Alterations to the Gastrointestinal Microbiome Associated with Methamphetamine Use among Young Men who have Sex with Men.

Methamphetamine (MA) use is a major public health problem in the United States, especially among people living with HIV (PLWH). Many MA-induced neurotoxic effects are mediated by inflammation and gut microbiota may play a role in this process, yet the effects of MA on the microbiome have not been adequately explored. Therefore, we performed 16S rRNA gene sequencing on rectal swab samples from 381 men who have sex with men, 48% of whom were PLWH and 41% of whom used MA. We compared microbiome composition between MA users and non-users while testing for potential interactions with HIV and controlling for numerous confounders using inverse probability of treatment weighting. We found that MA use explained significant variation in overall composition (R2 = 0.005, p = 0.008) and was associated with elevated Finegoldia, Parvimonas, Peptoniphilus, and Porphyromonas and reduced Butyricicoccus and Faecalibacterium, among others. Genera including Actinomyces and Streptobacillus interacted with HIV status, such that they were increased in HIV+ MA users. Finegoldia and Peptoniphilus increased with increasing frequency of MA use, among others. In summary, MA use was associated with a microbial imbalance favoring pro-inflammatory bacteria, including some with neuroactive potential and others that have previously been associated with poor HIV outcomes

An afferent explanation for sexual dimorphism in the aortic baroreflex of rat

Sex differences in baroreflex (BRx) function are well documented. Hormones likely contribute to this dimorphism, but many functional aspects remain unresolved. Our lab has been investigating a subset of vagal sensory neurons that constitute nearly 50% of the total population of myelinated aortic baroreceptors (BR) in female rats but less than 2% in male rats. Termed “Ah,” this unique phenotype has many of the nonoverlapping electrophysiological properties and chemical sensitivities of both myelinated A-type and unmyelinated C-type BR afferents. In this study, we utilize three distinct experimental protocols to determine if Ah-type barosensory afferents underlie, at least in part, the sex-related differences in BRx function. Electron microscopy of the aortic depressor nerve (ADN) revealed that female rats have less myelin (P < 0.03) and a smaller fiber cross-sectional area (P < 0.05) per BR fiber than male rats. Electrical stimulation of the ADN evoked compound action potentials and nerve conduction profiles that were markedly different (P < 0.01, n = 7 females and n = 9 males). Selective activation of ADN myelinated fibers evoked a BRx-mediated depressor response that was 3–7 times greater in female (n = 16) than in male (n = 17) rats. Interestingly, the most striking hemodynamic difference was functionally dependent upon the rate of myelinated barosensory fiber activation. Only 5–10 Hz of stimulation evoked a rapid, 20- to 30-mmHg reduction in arterial pressure of female rats, whereas rates of 50 Hz or higher were required to elicit a comparable depressor response from male rats. Collectively, our experimental results are suggestive of an alternative myelinated baroreceptor afferent pathway in females that may account for, at least in part, the noted sex-related differences in autonomic control of cardiovascular function

GRIDKIT: Pluggable overlay networks for Grid computing

A `second generation' approach to the provision of Grid middleware is now emerging which is built on service-oriented architecture and web services standards and technologies. However, advanced Grid applications have significant demands that are not addressed by present-day web services platforms. As one prime example, current platforms do not support the rich diversity of communication `interaction types' that are demanded by advanced applications (e.g. publish-subscribe, media streaming, peer-to-peer interaction). In the paper we describe the Gridkit middleware which augments the basic service-oriented architecture to address this particular deficiency. We particularly focus on the communications infrastructure support required to support multiple interaction types in a unified, principled and extensible manner-which we present in terms of the novel concept of pluggable overlay networks

Criteria for arrhythmogenicity in genetically-modified Langendorff-perfused murine hearts modelling the congenital long QT syndrome type 3 and the Brugada syndrome

The experiments investigated the applicability of two established criteria for arrhythmogenicity in Scn5a+/Δ and Scn5a+/− murine hearts modelling the congenital long QT syndrome type 3 (LQT3) and the Brugada syndrome (BrS). Monophasic action potentials (APs) recorded during extrasystolic stimulation procedures from Langendorff-perfused control hearts and hearts treated with flecainide (1 μM) or quinidine (1 or 10 μM) demonstrated that both agents were pro-arrhythmic in wild-type (WT) hearts, quinidine was pro-arrhythmic in Scn5a+/Δ hearts, and that flecainide was pro-arrhythmic whereas quinidine was anti-arrhythmic in Scn5a+/− hearts, confirming clinical findings. Statistical analysis confirmed a quadratic relationship between epicardial and endocardial AP durations (APDs) in WT control hearts. However, comparisons between plots of epicardial against endocardial APDs and this reference curve failed to correlate with arrhythmogenicity. Restitution curves, relating APD to diastolic interval (DI), were then constructed for the first time in a murine system and mono-exponential growth functions fitted to these curves. Significant (P < 0.05) alterations in the DI at which slopes equalled unity, an established indicator of arrhythmogenicity, now successfully predicted the presence or absence of arrhythmogenicity in all cases. We thus associate changes in the slopes of restitution curves with arrhythmogenicity in models of LQT3 and BrS

Atomic Structure and Dynamics of Single Platinum Atom Interactions with Monolayer MoS

We have studied atomic level interactions between single Pt atoms and the surface of monolayer MoS₂ using aberration-corrected annular dark field scanning transmission electron microscopy at an accelerating voltage of 60 kV. Strong contrast from single Pt atoms on the atomically resolved monolayer MoS₂ lattice enables their exact position to be determined with respect to the MoS₂ lattice, revealing stable binding sites. In regions of MoS₂ free from surface contamination, the Pt atoms are localized in S vacancy sites and exhibit dynamic hopping to nearby vacancy sites driven by the energy supplied by the electron beam. However, in areas of MoS₂ contaminated with carbon surface layers, the Pt atoms appear at various positions with respect to the underlying MoS₂ lattice, including on top of Mo and in off-axis positions. These variations are due to the Pt bonding with the surrounding amorphous carbon layer, which disrupts the intrinsic Pt-MoS₂ interactions, leading to more varied positions. Density functional theory (DFT) calculations reveal that Pt atoms on the surface of MoS₂ have a small barrier for migration and are stabilized when bound to either a single or double sulfur vacancies. DFT calculations have been used to understand how the catalytic activity of the MoS₂ basal plane for hydrogen evolution reaction is influenced by Pt dopants by variation of the hydrogen adsorption free energy. This strong dependence of catalytic effect on interfacial configurations is shown to be common for a series of dopants, which may provide a means to create and optimize reaction centers

Mobile Service Clouds: A self-managing infrastructure for autonomic mobile computing services

Abstract. We recently introduced Service Clouds, a distributed infrastructure designed to facilitate rapid prototyping and deployment of autonomic communication services. In this paper, we propose a model that extends Service Clouds to the wireless edge of the Internet. This model, called Mobile Service Clouds, enables dynamic instantiation, composition, configuration, and reconfiguration of services on an overlay network to support mobile computing. We have implemented a prototype of this model and applied it to the problem of dynamically instantiating and migrating proxy services for mobile hosts. We conducted a case study involving data streaming across a combination of PlanetLab nodes, local proxies, and wireless hosts. Results are presented demonstrating the effectiveness of the prototype in establishing new proxies and migrating their functionality in response to node failures.

Characterization of Bubble Shapes in Non‐Newtonian Fluids by Parametric Equations

Based on experiments with single air bubbles rising in stagnant non-Newtonian fluids, an innovative model containing the aspect ratio (E) and two parameters (alpha, beta) was proposed and proved to be capable of characterizing the bubble shape from spherical/ellipsoidal to prolate/oblate-tear with good accuracy. Several impacts on bubble deformation were investigated, involving the rheological properties of the fluids and different forces exerted on the bubble, which were quantified by multiple dimensionless numbers (e.g., Reynolds, Eotvos, and Deborah number). Within a wide range, the empirical correlations were obtained for parameter beta, and between alpha and beta. Together with the shape model, a complete system was set up for bubble shape characterization and prediction that will provide new ideas for future studies on bubble hydrodynamics

Erratum:BubR1 allelic effects drive phenotypic heterogeneity in mosaic-variegated aneuploidy progeria syndrome (Journal of Clinical Investigation (2020) 130:1 (171-188) DOI: 10.1172/JCI126863)

During the preparation of this manuscript, the same sample was inadvertently included for the +/L1002P and +/– images in Figure 2E. The authors were able to use the original samples to prepare a corrected version. The correct figure is below. The description in Methods for this panel has also been corrected, as below: To assess the mitotic index of spontaneous lymphatic tumors, mitotic cells were visualized by IF labelling of at least 1 paraffin section for pHH3 (EMD Millipore, catalog 06-570), as described (6, 46). The online version of the article has been updated with the corrected information. The authors regret the errors