Left parietal tACS at alpha frequency induces a shift of visuospatial attention

Background Voluntary shifts of visuospatial attention are associated with a lateralization of parieto-occipital alpha power (7-13Hz), i.e. higher power in the hemisphere ipsilateral and lower power contralateral to the locus of attention. Recent noninvasive neuromodulation studies demonstrated that alpha power can be experimentally increased using transcranial alternating current stimulation (tACS). Objective/Hypothesis We hypothesized that tACS at alpha frequency over the left parietal cortex induces shifts of attention to the left hemifield. However, spatial attention shifts not only occur voluntarily (endogenous/ top-down), but also stimulus-driven (exogenous/ bottom-up). To study the task-specificity of the potential effects of tACS on attentional processes, we administered three conceptually different spatial attention tasks. Methods 36 healthy volunteers were recruited from an academic environment. In two separate sessions, we applied either high-density tACS at 10Hz, or sham tACS, for 35–40 minutes to their left parietal cortex. We systematically compared performance on endogenous attention, exogenous attention, and stimulus detection tasks. Results In the endogenous attention task, a greater leftward bias in reaction times was induced during left parietal 10Hz tACS as compared to sham. There were no stimulation effects in either the exogenous attention or the stimulus detection task. Conclusion The study demonstrates that high-density tACS at 10Hz can be used to modulate visuospatial attention performance. The tACS effect is task-specific, indicating that not all forms of attention are equally susceptible to the stimulation

Genetic Fusions of a CFA/I/II/IV MEFA (Multiepitope Fusion Antigen) and a Toxoid Fusion of Heat-Stable Toxin (STa) and Heat-Labile Toxin (LT) of Enterotoxigenic Escherichia coli (ETEC) Retain Broad Anti-CFA and Antitoxin Antigenicity

Citation: Ruan, X. S., Sack, D. A., & Zhang, W. P. (2015). Genetic Fusions of a CFA/I/II/IV MEFA (Multiepitope Fusion Antigen) and a Toxoid Fusion of Heat-Stable Toxin (STa) and Heat-Labile Toxin (LT) of Enterotoxigenic Escherichia coli (ETEC) Retain Broad Anti-CFA and Antitoxin Antigenicity. Plos One, 10(3), 20. doi:10.1371/journal.pone.0121623Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2): 2439], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTa(A14Q)-dmLT or 3xSTa(N12S)-dmLT [IAI 2014, 82(5): 1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-(toxoid)-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-(toxoid)-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTa(N12S)-dmLT induced broadly protective anti-CFA and antitoxin immunity, suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent vaccine development

Monetary Policy Alternatives at the Zero Bound: An Empirical Assessment

macroeconomics, monetary policy, zero bound, empirical

Biodigital publics: personal genomes as digital media artifacts

The recent proliferation of personal genomics and direct-to-consumer (DTC) genomics has attracted much attention and publicity. Concern around these developments has mainly focused on issues of biomedical regulation and hinged on questions of how people understand genomic information as biomedical and what meaning they make of it. However, this publicity amplifies genome sequences which are also made as internet texts and, as such, they generate new reading publics. The practices around the generation, circulation and reading of genome scans do not just raise questions about biomedical regulation, they also provide the focus for an exploration of how contemporary public participation in genomics works. These issues around the public features of DTC genomic testing can be pursued through a close examination of the modes of one of the best known providers—23andMe. In fact, genome sequences circulate as digital artefacts and, hence, people are addressed by them. They are read as texts, annotated and written about in browsers, blogs and wikis. This activity also yields content for media coverage which addresses an indefinite public in line with Michael Warner’s conceptualisation of publics. Digital genomic texts promise empowerment, personalisation and community, but this promise may obscure the compliance and proscription associated with these forms. The kinds of interaction here can be compared to those analysed by Andrew Barry. Direct-to-consumer genetics companies are part of a network providing an infrastructure for genomic reading publics and this network can be mapped and examined to demonstrate the ways in which this formation both exacerbates inequalities and offers possibilities for participation in biodigital culture

Movers and shakers: Granular damping in microgravity

The response of an oscillating granular damper to an initial perturbation is studied using experiments performed in microgravity and granular dynamics mulations. High-speed video and image processing techniques are used to extract experimental data. An inelastic hard sphere model is developed to perform simulations and the results are in excellent agreement with the experiments. The granular damper behaves like a frictional damper and a linear decay of the amplitude is bserved. This is true even for the simulation model, where friction forces are absent. A simple expression is developed which predicts the optimal damping conditions for a given amplitude and is independent of the oscillation frequency and particle inelasticities.Comment: 9 pages, 9 figure

Parietal but not temporoparietal alpha-tACS modulates endogenous visuospatial attention

Visuospatial attention can either be voluntarily directed (endogenous/top-down attention) or automatically triggered (exogenous/bottom-up attention). Recent research showed that dorsal parietal transcranial alternating current stimulation (tACS) at alpha frequency modulates the spatial attentional bias in an endogenous but not in an exogenous visuospatial attention task. Yet, the reason for this task-specificity remains unexplored. Here, we tested whether this dissociation relates to the proposed differential role of the dorsal attention network (DAN) and ventral attention network (VAN) in endogenous and exogenous attention processes respectively. To that aim, we targeted the left and right dorsal parietal node of the DAN, as well as the left and right ventral temporoparietal node of the VAN using tACS at the individual alpha frequency. Every participant completed all four stimulation conditions and a sham condition in five separate sessions. During tACS, we assessed the behavioral visuospatial attention bias via an endogenous and exogenous visuospatial attention task. Additionally, we measured offline alpha power immediately before and after tACS using electroencephalography (EEG). The behavioral data revealed an effect of tACS on the endogenous but not exogenous attention bias, with a greater leftward bias during (sham-corrected) left than right hemispheric stimulation. In line with our hypothesis, this effect was brain area-specific, i.e., present for dorsal parietal but not ventral temporoparietal tACS. However, contrary to our expectations, there was no effect of ventral temporoparietal tACS on the exogenous visuospatial attention bias. Hence, no double dissociation between the two targeted attention networks. There was no effect of either tACS condition on offline alpha power. Our behavioral data reveal that dorsal parietal but not ventral temporoparietal alpha oscillations steer endogenous visuospatial attention. This brain-area specific tACS effect matches the previously proposed dissociation between the DAN and VAN and, by showing that the spatial attention bias effect does not generalize to any lateral posterior tACS montage, renders lateral cutaneous and retinal effects for the spatial attention bias in the dorsal parietal condition unlikely. Yet the absence of tACS effects on the exogenous attention task suggests that ventral temporoparietal alpha oscillations are not functionally relevant for exogenous visuospatial attention. We discuss the potential implications of this finding in the context of an emerging theory on the role of the ventral temporoparietal node

Immunological evaluation of the new stable ultrasound contrast agent LK565: a phase one clinical trial

BACKGROUND: Ultrasound contrast agents (UCAs) allow the enhancement of vascular definition, thereby providing more diagnostic information. LK565 is a new second-generation UCA based on synthetic polymers of aspartic acid which is eliminated from the blood stream via phagocytosis. LK565 forms very stable air-filled microspheres and is capable of repeated passage through the pulmonary capillary bed after peripheral intravenous injection. This characteristic allows examination of the cardiac function or extracardiac vessel abnormalities up to 15 minutes. METHODS: A phase one clinical study was conducted on 15 healthy volunteers to identify the development of an undesirable immune response. Phagocytosis capacity, TNF-α secretion, and MHC class II upregulation of monocytes was monitored, as well as microsphere specific antibody development (IgM, IgG). Furthermore, the kinetics of the activation surface markers CD69, CD25, CD71, and CD11b on leukocytes were analyzed. RESULTS: Due to LK565-metabolism the administration of the UCA led to saturation of phagocytes which was reversible after 24 hrs. Compared to positive controls neither significant TNF-α elevation, neither MHC class II and activation surface markers upregulation, nor specific antibody development was detectable. CONCLUSION: The administration of LK565 provides a comfortable duration of signal enhancement, esp. in echocardiography, without causing a major activation cascade or triggering an adaptive immune response. To minimize the risk of undesirable adverse events such as anaphylactoid reactions, immunological studies should be included in clinical trials for new UCAs. The use of LK565 as another new ultrasound contrast agent should be encouraged as a safe means to provide additional diagnostic information

Alterations of Central Liver Metabolism of Pediatric Patients with Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and is associated with overweight and insulin resistance (IR). Almost nothing is known about in vivo alterations of liver metabolism in NAFLD, especially in the early stages of non-alcoholic steatohepatitis (NASH). Here, we used a complex mathematical model of liver metabolism to quantify the central hepatic metabolic functions of 71 children with biopsy-proven NAFLD. For each patient, a personalized model variant was generated based on enzyme abundances determined by mass spectroscopy. Our analysis revealed statistically significant alterations in the hepatic carbohydrate, lipid, and ammonia metabolism, which increased with the degree of obesity and severity of NAFLD. Histologic features of NASH and IR displayed opposing associations with changes in carbohydrate and lipid metabolism but synergistically decreased urea synthesis in favor of the increased release of glutamine, a driver of liver fibrosis. Taken together, our study reveals already significant alterations in the NASH liver of pediatric patients, which, however, are differently modulated by the simultaneous presence of IR