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PURPOSE: QSM provides insight into healthy brain aging and neuropathologies such as multiple sclerosis (MS), traumatic brain injuries, brain tumors, and neurodegenerative diseases. Phase data for QSM are usually acquired from 3D gradient-echo (3D GRE) scans with long acquisition times that are detrimental to patient comfort and susceptible to patient motion. This is particularly true for scans requiring whole-brain coverage and submillimeter resolutions. In this work, we use a multishot 3D echo plannar imaging (3D EPI) sequence with shot-selective 2D CAIPIRIHANA to acquire high-resolution, whole-brain data for QSM with minimal distortion and blurring. METHODS: To test clinical viability, the 3D EPI sequence was used to image a cohort of MS patients at 1-mm isotropic resolution at 3 T. Additionally, 3D EPI data of healthy subjects were acquired at 1-mm, 0.78-mm, and 0.65-mm isotropic resolution with varying echo train lengths (ETLs) and compared with a reference 3D GRE acquisition. RESULTS: The appearance of the susceptibility maps and the susceptibility values for segmented regions of interest were comparable between 3D EPI and 3D GRE acquisitions for both healthy and MS participants. Additionally, all lesions visible in the MS patients on the 3D GRE susceptibility maps were also visible on the 3D EPI susceptibility maps. The interplay among acquisition time, resolution, echo train length, and the effect of distortion on the calculated susceptibility maps was investigated. CONCLUSION: We demonstrate that the 3D EPI sequence is capable of rapidly acquiring submillimeter resolutions and providing high-quality, clinically relevant susceptibility maps.
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Encéfalo , Imagen Eco-Planar , Imagenología Tridimensional , Esclerosis Múltiple , Humanos , Imagenología Tridimensional/métodos , Esclerosis Múltiple/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Imagen Eco-Planar/métodos , Adulto , Masculino , Femenino , Algoritmos , Persona de Mediana Edad , Mapeo Encefálico/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Interpretación de Imagen Asistida por Computador/métodosRESUMEN
BACKGROUND: Emerging evidence suggests that traumatic brain injury (TBI) is a major risk factor for developing neurodegenerative disease later in life. Quantitative susceptibility mapping (QSM) has been used by an increasing number of studies in investigations of pathophysiological changes in TBI. However, generating artefact-free quantitative susceptibility maps in brains with large focal lesions, as in the case of moderate-to-severe TBI (ms-TBI), is particularly challenging. To address this issue, we utilized a novel two-pass masking technique and reconstruction procedure (two-pass QSM) to generate quantitative susceptibility maps (QSMxT; Stewart et al., 2022, Magn Reson Med.) in combination with the recently developed virtual brain grafting (VBG) procedure for brain repair (Radwan et al., 2021, NeuroImage) to improve automated delineation of brain areas. We used QSMxT and VBG to generate personalised QSM profiles of individual patients with reference to a sample of healthy controls. METHODS: Chronic ms-TBI patients (Nâ¯=â¯8) and healthy controls (Nâ¯=â¯12) underwent (multi-echo) GRE, and anatomical MRI (MPRAGE) on a 3T Siemens PRISMA scanner. We reconstructed the magnetic susceptibility maps using two-pass QSM from QSMxT. We then extracted values of magnetic susceptibility in grey matter (GM) regions (following brain repair via VBG) across the whole brain and determined if they deviate from a reference healthy control group [Z-score < -3.43 or > 3.43, relative to the control mean], with the aim of obtaining personalised QSM profiles. RESULTS: Using two-pass QSM, we achieved susceptibility maps with a substantial increase in quality and reduction in artefacts irrespective of the presence of large focal lesions, compared to single-pass QSM. In addition, VBG minimised the loss of GM regions and exclusion of patients due to failures in the region delineation step. Our findings revealed deviations in magnetic susceptibility measures from the HC group that differed across individual TBI patients. These changes included both increases and decreases in magnetic susceptibility values in multiple GM regions across the brain. CONCLUSIONS: We illustrate how to obtain magnetic susceptibility values at the individual level and to build personalised QSM profiles in ms-TBI patients. Our approach opens the door for QSM investigations in more severely injured patients. Such profiles are also critical to overcome the inherent heterogeneity of clinical populations, such as ms-TBI, and to characterize the underlying mechanisms of neurodegeneration at the individual level more precisely. Moreover, this new personalised QSM profiling could in the future assist clinicians in assessing recovery and formulating a neuroscience-guided integrative rehabilitation program tailored to individual TBI patients.
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Neuroimaging research requires purpose-built analysis software, which is challenging to install and may produce different results across computing environments. The community-oriented, open-source Neurodesk platform ( https://www.neurodesk.org/ ) harnesses a comprehensive and growing suite of neuroimaging software containers. Neurodesk includes a browser-accessible virtual desktop, command-line interface and computational notebook compatibility, allowing for accessible, flexible, portable and fully reproducible neuroimaging analysis on personal workstations, high-performance computers and the cloud.
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Neuroimagen , Programas Informáticos , Neuroimagen/métodos , Humanos , Interfaz Usuario-Computador , Reproducibilidad de los Resultados , Encéfalo/diagnóstico por imagenRESUMEN
For more than a decade, Dr. Brendesha Tynes has been at the forefront of empirical research examining the role of race in youth experiences with technology. Tynes' expansive corpus of research highlights the psychological, academic, and socioemotional implications and impact of online racial discrimination on child and adolescent development, with a particular focus on Black youth. Using explicitly strengths-based frameworks in both her research and mentoring, Tynes' contributions to the fields of psychology and education are vast. Given the American Psychological Association's recent shift to intentionally and urgently address racism, Tynes' scholarship is more timely than ever. Using a narrative review approach, we trace the intellectual contributions that Tynes has made to psychology, specifically, and the study of race and racism more broadly throughout her career. Particularly, we highlight key conceptual, methodological, and empirical work that have influenced the study of race in psychology. We conclude by sharing implications and possibilities for Tynes' research to influence race-conscious practices in psychological research, clinical, and pedagogical spheres. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Desarrollo del Adolescente , Negro o Afroamericano , Desarrollo Infantil , Psicología , Racismo , Medios de Comunicación Sociales , Adolescente , Niño , Humanos , Población Negra , Estado de Conciencia , Escolaridad , Investigación Empírica , Racismo/psicología , Internet , Tutoría , Negro o Afroamericano/psicología , Psicología/educación , Psicología/historiaRESUMEN
Neuroscience research has expanded dramatically over the past 30 years by advancing standardization and tool development to support rigor and transparency. Consequently, the complexity of the data pipeline has also increased, hindering access to FAIR data analysis to portions of the worldwide research community. brainlife.io was developed to reduce these burdens and democratize modern neuroscience research across institutions and career levels. Using community software and hardware infrastructure, the platform provides open-source data standardization, management, visualization, and processing and simplifies the data pipeline. brainlife.io automatically tracks the provenance history of thousands of data objects, supporting simplicity, efficiency, and transparency in neuroscience research. Here brainlife.io's technology and data services are described and evaluated for validity, reliability, reproducibility, replicability, and scientific utility. Using data from 4 modalities and 3,200 participants, we demonstrate that brainlife.io's services produce outputs that adhere to best practices in modern neuroscience research.
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Transgenic Bt crops are important tools for growers to manage insect pests, but their durability is threatened by the evolution of insect resistance. Implementing a resistance monitoring program is essential to detect and mitigate resistance. For non-high-dose Bt crops, resistance monitoring is challenging, because insect control is not complete, so targeted insects and insect damage will be present even without resistance. Given these challenges, sentinel plots have been used to monitor for insect resistance to non-high-dose crops by assessing changes in the efficacy of a Bt crop over time relative to a non-Bt control. We optimized a sentinel plot resistance monitoring approach for MON 88702 ThryvOn™ cotton, a new non-high-dose Bt product targeting two sucking pest taxa-Lygus (L. lineolaris and L. hesperus) and thrips (Frankliniella fusca and F. occidentalis)-and report here on the thrips monitoring methods and results. Quantifying thrips immatures was the best metric to characterize the impact of the trait, with at least a 40-60% average reduction of thrips immatures on ThryvOn relative to the control cotton at all sites with higher thrips densities. These data can be used within a ThryvOn resistance monitoring program and represent a case study for establishing a resistance monitoring approach for a non-high-dose trait product.
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Neuroimaging data analysis often requires purpose-built software, which can be challenging to install and may produce different results across computing environments. Beyond being a roadblock to neuroscientists, these issues of accessibility and portability can hamper the reproducibility of neuroimaging data analysis pipelines. Here, we introduce the Neurodesk platform, which harnesses software containers to support a comprehensive and growing suite of neuroimaging software (https://www.neurodesk.org/). Neurodesk includes a browser-accessible virtual desktop environment and a command line interface, mediating access to containerized neuroimaging software libraries on various computing platforms, including personal and high-performance computers, cloud computing and Jupyter Notebooks. This community-oriented, open-source platform enables a paradigm shift for neuroimaging data analysis, allowing for accessible, flexible, fully reproducible, and portable data analysis pipelines.
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PURPOSE: Quantitative susceptibility mapping (QSM) estimates the spatial distribution of tissue magnetic susceptibilities from the phase of a gradient-echo signal. QSM algorithms require a signal mask to delineate regions with reliable phase for subsequent susceptibility estimation. Existing masking techniques used in QSM have limitations that introduce artifacts, exclude anatomical detail, and rely on parameter tuning and anatomical priors that narrow their application. Here, a robust masking and reconstruction procedure is presented to overcome these limitations and enable automated QSM processing. Moreover, this method is integrated within an open-source software framework: QSMxT. METHODS: A robust masking technique that automatically separates reliable from less reliable phase regions was developed and combined with a two-pass reconstruction procedure that operates on the separated sources before combination, extracting more information and suppressing streaking artifacts. RESULTS: Compared with standard masking and reconstruction procedures, the two-pass inversion reduces streaking artifacts caused by unreliable phase and high dynamic ranges of susceptibility sources. It is also robust across a range of acquisitions at 3 T in volunteers and phantoms, at 7 T in tumor patients, and in an in silico head phantom, with significant artifact and error reductions, greater anatomical detail, and minimal parameter tuning. CONCLUSION: The two-pass masking and reconstruction procedure separates reliable from less reliable phase regions, enabling a more accurate QSM reconstruction that mitigates artifacts, operates without anatomical priors, and requires minimal parameter tuning. The technique and its integration within QSMxT makes QSM processing more accessible and robust to streaking artifacts.
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Artefactos , Imagen por Resonancia Magnética , Algoritmos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Humanos , Procesamiento de Imagen Asistido por Computador , Fantasmas de ImagenRESUMEN
PURPOSE: Arm crank ergometry and adaptive rowing are existing exercise options for wheelchairs users, but not commonly available. This study was conducted to explore exercise participation of wheelchair users, as well as the usability of the adaptive rowing ergometer (aROW) and arm crank ergometer (ACE). METHODS: This mixed-methods study used a concurrent triangulation design. Following completion of both exercise sessions (5 min each), participants (n = 14) with spinal cord injury/disease (SCI/D) completed the System Usability Scale (SUS), and a semi-structured interview. Participants were asked about the use of both exercise modalities, and general exercise participation. SUS data were analyzed using a paired sample t-test and qualitative data were analyzed through conventional content analysis. RESULTS: Wheelchair users exercised for improved physical and mental health, as well as for functional independence, and community participation; however, lack of accessible equipment was a prominent barrier. Both the aROW and ACE have high usability, but the aROW was perceived as more enjoyable and effective for cardiovascular exercise. CONCLUSIONS: The implementation of the aROW into community gyms has the potential to help close the existing gap in inclusive equipment and may help people with disabilities to be more fully included in their community and lead healthier lives.Implications for rehabilitationWheelchair users perceive exercise as a meaningful activity that enhances physical health and risk of disease, functional independence, community participation, and overall social and emotional health.The adapted rowing machine was perceived as highly usable and was felt to be more enjoyable and effective for cardiovascular exercise compared to traditional arm crank ergometers.The adaptive rower provides an additional accessible equipment option for wheelchair users to obtain effective cardiovascular exercise.More available equipment may increase community participation and promote inclusion for wheelchair users.
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Personas con Discapacidad , Traumatismos de la Médula Espinal , Silla de Ruedas , Brazo , Ergometría , HumanosRESUMEN
BACKGROUND: Anticholinergic medications may increase risk of dementia and stroke, but prospective studies in healthy older people are lacking. OBJECTIVE: Compare risk of incident dementia and stroke by anticholinergic burden among initially healthy older people. DESIGN: Prospective cohort study. SETTING: Primary care (Australia and USA). PARTICIPANTS: 19,114 community-dwelling participants recruited for the ASPREE trial, aged 70+ years (65+ if US minorities) without major cardiovascular disease, dementia diagnosis, or Modified Mini-Mental State Examination score below 78/100. MEASUREMENTS: Baseline anticholinergic exposure was calculated using the Anticholinergic Cognitive Burden (ACB) score. Dementia was adjudicated using Diagnostic and Statistical Manual of Mental Disorders volume IV criteria, and stroke using the World Health Organization definition. RESULTS: At baseline, 15,000 participants (79%) had an ACB score of zero, 2930 (15%) a score of 1-2, and 1184 (6%) a score of ≥ 3 (indicating higher burden). After a median follow-up of 4.7 years and adjusting for baseline covariates, a baseline ACB score of ≥ 3 was associated with increased risk of ischemic stroke (adjusted HR 1.58, 95% CI 1.06, 2.35), or dementia (adjusted HR 1.36, 95% CI 1.01, 1.82), especially of mixed etiology (adjusted HR 1.53, 95% CI 1.06, 2.21). Results were similar for those exposed to moderate/highly anticholinergic medications. LIMITATIONS: Residual confounding and reverse causality are possible. Assessment of dose or duration was not possible. CONCLUSIONS: High anticholinergic burden in initially healthy older people was associated with increased risk of incident dementia and ischemic stroke. A vascular effect may underlie this association. These findings highlight the importance of minimizing anticholinergic exposure in healthy older people.
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Demencia , Accidente Cerebrovascular , Anciano , Australia , Antagonistas Colinérgicos/efectos adversos , Estudios de Cohortes , Demencia/inducido químicamente , Demencia/epidemiología , Humanos , Estudios Prospectivos , Accidente Cerebrovascular/inducido químicamente , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiologíaRESUMEN
Central and peripheral mechanisms are both required for proper control of energy homeostasis. Among circulating plasma proteins, C1q/TNF-related proteins (CTRPs) have recently emerged as important regulators of sugar and fat metabolism. CTRP4, expressed in brain and adipose tissue, is unique among the family members in having two tandem globular C1q domains. We previously showed that central administration of recombinant CTRP4 suppresses food intake, suggesting a central nervous system role in regulating ingestive physiology. Whether this effect is pharmacological or physiological remains unclear. We used a loss-of-function knockout (KO) mouse model to clarify the physiological role of CTRP4. Under basal conditions, CTRP4 deficiency increased serum cholesterol levels and impaired glucose tolerance in male but not female mice fed a control low-fat diet. When challenged with a high-fat diet, male and female KO mice responded differently to weight gain and had different food intake patterns. On an obesogenic diet, male KO mice had similar weight gain as wild-type littermates. When fed ad libitum, KO male mice had greater meal number, shorter intermeal interval, and reduced satiety ratio. Female KO mice, in contrast, had lower body weight and adiposity. In the refeeding period following food deprivation, female KO mice had significantly higher food intake due to longer meal duration and reduced satiety ratio. Collectively, our data provide genetic evidence for a sex-dependent physiological role of CTRP4 in modulating food intake patterns and systemic energy metabolism.
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Adipoquinas/genética , Adipoquinas/fisiología , Adiposidad/genética , Ingestión de Alimentos/genética , Adipoquinas/farmacología , Animales , Recuento de Células Sanguíneas , Colesterol/sangre , Dieta con Restricción de Grasas , Dieta Alta en Grasa , Femenino , Intolerancia a la Glucosa/genética , Intolerancia a la Glucosa/metabolismo , Masculino , Ratones , Ratones Noqueados , Ratones Obesos , Obesidad/metabolismo , Respuesta de Saciedad , Caracteres Sexuales , Aumento de Peso/genéticaRESUMEN
Host-plant resistance (HPR) is an important tool for pest management, affording both economic and environmental benefits. The mechanisms of aphid resistance in soybean are not well understood, but likely involve the induction of the jasmonic acid (JA) pathway, and possibly other phytohormone signals involved in plant defense responses. Despite the efficacy of aphid resistance in soybean, virulent aphids have overcome this resistance through mostly unknown mechanisms. Here, we have used metabolomic tools to define the role of plant phytohormones, especially the JA pathway, in regulating interactions between aphid-resistant soybean and virulent aphids. We hypothesized that virulent aphids avoid or suppress the JA pathway to overcome aphid resistance. Our results suggested that aphid-resistant soybean increased accumulation of JA-isoleucine (JA-Ile) only when infested with avirulent aphids; virulent aphids did not cause induction of JA-Ile. Further, applying JA-Ile to aphid-resistant soybean reduced subsequent virulent aphid populations. The concentrations of other phytohormones remained unchanged due to aphid feeding, highlighting the importance of JA-Ile in this interaction. These results increase our knowledge of soybean resistance mechanisms against soybean aphids and contribute to our understanding of aphid virulence mechanisms, which will in turn promote the durability of HPR.
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Áfidos , Animales , Ciclopentanos , Isoleucina , Oxilipinas , Defensa de la Planta contra la Herbivoria , Glycine maxRESUMEN
Myonectin/erythroferrone (also known as CTRP15) is a secreted hormone with metabolic function and a role in stress erythropoiesis. Despite its importance in physiologic processes, biochemical characterization of the protein is lacking. Here, we show that multiple protein modifications are critical for myonectin secretion and multimerization. Abolishing N-linked glycosylation by tunicamycin, glucosamine supplementation, or glutamine substitutions of all four potential Asn glycosylation sites blocked myonectin secretion. Mass spectrometry confirmed that Asn-229 and Asn-281 were glycosylated, and substituting both Asn sites with Gln prevented myonectin secretion. Although Asn-319 is not identified as glycosylated, Gln substitution caused protein misfolding and retention in the endoplasmic reticulum. Of the four conserved cysteines, Cys-273 and Cys-278 were required for proper protein folding; Ala substitution of either site inhibited protein secretion. In contrast, Ala substitutions of Cys-142, Cys-194, or both markedly enhanced protein secretion, suggesting endoplasmic reticulum retention that facilitates myonectin oligomer assembly. Secreted myonectin consists of trimers, hexamers, and high-molecular weight (HMW) oligomers. The formation of higher-order structures via intermolecular disulfide bonds depended on Cys-142 and Cys-194; while the C142A mutant formed almost exclusively trimers, the C194A mutant was impaired in HMW oligomer formation. Most Pro residues within the short collagen domain of myonectin were also hydroxylated, a modification that stabilized the collagen triple helix. Inhibiting Pro hydroxylation or deleting the collagen domain markedly reduced the rate of protein secretion. Together, our results reveal key determinants that are important for myonectin folding, secretion, and multimeric assembly and provide a basis for future structure-function studies.
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Citocinas/metabolismo , Proteínas Musculares/metabolismo , Animales , Citocinas/química , Glicosilación , Células HEK293 , Humanos , Hidroxilación , Ratones , Proteínas Musculares/química , Pliegue de Proteína , Multimerización de ProteínaRESUMEN
In agricultural systems, crops equipped with host-plant resistance (HPR) have enhanced protection against pests, and are used as a safe and sustainable tool in pest management. In soybean, HPR can control the soybean aphid (Aphis glycines), but certain aphid populations have overcome this resistance (i.e., virulence). The molecular mechanisms underlying aphid virulence to HPR are unknown, but likely involve effector proteins that are secreted by aphids to modulate plant defenses. Another mechanism to facilitate adaptation is through the activity of transposable elements, which can become activated by stress. In this study, we performed RNA sequencing of virulent and avirulent soybean aphids fed susceptible or resistant (Rag1 + Rag2) soybean. Our goal was to better understand the molecular mechanisms underlying soybean aphid virulence. Our data showed that virulent aphids mostly down regulate putative effector genes relative to avirulent aphids, especially when aphids were fed susceptible soybean. Decreased expression of effectors may help evade HPR plant defenses. Virulent aphids also transcriptionally up regulate a diverse set of transposable elements and nearby genes, which is consistent with stress adaptation. Our work demonstrates two mechanisms of pest adaptation to resistance, and identifies effector gene targets for future functional testing.
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Áfidos/fisiología , Regulación hacia Abajo , Glycine max/fisiología , Proteínas de Insectos/genética , Regulación hacia Arriba , Animales , Áfidos/genética , Elementos Transponibles de ADN/genética , Herbivoria , Proteínas de Insectos/metabolismo , Defensa de la Planta contra la Herbivoria , Activación Transcripcional/genéticaRESUMEN
OBJECTIVE: Pharmaceuticals play an important role in clinical care. However, in community-based research, medication data are commonly collected as unstructured free-text, which is prohibitively expensive to code for large-scale studies. The ASPirin in Reducing Events in the Elderly (ASPREE) study developed a two-pronged framework to collect structured medication data for 19,114 individuals. ASPREE provides an opportunity to determine whether medication data can be cost-effectively collected and coded, en masse from the community using this framework. METHODS: The ASPREE framework of type-to-search box with automated coding and linked free text entry was compared to traditional method of free-text only collection and post hoc coding. Reported medications were classified according to their method of collection and analysed by Anatomical Therapeutic Chemical (ATC) group. Relative cost of collecting medications was determined by calculating the time required for database set up and medication coding. RESULTS: Overall, 122,910 participant structured medication reports were entered using the type-to-search box and 5,983 were entered as free-text. Free-text data contributed 211 unique medications not present in the type-to-search box. Spelling errors and unnecessary provision of additional information were among the top reasons why medications were reported as free-text. The cost per medication using the ASPREE method was approximately USD $0.03 compared with USD $0.20 per medication for the traditional method. CONCLUSION: Implementation of this two-pronged framework is a cost-effective alternative to free-text only data collection in community-based research. Higher initial set-up costs of this combined method are justified by long term cost effectiveness and the scientific potential for analysis and discovery gained through collection of detailed, structured medication data.
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Recolección de Datos/métodos , Investigación Farmacéutica/métodos , Anciano , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Recolección de Datos/economía , Bases de Datos Factuales/economía , Quimioterapia , Humanos , Preparaciones Farmacéuticas/administración & dosificación , Investigación Farmacéutica/economíaRESUMEN
Interorgan communication mediated by secreted proteins plays a pivotal role in metabolic homeostasis, yet the function of many circulating secretory proteins remains unknown. Here, we describe the function of protease-associated domain-containing 1 (PRADC1), an enigmatic secretory protein widely expressed in humans and mice. In metabolically active tissues (liver, muscle, fat, heart, and kidney), we showed that Pradc1 expression is significantly suppressed by refeeding and reduced in kidney and brown fat in the context of obesity. PRADC1 is dispensable for whole-body metabolism when mice are fed a low-fat diet. However, in obesity induced by high-fat feeding, PRADC1-deficient female mice have reduced weight gain and adiposity despite similar caloric intake. Decreased fat mass is attributed, in part, to increased metabolic rate, physical activity, and energy expenditure in these animals. Reduced adiposity in PRADC1-deficient mice, however, does not improve systemic glucose and lipid metabolism, insulin sensitivity, liver steatosis, or adipose inflammation. Thus, in PRADC1-deficient animals, decreased fat mass and enhanced physical activity are insufficient to confer a healthy metabolic phenotype in the context of an obesogenic diet. Our results shed light on the physiologic function of PRADC1 and the complex regulation of metabolic health.-Rodriguez, S., Stewart, A. N., Lei, X., Cao, X., Little, H. C., Fong, V., Sarver, D. C., Wong, G. W. PRADC1: a novel metabolic-responsive secretory protein that modulates physical activity and adiposity.
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Adiposidad , Péptidos y Proteínas de Señalización Intercelular/fisiología , Metabolismo de los Lípidos , Movimiento , Tejido Adiposo/metabolismo , Animales , Femenino , Glucosa/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Riñón/metabolismo , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Miocardio/metabolismoRESUMEN
PURPOSE: Viral videos of the detainment of undocumented immigrants in cages and police killings of unarmed citizens are two of the most pressing traumatic events facing adolescents of color. However, little is known about whether these online experiences are linked to mental health outcomes. This study examines the association between exposure to such events online and mental health in a sample of African American and Latinx adolescents. METHODS: Data were collected from a national sample of 302 African American and Latinx adolescents aged 11-19 years. Participants reported their exposure to traumatic events online (TEO), depressive symptoms, post-traumatic stress disorder (PTSD) symptoms, and other sociodemographics. Multiple regression analyses were conducted. RESULTS: Analyses indicated a significant association between TEO and both PTSD symptoms and depressive symptoms, indicating that more frequent experiences of TEO were associated with higher levels of PTSD symptoms and depressive symptoms. In addition, regression analyses further indicated that girls reported higher PTSD and depressive symptoms than boys. Latinx participants also reported increased depressive symptoms. CONCLUSIONS: This study extends recent research that suggests police killings, as well as viewing distressing news directed at members of one's own racial-ethnic group or those who share the same immigration status, are related to poor mental health outcomes. Researchers should also explore what protective factors may buffer youth against the outcomes typically associated with these events.
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Depresión/epidemiología , Exposición a la Violencia/psicología , Medios de Comunicación de Masas , Medios de Comunicación Sociales , Trastornos por Estrés Postraumático/epidemiología , Adolescente , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Estudios Transversales , Depresión/etiología , Femenino , Hispánicos o Latinos/psicología , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , Racismo/psicología , Trastornos por Estrés Postraumático/etiología , Encuestas y CuestionariosRESUMEN
We recently described myonectin (also known as erythroferrone) as a novel skeletal muscle-derived myokine with metabolic functions. Here, we use a genetic mouse model to determine myonectin's requirement for metabolic homeostasis. Female myonectin-deficient mice had larger gonadal fat pads and developed mild insulin resistance when fed a high-fat diet (HFD) and had reduced food intake during refeeding after an unfed period but were otherwise indistinguishable from wild-type littermates. Male mice lacking myonectin, however, had reduced physical activity when fed ad libitum and in the postprandial state but not during the unfed period. When stressed with an HFD, myonectin-knockout male mice had significantly elevated VLDL-triglyceride (TG) and strikingly impaired lipid clearance from circulation following an oral lipid load. Fat distribution between adipose and liver was also altered in myonectin-deficient male mice fed an HFD. Greater fat storage resulted in significantly enlarged adipocytes and was associated with increased postprandial lipoprotein lipase activity in adipose tissue. Parallel to this was a striking reduction in liver steatosis due to significantly reduced TG accumulation. Liver metabolite profiling revealed additional significant changes in bile acids and 1-carbon metabolism pathways. Combined, our data affirm the physiologic importance of myonectin in regulating local and systemic lipid metabolism.-Little, H. C., Rodriguez, S., Lei, X., Tan, S. Y., Stewart, A. N., Sahagun, A., Sarver, D. C., Wong, G. W. Myonectin deletion promotes adipose fat storage and reduces liver steatosis.
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Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Citocinas/genética , Hígado Graso/genética , Hígado Graso/metabolismo , Metabolismo de los Lípidos/genética , Hígado/metabolismo , Proteínas Musculares/genética , Adipocitos/metabolismo , Adipocitos/patología , Adiposidad/genética , Animales , Citocinas/metabolismo , Dieta Alta en Grasa , Hígado Graso/patología , Femenino , Homeostasis/genética , Insulina/genética , Insulina/metabolismo , Resistencia a la Insulina/genética , Lipoproteínas VLDL/genética , Lipoproteínas VLDL/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Obesidad/genética , Obesidad/metabolismo , Obesidad/patología , Triglicéridos/genética , Triglicéridos/metabolismoRESUMEN
C1q/TNF-related protein 12 (CTRP12) is a secreted regulator of glucose and lipid metabolism. It circulates in plasma as a full-length protein or as a cleaved isoform generated by furin/PCSK3 cleavage. These isoforms preferentially activate different signaling pathways, and their ratio in plasma is altered in obesity and diabetes. Here, we show that three conserved asparagine residues (Asn-39, Asn-287, and Asn-297) play important roles in modulating CTRP12 cleavage, secretion, and stability. Mass spectrometry analysis provided direct evidence of Asn-39 glycosylation. When N-linked glycosylation was inhibited by tunicamycin or abolished by the N39Q, N39A, or T41A mutation, CTRP12 cleavage was enhanced. Complex-type N-glycans on CTRP12 blocked cleavage by the Golgi-localized furin. In N-acetylglucosaminyltransferase I (GnTI)-deficient cells that could not form hybrid and complex-type N-glycans in the Golgi, CTRP12 cleavage was enhanced, and re-expressing GnTI reduced cleavage. Replacing the nonglycosylated Asn-297 with glutamine or alanine also increased CTRP12 cleavage. Both Asn-39 and Asn-297 contributed independently to CTRP12 cleavage: maximum cleavage was observed in the double mutant. In addition, CTRP12 cleavage was abolished in furin-deficient cells and restored by furin re-expression. Replacing the nonglycosylated Asn-287 with glutamine or alanine resulted in protein misfolding and aggregation, leading to retention in the endoplasmic reticulum. Cycloheximide chase analyses indicated reduced protein stability for N39Q, T41A, and N297Q mutants. Lastly, we show that increasing the flux through the hexosamine biosynthesis pathway by exogenous glucosamine, known to disrupt protein glycosylation, also promoted CTRP12 cleavage. Combined, these data highlight glycosylation-dependent and -independent mechanisms regulating CTRP12 cleavage, secretion, and protein stability.