Immune or genetic-mediated disruption of CASPR2 causes pain hypersensitivity due to enhanced primary afferent excitability

Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2(-/-)) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens. Both primary afferent excitability and subsequent nociceptive transmission within the dorsal horn were increased in Cntnap2(-/-) mice. Either immune or genetic-mediated ablation of CASPR2 enhanced the excitability of DRG neurons in a cell-autonomous fashion through regulation of Kv1 channel expression at the soma membrane. This is the first example of passive transfer of an autoimmune peripheral neuropathic pain disorder and demonstrates that CASPR2 has a key role in regulating cell-intrinsic dorsal root ganglion (DRG) neuron excitability

Scale issues in soil moisture modelling: problems and prospects

Soil moisture storage is an important component of the hydrological cycle and plays a key role in land-surface-atmosphere interaction. The soil-moisture storage equation in this study considers precipitation as an input and soil moisture as a residual term for runoff and evapotranspiration. A number of models have been developed to estimate soil moisture storage and the components of the soil-moisture storage equation. A detailed discussion of the impli cation of the scale of application of these models reports that it is not possible to extrapolate processes and their estimates from the small to the large scale. It is also noted that physically based models for small-scale applications are sufficiently detailed to reproduce land-surface- atmosphere interactions. On the other hand, models for large-scale applications oversimplify the processes. Recently developed physically based models for large-scale applications can only be applied to limited uses because of data restrictions and the problems associated with land surface characterization. It is reported that remote sensing can play an important role in over coming the problems related to the unavailability of data and the land surface characterization of large-scale applications of these physically based models when estimating soil moisture storage.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Understanding the individual to implement the ecosystem approach to fisheries management

Ecosystem-based approaches to fisheries management (EAFMs) have emerged as requisite for sustainable use of fisheries resources. At the same time, however, there is a growing recognition of the degree of variation among individuals within a population, as well as the ecological consequences of this variation. Managing resources at an ecosystem level calls on practitioners to consider evolutionary processes, and ample evidence from the realm of fisheries science indicates that anthropogenic disturbance can drive changes in predominant character traits (e.g. size at maturity). Eco-evolutionary theory suggests that human-induced trait change and the modification of selective regimens might contribute to ecosystem dynamics at a similar magnitude to species extirpation, extinction and ecological dysfunction. Given the dynamic interaction between fisheries and target species via harvest and subsequent ecosystem consequences, we argue that individual diversity in genetic, physiological and behavioural traits are important considerations under EAFMs. Here, we examine the role of individual variation in a number of contexts relevant to fisheries management, including the potential ecological effects of rapid trait change. Using select examples, we highlight the extent of phenotypic diversity of individuals, as well as the ecological constraints on such diversity. We conclude that individual phenotypic diversity is a complex phenomenon that needs to be considered in EAFMs, with the ultimate realization that maintaining or increasing individual trait diversity may afford not only species, but also entire ecosystems, with enhanced resilience to environmental perturbations. Put simply, individuals are the foundation from which population- and ecosystem-level traits emerge and are therefore of central importance for the ecosystem-based approaches to fisheries management

Genotoxic effect induced by hydrogen peroxide in human hepatoma cells using comet assay

Background: Hydrogen peroxide is a common reactive oxygen intermediate generated by variousforms of oxidative stress. Aims: The aim of this study was to investigate the DNA damage capacity ofH2O2 in HepG2 cells. Methods: Cells were treated with H2O2 at concentrations of 25 μM or 50 μM for5 min, 30 min, 40 min, 1 h or 24 h in parallel. The extent of DNA damage was assessed by the cometassay. Results: Compared to the control, DNA damage by 25 μM and 50 μM H2O2 increasedsignificantly with increasing incubation time up to 1 h, but it was not increased at 24 h. Conclusions:Our Findings confirm that H2O2 is a typical DNA damage inducing agent and thus is a good modelsystem to study the effects of oxidative stress. DNA damage in HepG2 cells increased significantlywith H2O2 concentration and time of incubation but later decreased likely due to DNA repairmechanisms and antioxidant enzyme

Rho GTPase function in flies: insights from a developmental and organismal perspective.

Morphogenesis is a key event in the development of a multicellular organism and is reliant on coordinated transcriptional and signal transduction events. To establish the segmented body plan that underlies much of metazoan development, individual cells and groups of cells must respond to exogenous signals with complex movements and shape changes. One class of proteins that plays a pivotal role in the interpretation of extracellular cues into cellular behavior is the Rho family of small GTPases. These molecular switches are essential components of a growing number of signaling pathways, many of which regulate actin cytoskeletal remodeling. Much of our understanding of Rho biology has come from work done in cell culture. More recently, the fruit fly Drosophila melanogaster has emerged as an excellent genetic system for the study of these proteins in a developmental and organismal context. Studies in flies have greatly enhanced our understanding of pathways involving Rho GTPases and their roles in development

A global horizon scan of issues impacting marine and coastal biodiversity conservation

The biodiversity of marine and coastal habitats is experiencing unprecedented change. While there are well-known drivers of these changes, such as overexploitation, climate change and pollution, there are also relatively unknown emerging issues that are poorly understood or recognized that have potentially positive or negative impacts on marine and coastal ecosystems. In this inaugural Marine and Coastal Horizon Scan, we brought together 30 scientists, policymakers and practitioners with transdisciplinary expertise in marine and coastal systems to identify new issues that are likely to have a significant impact on the functioning and conservation of marine and coastal biodiversity over the next 5–10 years. Based on a modified Delphi voting process, the final 15 issues presented were distilled from a list of 75 submitted by participants at the start of the process. These issues are grouped into three categories: ecosystem impacts, for example the impact of wildfires and the effect of poleward migration on equatorial biodiversity; resource exploitation, including an increase in the trade of fish swim bladders and increased exploitation of marine collagens; and new technologies, such as soft robotics and new biodegradable products. Our early identification of these issues and their potential impacts on marine and coastal biodiversity will support scientists, conservationists, resource managers and policymakers to address the challenges facing marine ecosystems