Automaticity is a hallmark feature of walking in adults who are healthy and well-functioning. In the context of walking, "automaticity" refers to the ability of the nervous system to successfully ...control typical steady state walking with minimal use of attention-demanding executive control resources. Converging lines of evidence indicate that walking deficits and disorders are characterized in part by a shift in the locomotor control strategy from healthy automaticity to compensatory executive control. This is potentially detrimental to walking performance, as an executive control strategy is not optimized for locomotor control. Furthermore, it places excessive demands on a limited pool of executive reserves. The result is compromised ability to perform basic and complex walking tasks and heightened risk for adverse mobility outcomes including falls. Strategies for rehabilitation of automaticity are not well defined, which is due to both a lack of systematic research into the causes of impaired automaticity and to a lack of robust neurophysiological assessments by which to gauge automaticity. These gaps in knowledge are concerning given the serious functional implications of compromised automaticity. Therefore, the objective of this article is to advance the science of automaticity of walking by consolidating evidence and identifying gaps in knowledge regarding: (a) functional significance of automaticity; (b) neurophysiology of automaticity;
From killers to curers: Peptides from cone snail venoms are potential therapeutic agents for the treatment of neuropathic pain. Unfortunately, these peptides suffer from the disadvantage of short ...biological half‐lives and poor activity when taken orally. A new orally active conotoxin was developed to solve these problems.
The 'silent epidemic' of traumatic brain injury (TBI) has been placed in the spotlight as a result of clinical investigations and popular press coverage of athletes and veterans with single or ...repetitive head injuries. Neuroinflammation can cause acute secondary injury after TBI, and has been linked to chronic neurodegenerative diseases; however, anti-inflammatory agents have failed to improve TBI outcomes in clinical trials. In this Review, we therefore propose a new framework of targeted immunomodulation after TBI for future exploration. Our framework incorporates factors such as the time from injury, mechanism of injury, and secondary insults in considering potential treatment options. Structuring our discussion around the dynamics of the immune response to TBI - from initial triggers to chronic neuroinflammation - we consider the ability of soluble and cellular inflammatory mediators to promote repair and regeneration versus secondary injury and neurodegeneration. We summarize both animal model and human studies, with clinical data explicitly defined throughout this Review. Recent advances in neuroimmunology and TBI-responsive neuroinflammation are incorporated, including concepts of inflammasomes, mechanisms of microglial polarization, and glymphatic clearance. Moreover, we highlight findings that could offer novel therapeutic targets for translational and clinical research, assimilate evidence from other brain injury models, and identify outstanding questions in the field.
The capacity of reef-building corals to tolerate (or adapt to) heat stress is a key factor determining their resilience to future climate change. Changes in coral microbiome composition (particularly ...for microalgal endosymbionts and bacteria) is a potential mechanism that may assist corals to thrive in warm waters. The northern Red Sea experiences extreme temperatures anomalies, yet corals in this area rarely bleach suggesting possible refugia to climate change. However, the coral microbiome composition, and how it relates to the capacity to thrive in warm waters in this region, is entirely unknown.
We investigated microbiomes for six coral species (Porites nodifera, Favia favus, Pocillopora damicornis, Seriatopora hystrix, Xenia umbellata, and Sarcophyton trocheliophorum) from five sites in the northern Red Sea spanning 4° of latitude and summer mean temperature ranges from 26.6 °C to 29.3 °C. A total of 19 distinct dinoflagellate endosymbionts were identified as belonging to three genera in the family Symbiodiniaceae (Symbiodinium, Cladocopium, and Durusdinium). Of these, 86% belonged to the genus Cladocopium, with notably five novel types (19%). The endosymbiont community showed a high degree of host-specificity despite the latitudinal gradient. In contrast, the diversity and composition of bacterial communities of the surface mucus layer (SML)-a compartment particularly sensitive to environmental change-varied significantly between sites, however for any given coral was species-specific.
The conserved endosymbiotic community suggests high physiological plasticity to support holobiont productivity across the different latitudinal regimes. Further, the presence of five novel algal endosymbionts suggests selection of certain genotypes (or genetic adaptation) within the semi-isolated Red Sea. In contrast, the dynamic composition of bacteria associated with the SML across sites may contribute to holobiont function and broaden the ecological niche. In doing so, SML bacterial communities may aid holobiont local acclimatization (or adaptation) by readily responding to changes in the host environment. Our study provides novel insight about the selective and endemic nature of coral microbiomes along the northern Red Sea refugia.
Regrettably, the list of unique analgesic tools has expanded very slowly during the past few decades. Many very promising drugs have failed once tested in clinical populations, and the associated ...costs of these translational failures have been extremely high. Part of this problem can be traced to the ways we select and use preclinical tools and perhaps to the way we report our findings. We are beginning to reevaluate our selection of animal models and the methods we use to measure pain-related responses in these animals. In addition, many journals now require a clear statement of the experimental hypothesis, the details of the experimental methods, a description of the statistical approach to analyzing the data, and the disclosure of conflicts of interest. These new practices pose challenges to laboratory-based research groups. However, a more rigorous approach to preclinical investigations may be necessary for the successful development of new analgesics.
Complex regional pain syndrome (CRPS) is a highly enigmatic syndrome typically developing after injury or surgery to a limb. Severe pain and disability are common among those with chronic forms of ...this condition. Accumulating evidence suggests that CRPS may involve both autoinflammatory and autoimmune components. In this review article, evidence for dysfunction of both the innate and adaptive immune systems in CRPS is presented. Findings from human studies in which cytokines and other inflammatory mediators were measured in the skin of affected limbs are discussed. Additional results from studies of mediator levels in animal models are evaluated in this context. Similarly, the evidence from human, animal, and translational studies of the production of autoantibodies and the potential targets of those antibodies is reviewed. Compelling evidence of autoinflammation in skin and muscle of the affected limb has been collected from CRPS patients and laboratory animals. Cytokines including IL-1β, IL-6, TNFα, and others are reliably identified during the acute phases of the syndrome. More recently, autoimmune contributions have been suggested by the discovery of self-directed pain-promoting IgG and IgM antibodies in CRPS patients and model animals. Both the autoimmune and the autoinflammatory components of CRPS appear to be regulated by neuropeptide-containing peripheral nerve fibers and the sympathetic nervous system. While CRPS displays a complex neuroimmunological pathogenesis, therapeutic interventions could be designed targeting autoinflammation, autoimmunity, or the neural support for these phenomena.
Abstract
Background
Traumatic brain injury refers to a broad range of neurological, cognitive, and emotional factors that result from the application of an external force to the head. Individuals ...recovering from traumatic brain injury will frequently experience acute and chronic pain.
Objective
The objective of this paper is to discuss the pathophysiological changes resulting from traumatic brain injury and how these may be involved in the development and persistence of pain after injury.
Methods
We based our review on articles retrieved from the MEDLINE database of references and abstracts on life sciences and biomedical topics (1966 to present) using the search engine PubMed (United States National Library of Medicine). The published literature focused on traumatic brain injury and pain.
Conclusions
This review presents evidence that pain is common after traumatic brain injury. However, while there are many potential mechanisms explaining this problem such as neuroinflammation, excitotoxicity, and axonal degeneration, we have no clear understanding of which of them contribute in individual patients. The authors highlight the priorities for research that will expand our knowledge and that may lead to the rational design of therapies that both reduce pain and provide optimal overall outcomes after traumatic brain injury.
Geochemical models for Mars predict carbonate formation during aqueous alteration. Carbonate-bearing rocks had not previously been detected on Mars' surface, but Mars Reconnaissance Orbiter mapping ...reveals a regional rock layer with near-infrared spectral characteristics that are consistent with the presence of magnesium carbonate in the Nili Fossae region. The carbonate is closely associated with both phyllosilicate-bearing and olivine-rich rock units and probably formed during the Noachian or early Hesperian era from the alteration of olivine by either hydrothermal fluids or near-surface water. The presence of carbonate as well as accompanying clays suggests that waters were neutral to alkaline at the time of its formation and that acidic weathering, proposed to be characteristic of Hesperian Mars, did not destroy these carbonates and thus did not dominate all aqueous environments.
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