The past decade has experienced renewed interest in the physical processes that fold the developing cerebral cortex. Biomechanical models and experiments suggest that growth of the cortex, outpacing ...growth of underlying subcortical tissue (prospective white matter), is sufficient to induce folding. However, current models do not explain the well-established links between white matter organization and fold morphology, nor do they consider subcortical remodeling that occurs during the period of folding. Here we propose a framework by which cortical folding may induce subcortical fiber growth and organization. Simulations incorporating stress-induced fiber elongation indicate that subcortical stresses resulting from folding are sufficient to induce stereotyped fiber organization beneath gyri and sulci. Model predictions are supported by high-resolution ex vivo diffusion tensor imaging of the developing rhesus macaque brain. Together, results provide support for the theory of cortical growth-induced folding and indicate that mechanical feedback plays a significant role in brain connectivity.
Increased production of fetal hemoglobin (HbF) can ameliorate the severity of sickle cell disease and β-thalassemia. BCL11A has been identified as a key regulator of HbF silencing, although its ...precise mechanisms of action remain incompletely understood. Recent studies have identified pathogenic mutations that cause heterozygous loss-of-function of BCL11A and result in a distinct neurodevelopmental disorder that is characterized by persistent HbF expression. While the majority of cases have deletions or null mutations causing haploinsufficiency of BCL11A, several missense variants have also been identified. Here, we perform functional studies on these variants to uncover specific liabilities for BCL11A's function in HbF silencing. We find several mutations in an N-terminal C2HC zinc finger that increase proteasomal degradation of BCL11A. We also identify a distinct C-terminal missense variant in the fifth zinc finger domain that we demonstrate causes loss-of-function through disruption of DNA binding. Our analysis of missense variants causing loss-of-function in vivo illuminates mechanisms by which BCL11A silences HbF and also suggests potential therapeutic avenues for HbF induction to treat sickle cell disease and β-thalassemia.
Small-scale fisheries are an important source of food and livelihoods to coastal communities around the world. Understanding the seasonality of fisheries catch and composition is crucial to fisheries ...management, particularly in the context of changing environmental and socioeconomic conditions. While seasonal variability directly impacts the lives of fishers, most fisheries studies focus on longer-term change. Here we examine seasonal variability in the small-scale fisheries of Baja California Sur, Mexico based on 13 years of government fisheries data. We investigate how four fisheries indicators with direct relevance to ecological resilience-magnitude and variance of landed fish biomass, taxon richness and the proportion of top-trophic-level taxa in total catch-vary within and among years and at multiple spatial scales. We find that these resilience indicators vary both seasonally and spatially. These results highlight the value of finer-scale monitoring and management, particularly for data-poor fisheries.
Two commonly used insecticides, bifenthrin and fipronil, can accumulate in the prey of juvenile Chinook salmon, yet the effects of dietary exposure are not understood. Therefore, to better ...characterize the effect of a dietary exposure route, juvenile Chinook salmon were fed chironomids dosed with a concentration of 9 or 900 ng/g of bifenthrin, fipronil, or their mixture for 25 days at concentrations previously measured in field-collected samples. Chinook were assessed for maximum swimming performance (U max) using a short-duration constant acceleration test and biochemical responses related to energetic processes (glucose levels) and liver health (aspartate aminotransferase (AST) activity). Chinook exposed to bifenthrin and bifenthrin and fipronil mixtures had a significantly reduced swimming performance, although not when exposed to fipronil alone. The AST activity was significantly increased in bifenthrin and mixture treatments and glucose levels were increased in Chinook following a mixture treatment, although not when exposed to fipronil alone. These findings suggest that there are different metabolic processes between bifenthrin and fipronil following dietary uptake that may influence toxicity. The significant reductions in swimming performance and increased levels of biochemical processes involved in energetics and fish heath could have implications for foraging activity and predator avoidance in wild fish at sensitive life stages.
Properties of AGN coronae in the NuSTAR era Fabian, A. C.; Lohfink, A.; Kara, E. ...
Monthly notices of the Royal Astronomical Society,
08/2015, Volume:
451, Issue:
4
Journal Article
Peer reviewed
The focusing optics of NuSTAR have enabled high signal-to-noise ratio spectra to be obtained from many X-ray bright active galactic nuclei (AGN) and galactic black hole binaries (BHB). Spectral ...modelling then allows robust characterization of the spectral index and upper energy cutoff of the coronal power-law continuum, after accounting for reflection and absorption effects. Spectral-timing studies, such as reverberation and broad iron line fitting, of these sources yield coronal sizes, often showing them to be small and in the range of 3 to 10 gravitational radii in size. Our results indicate that coronae are hot and radiatively compact, lying close to the boundary of the region in the compactness–temperature (Θ − ℓ) diagram which is forbidden due to runaway pair production. The coincidence suggests that pair production and annihilation are essential ingredients in the coronae of AGN and BHB and that they control the shape of the observed spectra.
Objective To examine differences in lifetime prevalence of mental disorder and service use among U.S. adolescents by both immigrant generation and race/ethnicity. Method A total of 6,250 adolescents ...aged 13 to 18 years in the National Comorbidity Survey Replication Adolescent Supplement were assessed for lifetime prevalence of mood and/or anxiety disorders, behavior disorders, and mental health service use. Twelve groups defined by self-identified race/ethnicity (non-Hispanic white, Hispanic, non-Hispanic black, Asian) and immigrant generation (first, second, third, or more) were compared. Results Differences in prevalence of lifetime mental disorder were most apparent when immigrant generation and race/ethnicity were considered jointly. Compared to third+generation non-Hispanic white adolescents, the odds of mood/anxiety disorder were increased among second-generation Asian (adjusted odds ratio AOR = 2.51; 95% CI = 1.22−5.17) and third+generation Hispanic (AOR = 1.28; 95% CI = 1.00−1.63) but reduced among first-generation Asian (AOR = 0.27; 95% CI = 0.10−0.71) and second-generation non-Hispanic white adolescents (AOR = 0.50; 95% CI = 0.30−0.81). The odds of behavior disorder were lower among first-generation Asian (AOR = 0.26; 95% CI = 0.09−0.71) and all generations of non-Hispanic black adolescents (AOR range 0.43−0.55). Adjusting for lifetime disorder, first-generation Hispanic and non-Hispanic white adolescents and all generations of non-Hispanic black adolescents were less likely to receive mental health services (AOR range 0.24−0.55). Conclusions Variation in risk of disorder by immigrant generation and race/ethnicity underscores the importance of considering social, economic, and cultural influences in etiologic and treatment studies of adolescent psychopathology. Lower rates of service use, particularly among first-generation immigrant adolescents, highlight the need to identify and address barriers to recognition and treatment of mental disorders among adolescents from immigrant and racial/ethnic minority backgrounds.
General relativistic ray tracing simulations of the time-averaged spectrum and energy-dependent time delays in active galactic nuclei (AGN) are presented. We model the lamp-post geometry in which the ...accreting gas is illuminated by an X-ray source located on the rotation axis of the black hole. The spectroscopic features imprinted in the reflection component are modelled using reflionx. The associated time delays after the direct continuum, known as reverberation lags, are computed including the full effects of dilution and ionization gradients on the disc. We perform, for the first time, simultaneous fitting of the time-averaged and lag-energy spectra in three AGN: Mrk 335, IRAS 13224−3809 and Ark 564 observed with XMM–Newton. The best-fitting source height and central mass of each AGN partly agree with those previously reported. We find that including the ionization gradient in the model naturally explains lag-energy observations in which the 3 keV and 7–10 keV bands precede other bands. To obtain the clear 3 keV and 7–10 keV dips in the lag-energy profile, the model requires either a source height >5 r
g, or a disc that is highly ionized at small radii and is colder further out. We also show that fitting the lag or the mean spectra alone can lead to different results and interpretations. This is therefore important to combine the spectral and timing data in order to find the plausible but self-consistent fits which are achievable with our model.
IMPORTANCE: Indoor nighttime light exposure influences sleep and circadian rhythms and is known to affect mood-associated brain circuits in animals. However, little is known about the association ...between levels of nighttime outdoor light and sleep and mental health in the population, especially among adolescents. OBJECTIVE: To estimate associations of outdoor artificial light at night (ALAN) with sleep patterns and past-year mental disorder among US adolescents. DESIGN, SETTING, AND PARTICIPANTS: This population-based, cross-sectional study of US adolescents used the National Comorbidity Survey–Adolescent Supplement, a nationally representative cross-sectional survey conducted from February 2001 through January 2004. A probability sample of adolescents aged 13 to 18 years was included. Analyses were conducted between February 2019 and April 2020. EXPOSURES: Levels of outdoor ALAN, measured by satellite, with means calculated within census block groups. ALAN values were transformed into units of radiance (nW/cm2/sr). MAIN OUTCOMES AND MEASURES: Self-reported habitual sleep patterns (weeknight bedtime, weeknight sleep duration, weekend bedtime delay, and weekend oversleep) and past-year mood, anxiety, behavior, and substance use disorders, measured via an in-person structured diagnostic interview. Parent-reported information was included in behavior disorder diagnoses. RESULTS: Among 10 123 adolescents (4953 boys 51.3%; mean SE age, 15.2 0.06 years weighted; 6483 for behavior disorder outcomes), ALAN was positively associated with indicators of social disadvantage, such as racial/ethnic minority status (median IQR ALAN: white adolescents, 12.96 30.51 nW/cm2/sr; Hispanic adolescents: 38.54 47.84 nW/cm2/sr; non-Hispanic black adolescents: 37.39 51.88 nW/cm2/sr; adolescents of other races/ethnicities: 30.94 49.93 nW/cm2/sr; P < .001) and lower family income (median IQR ALAN by family income-to-poverty ratio ≤1.5: 26.76 52.48 nW/cm2/sr; >6: 21.46 34.38 nW/cm2/sr; P = .005). After adjustment for several sociodemographic characteristics, as well as area-level population density and socioeconomic status, this study found that higher ALAN levels were associated with later weeknight bedtime, and those in the lowest quartile of ALAN reported the longest weeknight sleep duration. Those in the highest quartile of ALAN went to bed 29 (95% CI, 15-43) minutes later and reported 11 (95% CI, 19-2) fewer minutes of sleep than those in the lowest quartile. ALAN was also positively associated with prevalence of past-year mood and anxiety disorder: each median absolute deviation increase in ALAN was associated with 1.07 (95% CI, 1.00-1.14) times the odds of mood disorder and 1.10 (95% CI, 1.05-1.16) times the odds of anxiety disorder. Further analyses revealed associations with bipolar disorder (odds ratio OR, 1.19 95% CI, 1.05-1.35), specific phobias (OR, 1.18 95% CI, 1.11-1.26), and major depressive disorder or dysthymia (OR, 1.07 95% CI, 1.00-1.15). Among adolescent girls, differences in weeknight bedtime by ALAN (third and fourth quartiles vs first quartile) were greater with increasing years since menarche (F3, 8.15; P < .001). CONCLUSIONS AND RELEVANCE: In this study, area-level outdoor ALAN was associated with less favorable sleep patterns and mood and anxiety disorder in adolescents. Future studies should elucidate whether interventions to reduce exposure to ALAN may positively affect mental and sleep health.
Migrants who reach EU asylum camps face various forms of spatialised violence that are bolstered by or produced within these geopolitical protracted spaces of waiting. Segregated from society, ...migrants experience processes of displacement, alienation and vulnerability as their legal status restricts their mobility and postpones employment or education opportunities. They are simultaneously suspended in a state of continuous disruption as they move through a series of camps while waiting for a decision on their applications. In remonstration, some migrants develop advocacy networks within and across camps in an attempt to challenge the hierarchical control of the everyday spaces and politics that migrants encounter in camps. Drawing on original fieldwork, this paper interrogates the intersection of the spatial production of geopolitical violence in camps and migrant agency within these distinctive political spaces. I argue that a state-centred examination of spaces of violence and migrant agency fails to attend to embodied and emotional landscapes when problematising the geographies of camps and those waiting in interim zones of confinement. In contrast, this examination of the embodied migrant experiences and advocacy networks brings the geopolitics of human and affective matter to the forefront. In this way, the article highlights migrant agency in response to their lived experience and the embodied geopolitical violence of control, categorisation and exclusion that is produced in the various spatialities of asylum seeking.
A central question in biology is the molecular origins of phenotypic diversity. While genetic changes are key to the genotype-phenotype relationship, alterations to chromatin structure and the ...physical packaging of histone proteins may also be important drivers of vertebrate divergence. We investigate the impact of such an epigenetic mechanism, histone acetylation, within a textbook example of an adaptive radiation. Cichlids of Lake Malawi have adapted diverse craniofacial structures, and here we investigate how histone acetylation influences morphological variation in these fishes. Specifically, we assessed the effect of inhibiting histone deacetylation using the drug trichostatin A (TSA) on developing facial structures. We examined this during three critical developmental windows in two cichlid species with alternate adult morphologies. Exposure to TSA during neural crest cell (NCC) migration and as postmigratory NCCs proliferate in the pharyngeal arches resulted in significant changes in lateral and ventral shape in Maylandia, but not in Tropheops. This included an overall shortening of the head, widening of the lower jaw, and steeper craniofacial profile, all of which are paedomorphic morphologies. In contrast, treatment with TSA during early chondrogenesis did not result in significant morphological changes in either species. Together, these data suggest a sensitivity to epigenetic alterations that are both time- and species-dependent. We find that morphologies are due to nonautonomous or potentially indirect effects on NCC development, including in part a global developmental delay. Our research bolsters the understanding that proper histone acetylation is essential for early craniofacial development and identifies a species-specific robustness to developmental change. Overall, this study demonstrates how epigenetic regulation may play an important role in both generating and buffering morphological variation.
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