The magnetofection method: Using magnetic force to enhance gene delivery

In order to enhance and target gene delivery we have previously established a novel method, termed magnetofection, which uses magnetic force acting on gene vectors that are associated with magnetic particles. Here we review the benefits, the mechanism and the potential of the method with regard to overcoming physical limitations to gene delivery. Magnetic particle chemistry and physics are discussed, followed by a detailed presentation of vector formulation and optimization work. While magnetofection does not necessarily improve the overall performance of any given standard gene transfer method in vitro, its major potential lies in the extraordinarily rapid and efficient transfection at low vector doses and the possibility of remotely controlled vector targeting in vivo

Theoretical analysis of flux amplification by soft magnetic material in a putative biological magnetic-field receptor

Birds are endowed with a magnetic sense that allows them to detectEarth’s magnetic field and to use it for orientation. Physiological andbehavioral experiments have shown the upper beak to host amagnetoreceptor. Putative magnetoreceptive structures in the beak arenerve terminals that each contain a dozen or so of micrometer-sizedclusters of superparamagnetic nanocrystals made of magnetite/maghemiteand numerous electron-opaque platelets filled with a so farunidentified, amorphous ferric iron compound. The platelets typicallyform chainlike structures, which have been proposed to function asmagnetic flux focusers for detecting the intensity of the geomagneticfield. Here, we test that proposition from first principles and developan unconstrained model to determine the equilibrium distribution ofmagnetization along a linear chain of platelets which we assume tobehave magnetically soft and to have no magnetic remanence. Ouranalysis, which is valid for arbitrary values of the intrinsic magneticsusceptibility chi, shows that chi needs to be much greater than unityto amplify the external field by two orders of magnitude in a chain ofplatelets. However, the high amplification is confined to the centralregion of the chain and subsides quadratically toward the ends of thechain. For large values of chi, the possibility opens up of realizingmagnetoreceptor mechanisms on the basis of attraction forces betweenadjacent platelets in a linear chain. The force in the central region ofthe chain may amount to several pN, which would be sufficient to convertmagnetic input energy into mechanical output energy. The strikingfeature of an ensemble of platelets is its ability to organize intotightly spaced chains under the action of an external field of givenstrength. We discuss how this property can be exploited for amagnetoreception mechanism

Gene networks in Drosophila melanogaster: integrating experimental data to predict gene function

The first computational interaction network built from Drosophila melanogaster protein-protein and genetic interaction data allows the functional annotation of orphan genes and reveals clusters of functionally-related genes

Efficacy of an Acoustic Hailing Device as an Avian Dispersal Tool

Bird strikes are a major safety and financial concern for modern aviation. Audible stimuli are common bird dispersal techniques, but their effectiveness is limited by the saliency and relevance of the stimulus. Furthermore, high ambient sound levels present at airfields might require that effective audible stimuli rely more on total volume (i.e., exceeding physiological tolerances) than ecological relevance. Acoustic hailing devices (AHD) are capable of sound output with a narrow beamwidth and at volumes high enough to cause physical discomfort at long distances. We tested the effectiveness of anAHD as a dispersal tool on freeranging birds recognized as hazardous to aviation safety at the Savannah River Site and Phinizy Swamp Nature Park in South Carolina and Georgia, USA, respectively, between October 2013 and March 2015. Our study design included experimental trials with timed-interval counts of birds directly before and after AHD treatment. For most species, counts of birds associated with treatment periods (use of AHD) and control periods (no use of AHD) occurred on different days. Sound treatments yielded variable success at dispersing birds. Specifically, AHD treatment was effective for dispersing vultures (Coragyps atratus and Cathartes aura) and gulls (Laridae), but ineffective for dispersing blackbirds (Icteridae), diving ducks (Aythya spp., Bucephala spp., Oxyura spp.), and coots (Fulica americana). Trials were conducted in a relatively quiet environment with birds that were unhabituated to excessive noise; thus, we cannot unequivocally recommend an AHD as a universally effective avian dispersing tool. However, future research should consider AHD testing integrated with other methods, as well as investigation of treatments that might be salient to specific target species

Identifying rate-limiting nodes in large-scale cortical networks for visuospatial processing: an illustration using fMRI

With the advent of functional neuroimaging techniques, in particular functional magnetic resonance imaging (fMRI), we have gained greater insight into the neural correlates of visuospatial function. However, it may not always be easy to identify the cerebral regions most specifically associated with performance on a given task. One approach is to examine the quantitative relationships between regional activation and behavioral performance measures. In the present study, we investigated the functional neuroanatomy of two different visuospatial processing tasks, judgement of line orientation and mental rotation. Twenty-four normal participants were scanned with fMRI using blocked periodic designs for experimental task presentation. Accuracy and reaction time (RT) to each trial of both activation and baseline conditions in each experiment was recorded. Both experiments activated dorsal and ventral visual cortical areas as well as dorsolateral prefrontal cortex. More regionally specific associations with task performance were identified by estimating the association between (sinusoidal) power of functional response and mean RT to the activation condition; a permutation test based on spatial statistics was used for inference. There was significant behavioral-physiological association in right ventral extrastriate cortex for the line orientation task and in bilateral (predominantly right) superior parietal lobule for the mental rotation task. Comparable associations were not found between power of response and RT to the baseline conditions of the tasks. These data suggest that one region in a neurocognitive network may be most strongly associated with behavioral performance and this may be regarded as the computationally least efficient or rate-limiting node of the network

On the Functional Significance of the P1 and N1 Effects to Illusory Figures in the Notch Mode of Presentation

The processing of Kanizsa figures have classically been studied by flashing the full “pacmen” inducers at stimulus onset. A recent study, however, has shown that it is advantageous to present illusory figures in the “notch” mode of presentation, that is by leaving the round inducers on screen at all times and by removing the inward-oriented notches delineating the illusory figure at stimulus onset. Indeed, using the notch mode of presentation, novel P1and N1 effects have been found when comparing visual potentials (VEPs) evoked by an illusory figure and the VEPs to a control figure whose onset corresponds to the removal of outward-oriented notches, which prevents their integration into one delineated form. In Experiment 1, we replicated these findings, the illusory figure was found to evoke a larger P1 and a smaller N1 than its control. In Experiment 2, real grey squares were placed over the notches so that one condition, that with inward-oriented notches, shows a large central grey square and the other condition, that with outward-oriented notches, shows four unconnected smaller grey squares. In response to these “real” figures, no P1 effect was found but a N1 effect comparable to the one obtained with illusory figures was observed. Taken together, these results suggest that the P1 effect observed with illusory figures is likely specific to the processing of the illusory features of the figures. Conversely, the fact that the N1 effect was also obtained with real figures indicates that this effect may be due to more global processes related to depth segmentation or surface/object perception

Perspectives and challenges for the use of radar in biological conservation

Radar is at the forefront for the study of broad-scale aerial movements of birds, bats and insects and related issues in biological conservation. Radar techniques are especially useful for investigating species which fly at high altitudes, in darkness, or which are too small for applying electronic tags. Here, we present an overview of radar applications in biological conservation and highlight its future possibilities. Depending on the type of radar, information can be gathered on local- to continental-scale movements of airborne organisms and their behaviour. Such data can quantify flyway usage, biomass and nutrient transport (bioflow), population sizes, dynamics and distributions, times and dimensions of movements, areas and times of mass emergence and swarming, habitat use and activity ranges. Radar also captures behavioural responses to anthropogenic disturbances, artificial light and man-made structures. Weather surveillance and other long-range radar networks allow spatially broad overviews of important stopover areas, songbird mass roosts and emergences from bat caves. Mobile radars, including repurposed marine radars and commercially dedicated ‘bird radars’, offer the ability to track and monitor the local movements of individuals or groups of flying animals. Harmonic radar techniques have been used for tracking short-range movements of insects and other small animals of conservation interest. However, a major challenge in aeroecology is determining the taxonomic identity of the targets, which often requires ancillary data obtained from other methods. Radar data have become a global source of information on ecosystem structure, composition, services and function and will play an increasing role in the monitoring and conservation of flying animals and threatened habitats worldwide

The Effect of Inappropriate Calibration: Three Case Studies in Molecular Ecology

Time-scales estimated from sequence data play an important role in molecular ecology. They can be used to draw correlations between evolutionary and palaeoclimatic events, to measure the tempo of speciation, and to study the demographic history of an endangered species. In all of these studies, it is paramount to have accurate estimates of time-scales and substitution rates. Molecular ecological studies typically focus on intraspecific data that have evolved on genealogical scales, but often these studies inappropriately employ deep fossil calibrations or canonical substitution rates (e.g., 1% per million years for birds and mammals) for calibrating estimates of divergence times. These approaches can yield misleading estimates of molecular time-scales, with significant impacts on subsequent evolutionary and ecological inferences. We illustrate this calibration problem using three case studies: avian speciation in the late Pleistocene, the demographic history of bowhead whales, and the Pleistocene biogeography of brown bears. For each data set, we compare the date estimates that are obtained using internal and external calibration points. In all three cases, the conclusions are significantly altered by the application of revised, internally-calibrated substitution rates. Collectively, the results emphasise the importance of judicious selection of calibrations for analyses of recent evolutionary events

Randomised controlled trial of simvastatin treatment for autism in young children with neurofibromatosis type 1 (SANTA)

Background: Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years using cognition/ behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes. Methods: A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression). Results: Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA (t(12) = − 2.12, p = .055), GABA/Glx ratio (t(12) = − 2.78, p = .016), and reduced grey nuclei Glx (ANCOVA p < 0.05, Mann-Whitney p < 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney p < 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney p < 0.01). Machine-learning classification of imaging outcomes achieved 79% (p < .05) accuracy differentiating groups at endpoint against chance level (64%, p = 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met ‘clinical responder’ criteria for behavioural outcome. Conclusions: We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network