Interoception refers to the representation of the internal states of an organism, and includes the processes by which it senses, interprets, integrates, and regulates signals from within itself. This ...review presents a unified research framework and attempts to offer definitions for key terms to describe the processes involved in interoception. We elaborate on these definitions through illustrative research findings, and provide brief overviews of central aspects of interoception, including the anatomy and function of neural and non-neural pathways, diseases and disorders, manipulations and interventions, and predictive modeling. We conclude with discussions about major research gaps and challenges.
Interoception refers to the representation of the internal world, and includes the processes by which an organism senses, interprets, integrates, and regulates signals from within itself.The brain communicates with internal organs via the peripheral nervous system and non-neuronal systems.Key components of a unified research framework of interoception include interoceptive signals, interoceptors, ascending and descending pathways, central interpreters, central integrators, central regulators, and interoceptive effectors.In-depth mechanistic studies linking anatomical findings to function are important for defining the roles of the key elements of interoception.Dysfunction of interoception may be an important component of many neurological, psychiatric, and behavioral disorders.Better understanding of the neural basis of interoception may provide therapeutic targets for interoceptive dysfunction and related nervous system disorders.
Background:
The clinical and prognostic value of programmed death-ligand 1, PD-L1, in glioblastoma remains controversial. The present study aimed to identify the expression of PD-L1 for its ...prognostic value in glioblastoma.
Methods:
A comprehensive literature search was performed using the PubMed and CNKI databases. The overall survival (OS) and disease-free survival (DFS) of GBM was analyzed based on Hazard ratios (HRs) and 95% confidence intervals (CIs). Furthermore, Odds ratios (ORs) and 95% CIs were summarized for clinicopathological parameters. The statistical analysis was using RevMan 5.3 software.
Results:
The meta-analysis was performed by using total nine studies including 806 patients who had glioblastoma. The pooled results indicated that PD-L1 expression in tumor tissues was significantly related to a poor OS (HR = 1.63, 95%CI: 1.19–2.24,
P
= 0.003, random effects model) with heterogeneity (
I
2
= 51%). In subgroup analyses, PD-L1 positivity was significantly associated with a worse OS for patients of American and Asian regions, but not for those of European regions. Moreover, PD-L1 expression implied a trend toward the mutation status of the
IDH1
gene coding the Isocitrate Dehydrogenase (NADP(+))-1 protein (HR = 9.92, 95%CI: 1.85–53.08,
P
= 0.007, fixed effects model). However, the prediction overall survival (OS) of the patients showed that PD-L1 expression was independent from other clinicopathological features, such as gender and age.
Conclusions:
Our analyses indicated that high expression of PD-L1 in glioblastoma tumor tissues is associated with poor survival of patients, and PD-L1 may act as a prognostic predictor and an effective therapeutic target for glioblastoma.
Mutations or duplications in
MECP2 cause Rett and Rett-like syndromes, neurodevelopmental disorders characterized by mental retardation, motor dysfunction, and autistic behaviors. MeCP2 is expressed ...in many mammalian tissues and functions as a global repressor of transcription; however, the molecular mechanisms by which MeCP2 dysfunction leads to the neural-specific phenotypes of RTT remain poorly understood. Here, we show that neuronal activity and subsequent calcium influx trigger the de novo phosphorylation of MeCP2 at serine 421 (S421) by a CaMKII-dependent mechanism. MeCP2 S421 phosphorylation is induced selectively in the brain in response to physiological stimuli. Significantly, we find that S421 phosphorylation controls the ability of MeCP2 to regulate dendritic patterning, spine morphogenesis, and the activity-dependent induction of
Bdnf transcription. These findings suggest that, by triggering MeCP2 phosphorylation, neuronal activity regulates a program of gene expression that mediates nervous system maturation and that disruption of this process in individuals with mutations in MeCP2 may underlie the neural-specific pathology of RTT.
Aging, the central nervous system, and mobility Rosso, Andrea L.; Hausdorff, Jeffrey M; O], [A.
The journals of gerontology. Series A, Biological sciences and medical sciences,
11/2013, Letnik:
68, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Mobility limitations are common and hazardous in community-dwelling older adults but are largely understudied, particularly regarding the role of the central nervous system (CNS). This has limited ...development of clearly defined pathophysiology, clinical terminology, and effective treatments. Understanding how changes in the CNS contribute to mobility limitations has the potential to inform future intervention studies.
A conference series was launched at the 2012 conference of the Gerontological Society of America in collaboration with the National Institute on Aging and the University of Pittsburgh. The overarching goal of the conference series is to facilitate the translation of research results into interventions that improve mobility for older adults.
Evidence from basic, clinical, and epidemiological studies supports the CNS as an important contributor to mobility limitations in older adults without overt neurologic disease. Three main goals for future work that emerged were as follows: (a) develop models of mobility limitations in older adults that differentiate aging from disease-related processes and that fully integrate CNS with musculoskeletal contributors; (b) quantify the contribution of the CNS to mobility loss in older adults in the absence of overt neurologic diseases; (c) promote cross-disciplinary collaboration to generate new ideas and address current methodological issues and barriers, including real-world mobility measures and life-course approaches.
In addition to greater cross-disciplinary research, there is a need for new approaches to training clinicians and investigators, which integrate concepts and methodologies from individual disciplines, focus on emerging methodologies, and prepare investigators to assess complex, multisystem associations.
Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the ...understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.
Mutations in MeCP2, which encodes a protein that has been proposed to function as a global transcriptional repressor, are the cause of Rett syndrome (RTT), an X-linked progressive neurological ...disorder. Although the selective inactivation of MeCP2 in neurons is sufficient to confer a Rett-like phenotype in mice, the specific functions of MeCP2 in postmitotic neurons are not known. We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene. Membrane depolarization triggers the calcium-dependent phosphorylation and release of MeCP2 from BDNF promoter III, thereby facilitating transcription. These studies indicate that MeCP2 plays a key role in the control of neuronal activity-dependent gene regulation and suggest that the deregulation of this process may underlie the pathology of RTT.
Radio observations of pulsars offer a potential method to probe the intricate microstructure in the turbulent interstellar medium. Here we report on a high-resolution dynamic spectral analysis of the ...“swooshing pulsar” B0919+06 observed with the Five-hundred-meter Aperture Spherical radio Telescope over multiple epochs and with the ultrawideband receiver on the Parkes radio telescope. For all observations, the dynamic scintillation spectra, two-dimensional autocovariance functions, and secondary spectra are presented. At 1250 MHz, the decorrelation bandwidth, diffraction timescale, and the drift rate are determined to be Δνd = 25.89 ± 7.55 MHz, Δτd=14.42±3.98 minutes, and dt/dν=0.07±0.14minutes MHz−1, respectively. The frequency dependencies of the scintillation parameters exhibit single power-law spectral behaviors, indicating that the electron density fluctuations in the interstellar medium approximately follow the Kolmogorov spectrum. The secondary spectra exhibit two distinct parabolic arcs with well-determined curvatures of 0.002 and 0.02 s3 for the outer and inner arcs, respectively. The locations of the scattering screens are approximately determined to be 157.3 and 726.0 pc, respectively, from the pulsar for isotropic scattering. The inner scintillation arc is present contemporaneously over a wide frequency range, indicating that the scintillation arc is a broadband phenomenon. The arc curvature scales with observing frequency as a power law with an index of −2.05 ± 0.05, which implies that the scattering screen spans a physical distance from 689.7 to 883.3 pc from the pulsar.
...genomic analysis and advanced computational technologies, including artificial intelligence, might have a role in research to illuminate new pathways and relationships between MBIs, development, ...and health. MBIs, when integrated with other conventional and complementary approaches, can offer an approach that considers mind, interconnection, and the whole person.5 In addition to conventional randomised controlled trials, innovative methods such as sequential multiple assignment randomised trials, a multiphase optimisation strategy, and pragmatic clinical trials could provide nuanced insights, help researchers and health-care providers better understand and optimise an intervention's impact, and hasten the integration of MBIs into health care.7–9 As we chart this course, the implementation of MBIs in health-care systems must not be an afterthought. The integration of evidence-based health practices into clinical and community health-care-based music programmes that benefit children, older adults, and people with chronic diseases could help to improve patient outcomes and benefit population health.10–14 Hybrid studies that merge the testing of intervention effectiveness and implementation research are gaining ground,15 and MBIs must not be omitted from these developments.
Music-based interventions (MBIs) show promise for managing symptoms of various brain disorders. To fully realize the potential of MBIs and dispel the outdated misconception that MBIs are rooted in ...soft science, the NIH is promoting rigorously designed, well-powered MBI clinical trials. The pressing need of guidelines for scientifically rigorous studies with enhanced data collection brought together the Renée Fleming Foundation, the Foundation for the NIH, the Trans-NIH Music and Health Working Group, and an interdisciplinary scientific expert panel to create the NIH MBI Toolkit for research on music and health across the lifespan. The Toolkit defines the building blocks of MBIs, including a consolidated set of common data elements for MBI protocols, and core datasets of outcome measures and biomarkers for brain disorders of aging that researchers may select for their studies. Utilization of the guiding principles in this Toolkit will be strongly recommended for NIH-funded studies of MBIs.
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