The study of age at onset of mental health disorders is technically and conceptually difficult. It is important to consider these age distributions in order to understand causes and mechanisms of ...illness and to intervene at an appropriate juncture for primary and secondary prevention. This article reviews some of the approaches to studying age at onset, sets out the evidence to support the assertion that adult mental disorders begin in adolescence, and finds that perhaps half of all adult mental health disorders have begun by the teenage years. The paper then discusses whether this fits what is known about the developmental neurobiology of the brain and introduces the implications for mental health services.
Oxidative Stress Sies, Helmut; Berndt, Carsten; Jones, Dean P
Annual review of biochemistry,
06/2017, Volume:
86, Issue:
1
Journal Article
Peer reviewed
Oxidative stress is two sided: Whereas excessive oxidant challenge causes damage to biomolecules, maintenance of a physiological level of oxidant challenge, termed oxidative eustress, is essential ...for governing life processes through redox signaling. Recent interest has focused on the intricate ways by which redox signaling integrates these converse properties. Redox balance is maintained by prevention, interception, and repair, and concomitantly the regulatory potential of molecular thiol-driven master switches such as Nrf2 Keap1 or NF-κB IκB is used for system-wide oxidative stress response. Nonradical species such as hydrogen peroxide (H
2
O
2
) or singlet molecular oxygen, rather than free-radical species, perform major second messenger functions. Chemokine-controlled NADPH oxidases and metabolically controlled mitochondrial sources of H
2
O
2
as well as glutathione- and thioredoxin-related pathways, with powerful enzymatic back-up systems, are responsible for fine-tuning physiological redox signaling. This makes for a rich research field spanning from biochemistry and cell biology into nutritional sciences, environmental medicine, and molecular knowledge-based redox medicine.
Singly ionized ytterbium, with ultranarrow optical clock transitions at 467 and 436 nm, is a convenient system for the realization of optical atomic clocks and tests of present-day variation of ...fundamental constants. We present the first direct measurement of the frequency ratio of these two clock transitions, without reference to a cesium primary standard, and using the same single ion of Yb+171. The absolute frequencies of both transitions are also presented, each with a relative standard uncertainty of 6x10-16. Combining our results with those from other experiments, we report a threefold improvement in the constraint on the time variation of the proton-to-electron mass ratio, mu super(.)/ mu =0.2(1.1)x10-16 yr-1, along with an improved constraint on time variation of the fine structure constant, alpha super(.)/ alpha =-0.7(2.1)x10-17 yr-1
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Division of Pulmonary, Allergy and Critical Care Medicine, Clinical Biomarkers Laboratory, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
Submitted 31 May 2008
; ...accepted in final form 31 July 2008
ABSTRACT
Free radical-induced macromolecular damage has been studied extensively as a mechanism of oxidative stress, but large-scale intervention trials with free radical scavenging antioxidant supplements show little benefit in humans. The present review summarizes data supporting a complementary hypothesis for oxidative stress in disease that can occur without free radicals. This hypothesis, which is termed the "redox hypothesis," is that oxidative stress occurs as a consequence of disruption of thiol redox circuits, which normally function in cell signaling and physiological regulation. The redox states of thiol systems are sensitive to two-electron oxidants and controlled by the thioredoxins (Trx), glutathione (GSH), and cysteine (Cys). Trx and GSH systems are maintained under stable, but nonequilibrium conditions, due to a continuous oxidation of cell thiols at a rate of about 0.5% of the total thiol pool per minute. Redox-sensitive thiols are critical for signal transduction (e.g., H-Ras, PTP-1B), transcription factor binding to DNA (e.g., Nrf-2, nuclear factor- B), receptor activation (e.g., IIbβ3 integrin in platelet activation), and other processes. Nonradical oxidants, including peroxides, aldehydes, quinones, and epoxides, are generated enzymatically from both endogenous and exogenous precursors and do not require free radicals as intermediates to oxidize or modify these thiols. Because of the nonequilibrium conditions in the thiol pathways, aberrant generation of nonradical oxidants at rates comparable to normal oxidation may be sufficient to disrupt function. Considerable opportunity exists to elucidate specific thiol control pathways and develop interventional strategies to restore normal redox control and protect against oxidative stress in aging and age-related disease.
thioredoxin; glutathione; cysteine; hydrogen peroxide; redox signaling; protein thiol
Address for reprint requests and other correspondence: D. P. Jones, Div. Pulmonary Medicine/Dept. of Medicine, Emory Univ. School of Medicine, 615 Michael St., Suite 205P, Atlanta, GA 30322 (e-mail: dpjones{at}emory.edu )
This article gives an overview of the constitution, physical conditions, and observables of dust in the interstellar medium of nearby galaxies. We first review the macroscopic, spatial distribution ...of dust in these objects and its consequences for our ability to study grain physics. We also discuss the possibility of using dust tracers as diagnostic tools. We then survey the current understanding of the microscopic, intrinsic properties of dust in different environments, derived from different observables: emission, extinction, polarization, and depletions, over the whole electromagnetic spectrum. Finally, we summarize the clues about grain evolution, evidenced either on local scales or over cosmic time. We put in perspective the different evolution scenarios. We attempt a comprehensive presentation of the main observational constraints, analysis methods, and modeling frameworks of the distinct processes. We discuss neither the dust properties of the Milky Way and distant galaxies, nor circumstellar or active galactic nucleus torus dust.
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Global forest restoration targets have been set, yet policy makers and land managers lack guiding principles on how to invest limited resources to achieve them. We conducted a meta-analysis of 166 ...studies in naturally regenerating and actively restored forests worldwide to answer: (1) To what extent do floral and faunal abundance and diversity and biogeochemical functions recover? (2) Does recovery vary as a function of past land use, time since restoration, forest region, or precipitation? (3) Does active restoration result in more complete or faster recovery than passive restoration? Overall, forests showed a high level of recovery, but the time to recovery depended on the metric type measured, past land use, and region. Abundance recovered quickly and completely, whereas diversity recovered slower in tropical than in temperate forests. Biogeochemical functions recovered more slowly after agriculture than after logging or mining. Formerly logged sites were mostly passively restored and generally recovered quickly. Mined sites were nearly always actively restored using a combination of planting and either soil amendments or recontouring topography, which resulted in rapid recovery of the metrics evaluated. Actively restoring former agricultural land, primarily by planting trees, did not result in consistently faster or more complete recovery than passively restored sites. Our results suggest that simply ending the land use is sufficient for forests to recover in many cases, but more studies are needed that directly compare the value added of active versus passive restoration strategies in the same system. Investments in active restoration should be evaluated relative to the past land use, the natural resilience of the system, and the specific objectives of each project.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cocaine addiction is a major public health problem that is particularly difficult to treat. Without medically proven pharmacological treatments, interventions to change the maladaptive behavior of ...addicted individuals mainly rely on psychosocial approaches. Here we report on impairment in cocaine-addicted patients to act purposefully toward a given goal and on the influence of extended training on their behavior. When patients were rewarded for their behavior, prolonged training improved their response rate toward the goal but simultaneously rendered them insensitive to the consequences of their actions. By contrast, overtraining of avoidance behavior had no effect on patient performance. Our findings illustrate the ineffectiveness of punitive approaches and highlight the potential for interventions that focus on improving goal-directed behavior and implementing more desirable habits to replace habitual drug-taking.
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BFBNIB, NMLJ, NUK, ODKLJ, PNG, SAZU, UL, UM, UPUK
A growing body of preclinical evidence indicates that addiction to cocaine is associated with neuroadaptive changes in frontostriatal brain systems. Human studies in cocaine-dependent individuals ...have shown alterations in brain structure, but it is less clear how these changes may be related to the clinical phenotype of cocaine dependence characterized by impulsive behaviours and compulsive drug-taking. Here we compared self-report, behavioural and structural magnetic resonance imaging data on a relatively large sample of cocaine-dependent individuals (n = 60) with data on healthy volunteers (n = 60); and we investigated the relationships between grey matter volume variation, duration of cocaine use, and measures of impulsivity and compulsivity in the cocaine-dependent group. Cocaine dependence was associated with an extensive system of abnormally decreased grey matter volume in orbitofrontal, cingulate, insular, temporoparietal and cerebellar cortex, and with a more localized increase in grey matter volume in the basal ganglia. Greater duration of cocaine dependence was correlated with greater grey matter volume reduction in orbitofrontal, cingulate and insular cortex. Greater impairment of attentional control was associated with reduced volume in insular cortex and increased volume of caudate nucleus. Greater compulsivity of drug use was associated with reduced volume in orbitofrontal cortex. Cocaine-dependent individuals had abnormal structure of corticostriatal systems, and variability in the extent of anatomical changes in orbitofrontal, insular and striatal structures was related to individual differences in duration of dependence, inattention and compulsivity of cocaine consumption.
► We develop a framework which documents relationships between greenspace and health. ► The framework highlights key mediators which underpin the relationship. ► Moderators affect the relationship, ...such as socio-economic status and greenspace type. ► The framework can be used to inform and improve planning of research studies.
A growing body of evidence investigates whether access to greenspace, such as parks and woodland, is beneficial to well-being. Potential health benefits of greenspace exposure include opportunity for activities within the space and psychological benefits of viewing and interacting with nature. However, empirical research evidence on the effects of greenspace exposure shows mixed findings. Hence we suggest that the key questions of “if, why and how?” greenspace influences health remain largely unanswered. We argue that researchers have inadequately considered the causal pathways which drive the relationship. In particular, an improved understanding is needed of potential mediators and moderators. In this paper we draw on social–ecological theories and a review of the literature to develop a novel theoretical framework which summarises current knowledge about hypothetical causal pathways between access to greenspace and health outcomes. The framework highlights how mediators – such as use of greenspace and perceptions of the living environment – drive associations between access and both physical and psychological health outcomes. We propose key moderators based on evidence that associations between greenspace and health differ by demographic factors such as gender, ethnicity and socio-economic status, living context, greenspace type and climate. We discuss the evidence for how and why these factors act as moderators and consider the implications which arise from this improved understanding of the relationship between greenspace and health. In conclusion, we discuss how the framework can be used to inform planning of research studies, and how it may be developed in the future as more evidence emerges.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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