Force sensor in simulated skin and neural model mimic tactile SAI afferent spiking response to ramp and hold stimuli

The next generation of prosthetic limbs will restore sensory feedback to the nervous system by mimicking how skin mechanoreceptors, innervated by afferents, produce trains of action potentials in response to compressive stimuli. Prior work has addressed building sensors within skin substitutes for robotics, modeling skin mechanics and neural dynamics of mechanotransduction, and predicting response timing of action potentials for vibration. The effort here is unique because it accounts for skin elasticity by measuring force within simulated skin, utilizes few free model parameters for parsimony, and separates parameter fitting and model validation. Additionally, the ramp-and-hold, sustained stimuli used in this work capture the essential features of the everyday task of contacting and holding an object. This systems integration effort computationally replicates the neural firing behavior for a slowly adapting type I (SAI) afferent in its temporally varying response to both intensity and rate of indentation force by combining a physical force sensor, housed in a skin-like substrate, with a mathematical model of neuronal spiking, the leaky integrate-and-fire. Comparison experiments were then conducted using ramp-and-hold stimuli on both the spiking-sensor model and mouse SAI afferents. The model parameters were iteratively fit against recorded SAI interspike intervals (ISI) before validating the model to assess its performance. Model-predicted spike firing compares favorably with that observed for single SAI afferents. As indentation magnitude increases (1.2, 1.3, to 1.4 mm), mean ISI decreases from 98.81 ± 24.73, 54.52 ± 6.94, to 41.11 ± 6.11 ms. Moreover, as rate of ramp-up increases, ISI during ramp-up decreases from 21.85 ± 5.33, 19.98 ± 3.10, to 15.42 ± 2.41 ms. Considering first spikes, the predicted latencies exhibited a decreasing trend as stimulus rate increased, as is observed in afferent recordings. Finally, the SAI afferent’s characteristic response of producing irregular ISIs is shown to be controllable via manipulating the output filtering from the sensor or adding stochastic noise. This integrated engineering approach extends prior works focused upon neural dynamics and vibration. Future efforts will perfect measures of performance, such as first spike latency and irregular ISIs, and link the generation of characteristic features within trains of action potentials with current pulse waveforms that stimulate single action potentials at the peripheral afferent

Distinct evolutionary patterns of Neisseria meningitidis serogroup B disease outbreaks at two universities in the USA

L. H., L. A., S. W., P. L. and A. S. A. are current employees of Pfizer, and this work was funded by Pfizer Inc.Neisseria meningitidis serogroup B (MnB) was responsible for two independent meningococcal disease outbreaks at universities in the USA during 2013. The first at University A in New Jersey included nine confirmed cases reported between March 2013 and March 2014. The second outbreak occurred at University B in California, with four confirmed cases during November 2013. The public health response to these outbreaks included the approval and deployment of a serogroup B meningococcal vaccine that was not yet licensed in the USA. This study investigated the use of whole-genome sequencing(WGS) to examine the genetic profile of the disease-causing outbreak isolates at each university. Comparative WGS revealed differences in evolutionary patterns between the two disease outbreaks. The University A outbreak isolates were very closely related, with differences primarily attributed to single nucleotide polymorphisms/insertion-deletion (SNP/indel) events. In contrast, the University B outbreak isolates segregated into two phylogenetic clades, differing in large part due to recombination events covering extensive regions (>30 kb) of the genome including virulence factors. This high-resolution comparison of two meningococcal disease outbreaks further demonstrates the genetic complexity of meningococcal bacteria as related to evolution and disease virulence.Publisher PDFPeer reviewe

Carbonation reactions and coupled element and isotope redistribution during shallow crustal gold mineralisation, New Zealand

Hydrothermal alteration zones rich in carbonate are excellent vectors for orogenic gold-bearing veins, but the extent of element mobility is difficult to establish. Whole rock and in situ mineral analysis was performed to better understand the element and isotope (Sr, Nd, C) redistribution around Miocene quartz-carbonate-sulphide-gold-bearing veins in meta-turbidite (greyschist) and meta-basite (greenschist) in the Otago Schist in New Zealand. The new data provide insight into the fluid-rock interaction within a lithologically, chemically and isotopically heterogeneous upper few kilometres (<5km) of crust. The relative resistance of metamorphic minerals to complete breakdown in mineralising fluids with high CO2 activity was epidote < titanite < actinolite < chlorite and muscovite, with their breakdown promoting simultaneous precipitation of carbonate, white mica, rutile, quartz, pyrite, arsenopyrite, barite, scheelite and gold. At the hand specimen scale, mass balance calculations suggest that major elements and large-ion lithophile elements (K, Rb, Cs, Ba +/- Sr) were mobile, whereas high-field strength elements (HFSE; Ti, Nb, Zr, Hf) were immobile. In detail, however, Zr and Hf were mobile at the microscopic scale during the replacement of metamorphic titanite. Similarly, rare earth elements (REE; La to Lu) appeared immobile at the hand specimen scale but were mobile at the microscopic scale because epidote, the main metamorphic REE reservoir, was replaced by REE-free white mica. The limited hand specimen-scale REE mobility was due to the formation of hydrothermal calcite, ankerite and magnesite, which almost immediately bound these elements into their crystal structures. Conventionally obtained C-13 and bulk Sr-87/Sr-86 isotopes, augmented with in situ laser ablation analysis of Sr-87/Sr-86 of hydrothermal carbonate and metamorphic epidote, show that the mineralising fluids reacted with greyschists and greenschists, even when these lithologies were not close by. The elemental and isotopic compositions of the hydrothermal minerals in this shallow gold-bearing system were evidently affected by distal and proximal metasomatic reactions

The Regularity of Sustained Firing Reveals Two Populations of Slowly Adapting Touch Receptors in Mouse Hairy Skin

Touch is initiated by diverse somatosensory afferents that innervate the skin. The ability to manipulate and classify receptor subtypes is prerequisite for elucidating sensory mechanisms. Merkel cell–neurite complexes, which distinguish shapes and textures, are experimentally tractable mammalian touch receptors that mediate slowly adapting type I (SAI) responses. The assessment of SAI function in mutant mice has been hindered because previous studies did not distinguish SAI responses from slowly adapting type II (SAII) responses, which are thought to arise from different end organs, such as Ruffini endings. Thus we sought methods to discriminate these afferent types. We developed an epidermis-up ex vivo skin–nerve chamber to record action potentials from afferents while imaging Merkel cells in intact receptive fields. Using model-based cluster analysis, we found that two types of slowly adapting receptors were readily distinguished based on the regularity of touch-evoked firing patterns. We identified these clusters as SAI (coefficient of variation = 0.78 ± 0.09) and SAII responses (0.21 ± 0.09). The identity of SAI afferents was confirmed by recording from transgenic mice with green fluorescent protein–expressing Merkel cells. SAI receptive fields always contained fluorescent Merkel cells (n = 10), whereas SAII receptive fields lacked these cells (n = 5). Consistent with reports from other vertebrates, mouse SAI and SAII responses arise from afferents exhibiting similar conduction velocities, receptive field sizes, mechanical thresholds, and firing rates. These results demonstrate that mice, like other vertebrates, have two classes of slowly adapting light-touch receptors, identify a simple method to distinguish these populations, and extend the utility of skin–nerve recordings for genetic dissection of touch receptor mechanisms

Invasion of the body snatchers the diversity and evolution of manipulative strategies in host-parasite interactions

Parasite-induced alteration of host behaviour is a widespread transmission strategy among pathogens. Understanding how it works is an exciting challenge from both a mechanistic and an evolutionary perspective. In this review, we use key examples to examine the proximate mechanisms by which parasites are known to control the behaviour of their hosts. Special attention is given to the recent developments of post-genomic tools, such as proteomics, for determining the genetic basis of parasitic manipulation. We then discuss two novel perspectives on host manipulation (mafia-like strategy and exploitation of host compensatory responses), arguing that parasite-manipulated behaviours could be the result of compromises between host and parasite strategies. Such compromises may occur when collaborating with the parasite is less costly for the host in terms of fitness than is resisting parasite-induced changes. Therefore, even when changes in host behaviour benefit the parasite, the host may still play some role in the switch in host behaviour. in other words, the host does not always become part of the parasite's extended phenotype. For example, parasites that alter host behaviour appear to induce widely disseminated changes in the hosts' central nervous system, as opposed to targeted attacks on specific neural circuits. In some host-parasite systems, the change in host behaviour appears to require the active participation of the host (e.g., via host immune-neural connections). Even when the change in host behaviour results in clear fitness benefits for the parasite, these behavioural changes may sometimes be produced by the host. Changes in host behaviour that decrease the fitness costs of infection could be selected for, even if these changes also benefit the parasite