Regulation Of Circuitry Research Articles

The neural circuitry of emotional regulation: evidence from multimodal imaging

The neural circuitry of emotional regulation: evidence from multimodal imaging

RNA-binding protein RBM5 plays an essential role in acute myeloid leukemia by activating the oncogenic protein HOXA9

BackgroundThe oncogenic protein HOXA9 plays a critical role in leukemia transformation and maintenance, and its aberrant expression is a hallmark of most aggressive acute leukemia. Although inhibiting the upstream regulators of HOXA9 has been proven as a significant therapeutic intervention, the comprehensive regulation network controlling HOXA9 expression in leukemia has not been systematically investigated.ResultsHere, we perform genome-wide CRISPR/Cas9 screening in the HOXA9-driven reporter acute leukemia cells. We identify a poorly characterized RNA-binding protein, RBM5, as the top candidate gene required to maintain leukemia cell fitness. RBM5 is highly overexpressed in acute myeloid leukemia (AML) patients compared to healthy individuals. RBM5 loss triggered by CRISPR knockout and shRNA knockdown significantly impairs leukemia maintenance in vitro and in vivo. Through domain CRISPR screening, we reveal that RBM5 functions through a noncanonical transcriptional regulation circuitry rather than RNA splicing, such an effect depending on DNA-binding domains. By integrative analysis and functional assays, we identify HOXA9 as the downstream target of RBM5. Ectopic expression of HOXA9 rescues impaired leukemia cell proliferation upon RBM5 loss. Importantly, acute protein degradation of RBM5 through auxin-inducible degron system immediately reduces HOXA9 transcription.ConclusionsWe identify RBM5 as a new upstream regulator of HOXA9 and reveal its essential role in controlling the survival of AML. These functional and molecular mechanisms further support RBM5 as a promising therapeutic target for myeloid leukemia treatment.

Development Of Solar Powered Static Wireless Charging System For Electric Vehicles

Abstract: Electric vehicles have been introduced to the contemporary world, aligning with the increasing integration of new technologies into daily life. Despite the use of electric vehicles, certain limitations persist, including issues such as heating during charging, potential charging depletion, a scarcity of charging stations, and the high installation cost of such stations. Addressing these challenges, this project proposes a wireless electric vehicle charging station with monitoring capabilities. The aims include preventing overcharging, monitoring battery levels, ensuring cost-effectiveness, promoting eco-friendliness, and strategically placing charging stations in urban areas. The project specifically focuses on the design of a solar-powered electric vehicle charging system, offering a solution to the key issues of fuel dependency and environmental pollution. Electric vehicles have gained global traction and are progressively becoming more prevalent. Beyond their environmental advantages, electric vehicles contribute to cost reduction by substituting electricity for fuel, which is a more economical alternative. This project presents an innovative solution for EV charging, eliminating the need for wires, enabling charging while in motion, harnessing solar power to sustain the charging system, and operating without external power supply requirements. The system incorporates components such as a solar panel, battery, transformer, regulator circuitry, copper coils, AC to DC converter, Atmega controller, and LCD display. Through this integration, the system showcases the wireless charging capability for electric vehicles at charging stations. The LCD display provides real-time information on the total cost, eliminating the necessity for halting the vehicle during the charging process. In summary, the project demonstrates the viability of a solar-powered wireless charging system for electric vehicles, presenting a forward-looking approach to integration.

Neurofeedback and Affect Regulation Circuitry in Depressed and Healthy Adolescents.

Neurodevelopmental psychopathology seeks to understand higher-order emotion regulation circuitry to develop new therapies for adolescents with depression. Depressed (N = 34) and healthy youth (N = 19) completed neurofeedback (NF) training and exhibited increased bilateral amygdala and hippocampus activity in the region of interest (ROI) analyses by recalling positive autobiographical memories. We tested factors supportive of the engagement of emotion regulation's neural areas during NF (i.e., parental support, medication, and gender effects upon anterior cingulate cortex (ACC) engagement). Whole-brain analyses yielded effects of NF vs. control condition and effects of diagnosis. Youth showed higher amygdala and hippocampus (AMYHIPPO) activity during the NF vs. control condition, particularly in the left hippocampus. ACC's activity was also higher during NF vs. control. Higher average ACC activity was linked to better parental support, absent depression, female gender, and absent medication. Control youth showed higher average AMYHIPPO and ACC activity throughout the task and a faster decline in activity vs. depressed youths. Whole-brain level analyses showed higher activity in the frontotemporal network during the NF vs. control conditions, suggesting targeting their connectivity in future neurofeedback trials.

Cerebellar morphological differences and associations with extrinsic factors in bipolar disorder type I

BackgroundThe neural underpinnings of bipolar disorder (BD) remain poorly understood. The cerebellum is ideally positioned to modulate emotional regulation circuitry yet has been understudied in BD. Literature suggests differences in cerebellar activity and metabolism in BD, however findings on structural differences remain contradictory. Potential reasons include combining BD subtypes, small sample sizes, and potential moderators such as genetics, adverse childhood experiences (ACEs), and pharmacotherapy. MethodsWe collected 3 T MRI scans from participants with (N = 131) and without (N = 81) BD type I, as well as blood and questionnaires. We assessed differences in cerebellar volumes and explored potentially influential factors. ResultsThe cerebellar cortex was smaller bilaterally in participants with BD. Polygenic propensity score did not predict any cerebellar volumes, suggesting that non-genetic factors may have greater influence on the cerebellar volume difference we observed in BD. Proportionate cerebellar white matter volumes appeared larger with more ACEs, but this may result from reduced ICV. Time from onset and symptom burden were not associated with cerebellar volumes. Finally, taking sedatives was associated with larger cerebellar white matter and non-significantly larger cortical volume. LimitationsThis study was cross-sectional, limiting interpretation of possible mechanisms. Most of our participants were White, which could limit the generalizability. Additionally, we did not account for potential polypharmacy interactions. ConclusionsThese findings suggest that external factors, such as sedatives and childhood experiences, may influence cerebellum structure in BD and may mask underlying differences. Accounting for such variables may be critical for consistent findings in future studies.

Transcriptomics-Driven Characterization of LUZ100, a T7-like Pseudomonas Phage with Temperate Features.

Autographiviridae is a diverse yet distinct family of bacterial viruses marked by a strictly lytic lifestyle and a generally conserved genome organization. Here, we characterized Pseudomonas aeruginosa phage LUZ100, a distant relative of type phage T7. LUZ100 is a podovirus with a limited host range which likely uses lipopolysaccharide (LPS) as a phage receptor. Interestingly, infection dynamics of LUZ100 indicated moderate adsorption rates and low virulence, hinting at temperate characteristics. This hypothesis was supported by genomic analysis, which showed that LUZ100 shares the conventional T7-like genome organization yet carries key genes associated with a temperate lifestyle. To unravel the peculiar characteristics of LUZ100, ONT-cappable-seq transcriptomics analysis was performed. These data provided a bird's-eye view of the LUZ100 transcriptome and enabled the discovery of key regulatory elements, antisense RNA, and transcriptional unit structures. The transcriptional map of LUZ100 also allowed us to identify new RNA polymerase (RNAP)-promoter pairs that can form the basis for biotechnological parts and tools for new synthetic transcription regulation circuitry. The ONT-cappable-seq data revealed that the LUZ100 integrase and a MarR-like regulator (proposed to be involved in the lytic/lysogeny decision) are actively cotranscribed in an operon. In addition, the presence of a phage-specific promoter transcribing the phage-encoded RNA polymerase raises questions on the regulation of this polymerase and suggests that it is interwoven with the MarR-based regulation. This transcriptomics-driven characterization of LUZ100 supports recent evidence that T7-like phages should not automatically be assumed to have a strictly lytic life cycle. IMPORTANCE Bacteriophage T7, considered the "model phage" of the Autographiviridae family, is marked by a strictly lytic life cycle and conserved genome organization. Recently, novel phages within this clade have emerged which display characteristics associated with a temperate life cycle. Screening for temperate behavior is of utmost importance in fields like phage therapy, where strictly lytic phages are generally required for therapeutic applications. In this study, we applied an omics-driven approach to characterize the T7-like Pseudomonas aeruginosa phage LUZ100. These results led to the identification of actively transcribed lysogeny-associated genes in the phage genome, pointing out that temperate T7-like phages are emerging more frequent than initially thought. In short, the combination of genomics and transcriptomics allowed us to obtain a better understanding of the biology of nonmodel Autographiviridae phages, which can be used to optimize the implementation of phages and their regulatory elements in phage therapy and biotechnological applications, respectively.

Neural Basis of Internal Attention in Adults with Pure and Comorbid ADHD

Objective: To examine whether putatively atypical neuronal activity during internal attention in ADHD yields insights into processes underlying emotion dysregulation. Methods: We used a word processing paradigm to assess neural activations in adults with ADHD (N = 46) compared to controls (N = 43). We measured effects of valence, applied partial-least squares correlation analysis to assess multivariate brainbehavior relationships and ran subgroup analyses to isolate results driven by pure ADHD (N = 18). Results: During internal attention, ADHD, compared to controls, have (1) increased activation in the right angular gyrus (rAG), which appears driven by pure, not comorbid, ADHD and (2) diminished activation in the insula and fronto-striatal circuitry. Diminished activations were driven by negatively-valenced internal attention and negatively correlated with increased affective lability within the ADHD group. Conclusion: Internal attention in ADHD is associated with increased rAG activation, possibly reflecting difficulty converging external and internal information, and diminished activation within emotion regulation circuitry.

Wearable E‐Skin Microgrid with Battery‐Based, Self‐Regulated Bioenergy Module for Epidermal Sweat Sensing

AbstractEnergy‐autonomous wearable systems and wearable microgrids have been a focus of developing the next‐generation wearable electronics due to their ability to harvest energy and to fully support the sustainable operation of wearable electronics. However, existing bioenergy harvesters require complex and low‐efficiency voltage regulation circuitry and have not achieved reliable extended operation and energy storage. In this work, the first example of integrating sweat lactate biofuel cells with a rechargeable Zn–AgCl battery into a bioenergy module for regulation‐free, high‐efficiency, extended biochemical energy harvesting and storage is demonstrated. The integrated bioenergy module is able to operate at its best efficiency due to their matching operating potentials and is characterized by robust mechanical durability enduring over 1000 cycles of repeated tensile deformation, as well as the outstanding long‐term autonomous operation that harvest 2.9 J of energy overnight from 20 min of exercise without measurable self‐discharge. A fully integrated wearable electronic skin patch, powered by two such bioenergy modules, is developed to wirelessly perform continuous sweat pH, ascorbic acid, and lactate sensing. The presented bioenergy module, adapting the wearable microgrid design considerations, delivers a practical, high‐efficiency, and reliable solution for next‐generation wearable electronics that features compatible form factors, commensurate performance, and complementary characteristics.

TOP2B Is Required to Maintain the Adrenergic Neural Phenotype and for ATRA-Induced Differentiation of SH-SY5Y Neuroblastoma Cells

The neuroblastoma cell line SH-SY5Y is widely used to study retinoic acid (RA)-induced gene expression and differentiation and as a tool to study neurodegenerative disorders. SH-SY5Y cells predominantly exhibit adrenergic neuronal properties, but they can also exist in an epigenetically interconvertible alternative state with more mesenchymal characteristics; as a result, these cells can be used to study gene regulation circuitry controlling neuroblastoma phenotype. Using a combination of pharmacological inhibition and targeted gene inactivation, we have probed the requirement for DNA topoisomerase IIB (TOP2B) in RA-induced gene expression and differentiation and in the balance between adrenergic neuronal versus mesenchymal transcription programmes. We found that expression of many, but not all genes that are rapidly induced by ATRA in SH-SY5Y cells was significantly reduced in the TOP2B null cells; these genes include BCL2, CYP26A1, CRABP2, and NTRK2. Comparing gene expression profiles in wild-type versus TOP2B null cells, we found that long genes and genes expressed at a high level in WT SH-SY5Y cells were disproportionately dependent on TOP2B. Notably, TOP2B null SH-SY5Y cells upregulated mesenchymal markers vimentin (VIM) and fibronectin (FN1) and components of the NOTCH signalling pathway. Enrichment analysis and comparison with the transcription profiles of other neuroblastoma-derived cell lines supported the conclusion that TOP2B is required to fully maintain the adrenergic neural-like transcriptional signature of SH-SY5Y cells and to suppress the alternative mesenchymal epithelial-like epigenetic state.

CRISPR-Based Approaches for Gene Regulation in Non-Model Bacteria.

CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) have become ubiquitous approaches to control gene expression in bacteria due to their simple design and effectiveness. By regulating transcription of a target gene(s), CRISPRi/a can dynamically engineer cellular metabolism, implement transcriptional regulation circuitry, or elucidate genotype-phenotype relationships from smaller targeted libraries up to whole genome-wide libraries. While CRISPRi/a has been primarily established in the model bacteria Escherichia coli and Bacillus subtilis, a growing numbering of studies have demonstrated the extension of these tools to other species of bacteria (here broadly referred to as non-model bacteria). In this mini-review, we discuss the challenges that contribute to the slower creation of CRISPRi/a tools in diverse, non-model bacteria and summarize the current state of these approaches across bacterial phyla. We find that despite the potential difficulties in establishing novel CRISPRi/a in non-model microbes, over 190 recent examples across eight bacterial phyla have been reported in the literature. Most studies have focused on tool development or used these CRISPRi/a approaches to interrogate gene function, with fewer examples applying CRISPRi/a gene regulation for metabolic engineering or high-throughput screens and selections. To date, most CRISPRi/a reports have been developed for common strains of non-model bacterial species, suggesting barriers remain to establish these genetic tools in undomesticated bacteria. More efficient and generalizable methods will help realize the immense potential of programmable CRISPR-based transcriptional control in diverse bacteria.

SOLAR WIRELESS ELECTRIC VEHICLE CHARGING SYSTEM

This paper describes the design of solar powered charging station for charging of electric vehicle describes design of solar powered charging station for charging of electric vehicle that solves the key downside of fuel and pollution. Electric vehicles have now hit the road worldwide and are slowly growing in numbers. Apart from environmental benefits electric vehicles have also proven helpful in reducing cost of travel by replacing fuel by electricity which is way cheaper. Well here we develop an EV charging system that solves with a unique innovative solution. This EV charging of vehicles without any wires, No need of stop for charging, vehicle charges while moving, Solar power for keeping the charging system going, No external power supply needed. The system makes use of a solar panel, battery, transformer, regulator circuitry, copper coils, AC to DC converter, atmega controller and LCD display to develop the system. The system demonstrates how electric vehicles can be charged while moving on the road, eliminating the need to stop for charging. Thus the system demonstrates a solar powered wireless charging system for electric vehicles that can be integrated in the road. Keywords: Battery; Micro Controller; Embedded System; Transformer; Microprocessor; Electric Vehicle;

Assessment of Plasma-Endogenous Opioid Neuropeptide Levels and Psychometric Properties of Non-Suicidal Self-Injury in Adolescents

Objective Non-suicidal self-injury (NSSI) is one of the most common mental health problems and growing public-health issues, coupled with a significant population-level burden among adolescents in both developed and developing countries. We aimed to assess the role of endogenous opioid system–emotion regulation circuitry in NSSI through measurement of plasma beta-endorphin (β-EP), met-enkephalin (MENK) levels, and determination of psychometric features of Turkish adolescent subjects. Method In this research, we measured plasma β-EP and MENK levels of 49 adolescents with NSSI and 39 control subjects without NSSI between the ages of 12–18 years. All adolescent subjects were observed in the outpatient clinic, and their clinical and sociodemographic characteristics were examined. All subjects were assessed using the Brief Symptom Inventory (BSI) and Inventory of Statements About Self Injury (ISAS). Results Plasma β-EP levels were statistically lower in adolescents with NSSI than control group, whereas there was no statistically significant difference in MENK levels. β-EP levels showed a negative correlation with depression severity. The data obtained from BSI and ISAS were not found to be associated with both β-EP and MENK levels, while subscale scores exhibited versatile correlations. Conclusion Our findings supported the salient role of β-EP in NSSI behavior. Also, decreased plasma β-EP could be assessed as a reliable indicator for NSSI. However, it is possible that measurement of basal plasma levels of neuropeptides might also bring many confounders and could cause bias. Therefore, repeated measurements of plasma-endogenous opioid neuropeptides in a time-dependent manner—concomitant to engage of NSSI behavior—might give more reliable results.

Transdiagnostic alterations in neural emotion regulation circuits \u2013 neural substrates of cognitive reappraisal in patients with depression and post-traumatic stress disorder

BackgroundImpaired cognitive reappraisal, associated with the social functioning and well-being of patients affected by mood or anxiety disorders, is characterized by distinct neural activation patterns across clinical populations. To date, studies dedicated to identifying common and distinct neural activation profiles need to be clarified. The aim of the present study was to investigate transdiagnostic differences and commonalities in brain activation patterns during reappraisal-mediated downregulation of emotions.MethodsCognitive reappraisal of negative images was contrasted with maintaining emotions during a control viewing condition. Brain activation in 35 patients with major depressive disorder (MDD), 20 patients with post-traumatic stress disorder (PTSD), and 34 healthy controls (HC) during cognitive reappraisal was compared. Moreover, the neural circuitry of emotion regulation in these clinical populations was examined using seed-to-voxel and voxel-to-voxel functional connectivity analyses.ResultsWhole-brain fMRI analyses showed less right-lateralized activation of the inferior, middle, and superior frontal gyrus during cognitive reappraisal compared to viewing of negative images in MDD and PTSD patients compared to HCs. Right IFG activation was negatively correlated with the severity of anxiety and depressive symptomatology. In addition, increased seed-to-voxel connectivity of the right IFG as well as increased voxel-to-voxel connectivity was observed in PTSD patients compared to HCs and MDD patients.ConclusionsFMRI results therefore suggested a common deficit of depression and anxiety symptomatology reflected by reduced activation in right IFG during cognitive reappraisal as well as diagnosis specific effects in patients with PTSD based on seed-to-voxel and voxel-to-voxel connectivity showing an overactive and hyperconnected salience network. Findings highlight the role of transdiagnostic research to identify disorder specific brain patterns as well as patterns common across disorders.

Platform imperialism, communications law and relational sovereignty

While many have asked whether the law can keep up with new technologies, we may need to ask bigger questions, lest in ‘updating’ we redraw the circuits of inequitable power relations. The fundamental ideas of autonomy and sovereignty that sit at the heart of the circuitry of platform and technological regulation must be reconsidered. How can we rewire this system? Examining the ways that relational thinking has been employed normatively, particularly in areas of communications law, this article suggests that we can draw on relational thinking, understood through critical theories that deal with historical structural relations, for guidance on how to rewire our legal operating system. Critical theories can infuse a relational approach to understanding communication law, which can be drawn on to rewire our legal operating system.

Regulation of sensorimotor gating via Disc1/Huntingtin-mediated Bdnf transport in the cortico-striatal circuit.

Sensorimotor information processing underlies normal cognitive and behavioral traits and has classically been evaluated through prepulse inhibition (PPI) of a startle reflex. PPI is a behavioral dimension deregulated in several neurological and psychiatric disorders, yet the mechanisms underlying the cross-diagnostic nature of PPI deficits across these conditions remain to be understood. To identify circuitry mechanisms for PPI, we performed circuitry recording over the prefrontal cortex and striatum, two brain regions previously implicated in PPI, using wild-type (WT) mice compared to Disc1-locus-impairment (LI) mice, a model representing neuropsychiatric conditions. We demonstrated that the corticostriatal projection regulates neurophysiological responses during the PPI testing in WT, whereas these circuitry responses were disrupted in Disc1-LI mice. Because our biochemical analyses revealed attenuated brain-derived neurotrophic factor (Bdnf) transport along the corticostriatal circuit in Disc1-LI mice, we investigated the potential role of Bdnf in this circuitry for regulation of PPI. Virus-mediated delivery of Bdnf into the striatum rescued PPI deficits in Disc1-LI mice. Pharmacologically augmenting Bdnf transport by chronic lithium administration, partly via phosphorylation of Huntingtin (Htt) serine-421 and its integration into the motor machinery, restored striatal Bdnf levels and rescued PPI deficits in Disc1-LI mice. Furthermore, reducing the cortical Bdnf expression negated this rescuing effect of lithium, confirming the key role of Bdnf in lithium-mediated PPI rescuing. Collectively, the data suggest that striatal Bdnf supply, collaboratively regulated by Htt and Disc1 along the corticostriatal circuit, is involved in sensorimotor gating, highlighting the utility of dimensional approach in investigating pathophysiological mechanisms across neuropsychiatric disorders.

Frontostriatal functional connectivity underlies self-enhancement during social evaluation.

Self-enhancement, the tendency to view oneself positively, is a pervasive social motive widely investigated in the psychological sciences. Relatively little is known about the neurocognitive mechanisms underlying this motive, specifically in social-evaluative situations. To investigate whether positive emotion regulation circuitry, circuitry involved in modulating positive affect, relates to the self-enhancement motive in social contexts, we conducted an functional magnetic resonance imaging (fMRI) study in a healthy young adult sample. We hypothesized that self-enhancement indices (state and trait self-esteem) would relate to greater functional connectivity between right ventrolateral prefrontal cortex (RVLPFC), a region implicated in emotion regulation, and the ventral striatum (VS), a region associated with reward-related affect, during a social feedback task. Following social evaluation, participants experienced stable or decreased state self-esteem. Results showed that stable state self-esteem from pre- to post-scan and higher trait self-esteem related to greater RVLPFC–VS connectivity during positive evaluation. Stable-state self-esteem also related to greater RVLPFC–VS connectivity during negative evaluation. Moreover, RVLPFC activation during all types of feedback processing and left VS activation during negative feedback processing was greater for participants with stable-state self-esteem. These findings implicate neurocognitive mechanisms underlying emotion regulation in the self-enhancement motive and highlight a pathway through which self-enhancement may restore feelings of self-worth during threatening situations.

Dual role of a dedicated GAPDH in the biosynthesis of volatile and non-volatile metabolites- novel insights into the regulation of secondary metabolism in Trichoderma virens

Trichoderma virens produces viridin/viridiol, heptelidic (koningic) acid, several volatile sesquiterpenes and gliotoxin (Q strains) or gliovirin (P strains). We earlier reported that deletion of the terpene cyclase vir4 and a glyceraldehyde-3-phosphate dehydrogenase (GAPDH, designated as vGPD) associated with the “vir” cluster abrogated the biosynthesis of several volatile sesquiterpene metabolites. Here we show that, the deletion of this GAPDH also impairs the biosynthesis of heptelidic acid (a non-volatile sesquiterpene), viridin (steroid) and gliovirin (non-ribosomal peptide), indicating regulation of non-volatile metabolite biosynthesis by this GAPDH that is associated with a secondary metabolism gene cluster. To gain further insights into the details of this novel form of regulation, we identified the terpene cyclase gene responsible for heptelidic acid biosynthesis (hereafter designated as has1) and prove that the expression of this gene is regulated by vGPD. Interestingly, deletion of has1 impaired biosynthesis of heptelidic acid (HA), viridin and gliovirin, but not of volatile sesquiterpenes. Deletion of the vir cluster associated terpene cyclase gene (vir4), located next to the vGPD gene, did not impair biosynthesis of HA, viridin or gliovirin. We thus unveil a novel circuitry of regulation of secondary metabolism where an HA-tolerant GAPDH isoform (vGPD) regulates HA biosynthesis through the transcriptional regulation of the HA-synthase gene (which is not part of the “vir” cluster). Interestingly, impairment of HA biosynthesis leads to the down-regulation of biosynthesis of other non-volatile secondary metabolites, but not of volatile secondary metabolites. We thus provide evidence that the “vir” cluster associated, HA-tolerant GAPDH in T. virens participates in the biosynthesis of volatile sesquiterpenes as a biosynthetic enzyme, and regulates the production of non-volatile metabolites via regulation of HA biosynthesis. The orthologue of the “vir” cluster in Aspergillus oryzae was earlier reported to synthesize HA by another group. Our study thus proves that the same gene cluster can code for unrelated metabolites in different species.

Designing a Wind Energy Harvester for Connected Vehicles in Green Cities

Electric vehicles (EVs) have recently gained momentum as an integral part of the Internet of Vehicles (IoV) when authorities started expanding their low emission zones (LEZs) in an effort to build green cities with low carbon footprints. Energy is one of the key requirements of EVs, not only to support the smooth and sustainable operation of EVs, but also to ensure connectivity between the vehicle and the infrastructure in the critical times such as disaster recovery operation. In this context, renewable energy sources (such as wind energy) have an important role to play in the automobile sector towards designing energy-harvesting electric vehicles (EH-EV) to mitigate energy reliance on the national grid. In this article, a novel approach is presented to harness energy from a small-scale wind turbine due to vehicle mobility to support the communication primitives in electric vehicles which enable plenty of IoV use cases. The harvested power is then processed through a regulation circuitry to consequently achieve the desired power supply for the end load (i.e., battery or super capacitor). The suitable orientation for optimum conversion efficiency is proposed through ANSYS-based aerodynamics analysis. The voltage-induced by the DC generator is 35 V under the no-load condition while it is 25 V at a rated current of 6.9 A at full-load, yielding a supply of 100 W (on constant voltage) at a speed of 90 mph for nominal battery charging.

Exposure to phthalates in relation to sleep duration and social jetlag among adolescent boys and girls in Mexico City

BACKGROUND AND AIM: Emerging research has demonstrated the importance of environmental toxicants, such as phthalates, for sleep health, as they may disrupt neuronal sleep regulation circuitry. However, the impact of high-molecular-weight (HMW) versus low-molecular-weight (LMW) phthalates remains unknown. Among Mexican adolescents, we evaluated the association between exposure to HMW and LMW phthalates with sleep duration and social jetlag (a circadian marker that measures the discrepancy between weekend and weekday sleep duration). METHODS: Participants included 413 adolescents from the Early Life Exposures in Mexico to ENvironmental Toxicants (ELEMENT) study. In 2015, urinary concentrations of 13 phthalates were measured from spot urine samples, and sleep duration was assessed with wrist-actigraph devices over 7consecutive days. We examined associations between phthalates with mean weekday and weekend sleep duration and social jetlag using linear regression models, adjusted for specific-gravity, sex, age, BMI z-score, total energy intake, caffeine intake, and physical activity. RESULTS:The mean (SD) age was 15.6 (2.0) years; 53.5% were girls. The mean (SD) sleep duration was 8.4 (1.2) hr/night on weekdays and 9.0 (1.3) hr/night on weekends. In adjusted models, each IQR increase in the HMW phthalate, mono-(2-ethyl-5-oxohexyl) phthalate was associated with a 13.3 minute (95%CI: -26.3, -0.41; p 0.05) lower social jetlag, and each IQR increase in mono-benzyl phthalate was associated with an 8.0 minute (95% CI: -16.8, -0.72; p 0.05) shorter sleep duration on weekends. Among LMW phthalates, we found that each IQR increase in monoethyl phthalate was associated with an 8.6 minute (95% CI: -17.9, -0.63; p 0.05) shorter sleep duration on weekends and a 15.3 minute (95% CI: -29.0, -1.6; p 0.05) lower social jetlag. CONCLUSIONS:In contrast to other literature, higher phthalate exposure was related to shorter weekend sleep duration and lower social jetlag among Mexican adolescents, sleep characteristics that may be indicative of better sleep health. KEYWORDS: phthalates; environmental epidemiology; adolescent sleep health; social jetlag, sleep duration, wrist-actigraphy

Whole-brain mapping of amylin-induced neuronal activity in receptor activity-modifying protein 1/3 knockout mice.

The pancreatic hormone amylin plays a central role in regulating energy homeostasis and glycaemic control by stimulating satiation and reducing food reward, making amylin receptor agonists attractive for the treatment of metabolic diseases. Amylin receptors consist of heterodimerized complexes of the calcitonin receptor and receptor-activity modifying proteins subtype 1-3 (RAMP1-3). Neuronal activation in response to amylin dosing has been well characterized, but only in selected regions expressing high levels of RAMPs. The current study identifies global brain-wide changes in response to amylin and by comparing wild type and RAMP1/3 knockout mice reveals the importance of RAMP1/3 in mediating this response. Amylin dosing resulted in neuronal activation as measured by an increase in c-Fos labelled cells in 20 brain regions, altogether making up the circuitry of neuronal appetite regulation (e.g., area postrema (AP), nucleus of the solitary tract (NTS), parabrachial nucleus (PB), and central amygdala (CEA)). c-Fos response was also detected in distinct nuclei across the brain that typically have not been linked with amylin signalling. In RAMP1/3 knockout amylin induced low-level neuronal activation in seven regions, including the AP, NTS and PB, indicating the existence of RAMP1/3-independent mechanisms of amylin response. Under basal conditions RAMP1/3 knockout mice show reduced neuronal activity in the hippocampal formation as well as reduced hippocampal volume, suggesting a role for RAMP1/3 in hippocampal physiology and maintenance. Altogether these data provide a global map of amylin response in the mouse brain and establishes the significance of RAMP1/3 receptors in relaying this response.