In format provided by Birmingham et al. (JUNE 2014) NATURE REVIEWS | DRUG DISCOVERY www.nature.com/reviews/drugdisc Box S1 | Bioelectronic medicines: the detailed research roadmap Creation of a visceral nerve atlas Structural mappingOverall objective: Create organ-centric wiring diagrams in models representative of human anatomy. Research imperatives:• Generate tools for high-resolution tracing of the fibre anatomy and taxonomy to and from individual organs o Build a library of tracers to visualize the full length of pre-ganglionic axons, ganglionic cell bodies, post-ganglionic axons, and intrinsic neurons 1 , with particular focus on tracing that starts at the target organ 2-5 o Advance approaches for high-resolution labelling of peripheral neurotransmitters, their receptors and co-receptors, and for imaging of myelination, peri-and epineurium o Develop and adapt micrometer-resolution imaging and 3D reconstruction techniques for visceral organs and peripheral nerves (for example, automated tissue slicing, clearing, in situ hybridization, multi-photon imaging) 6-12 • Explore inter-and intra-species variation in neuroanatomy and establish the optimal animal models for detailed mapping of each organ o Update and extend the macro-level innervation map of the major visceral organs in key animal model species and establish the extent to which this map is conserved in humans o Characterise the variability in different parts of these maps between individuals • Build organ-centric high-resolution maps for each visceral organ in their most representative animal model o Conduct high-resolution nerve tracing, labelling, and imaging in the animal model of choice, taking the organ as the starting point o Standardise and coordinate mapping, data management and 3D visualisation across organs • Establish methods to image and find nerves in the clinical setting o Develop tracers and associated imaging techniques that can be used in human preoperative and intra-operative settings to identify and localize peripheral nerves o Identify anatomical landmarks associated with putative intervention points for surgery Functional mappingOverall objective: Map the neural signalling patterns that control individual organ functions. Research imperatives:• Generate simultaneous recordings of neural signal pattern and organ function o Record both afferent (sensory) and efferent (motor) neural signals and associated end-organ biomarkers at a range of physiological stimuli

Due to the limited regenerative ability of neural tissue, a diverse set of biochemical and biophysical cues for increasing nerve growth has been investigated, including neurotrophic factors, topography, and electrical stimulation. In this report, we explore optogenetic control of neurite growth as a cell-specific alternative to electrical stimulation. By investigating a broad range of optical stimulation parameters on dorsal root ganglia (DRGs) expressing channelrhodopsin 2 (ChR2), we identified conditions that enhance neurite outgrowth by three-fold as compared to unstimulated or wild-type (WT) controls. Furthermore, optogenetic stimulation of ChR2 expressing DRGs induces directional outgrowth in WT DRGs co-cultured within a 10 mm vicinity of the optically sensitive ganglia. This observed enhancement and polarization of neurite growth was accompanied by an increased expression of neural growth and brain derived neurotrophic factors (NGF, BDNF). This work highlights the potential for implementing optogenetics to drive nerve growth in specific cell populations.

A truncating mutation in canine ADAMTS17 causes PLL, a well-characterized veterinary disease, which can now be compared to a recently described rare WMS-like disease caused by truncating mutations of the human ADAMTS17 ortholog.

Primary lens luxation (PLL) is a well-recognized, painful and potentially blinding inherited ocular condition in dogs. We screened PLL-affected dogs of 30 different breeds, to identify those which carried a previously described c.1473+1 G>A mutation in ADAMTS17 that is associated with PLL in Miniature Bull terriers, Lancashire Heelers, and Jack Russell terriers. This ADAMTS17 mutation was identified in PLL-affected dogs from 14 additional breeds. PLL-affected dogs from some breeds (most notably the Shar pei and the Brittany spaniel) did not carry the G1473+1A ADAMTS17 mutation, indicating they must suffer from a genetically distinct form of the condition. We also estimated the frequency of this ADAMTS17 mutation in some of the breeds. Our findings indicate the mutation segregates in a large number of different breeds of dog, many of which are terriers or breeds with terrier co-ancestry, but some of which have more diverse origins. Our results also indicate that the mutation is present at high frequency within most of the breeds in which it segregates. In the miniature bull terrier breed estimates of mutation frequency ranged from 0.27 to 0.39, corresponding to 7.3-15.2% PLL-affected dogs in this breed. We also identified an increased risk of PLL associated with heterozygosity at ADAMTS17, suggesting that carriers carry a low risk of developing PLL.

Each year, approximately 185,000 Americans suffer the devastating loss of a limb. The effects of upper limb amputations are profound because a person's hands are tools for everyday functioning, expressive communication, and other uniquely human attributes. Despite the advancements in prosthetic technology, current upper limb prostheses are still limited in terms of complex motor control and sensory feedback. Sensory feedback is critical to restoring full functionality to amputated patients because it would relieve the cognitive burden of relying solely on visual input to monitor motor commands and provide tremendous psychological benefits. This article reviews the latest innovations in sensory feedback and argues in favor of peripheral nerve interfaces. First, the authors examine the structure of the peripheral nerve and its importance in the development of a sensory interface. Second, the authors discuss advancements in targeted muscle reinnervation and direct neural stimulation by means of intraneural electrodes. The authors then explore the future of prosthetic sensory feedback using innovative technologies for neural signaling, specifically, the sensory regenerative peripheral nerve interface and optogenetics. These breakthroughs pave the way for the development of a prosthetic limb with the ability to feel.

There is increasing importance for scholars to distinguish the effects of expression from reception to understand the processes involved in producing psychosocial benefits. This study shows that emotional support is more than something cancer patients receive; it is part of an active, complex process that can be facilitated by social media.

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Scholars contend that correctly applying religious cues is crucial to winning political elections. This article examines the effect of general religious cues by conducting an experiment on a national sample (N = 520). Through the use of a fictitious congressional candidate's webpage, we examine how subtle and overt religious cues interact with citizen religiosity to affect political evaluations. The findings demonstrate that politicians who use overt religious cues run the risk of alienating a large portion of potential voters. Religious cues do, however, appear to become more effective as citizens become more religious. We also find some evidence that overt religious cues are more polarizing than subtle religious cues. This article provides a foundation from which to more thoroughly consider how general religious cues can affect political outcomes and how these cues may interact with other factors.