Planarian activity differences when maintained in water pre-treated with magnetic fields: a nonlinear effect

There have been multiple claims that exposing water to a static magnetic field affects its properties which influence living systems. To test this hypothesis, planarian subsequent to dissection were maintained in spring water that had been previously exposed for only one day to one of three (16, 160, or 1,600 G) intensity static magnetic fields or to a reference condition. Although there was no significant difference in regeneration rates over the subsequent seven-day period, there was a statistically significant nonlinear effect for planarian mobility and diffusion rates. Both mobility rates and diffusion velocity of a liquid within the water that had been exposed to the 16 G field was about twice that for water exposed to the other intensities. These results imply that nonlinear biophysical effects may emerge under specific conditions of intensity ranges for particular volumes of water.     

Tutorial: Analysis of motor unit discharge characteristics from high-density surface EMG signals

Recent work demonstrated that it is possible to identify motor unit discharge times from high-density surface EMG (HDEMG) decomposition. Since then, the number of studies that use HDEMG decomposition for motor unit investigations has increased considerably. Although HDEMG decomposition is a semi-automatic process, the analysis and interpretation of the motor unit pulse trains requires a thorough inspection of the output of the decomposition result. Here, we report guidelines to perform an accurate extraction of motor unit discharge times and interpretation of the signals. This tutorial includes a discussion of the differences between the extraction of global EMG signal features versus the identification of motor unit activity for physiological investigations followed by a comprehensive guide on how to acquire, inspect, and decompose HDEMG signals, and robust extraction of motor unit discharge characteristics.     

Human land uses reduce climate connectivity across North America

Climate connectivity, the ability of a landscape to promote or hinder the movement of organisms in response to a changing climate, is contingent on multiple factors including the distance organisms need to move to track suitable climate over time (i.e. climate velocity) and the resistance they experience along such routes. An additional consideration which has received less attention is that human land uses increase resistance to movement or alter movement routes and thus influence climate connectivity. Here we evaluate the influence of human land uses on climate connectivity across North America by comparing two climate connectivity scenarios, one considering climate change in isolation and the other considering climate change and human land uses. In doing so, we introduce a novel metric of climate connectivity, ‘human exposure’, that quantifies the cumulative exposure to human activities that organisms may encounter as they shift their ranges in response to climate change. We also delineate potential movement routes and evaluate whether the protected area network supports movement corridors better than non‐protected lands. We found that when incorporating human land uses, climate connectivity decreased; climate velocity increased on average by 0.3 km/year and cumulative climatic resistance increased for ~83% of the continent. Moreover, ~96% of movement routes in North America must contend with human land uses to some degree. In the scenario that evaluated climate change in isolation, we found that protected areas do not support climate corridors at a higher rate than non‐protected lands across North America. However, variability is evident, as many ecoregions contain protected areas that exhibit both more and less representation of climate corridors compared to non‐protected lands. Overall, our study indicates that previous evaluations of climate connectivity underestimate climate change exposure because they do not account for human impacts.     

Epithelial-to-mesenchymal transition and different migration strategies as viewed from the neural crest

Epithelial-to-mesenchymal transition (EMT) is a dynamic process that produces migratory cells from epithelial precursors. However, EMT is not binary; rather it results in migratory cells which adopt diverse strategies including collective and individual cell migration to arrive at target destinations. Of the many embryonic cells that undergo EMT, the vertebrate neural crest is a particularly good example which has provided valuable insight into these processes. Neural crest cells from different species often adopt different migratory strategies with collective migration predominating in anamniotes, whereas individual cell migration is more prevalent in amniotes. Here, we will provide a perspective on recent work toward understanding the process of neural crest EMT focusing on how these cells undergo collective and individual cell migration.     

Oligomerization of RIG‐I and MDA5 2CARD domains

The innate immune system is the first line of defense against invading pathogens. The retinoic acid‐inducible gene I (RIG‐I) like receptors (RLRs), RIG‐I and melanoma differentiation‐associated protein 5 (MDA5), are critical for host recognition of viral RNAs. These receptors contain a pair of N‐terminal tandem caspase activation and recruitment domains (2CARD), an SF2 helicase core domain, and a C‐terminal regulatory domain. Upon RLR activation, 2CARD associates with the CARD domain of MAVS, leading to the oligomerization of MAVS, downstream signaling and interferon induction. Unanchored K63‐linked polyubiquitin chains (polyUb) interacts with the 2CARD domain, and in the case of RIG‐I, induce tetramer formation. However, the nature of the MDA5 2CARD signaling complex is not known. We have used sedimentation velocity analytical ultracentrifugation to compare MDA5 2CARD and RIG‐I 2CARD binding to polyUb and to characterize the assembly of MDA5 2CARD oligomers in the absence of polyUb. Multi‐signal sedimentation velocity analysis indicates that Ub₄ binds to RIG‐I 2CARD with a 3:4 stoichiometry and cooperatively induces formation of an RIG‐I 2CARD tetramer. In contrast, Ub₄ and Ub₇ interact with MDA5 2CARD weakly and form complexes with 1:1 and 2:1 stoichiometries but do not induce 2CARD oligomerization. In the absence of polyUb, MDA5 2CARD self‐associates to forms large oligomers in a concentration‐dependent manner. Thus, RIG‐I and MDA5 2CARD assembly processes are distinct. MDA5 2CARD concentration‐dependent self‐association, rather than polyUb binding, drives oligomerization and MDA5 2CARD forms oligomers larger than tetramer. We propose a mechanism where MDA5 2CARD oligomers, rather than a stable tetramer, function to nucleate MAVS polymerization.     

AlCl3 exposure regulates neuronal development by modulating DNA modification

BACKGROUNDAs the third most abundant element, aluminum is widespread in the environment. Previous studies have shown that aluminum has a neurotoxic effect and its exposure can impair neuronal development and cognitive function.AIMTo study the effects of aluminum on epigenetic modification in neural stem cells and neurons. METHODSNeural stem cells were isolated from the forebrain of adult mice. Neurons were isolated from the hippocampi tissues of embryonic day 16-18 mice. AlCl₃ at 100 and 200 μmol/L was applied to stem cells and neurons. RESULTSAluminum altered the differentiation of adult neural stem cells and caused apoptosis of newborn neurons while having no significant effects on the proliferation of neural stem cells. Aluminum application also significantly inhibited the dendritic development of hippocampal neurons. Mechanistically, aluminum exposure significantly affected the levels of DNA 5-hydroxy-methylcytosine, 5-methylcytosine, and N⁶-methyladenine in stem cells and neurons. CONCLUSIONOur findings indicate that aluminum may regulate neuronal development by modulating DNA modifications.     

Portrait of visual cortical circuits for generating neural oscillation dynamics

The mouse primary visual cortex (V1) has emerged as a classical system to study neural circuit mechanisms underlying visual function and plasticity. A variety of efferent-afferent neuronal connections exists within the V1 and between the V1 and higher visual cortical areas or thalamic nuclei, indicating that the V1 system is more than a mere receiver in information processing. Sensory representations in the V1 are dynamically correlated with neural activity oscillations that are distributed across different cortical layers in an input-dependent manner. Circuits consisting of excitatory pyramidal cells (PCs) and inhibitory interneurons (INs) are the basis for generating neural oscillations. In general, INs are clustered with their adjacent PCs to form specific microcircuits that gate or filter the neural information. The interaction between these two cell populations has to be coordinated within a local circuit in order to preserve neural coding schemes and maintain excitation–inhibition (E–I) balance. Phasic alternations of the E–I balance can dynamically regulate temporal rhythms of neural oscillation. Accumulating experimental evidence suggests that the two major sub-types of INs, parvalbumin-expressing (PV⁺) cells and somatostatin-expressing (SOM⁺) INs, are active in controlling slow and fast oscillations, respectively, in the mouse V1. The review summarizes recent experimental findings on elucidating cellular or circuitry mechanisms for the generation of neural oscillations with distinct rhythms in either developing or matured mouse V1, mainly focusing on visual relaying circuits and distinct local inhibitory circuits.     

Disease modifying treatment of spinal cord injury with directly reprogrammed neural precursor cells in non-human primates

BACKGROUNDThe development of regenerative therapy for human spinal cord injury (SCI) is dramatically restricted by two main challenges: the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical testing. Direct reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first challenge. The use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human SCI.AIMTo investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells (drNPCs).METHODSSeven non-human primates with verified complete thoracic SCI were divided into two groups: drNPC group (n = 4) was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury, and lesion control (n = 3) was injected identically with the equivalent volume of vehicle.RESULTSFollow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured pathways. Magnetic resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid circulation. Subsequent immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk, migrating to areas of axon growth cones.CONCLUSIONOur data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI, based on neurological status assessment and neurophysiological recovery within 12 wk after transplantation. The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs. Instead, directed drNPCs migration to the areas of active growth cone formation may provide exosome and paracrine trophic support, thereby further supporting the regeneration processes.     

A critical examination of the maximum velocity of shortening used in simulation models of human movement

The maximum velocity of shortening of a muscle is an important parameter in musculoskeletal models. The most commonly used values are derived from animal studies; however, these values are well above the values that have been reported for human muscle. The purpose of this study was to examine the sensitivity of simulations of maximum vertical jumping performance to the parameters describing the force–velocity properties of muscle. Simulations performed with parameters derived from animal studies were similar to measured jump heights from previous experimental studies. While simulations performed with parameters derived from human muscle were much lower than previously measured jump heights. If current measurements of maximum shortening velocity in human muscle are correct, a compensating error must exist. Of the possible compensating errors that could produce this discrepancy, it was concluded that reduced muscle fibre excursion is the most likely candidate.