-linking induced its translocation to flotillin-rich membrane domains where its ITIM was phosphorylated in a Src-dependent manner. Phosphoproteomic analysis identified candidate signaling molecules regulated by CLEC12A that include MAPKs, phosphoinositol kinases and members of the JAK-STAT pathway. Stimulating neutrophils with uric acid crystals, the etiological agent of gout, drove the hyperphosphorylation of p38 and Akt. Ultimately, one of the pathways through which CLEC12A regulates uric acid crystal-stimulated release of IL-8 by neutrophils is through a p38/PI3K-Akt signaling pathway. In summary this work defines early molecular events that underpin CLEC12A signaling in human neutrophils to modulate cytokine synthesis. Targeting this pathway could be useful therapeutically to dampen inflammation