Primitive roles for inhibitory interneurons in developing frog spinal cord

Understanding the neuronal networks in the mammal spinal cord is hampered by the diversity of neurons and their connections. The simpler networks in developing lower vertebrates may offer insights into basic organization. To investigate the function of spinal inhibitory interneurons in Xenopus tadpoles, paired whole-cell recordings were used. We show directly that one class of interneuron, with distinctive anatomy, produces glycinergic, negative feedback inhibition that can limit firing in motoneurons and interneurons of the central pattern generator during swimming. These same neurons also produce inhibitory gating of sensory pathways during swimming. This discovery raises the possibility that some classes of interneuron, with distinct functions later in development, may differentiate from an earlier class in which these functions are shared. Preliminary evidence suggests that these inhibitory interneurons express the transcription factor engrailed, supporting a probable homology with interneurons in developing zebrafish that also express engrailed and have very similar anatomy and functions

Sensory initiation of a co-ordinated motor response: synaptic excitation underlying simple decision-making.

This is the final version of the article. Available from Wiley via the DOI in this record.KEY POINTS: Deciding whether or how to initiate a motor response to a stimulus can be surprisingly slow and the underlying processes are not well understood. The neuronal circuitry that allows frog tadpoles to swim in response to touch is well characterized and includes excitatory reticulospinal neurons that drive swim circuit neurons. Build-up of excitation to reticulospinal neurons is the key decision-making step for swimming. Asymmetry in this build-up between the two sides allows bilateral initiation at the same time as avoiding inappropriate co-activation of motor antagonists. Following stronger stimuli, reticulospinal neurons are excited through a trigeminal nucleus pathway and swimming starts first on the stimulated side. If this pathway fails or is lesioned, swimming starts later on the unstimulated side. The mechanisms underlying initiation of a simple tadpole motor response may share similarities with more complex decisions in other animals, including humans. ABSTRACT: Animals take time to make co-ordinated motor responses to a stimulus. How can sensory input initiate organized movements, activating all necessary elements at the same time as avoiding inappropriate co-excitation of antagonistic muscles? In vertebrates, this process usually results in the activation of reticulospinal pathways. Young Xenopus tadpoles can respond to head-skin touch by swimming, which may start on either side. We investigate how motor networks in the brain are organized, and whether asymmetries in touch sensory pathways avoid co-activation of antagonists at the same time as producing co-ordinated movements. We record from key reticulospinal neurons in the network controlling swimming. When the head skin is stimulated unilaterally, excitation builds up slowly and asymmetrically in these neurons such that those on both sides do not fire synchronously. This build-up of excitation to threshold is the key decision-making step and determines whether swimming will start, as well as on which side. In response to stronger stimuli, the stimulated side tends to 'win' because excitation from a shorter, trigeminal nucleus pathway becomes reliable and can initiate swimming earlier on the stimulated side. When this pathway fails or is lesioned, swimming starts later and on the unstimulated side. Stochasticity in the trigeminal nucleus pathway allows unpredictable turning behaviour to weaker stimuli, conferring potential survival benefits. We locate the longer, commissural sensory pathway carrying excitation to the unstimulated side and record from its neurons. These neurons fire to head-skin stimuli but excite reticulospinal neurons indirectly. We propose that asymmetries in the sensory pathways exciting brainstem reticulospinal neurons ensure alternating and co-ordinated swimming activity from the start.This work was supported by the BBSRC grant (BB/G006652/1)

Mathematical modelling of nanoparticle delivery to vascular tumours

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.The goal of any cancer therapy is to achieve efficient, tissue-specific targeting of drugs to cancer cells. However, most anticancer agents act on healthy and malignant tissue alike, potentially resulting in side effects to healthy tissue. This has motivated the development of treatment strategies that are cancer-cell specific; one approach uses biomimetic polymer vesicles (BPV) to deliver chemotherapeutic drugs into cells before releasing them. BPVs are synthetic membrane enclosed, nanometre-sized structures, and provide ideal drug delivery vectors because specific targeting to cancer cells can be achieved by coating with tumourspecific molecules. We present several mathematical models covering a wide range of length-scales pertinent to BPV-mediated delivery protocols and focus on capturing the in vivo environment by evaluating the impact of the underlying vascular structure upon the governing transport mechanisms. Firstly, we present models of specific binding of BPVs to cancer cells. Subsequently we examine the implications of these model outputs in the contexts of both discrete capillary architectures and higher level homogenized-models that track blood and BPV transport at the tissue scale (both intra- and extra-tumorally). Numerical solutions are discussed, and recommendations are presented on that optimal integration of the models to generate quantitative predictions associated with BPV treatment efficacy

Commentary: Ensuring health statistics in conflict are evidence-based

The author argues that measuring mortality in conflict settings is fraught with limitations which mostly result in under-estimation of mortality. Some recent publications on this subject have been based upon convenient surveillance processes, or even press reports. The author calls for vigilance against such studies and argues that war related surveillance-based mortality estimates should include measures of sensitivity and representativeness

The effect of action observation and motor imagery combinations on upper limb kinematics and EMG during dart-throwing

Recent research has begun to employ interventions that combine action observation and motor imagery (AOMI) with positive results. However, little is known about the underpinning facilitative effect on performance. Participants (n = 50) were randomly allocated to one of five training groups: action observation (AO), motor imagery (MI), simultaneous action observation and motor imagery (S‐AOMI), alternate action observation and motor imagery (A‐AOMI), and control. The task involved dart‐throwing at a concentric circle dartboard at pre‐ and post‐test. Interventions were conducted 3 times per week for 6 weeks. Data were collected from performance outcomes and mean muscle activation of the upper and forearm muscles. Angular velocity and peak angular velocity measurements of the elbow were also collected from the throwing arm. Results showed performance of the A‐AOMI group improved to a significantly greater degree than the AO (P = .04), MI (P = .04), and control group (P = .02), and the S‐AOMI group improved to a greater degree than the control group (P = .02). Mean muscle activation of the triceps brachii significantly reduced in the S‐AOMI and A‐AOMI (P < .01) groups, and participants in the AO (P = .04), A‐AOMI, and S‐AOMI (P < .01) groups significantly reduced activation in the bicep brachii from pre‐ to post‐test. Peak angular velocity significantly decreased from pre‐ to post‐test in both A‐AOMI and S‐AOMI (P < .01) groups. The results reaffirm the benefits of AOMI for facilitating skill learning and provide an insight how these interventions produce favorable changes in EMG and movement kinematics

Modeling the connectome of a simple spinal cord.

In this paper we develop a computational model of the anatomy of a spinal cord. We address a long-standing ambition of neuroscience to understand the structure-function problem by modeling the complete spinal cord connectome map in the 2-day old hatchling Xenopus tadpole. Our approach to modeling neuronal connectivity is based on developmental processes of axon growth. A simple mathematical model of axon growth allows us to reconstruct a biologically realistic connectome of the tadpole spinal cord based on neurobiological data. In our model we distribute neuron cell bodies and dendrites on both sides of the body based on experimental measurements. If growing axons cross the dendrite of another neuron, they make a synaptic contact with a defined probability. The total neuronal network contains ∼1,500 neurons of six cell-types with a total of ∼120,000 connections. The anatomical model contains random components so each repetition of the connectome reconstruction procedure generates a different neuronal network, though all share consistent features such as distributions of cell bodies, dendrites, and axon lengths. Our study reveals a complex structure for the connectome with many interesting specific features including contrasting distributions of connection length distributions. The connectome also shows some similarities to connectivity graphs for other animals such as the global neuronal network of C. elegans. In addition to the interesting intrinsic properties of the connectome, we expect the ability to grow and analyze a biologically realistic spinal cord connectome will provide valuable insights into the properties of the real neuronal networks underlying simple behavior

Influence of Flow Field Design on Zinc Deposition and Performance in a Zinc-Iodide Flow Battery

Among the aqueous redox flow battery systems, redox chemistries using a zinc negative electrode have a relatively high energy density, but the potential of achieving high power density and long cycle life is hindered by dendrite growth at the anode. In this study, a new cell design with a narrow gap between electrode and membrane was applied in a zinc-iodide flow battery. In this design, some of the electrolyte flows over the electrode surface and a fraction of the flow passes through the porous felt electrode in the direction of current flow. The flow battery was tested under constant current density over 40 cycles, and the efficiency, discharge energy density, and power density of the battery were significantly improved compared to conventional flow field designs. The power density obtained in this study is one of the highest power densities reported for the zinc-iodide battery. The morphology of the zinc deposition was studied using scanning electron microscopy and optical profilometry. It was found that the flow through the electrode led to a thinner zinc deposit with lower roughness on the surface of the electrode, in comparison to the case where there was no flow through the electrode. In addition, inhibition of dendrite formation enabled operation at a higher range of current density. Ex situ tomographic measurements were used to image the zinc deposited on the surface and inside the porous felt. Volume rendering of graphite felt from X-ray computed tomography images showed that in the presence of flow through the electrode, more zinc deposition occurred inside the porous felt, resulting in a compact and thinner surface deposit, which may enable higher battery capacity and improved performance

The effectiveness and efficiency of home-based nursing health promotion for older people: A review of the literature

Despite the large potential role that community nurses have in providing individualized health promotion to older people, there is a lack of consensus in the literature regarding this role's effectiveness and efficiency. This article presents a literature review and synthesis of 12 randomized controlled trials selected from 344 published studies on preventive home visitation programs for older people. The findings suggest that a diversity of home visiting interventions carried out by nurses can favorably affect health and functional status, mortality rates, use of hospitalization and nursing homes, and costs. Further research is needed that focuses on the outcomes of quality of life, mental health, social support, caregiver burden, the acceptability of intervention, and specific subgroups of clients who benefit most. Findings also indicate the need for a theoretical foundation, increased emphasis on health-promotion strategies, and more research using a more complete economic evaluation to establish efficiency