FMDV replicons encoding green fluorescent protein are replication competent

The study of replication of viruses that require high bio-secure facilities can be accomplished with less stringent containment using non-infectious 'replicon' systems. The FMDV replicon system (pT7rep) reported by Mclnerney et al. (2000) was modified by the replacement of sequences encoding chloramphenicol acetyl-transferase (CAT) with those encoding a functional L proteinase (Lpro) linked to a bi-functional fluorescent/antibiotic resistance fusion protein (green fluorescent protein/puromycin resistance, [GFP-PAC]). Cells were transfected with replicon-derived transcript RNA and GFP fluorescence quantified. Replication of transcript RNAs was readily detected by fluorescence, whilst the signal from replication-incompetent forms of the genome was >2-fold lower. Surprisingly, a form of the replicon lacking the Lpro showed a significantly stronger fluorescence signal, but appeared with slightly delayed kinetics. Replication can, therefore, be quantified simply by live-cell imaging and image analyses, providing a rapid and facile alternative to RT-qPCR or CAT assays

The effect of water immersion on short-latency somatosensory evoked potentials in human

<p>Abstract</p> <p>Background</p> <p>Water immersion therapy is used to treat a variety of cardiovascular, respiratory, and orthopedic conditions. It can also benefit some neurological patients, although little is known about the effects of water immersion on neural activity, including somatosensory processing. To this end, we examined the effect of water immersion on short-latency somatosensory evoked potentials (SEPs) elicited by median nerve stimuli. Short-latency SEP recordings were obtained for ten healthy male volunteers at rest in or out of water at 30°C. Recordings were obtained from nine scalp electrodes according to the 10-20 system. The right median nerve at the wrist was electrically stimulated with the stimulus duration of 0.2 ms at 3 Hz. The intensity of the stimulus was fixed at approximately three times the sensory threshold.</p> <p>Results</p> <p>Water immersion significantly reduced the amplitudes of the short-latency SEP components P25 and P45 measured from electrodes over the parietal region and the P45 measured by central region.</p> <p>Conclusions</p> <p>Water immersion reduced short-latency SEP components known to originate in several cortical areas. Attenuation of short-latency SEPs suggests that water immersion influences the cortical processing of somatosensory inputs. Modulation of cortical processing may contribute to the beneficial effects of aquatic therapy.</p> <p>Trial Registration</p> <p>UMIN-CTR (UMIN000006492)</p

Generation of NSE-MerCreMer Transgenic Mice with Tamoxifen Inducible Cre Activity in Neurons

To establish a genetic tool for conditional deletion or expression of gene in neurons in a temporally controlled manner, we generated a transgenic mouse (NSE-MerCreMer), which expressed a tamoxifen inducible type of Cre recombinase specifically in neurons. The tamoxifen inducible Cre recombinase (MerCreMer) is a fusion protein containing Cre recombinase with two modified estrogen receptor ligand binding domains at both ends, and is driven by the neural-specific rat neural specific enolase (NSE) promoter. A total of two transgenic lines were established, and expression of MerCreMer in neurons of the central and enteric nervous systems was confirmed. Transcript of MerCreMer was detected in several non-neural tissues such as heart, liver, and kidney in these lines. In the background of the Cre reporter mouse strain Rosa26R, Cre recombinase activity was inducible in neurons of adult NSE-MerCreMer mice treated with tamoxifen by intragastric gavage, but not in those fed with corn oil only. We conclude that NSE-MerCreMer lines will be useful for studying gene functions in neurons for the conditions that Cre-mediated recombination resulting in embryonic lethality, which precludes investigation of gene functions in neurons through later stages of development and in adult

The texture and taste of food in the brain

Oral texture is represented in the brain areas that represent taste, including the primary taste cortex, the orbitofrontal cortex, and the amygdala. Some neurons represent viscosity, and their responses correlate with the subjective thickness of a food. Other neurons represent fat in the mouth, and represent it by its texture not by its chemical composition, in that they also respond to paraffin oil and silicone in the mouth. The discovery has been made that these fat-responsive neurons encode the coefficient of sliding friction and not viscosity, and this opens the way for the development of new foods with the pleasant mouth feel of fat and with health-promoting designed nutritional properties. A few other neurons respond to free fatty acids (such as linoleic acid), do not respond to fat in the mouth, and may contribute to some 'off' tastes in the mouth. Some other neurons code for astringency. Others neurons respond to other aspects of texture such as the crisp fresh texture of a slice of apple vs the same apple after blending. Different neurons respond to different combinations of these texture properties, oral temperature, taste, and in the orbitofrontal cortex to olfactory and visual properties of food. In the orbitofrontal cortex, the pleasantness and reward value of the food is represented, but the primary taste cortex represents taste and texture independently of value. These discoveries were made in macaques that have similar cortical brain areas for taste and texture processing as humans, and complementary human functional neuroimaging studies are described. This article is protected by copyright. All rights reserved. [Abstract copyright: This article is protected by copyright. All rights reserved.

Coulomb breakup of 17Ne from the viewpoint of nuclear astrophysics

By the Coulomb breakup of 17Ne, the time-reversed reaction 15O(2p,γ)17Ne has been studied. This reaction might play an important role in the rp process, as a break-out reaction of the hot CNO cycle. The secondary 17Ne ion beam with an energy of 500 MeV/nucleon has been dissociated in a Pb target. The reaction products have been detected with the LAND-R3B experimental setup at GSI. The preliminary differential and integral Coulomb dissociation cross section sCoul has been determined, which then will be converted into a photo-absorption cross section sphoto, and a two-proton radiative capture cross section σcap. Additionally, information about the structure of the 17Ne, a potential two-proton halo nucleus, will be received. The analysis is in progress. \ua9 Copyright owned by the author(s) under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike Licence

A review of diagnostic and functional imaging in headache

The neuroimaging of headache patients has revolutionised our understanding of the pathophysiology of primary headaches and provided unique insights into these syndromes. Modern imaging studies point, together with the clinical picture, towards a central triggering cause. The early functional imaging work using positron emission tomography shed light on the genesis of some syndromes, and has recently been refined, implying that the observed activation in migraine (brainstem) and in several trigeminal-autonomic headaches (hypothalamic grey) is involved in the pain process in either a permissive or triggering manner rather than simply as a response to first-division nociception per se. Using the advanced method of voxel-based morphometry, it has been suggested that there is a correlation between the brain area activated specifically in acute cluster headache — the posterior hypothalamic grey matter — and an increase in grey matter in the same region. No structural changes have been found for migraine and medication overuse headache, whereas patients with chronic tension-type headache demonstrated a significant grey matter decrease in regions known to be involved in pain processing. Modern neuroimaging thus clearly suggests that most primary headache syndromes are predominantly driven from the brain, activating the trigeminovascular reflex and needing therapeutics that act on both sides: centrally and peripherally

Beyond outputs: pathways to symmetrical evaluations of university sustainable development partnerships

As the United Nations Decade of Education for Sustainable Development (2005–2014) draws to a close, it is timely to review ways in which the sustainable development initiatives of higher education institutions have been, and can be, evaluated. In their efforts to document and assess collaborative sustainable development program outcomes and impacts, universities in the North and South are challenged by similar conundrums that confront development agencies. This article explores pathways to symmetrical evaluations of transnationally partnered research, curricula, and public-outreach initiatives specifically devoted to sustainable development. Drawing on extensive literature and informed by international development experience, the authors present a novel framework for evaluating transnational higher education partnerships devoted to sustainable development that addresses design, management, capacity building, and institutional outreach. The framework is applied by assessing several full-term African higher education evaluation case studies with a view toward identifying key limitations and suggesting useful future symmetrical evaluation pathways. University participants in transnational sustainable development initiatives, and their supporting donors, would be well-served by utilizing an inclusive evaluation framework that is infused with principles of symmetry

Somatosensory System Deficits in Schizophrenia Revealed by MEG during a Median-Nerve Oddball Task

Although impairments related to somatosensory perception are common in schizophrenia, they have rarely been examined in functional imaging studies. In the present study, magnetoencephalography (MEG) was used to identify neural networks that support attention to somatosensory stimuli in healthy adults and abnormalities in these networks in patient with schizophrenia. A median-nerve oddball task was used to probe attention to somatosensory stimuli, and an advanced, high-resolution MEG source-imaging method was applied to assess activity throughout the brain. In nineteen healthy subjects, attention-related activation was seen in a sensorimotor network involving primary somatosensory (S1), secondary somatosensory (S2), primary motor (M1), pre-motor (PMA), and paracentral lobule (PCL) areas. A frontal–parietal–temporal “attention network”, containing dorsal- and ventral–lateral prefrontal cortex (DLPFC and VLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), superior parietal lobule (SPL), inferior parietal lobule (IPL)/supramarginal gyrus (SMG), and temporal lobe areas, was also activated. Seventeen individuals with schizophrenia showed early attention-related hyperactivations in S1 and M1 but hypo-activation in S1, S2, M1, and PMA at later latency in the sensorimotor network. Within this attention network, hypoactivation was found in SPL, DLPFC, orbitofrontal cortex, and the dorsal aspect of ACC. Hyperactivation was seen in SMG/IPL, frontal pole, and the ventral aspect of ACC in patients. These findings link attention-related somatosensory deficits to dysfunction in both sensorimotor and frontal–parietal–temporal networks in schizophrenia

World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF) Core Set Development for Interstitial Lung Disease

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData availability statement: The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors.Background: The World Health Organization (WHO) introduced the International Classification of Functioning, Disability, and Health (ICF) as a scientific method of disability data collection comprised of >1,200 categories describing the spectrum of impairment types (functional, symptoms-based and anatomical) under the bio-psycho-social model with consideration of environmental and personal factors (pf). ICF Core Sets and ICF Checklists are streamlined disease-specific resources for clinical use, service provision, and for use in health economics and health policy. ICF can disclose strengths and weaknesses across multiple patient-reported outcome measures (PROMs) and help consolidate best-fitting question-items from multiple PROMs. Interstitial lung diseases (ILDs), are generally progressive, with restrictive physiology sometimes occurring in the context of multi-organ autoimmunity/inflammatory conditions such as connective tissue diseases (CTDs). In spite of significant associated morbidity and potential disability, ILD has yet to be linked to the ICF. Methods: Each instrument and their question-items within the consensus-recommended core sets for clinical trials in ILD were deconstructed to single concept units, and then linked per updated ICF linkage rules. Inter-linker agreement was established. Three additional subsequently validated measures were also included. Results: One-hundred-eleven ICF categories were identified for ten PROMs and three traditional objective measures that were amenable to ICF linkage. The proportion of agreement ranged from 0.79 (95% CI: 0.62, 0.91) to 0.93 (0.76, 0.99) with the overall proportion of inter-linker agreement being very high 0.86 (0.82, 0.89) for the initial instruments, with 94–100% for the three additional PROMs. Thirty-four new ‘Personal Factors’ emerged to capture disease-specific qualities not elsewhere described in ICF, e.g. ‘pf_embarrassed by cough’ or ‘pf_panic/afraid when can’t get a breath’. Conclusion: This first known effort in ICF linkage of ILD has provided important revelations on the current utility of the ICF in lung disease. Results have indicated areas for meaningful assessment of ICF descriptors for lung impairment. The mapping across PROMs provides insight into possibilities of developing more streamline and precise instrumentation. Finally, familiarity with the ICF in ILD may enable clinicians to experience a smoother transition with the imminent harmonization of ICD and ICF, ICD-11