Highly excited electronic image states of metallic nanorings

We study electronic image states around a metallic nanoring and show that the interplay between the attractive polarization force and a repulsive centrifugal force gives rise to Rydberg-like image states trapped several nanometers away from the surface. The nanoring is modeled as a perfectly conducting isolated torus whose electrostatic image potential is derived analytically. The image states are computed via a two-dimensional finite-difference scheme as solutions of the effective Schr\"odinger equation describing the outer electron subject to this image potential. These findings demonstrate not only the existence of detached image states around nanorings but allow us also to provide general criteria on the ring geometry, i.e. the aspect ratio of the torus, that need to be fulfilled in order to support such states

Regulating functional and hedonic emotions in the pursuit of musical practice goals

Individuals can regulate their emotions in order to feel better and avoid feeling worse. However, individuals can also regulate emotions if doing so is believed to be beneficial to the pursuit of a goal. When pursuing a long-term goal, an individual may choose to delay immediate hedonic emotional reward in order to maximize the functional influence of emotions. This study investigates emotion regulation in the context of musical practice. We examine whether musicians adopt specific emotional stances which support their goal orientation, and which are in line with their beliefs about the functional influence of emotions. Via an online questionnaire, musicians (N = 421) reported their goals, meta-emotion beliefs, and emotion regulation behaviour. Musicians used affect-improvement strategies in their practice more often than affect-worsening strategies. Greater use of affect-worsening strategies was associated with stronger support for the utility of unpleasant emotions. Musicians who more strongly endorsed this belief more strongly pursed mastery goals than enjoyment goals. An examination of specific regulated emotions to support musical practice indicated that musicians generally sought to reduce unpleasant emotions, instead preferring pleasant, energizing emotions. However, a subgroup of mastery-oriented musicians may seek a mixed emotional state, increasing anger and nervousness alongside a range of pleasant emotions. Musicians who pursue mastery may be motivated to experience emotions that combine functional and hedonic benefits. Functional emotions may be less relevant for musicians who practice for enjoyment. Research in this field may equip musicians with novel skills for better pursuit of their practice goals

Functional Characterization of Rare RAB12 Variants and Their Role in Musician's and Other Dystonias

Mutations in RAB (member of the Ras superfamily) genes are increasingly recognized as cause of a variety of disorders including neurological conditions. While musician's dystonia (MD) and writer's dystonia (WD) are task-specific movement disorders, other dystonias persistently affect postures as in cervical dystonia. Little is known about the underlying etiology. Next-generation sequencing revealed a rare missense variant (c.586A> G; p.Ile196Val) in RAB12 in two of three MD/WD families. Next, we tested 916 additional dystonia patients; 512 Parkinson's disease patients; and 461 healthy controls for RAB12 variants and identified 10 additional carriers of rare missense changes among dystonia patients (1.1%) but only one carrier in non-dystonic individuals (0.1%; p = 0.005). The detected variants among index patients comprised p.Ile196Val (n = 6); p.Ala174Thr (n = 3); p.Gly13Asp; p.Ala148Thr; and p.Arg181Gln in patients with MD; cervical dystonia; or WD. Two relatives of MD patients with WD also carried p.Ile196Val. The two variants identified in MD patients (p.Ile196Val; p.Gly13Asp) were characterized on endogenous levels in patient-derived fibroblasts and in two RAB12-overexpressing cell models. The ability to hydrolyze guanosine triphosphate (GTP), so called GTPase activity, was increased in mutants compared to wildtype. Furthermore, subcellular distribution of RAB12 in mutants was altered in fibroblasts. Soluble Transferrin receptor 1 levels were reduced in the blood of all three tested p.Ile196Val carriers. In conclusion, we demonstrate an enrichment of missense changes among dystonia patients. Functional characterization revealed altered enzyme activity and lysosomal distribution in mutants suggesting a contribution of RAB12 variants to MD and other dystonias

CRAGE-Duet Facilitates Modular Assembly of Biological Systems for Studying Plant-Microbe Interactions

Developing sustainable agricultural practices will require increasing our understanding of plant-microbe interactions. To study these interactions, new genetic tools for manipulating nonmodel microbes will be needed. To help meet this need, we recently reported development of chassis-independent recombinase-assisted genome engineering (CRAGE). CRAGE relies on cassette exchange between two pairs of mutually exclusive lox sites and allows direct, single-step chromosomal integration of large, complex gene constructs into diverse bacterial species. We then extended CRAGE by introducing a third mutually exclusive lox site, creating CRAGE-Duet, which allows modular integration of two constructs. CRAGE-Duet offers advantages over CRAGE, especially when a cumbersome recloning step is required to build single-integration constructs. To demonstrate the utility of CRAGE-Duet, we created a set of strains from the plant-growth-promoting rhizobacterium Pseudomonas simiae WCS417r that expressed various fluorescence marker genes. We visualized these strains simultaneously under a confocal microscope, demonstrating the usefulness of CRAGE-Duet for creating biological systems to study plant-microbe interactions

Testosterone-induced, sulfonamide-resistant carbonic anhydrase isozyme of rat liver is indistinguishable from skeletal muscle carbonic anhydrase III

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24353/1/0000622.pd

The nucleotide sequence and derived amino acid sequence of cDNA coding for mouse carbonic anhydrase II

The nucleotide sequence of a clone containing mouse carbonic anhydrase (CA) cDNA in pBR322 has been determined. The cloned cDNA contains all of the coding region except for nucleotides specifying the first eight amino acids, and all of the 3' noncoding region, which consists of 700 nucleotides. A cDNA clone was identified which contains an additional 54 by at the 5' end, so that the complete amino acid sequence of mouse CA could be deduced. This sequence showed a 73-81 % homology with other mammalian CA form II isozymes, 56-63 with form I isozymes, and 52-56 % with form III isozymes. By examination of the amino acids which are unique and invariant for each isozyme, the mouse amino acid sequence was found to contain 16 of the 23 residues that are unique and invariant to mammalian CA form II isozymes, but only one or no residue for forms I and III, respectively.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25074/1/0000505.pd

Altered striatal endocannabinoid signaling in a transgenic mouse model of spinocerebellar ataxia type-3

Spinocerebellar ataxia type-3 (SCA-3) is the most prevalent autosomal dominant inherited ataxia. We recently found that the endocannabinoid system is altered in the post-mortem cerebellum of SCA-3 patients, and similar results were also found in the cerebellar and brainstem nuclei of a SCA-3 transgenic mouse model. Given that the neuropathology of SCA-3 is not restricted to these two brain regions but rather, it is also evident in other structures (e.g., the basal ganglia), we studied the possible changes to endocannabinoid signaling in the striatum of these transgenic mice. SCA-3 mutant mice suffer defects in motor coordination, balance and they have an abnormal gait, reflecting a cerebellar/brainstem neuropathology. However, they also show dystonia-like behavior (limb clasping) that may be related to the malfunction/deterioration of specific neurons in the striatum. Indeed, we found a loss of striatal projecting neurons in SCA-3 mutant mice, accompanied by a reduction in glial glutamate transporters that could potentially aggravate excitotoxic damage. In terms of endocannabinoid signaling, no changes in CB2 receptors were evident, yet an important reduction in CB1 receptors was detected by qPCR and immunostaining. The reduction in CB1 receptors was presumed to occur in striatal afferent and efferent neurons, also potentially aggravating excitotoxicity. We also measured the endocannabinoid lipids in the striatum and despite a marked increase in the FAAH enzyme in this area, no overall changes in these lipids were found. Collectively, these studies confirm that the striatal endocannabinoid system is altered in SCA-3 mutant mice, adding to the equivalent changes found in other strongly affected CNS structures in this type of ataxia (i.e.: the cerebellum and brainstem). These data open the way to search for drugs that might correct these changes.Funding: This study has been supported: (i) by MICINN (SAF2009-11847 and SAF2015-68580-C2-1-R), CIBERNED (CB06/05/0089) and “Fundación Eugenio Rodríguez Pascual”, to JFR; (ii) by the Research and Education Component of the Advancing a Healthier Wisconsin Endowment at the Medical College of Wisconsin, to CJH; and (iii) by Fundação para a Ciência e Tecnologia through the project POCI-01-0145-FEDER-016818 (PTDC/NEU-NMC/3648/2014) and co-financed by the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER), to PM. Carmen Rodríguez-Cueto was a predoctoral fellow supported by FPI Program-Ministry of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Heterogeneity of human adipose blood flow

BACKGROUND: The long time pharmacokinetics of highly lipid soluble compounds is dominated by blood-adipose tissue exchange and depends on the magnitude and heterogeneity of adipose blood flow. Because the adipose tissue is an infinite sink at short times (hours), the kinetics must be followed for days in order to determine if the adipose perfusion is heterogeneous. The purpose of this paper is to quantitate human adipose blood flow heterogeneity and determine its importance for human pharmacokinetics. METHODS: The heterogeneity was determined using a physiologically based pharmacokinetic model (PBPK) to describe the 6 day volatile anesthetic data previously published by Yasuda et. al. The analysis uses the freely available software PKQuest and incorporates perfusion-ventilation mismatch and time dependent parameters that varied from the anesthetized to the ambulatory period. This heterogeneous adipose perfusion PBPK model was then tested by applying it to the previously published cannabidiol data of Ohlsson et. al. and the cannabinol data of Johansson et. al. RESULTS: The volatile anesthetic kinetics at early times have only a weak dependence on adipose blood flow while at long times the pharmacokinetics are dominated by the adipose flow and are independent of muscle blood flow. At least 2 adipose compartments with different perfusion rates (0.074 and 0.014 l/kg/min) were needed to describe the anesthetic data. This heterogeneous adipose PBPK model also provided a good fit to the cannabinol data. CONCLUSION: Human adipose blood flow is markedly heterogeneous, varying by at least 5 fold. This heterogeneity significantly influences the long time pharmacokinetics of the volatile anesthetics and tetrahydrocannabinol. In contrast, using this same PBPK model it can be shown that the long time pharmacokinetics of the persistent lipophilic compounds (dioxins, PCBs) do not depend on adipose blood flow. The ability of the same PBPK model to describe both the anesthetic and cannabinol kinetics provides direct qualitative evidence that their kinetics are flow limited and that there is no significant adipose tissue diffusion limitation