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1.
AJPM Focus ; 3(3): 100208, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38560402

RESUMO

Introduction: Consumption of fast food has been linked to psychiatric distress, violent behaviors, and impulsivity in adolescents. The relationship between eating fast food, anger, and impulsivity has not been widely investigated. The National Consortium on Alcohol and Neurodevelopment in Adolescence community-based cohort consists of 831 youth, half at elevated risk factors for substance use disorders during adolescence, followed annually. Methods: Impulsivity using Urgency, Premeditation, Perseverance, and Sensation Seeking Impulsive Behavior scale from annual assessments was examined in relation to self-reported fast-food consumption frequency and mobile application questions of anger. This study tested the hypotheses that youth anger may be predicted by fast-food consumption frequency and impulsivity using multiple regression, in addition to whether adolescent fast-food consumption frequency may be predicted by anger and impulsivity. Results: Among youth, higher anger levels and impulsivity predicted greater frequency of fast-food consumption, and greater fast-food consumption frequency and impulsivity predicted higher anger levels. Conclusions: This study's longitudinal findings are consistent with those of other studies that have found fast-food consumption and anger associated with impulsivity and also reveal a bidirectional link between anger and fast-food consumption. These results may point attention to food selection considerations for those at risk of anger and poorer psychiatric outcomes.

2.
J Stud Alcohol Drugs ; 85(3): 389-394, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38227391

RESUMO

OBJECTIVE: The purpose of this study was to test two non-exclusive mechanisms by which parental monitoring might reduce teen substance use. The first mechanism (M1) is that monitoring increases punishment for substance use since parents who monitor more are more likely to find out when substance use occurs. The second mechanism (M2) is that monitoring directly prevents/averts teens from using substances in the first place for fear that parents would find out. METHOD: A total of 4,503 teens ages 11-15 years old in 21 communities across the United States completed a survey reporting on parents' monitoring/knowledge and teens' substance use. RESULTS: We found no support for M1: Parents with greater parental monitoring were not more likely to be aware when the teen had used substances (odds ratios = 0.79-0.93, ps = .34-.85), so they could not have increased the rate of punishment. We found support for M2: When asked directly, teens identified instances in which they planned to or had a chance to use substances but did not because their parents got in the way or would have found out (p < .01). Had all those opportunities for substance use occurred rather than been averted by parents, the prevalence of substance use in the sample would have been 1.4 times higher. CONCLUSIONS: In this community-based sample of teens, we failed to support prior punishment-centric theories of how monitoring might reduce teen substance use. Rather, monitoring may directly discourage teens from using substances regardless of whether it increases parents' awareness of substance use or results in more punishment. Replication in other samples and contexts is needed.


Assuntos
Comportamento do Adolescente , Relações Pais-Filho , Poder Familiar , Transtornos Relacionados ao Uso de Substâncias , Humanos , Adolescente , Feminino , Masculino , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Criança , Poder Familiar/psicologia , Estados Unidos/epidemiologia , Comportamento do Adolescente/psicologia , Punição , Pais
3.
J Psychiatr Res ; 167: 119-124, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37866325

RESUMO

Circadian rhythm disturbances, especially circadian phase delays are associated with impulsive behaviors and have been implicated in psychiatric disorders. Chronotype is a developmentally regulated proxy measure of circadian phase. Past studies have investigated the relationship between chronotype and trauma and found that trauma is associated with evening chronotypes, suggesting the course of chronotype development may be affected by adverse childhood experiences (ACEs). However, the relationships among chronotype, impulsivity and ACEs have largely been studied in a pairwise manner using small, cross-sectional cohorts. We hypothesized that in a cohort of high-risk youth, childhood trauma would be associated with later chronotype, and later chronotype would be associated with higher rates of impulsivity. We analyzed a cross-sectional sample (n = 966) from Year 2 of adolescents at high risk for psychiatric disorders from the ABCD study who were characterized for chronotype, stressful life events, and impulsivity. We used a hierarchical regression model to examine the relationship between chronotype, stressful life events, and impulsivity using the Munich Chronotype Questionnaire (MCTQ), the Life Events Scale, Urgency, Premeditation, Perseverance and Sensation Seeking (UPPS) Impulsive Behavior scale. We found associations between eveningness, stressful life events, and all dimensions of impulsivity. Increased eveningness was associated with a higher number of stressful life events and increased impulsivity. Understanding the role of stressful life events and impulsivity in those predisposed towards eveningness is useful because it may improve our understanding of the biological mechanisms that contribute to psychiatric disorders, and lead to better prevention and treatment efforts using interventions such as increased lifestyle regularity and daytime light exposure.

4.
Psychoneuroendocrinology ; 151: 106070, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36863129

RESUMO

BACKGROUND: The role of the hypothalamic-pituitary-adrenal (HPA) axis in human aggressive behavior is poorly characterized, though some studies report that, unlike depression, circulating or salivary levels of cortisol are low compared with controls. METHODS: In this study, we collected three salivary cortisol levels (two in the morning and one in the evening) on three separate days in 78 adult study participants with (n = 28) and without (n = 52) prominent histories of impulsive aggressive behavior. Plasma C-Reactive Protein (CRP) and Interleukin-6 (IL-6) were also collected in most study participants. Aggressive study participants meet DSM-5 criteria for Intermittent Explosive Disorder (IED) while non-aggressive participants either had a history of a psychiatric disorder or no such history (Controls). RESULTS: Morning, but not evening, salivary cortisol levels were significantly lower in IED (p < 0.05), compared with control, study participants. In addition, salivary cortisol levels correlated with measures of trait anger (partial r = -0.26, p < 0.05) and aggression (partial r = -0.25, p < 0.05) but not with measures of impulsivity, psychopathy, depression, history of childhood maltreatment, or other tested variables that often differ in individuals with IED. Finally, plasma CRP levels correlated inversely with morning salivary cortisol levels (partial r = -0.28, p < 0.05); plasma IL-6 levels showed a similar, though not statistically significant (rp = -0.20, p = 0.12) relationship with morning salivary cortisol levels. CONCLUSION: The cortisol awakening response appears to be lower in individuals with IED compared with controls. In all study participants, morning salivary cortisol levels correlated inversely with trait anger, trait aggression, and plasma CRP, a marker of systemic inflammation. This suggests the present of a complex interaction between chronic-low level inflammation, the HPA axis, and IED that warrants further investigation.


Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta , Hidrocortisona , Adulto , Humanos , Sistema Hipotálamo-Hipofisário , Interleucina-6 , Sistema Hipófise-Suprarrenal , Agressão/fisiologia , Inflamação , Sujeitos da Pesquisa
5.
Drug Alcohol Depend ; 243: 109761, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36621201

RESUMO

BACKGROUND: Between 20 % and 30 % of teens suffer from depression or anxiety before reaching adulthood, and up to half also use or misuse alcohol. Although theories suggest bidirectional links between harmful alcohol use (e.g., binge drinking) and internalizing symptoms (i.e., depression and anxiety), empirical evidence to-date has been mixed. Systematic reviews have attributed mixed findings to limitations in study design, such as the utilization of between-person analyses and the focus on unidirectional effects. The goal of this study was to address these limitations by assessing bidirectional within-person associations between internalizing symptoms and binge drinking over the course of 5 years in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) sample, a large cohort recruited at ages 12-21 and followed annually on substance use and psychiatric functioning. METHODS: We used latent curve models with structured residuals to examine within-person lagged associations between depression, anxiety, and past month counts of binge drinking using NCANDA data (N = 831). Analyses were supplemented with post-hoc power simulations. RESULTS: We found marginal evidence linking binge drinking with subsequent depression symptoms one year later among females. We found no evidence that depression or anxiety predicted subsequent binge drinking despite sufficient power. CONCLUSIONS: Social and cognitive consequences of binge drinking may predict later depression symptoms in adolescence and young adulthood for young women, though there was little evidence favoring self-medication models for binge drinking. We note several moderating variables and common factor mechanisms that may better explain this link.


Assuntos
Alcoolismo , Consumo Excessivo de Bebidas Alcoólicas , Humanos , Adolescente , Feminino , Adulto Jovem , Adulto , Criança , Consumo Excessivo de Bebidas Alcoólicas/epidemiologia , Consumo Excessivo de Bebidas Alcoólicas/psicologia , Depressão/epidemiologia , Depressão/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Transtornos de Ansiedade , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia
6.
JAMA Netw Open ; 4(9): e2126626, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34570207

RESUMO

Importance: Anger is linked to adverse outcomes in military populations; however, whether pre-enlistment anger attacks are associated with postenlistment mental disorders and suicidality is unknown. Objective: To explore the associations of pre-enlistment anger attacks with postenlistment mental health. Design, Setting, and Participants: In this observational cohort study, the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) New Soldier Study (NSS) surveyed soldiers entering basic training from April 2011 to November 2012, with a subsample recruited for wave 1 of the STARRS Longitudinal Study (STARRS-LS) (conducted September 2016 to April 2018). Participants were recruited from 3 US Army installations for the NSS survey. Those who were subsequently contacted for STARRS-LS completed the follow-up survey via web or telephone. Prospective analyses were based on a weighted NSS subsample included in wave 1 of STARRS-LS. Data were analyzed from May 22, 2020, to March 17, 2021. Exposures: History of anger attacks at baseline (NSS). Survey responses were used to classify new soldiers as having nonimpairing anger attacks (>2 attacks without interference in work or personal life), impairing anger attacks (>2 attacks with interference in work or personal life), or no significant history of anger attacks. Main Outcomes and Measures: Baseline analyses examined sociodemographic and clinical correlates of a history of anger attacks. Prospective logistic regression models estimated associations of baseline history of anger attacks with new onset and persistence of posttraumatic stress disorder, major depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder, mania/hypomania, substance use disorder, suicidal ideation, and suicide attempt at wave 1 of STARRS-LS. Results: Of the 38 507 baseline participants (83.0% male and 17.0% female; mean [SD] age, 20.97 [3.57] years), 6216 were selected for and completed wave 1 of the STARRS-LS. Baseline prevalence (SE) of nonimpairing and impairing anger attacks was 8.83% (0.16%) and 5.75% (0.15%), respectively. Prospective models showed that impairing anger attacks were associated with new onset of MDD (adjusted odds ratio [AOR], 1.98; 95% CI, 1.31-2.99), GAD (AOR, 2.39; 95% CI, 1.66-3.45), panic disorder (AOR, 2.02; 95% CI, 1.34-3.05), and suicidal ideation (AOR, 2.11; 95% CI, 1.45-3.07). When baseline psychiatric comorbidity was controlled for, impairing attacks remained associated with onset of GAD (AOR, 1.75; 95% CI, 1.19-2.58) and suicidal ideation (AOR, 1.62; 95% CI, 1.09-2.42). Anger attacks were not significantly associated with persistence of pre-enlistment mental disorders. Conclusions and Relevance: The findings of this study suggest that a pre-enlistment history of impairing anger attacks may be associated with elevated risk of developing GAD, MDD, and suicidality after enlistment. Detection of impairing anger attacks could aid in assessing psychiatric risk in new soldiers.


Assuntos
Ira , Transtornos de Ansiedade/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Militares/psicologia , Ideação Suicida , Adolescente , Adulto , Transtornos de Ansiedade/psicologia , Estudos de Coortes , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Masculino , Transtorno de Pânico , Inquéritos e Questionários , Estados Unidos/epidemiologia , Adulto Jovem
8.
Alcohol Clin Exp Res ; 45(6): 1249-1264, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33991389

RESUMO

BACKGROUND: Dual systems theories suggest that greater imbalance between higher reward sensitivity and lower cognitive control across adolescence conveys risk for behaviors such as heavy episodic drinking (HED). Prior research demonstrated that psychological analogues of these systems, sensation seeking and premeditation, change from childhood through emerging adulthood, and each has been independently linked with HED. However, few studies have assessed whether change over time in these developing analogues is prospectively associated with HED. Moreover, we know of no research that has shown whether within-person differences between higher sensation seeking and relatively lower premeditation across the adolescent period predict HED in emerging adulthood. METHODS: Prospective data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study (n = 715) were used to examine the association of sensation seeking and premeditation with HED among adolescents ages 16 to 20 years. We used novel applications of latent difference score modeling and growth curve analysis to test whether increasing sensation seeking, premeditation, and their imbalance over time are associated with HED across the study period, and whether these associations differed by sex. RESULTS: Whereas premeditation increased linearly from adolescence through emerging adulthood across sexes, males reported growth and females reported decline in sensation seeking. Sensation seeking in adolescence (and not premeditation) was associated with higher levels of HED by emerging adulthood. Importantly, greater imbalance between sensation seeking and premeditation was associated with higher levels of HED by emerging adulthood though we note that variability capturing this imbalance correlated highly (r = 0.86) with baseline levels of sensation seeking. CONCLUSIONS: Developmental imbalance between higher sensation seeking and lower premeditation in late adolescence may be a risk factor for greater HED in emerging adulthood.


Assuntos
Comportamento do Adolescente , Desenvolvimento do Adolescente , Consumo Excessivo de Bebidas Alcoólicas/etiologia , Consumo Excessivo de Bebidas Alcoólicas/psicologia , Adolescente , Feminino , Humanos , Estudos Longitudinais , Masculino , Modelos Estatísticos , Assunção de Riscos , Sensação , Adulto Jovem
9.
J Affect Disord ; 287: 380-386, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33836366

RESUMO

BACKGROUND: Adolescents are at increased risk of developing major depressive disorder (MDD) than many other age groups. Although the neural correlates of MDD in adults have been studied prospectively, such adolescent depression studies are mainly cross-sectional. We extracted data regarding the relationship between cortical thickness and later development of adolescent MDD from a national community study that uses an accelerated longitudinal design to examine the psychological, environmental, and neural differences related to drinking and brain development. METHODS: 692 subjects (age 12-21 years; 50% female) without a history of MDD were assessed with structural neuroimaging at baseline. We compared those 101 subjects who transitioned to MDD by 1-year follow-up to those who remained non-depressed over the same time period. FreeSurfer's autosegmentation process estimated vertex-wide cortical thicknesses and its Query, Design, Estimate, Contrast (Qdec) application investigated cortical thickness between those who later developed MDD and those who remained without MDD (Monte Carlo corrected for multiple comparisons, vertex-wise cluster threshold of 1.3, p < 0.01). RESULTS: Those who transitioned in the next year to MDD had, at baseline, thinner cortices in the superior frontal cortex, precentral and postcentral regions, and superior temporal cortex, above and beyond effects attributable to age and sex. No cortical thickness sex differences or sex-by-depression interactions were observed. LIMITATIONS: A larger sample size could improve statistical power and future investigations will be needed to confirm our results. CONCLUSIONS: Thinner cortices over frontal and temporal regions may be linked to enhanced vulnerability for future depression during the adolescent-young adulthood transition.


Assuntos
Transtorno Depressivo Maior , Adolescente , Adulto , Córtex Cerebral/diagnóstico por imagem , Criança , Estudos Transversais , Depressão , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Adulto Jovem
10.
11.
Brain Imaging Behav ; 14(6): 2679-2691, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31903528

RESUMO

Academic performance significantly influences educational advancement, career opportunities, and life outcomes. The extent to which adolescent substance use and brain morphology predict academic achievement has not been extensively explored. We examined grade point average (GPA) at the time alcohol and cannabis use often starts (7th - 9th grade) and subsequently during 11th and 12th grade in a 170 physically healthy adolescents in a longitudinal study. Covariance analysis examined predictive features from 36 metrics of middle school academic performance and initiation of alcohol and cannabis use. Using a machine learning approach, GPA from 7th, 8th, and 9th grade strongly predicted 11th and 12th grade GPA, followed in predictive power by alcohol use age of onset. A machine learning approach determined 16 (from 336) baseline neuroimaging features that reflected lower thickness, area, or volume in average high school GPA drinkers compared to nondrinkers. Features that distinguished average performing drinkers from nondrinkers suggested accelerated gray matter loss during adolescence for drinkers, while high performing drinkers compared to nondrinkers may have attenuated gray matter maturation. Additional possibilities are discussed.


Assuntos
Sucesso Acadêmico , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Escolaridade , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
12.
Brain Imaging Behav ; 13(4): 945-952, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29911279

RESUMO

Academic performance in adolescence strongly influences adult prospects. Intelligence quotient (IQ) has historically been considered a strong predictor of academic performance. Less objectively explored have been morphometric features. We analyzed brain MRI morphometry metrics in early adolescence (age 12-14 years) as quantitative predictors of academic performance over high school using a naïve Bayesian classifier approach with n = 170 subjects. Based on the mean GPA, subjects were divided into high (GPA ≥3.54; n = 87) and low (GPA <3.54; n = 83) academic performers. Covariance analysis was performed to look at the influence of subject demographics. We examined predictive features from the 343 available regions (surface areas, cortical thickness, and subcortical volumes) and applied 4 algorithms for selection and reduction of attributes using Weka. Cortical thickness measures performed better than surface areas or subcortical volumes as predictors of academic performance. We identified 15 cortical thickness regions most predictive of academic performance, three of which have not been described in the literature predictive of academic performance. These were in the left hemisphere fusiform, bilateral insula, and left hemisphere paracentral regions. Prediction had a sensitivity of 0.65 and specificity of 0.73 with independent validation. Follow-up independent t-test analyses between high and low academic achievers on 10 of 15 regions showed between-group significance at the p < 0.05 level. High achievers demonstrated thicker cortices than low achievers. These newly identified regions may help pinpoint new targets for further study in understanding the developing adolescent brain in the classroom setting.


Assuntos
Cognição/fisiologia , Previsões/métodos , Imageamento por Ressonância Magnética/métodos , Sucesso Acadêmico , Adolescente , Teorema de Bayes , Biomarcadores , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Mapeamento Encefálico/métodos , Córtex Cerebral/diagnóstico por imagem , Criança , Feminino , Humanos , Testes de Inteligência , Masculino , Sensibilidade e Especificidade
13.
Dev Cogn Neurosci ; 16: 101-109, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25953106

RESUMO

Studies suggest marijuana impacts gray and white matter neural tissue development, however few prospective studies have determined the relationship between cortical thickness and cannabis use spanning adolescence to young adulthood. This study aimed to understand how heavy marijuana use influences cortical thickness trajectories across adolescence. Subjects were adolescents with heavy marijuana use and concomitant alcohol use (MJ+ALC, n=30) and controls (CON, n=38) with limited substance use histories. Participants underwent magnetic resonance imaging and comprehensive substance use assessment at three independent time points. Repeated measures analysis of covariance was used to look at main effects of group, time, and Group × Time interactions on cortical thickness. MJ+ALC showed thicker cortical estimates across the brain (23 regions), particularly in frontal and parietal lobes (ps<.05). More cumulative marijuana use was associated with increased thickness estimates by 3-year follow-up (ps<.05). Heavy marijuana use during adolescence and into young adulthood may be associated with altered neural tissue development and interference with neuromaturation that can have neurobehavioral consequences. Continued follow-up of adolescent marijuana users will help understand ongoing neural changes that are associated with development of problematic use into adulthood, as well as potential for neural recovery with cessation of use.


Assuntos
Alcoolismo/patologia , Córtex Cerebral/patologia , Abuso de Maconha/patologia , Adolescente , Idade de Início , Feminino , Lobo Frontal/patologia , Nível de Saúde , Humanos , Imageamento por Ressonância Magnética , Masculino , Saúde Mental , Lobo Parietal/patologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores Socioeconômicos , Adulto Jovem
14.
Neuropsychology ; 29(6): 829-843, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25938918

RESUMO

OBJECTIVE: The effect of adolescent marijuana use on brain development remains unclear despite relaxing legal restrictions, decreased perceived harm, and increasing use rates among youth. The aim of this 3-year prospective study was to evaluate the long-term neurocognitive effects of adolescent marijuana use. METHOD: Adolescent marijuana users with concomitant alcohol use (MJ + ALC, n = 49) and control teens with limited substance use histories (CON, n = 59) were given neuropsychological and substance use assessments at project baseline, when they were ages 16-19. They were then reassessed 18 and 36 months later. Changes in neuropsychological measures were evaluated with repeated measures analysis of covariance (ANCOVA), controlling for lifetime alcohol use, and examined the effects of group, time, and group by time interactions on cognitive functioning. RESULTS: MJ + ALC users performed significantly worse than controls, across time points, in the domains of complex attention, memory, processing speed, and visuospatial functioning (ps <.05). Earlier age of marijuana use onset was associated with poorer processing speed and executive functioning by the 3-year follow-up (ps ≤.02). CONCLUSIONS: Frequent marijuana use throughout adolescence and into young adulthood appeared linked to worsened cognitive performance. Earlier age of onset appears to be associated with poorer neurocognitive outcomes that emerge by young adulthood, providing further support for the notion that the brain may be uniquely sensitive to frequent marijuana exposure during the adolescent phase of neurodevelopment. Continued follow-up of adolescent marijuana users will determine the extent of neural recovery that may occur if use abates.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Transtornos Cognitivos/induzido quimicamente , Fumar Maconha/efeitos adversos , Desempenho Psicomotor/efeitos dos fármacos , Adolescente , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Consumo de Álcool por Menores , Adulto Jovem
15.
Protein Sci ; 21(11): 1746-53, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23001966

RESUMO

The evolutionary adaptations of thermophilic water-soluble proteins required for maintaining stability at high temperature have been extensively investigated. Little is known about the adaptations in membrane proteins, however. Here, we compare many properties of mesophilic and thermophilic membrane protein structures, including side-chain burial, packing, hydrogen bonding, transmembrane kinks, loop lengths, hydrophobicity, and other sequence features. Most of these properties are quite similar between mesophiles and thermophiles although we observe a slight increase in side-chain burial and possibly a slight decrease in the frequency of transmembrane kinks in thermophilic membrane protein structures. The most striking difference is the increased hydrophobicity of thermophilic transmembrane helices, possibly reflecting more stringent hydrophobicity requirements for membrane partitioning at high temperature. In agreement with prior work examining transmembrane sequences, we find that thermophiles have an increase in small residues (Gly, Ala, Ser, and Val) and a strong suppression of Cys. We also find a relative dearth of most strongly polar residues (Asp, Asn, Glu, Gln, and Arg). These results suggest that in thermophiles, there is significant evolutionary pressure to offload destabilizing polar amino acids, to decrease the entropy cost of side chain burial, and to eliminate thermally sensitive amino acids.


Assuntos
Proteínas de Membrana/química , Aminoácidos/química , Bases de Dados de Proteínas , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Dobramento de Proteína , Estabilidade Proteica , Estrutura Terciária de Proteína , Proteômica , Solubilidade , Temperatura
16.
Protein Sci ; 20(7): 1256-64, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21563225

RESUMO

A hallmark of membrane protein structure is the large number of distorted transmembrane helices. Because of the prevalence of bends, it is important to not only understand how they are generated but also to learn how to predict their occurrence. Here, we find that there are local sequence preferences in kinked helices, most notably a higher abundance of proline, which can be exploited to identify bends from local sequence information. A neural network predictor identifies over two-thirds of all bends (sensitivity 0.70) with high reliability (specificity 0.89). It is likely that more structural data will allow for better helix distortion predictors with increased coverage in the future. The kink predictor, TMKink, is available at http://tmkinkpredictor.mbi.ucla.edu/.


Assuntos
Proteínas de Membrana/química , Prolina/química , Algoritmos , Bases de Dados de Proteínas , Modelos Moleculares , Redes Neurais de Computação , Estrutura Secundária de Proteína
17.
Proteins ; 74(1): 1-5, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18831011

RESUMO

Sterile alpha motif (SAM) domains are common protein modules in eukaryotic cells. It has not been possible to assign functions to uncharacterized SAM domains because they have been found to participate in diverse functions ranging from protein-protein interactions to RNA binding. Here we computationally identify likely members of the subclass of SAM domains that form polymers. Sequences were virtually threaded onto known polymer structures and then evaluated for compatibility with the polymer. We find that known SAM polymers score better than the vast majority of known nonpolymers: 100% (7 of 7) of known polymers and only 8% of known nonpolymers (1 of 12) score above a defined threshold value. Of 2901 SAM family members, we find 694 that score above the threshold and are likely polymers, including SAM domains from the proteins Lethal Malignant Brain Tumor, Bicaudal-C, Liprin-beta, Adenylate Cyclase, and Atherin.


Assuntos
Algoritmos , Motivos de Aminoácidos , Polímeros/química , Proteínas/química , Sequência de Aminoácidos , Sítios de Ligação , Modelos Químicos , Polímeros/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas/metabolismo
18.
Development ; 134(4): 669-79, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17215301

RESUMO

During C. elegans development, LIN-12 (Notch) signaling specifies the anchor cell (AC) and ventral uterine precursor cell (VU) fates from two equivalent pre-AC/pre-VU cells in the hermaphrodite gonad. Once specified, the AC induces patterned proliferation of vulva via expression of LIN-3 (EGF) and then invades into the vulval epithelium. Although these cellular processes are essential for the proper organogenesis of vulva and appear to be temporally regulated, the mechanisms that coordinate the processes are not well understood. We computationally identified egl-43 as a gene likely to be expressed in the pre-AC/pre-VU cells and the AC, based on the presence of an enhancer element similar to the one that transcribes lin-3 in the same cells. Genetic epistasis analyses reveal that egl-43 acts downstream of or parallel to lin-12 in AC/VU cell fate specification at an early developmental stage, and functions downstream of fos-1 as well as upstream of zmp-1 and him-4 to regulate AC invasion at a later developmental stage. Characterization of the egl-43 regulatory region suggests that EGL-43 is a direct target of LIN-12 and HLH-2 (E12/47), which is required for the specification of the VU fate during AC/VU specification. EGL-43 also regulates basement membrane breakdown during AC invasion through a FOS-1-responsive regulatory element that drives EGL-43 expression in the AC and VU cells at the later stage. Thus, egl-43 integrates temporally distinct upstream regulatory events and helps program cell fate specification and cell invasion.


Assuntos
Proteínas de Caenorhabditis elegans/fisiologia , Movimento Celular/fisiologia , Indução Embrionária , Proteínas de Membrana/fisiologia , Células-Tronco/citologia , Fatores de Transcrição/fisiologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Caenorhabditis elegans/crescimento & desenvolvimento , Biologia Computacional , Transtornos do Desenvolvimento Sexual , Fator de Crescimento Epidérmico , Epistasia Genética , Gônadas/crescimento & desenvolvimento , Organogênese , Receptores Notch/fisiologia
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