Neural activation associated with the cognitive emotion regulation of sadness in healthy children

AbstractWhen used effectively, cognitive reappraisal of distressing events is a highly adaptive cognitive emotion regulation (CER) strategy, with impairments in cognitive reappraisal associated with greater risk for psychopathology. Despite extensive literature examining the neural correlates of cognitive reappraisal in healthy and psychiatrically ill adults, there is a dearth of data to inform the neural bases of CER in children, a key gap in the literature necessary to map the developmental trajectory of cognitive reappraisal. In this fMRI study, psychiatrically healthy schoolchildren were instructed to use cognitive reappraisal to modulate their emotional reactions and responses of negative affect after viewing sad photos. Consistent with the adult literature, when actively engaged in reappraisal compared to passively viewing sad photos, children showed increased activation in the vlPFC, dlPFC, and dmPFC as well as in parietal and temporal lobe regions. When children used cognitive reappraisal to minimize their experience of negative affect after viewing sad stimuli they exhibited dampened amygdala responses. Results are discussed in relation to the importance of identifying and characterizing neural processes underlying adaptive CER strategies in typically developing children in order to understand how these systems go awry and relate to the risk and occurrence of affective disorders

Genetic and Molecular Characterization of a Cryptochrome from the Filamentous Fungus Neurospora Crassa

In plants and animals, cryptochromes function as either photoreceptors or circadian clock components. We have examined the cryptochrome from the filamentous fungus Neurospora crassa and demonstrate that Neurospora cry encodes a DASH-type cryptochrome that appears capable of binding flavin adenine dinucleotide (FAD) and methenyltetrahydrofolate (MTHF). The cry transcript and CRY protein levels are strongly induced by blue light in a wc-1-dependent manner, and cry transcript is circadianly regulated, with a peak abundance opposite in phase to frq. Neither deletion nor overexpression of cry appears to perturb the free-running circadian clock. However, cry disruption knockout mutants show a small phase delay under circadian entrainment. Using electrophoretic mobility shift assays (EMSA), we show that CRY is capable of binding single- and double-stranded DNA (ssDNA and dsDNA, respectively) and ssRNA and dsRNA. Whole-genome microarray experiments failed to identify substantive transcriptional regulatory activity of cry under our laboratory conditions

Brain-behavior relationships in the experience and regulation of negative emotion in healthy children: Implications for risk for childhood depression

Structural and functional alterations in a variety of brain regions have been associated with depression and risk for depression across the life span. A majority of these regions are associated with emotion reactivity and/or regulation. However, it is generally unclear what mechanistic role these alterations play in the etiology of depression. A first step toward understanding this is to characterize the relationships between variation in brain structure/function and individual differences in depression severity and related processes, particularly emotion regulation. To this end, the current study examines how brain structure and function predict concurrent and longitudinal measures of depression symptomology and emotion regulation skills in psychiatrically healthy school-age children (N = 60). Specifically, we found that smaller hippocampus volumes and greater responses to sad faces in emotion reactivity regions predict increased depressive symptoms at the time of scan, whereas larger amygdala volumes, smaller insula volumes, and greater responses in emotion reactivity regions predict decreased emotion regulation skills. In addition, larger insula volumes predict improvements in emotion regulation skills even after accounting for emotion regulation at the time of scan. Understanding brain–behavior relationships in psychiatrically healthy samples, especially early in development, will help inform normative developmental trajectories and neural alterations in depression and other affective pathology

Functional connectivity of the amygdala and subgenual cingulate during cognitive reappraisal of emotions in children with MDD history is associated with rumination

AbstractMajor Depressive Disorder (MDD) is characterized by poor emotion regulation. Rumination, a maladaptive strategy for dealing with negative emotions, is common in MDD, and is associated with impaired inhibition and cognitive inflexibility that may contribute to impaired emotion regulation abilities. However, it is unclear whether rumination is differently associated with emotion regulation in individuals with MDD history (MDD-ever) and healthy individuals. In this study, children (8–15 years old) performed a cognitive reappraisal task in which they attempted to decrease their emotional response to sad images during fMRI scanning. Functional connectivity (FC) between both the amygdala and subgenual anterior cingulate (sACC) increased with cortical control regions during reappraisal as rumination increased in MDD-ever, while connectivity between those regions decreased during reappraisal as rumination increased in healthy controls. As the role of cortical control regions is to down-regulate activity of emotion processing regions during reappraisal, this suggests that rumination in MDD-ever, but not controls, is associated with inefficient regulation. This finding suggests that rumination may be particularly associated with poor emotion regulation in MDD-ever, and may also indicate qualitative group differences in whether rumination is maladaptive. These differences in rumination may provide important insight into depressive risk and potential avenues for treatment

Role of activating transcription factor 4 in the hepatic response to amino acid depletion by asparaginase

The anti-leukemic agent asparaginase activates the integrated stress response (ISR) kinase GCN2 and inhibits signaling via mechanistic target of rapamycin complex 1 (mTORC1). The study objective was to investigate the protective role of activating transcription factor 4 (ATF4) in controlling the hepatic transcriptome and mediating GCN2-mTORC1 signaling during asparaginase. We compared global gene expression patterns in livers from wildtype, Gcn2 -/-, and Atf4 -/- mice treated with asparaginase or excipient and further explored selected responses in livers from Atf4 +/- mice. Here, we show that ATF4 controls a hepatic gene expression profile that overlaps with GCN2 but is not required for downregulation of mTORC1 during asparaginase. Ingenuity pathway analysis indicates GCN2 independently influences inflammation-mediated hepatic processes whereas ATF4 uniquely associates with cholesterol metabolism and endoplasmic reticulum (ER) stress. Livers from Atf4 -/- or Atf4 +/- mice displayed an amplification of the amino acid response and ER stress response transcriptional signatures. In contrast, reduction in hepatic mTORC1 signaling was retained in Atf4 -/- mice treated with asparaginase

More than skin deep: Functional genomic basis for resistance to Amphibian Chytridiomycosis

The amphibian-killing chytrid fungus Batrachochytriumdendrobatidis (Bd) is one of themost generalist pathogens known, capable of infecting hundreds of species globally and causing widespread population declines and extinctions. However, some host species are seemingly unaffected by Bd, tolerating or clearing infections without clinical signs of disease. Variation in host immune responses is commonly evoked for these resistant or tolerant species, yet to date,we have nodirect comparisonof amphibian species responses to infection at the level of gene expression. In this study,we challenged four CentralAmerican frog species that vary in Bd susceptibility, with a sympatric virulent strain of the pathogen. We compared skin and spleen orthologous gene expression using differential expression tests and coexpression gene network analyses.Wefound that resistant species have reduced skin inflammatory responses andincreased expressionofgenes involved inskin integrity. Incontrast, onlyhighly susceptible species exhibited suppressionof splenic T-cell genes. We conclude that resistance to chytridiomycosis may be related to a species’ ability to escape the immunosuppressive activity of the fungus. Moreover, our results indicate that within-species differences in splenic proteolytic enzyme gene expression may contribute to intraspecific variation in survival. This first comparison of amphibian functional immunogenomic architecture in response to Bd provides insights into key genetic mechanisms underlying variation in disease outcomes among amphibian species

Managed Aquifer Recharge as a Tool to Enhance Sustainable Groundwater Management in California

A growing population and an increased demand for water resources have resulted in a global trend of groundwater depletion. Arid and semi-arid climates are particularly susceptible, often relying on groundwater to support large population centers or irrigated agriculture in the absence of sufficient surface water resources. In an effort to increase the security of groundwater resources, managed aquifer recharge (MAR) programs have been developed and implemented globally. MAR is the approach of intentionally harvesting and infiltrating water to recharge depleted aquifer storage. California is a prime example of this growing problem, with three cities that have over a million residents and an agricultural industry that was valued at 47 billion dollars in 2015. The present-day groundwater overdraft of over 100 km3 (since 1962) indicates a clear disparity between surface water supply and water demand within the state. In the face of groundwater overdraft and the anticipated effects of climate change, many new MAR projects are being constructed or investigated throughout California, adding to those that have existed for decades. Some common MAR types utilized in California include injection wells, infiltration basins (also known as spreading basins, percolation basins, or recharge basins), and low-impact development. An emerging MAR type that is actively being investigated is the winter flooding of agricultural fields using existing irrigation infrastructure and excess surface water resources, known as agricultural MAR. California therefore provides an excellent case study to look at the historical use and performance of MAR, ongoing and emerging challenges, novel MAR applications, and the potential for expansion of MAR. Effective MAR projects are an essential tool for increasing groundwater security, both in California and on a global scale. This chapter aims to provide an overview of the most common MAR types and applications within the State of California and neighboring semi-arid regions