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2.
Am Psychol ; 69(3): 269-84, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24750076

RESUMO

Research on social networks has grown exponentially in recent years. However, despite its relevance, the field of psychology has been relatively slow to explain the underlying goal pursuit and resistance processes influencing social networks in the first place. In this vein, this article aims to demonstrate how a dynamic network theory perspective explains the way in which social networks influence these processes and related outcomes, such as goal achievement, performance, learning, and emotional contagion at the interpersonal level of analysis. The theory integrates goal pursuit, motivation, and conflict conceptualizations from psychology with social network concepts from sociology and organizational science to provide a taxonomy of social network role behaviors, such as goal striving, system supporting, goal preventing, system negating, and observing. This theoretical perspective provides psychologists with new tools to map social networks (e.g., dynamic network charts), which can help inform the development of change interventions. Implications for social, industrial-organizational, and counseling psychology as well as conflict resolution are discussed, and new opportunities for research are highlighted, such as those related to dynamic network intelligence (also known as cognitive accuracy), levels of analysis, methodological/ethical issues, and the need to theoretically broaden the study of social networking and social media behavior. (PsycINFO Database Record (c) 2014 APA, all rights reserved).


Assuntos
Relações Interpessoais , Psicologia , Rede Social , Apoio Social , Humanos , Motivação , Pesquisa , Comportamento Social
3.
Nucleic Acids Res ; 42(1): 475-84, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24057216

RESUMO

Cdc13, the telomere end-binding protein from Saccharomyces cerevisiae, is a multidomain protein that specifically binds telomeric single-stranded DNA (ssDNA) with exquisitely high affinity to coordinate telomere maintenance. Recent structural and genetic data have led to the proposal that Cdc13 is the paralog of RPA70 within a telomere-specific RPA complex. Our understanding of Cdc13 structure and biochemistry has been largely restricted to studies of individual domains, precluding analysis of how each domain influences the activity of the others. To better facilitate a comparison to RPA70, we evaluated the ssDNA binding of full-length S. cerevisiae Cdc13 to its minimal substrate, Tel11. We found that, unlike RPA70 and the other known telomere end-binding proteins, the core Cdc13 ssDNA-binding activity is wholly contained within a single tight-binding oligosaccharide/oligonucleotide/oligopeptide binding (OB)-fold. Because two OB-folds are implicated in dimerization, we also evaluated the relationship between dimerization and ssDNA-binding activity and found that the two activities are independent. We also find that Cdc13 binding exhibits positive cooperativity that is independent of dimerization. This study reveals that, while Cdc13 and RPA70 share similar domain topologies, the corresponding domains have evolved different and specialized functions.


Assuntos
DNA de Cadeia Simples/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Ligação a Telômeros/metabolismo , Telômero/metabolismo , Ligação Proteica , Multimerização Proteica , Estrutura Terciária de Proteína , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Ligação a Telômeros/química
4.
Biochemistry ; 52(45): 7890-900, 2013 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-24070253

RESUMO

Villin is a gelsolin-like cytoskeleton regulator localized in the brush border at the apical end of epithelial cells. Villin regulates microvilli by bundling F-actin at low calcium levels and severing it at high calcium levels. The villin polypeptide consists of six gelsolin-like repeats (V1-V6) and the unique, actin binding C-terminal headpiece domain (HP). Villin modular fragment V6-HP requires calcium to stay monomeric and bundle F-actin. Our data show that isolated V6 is monomeric and does not bind F-actin at any level of calcium. We propose that the 40-residue unfolded V6-to-HP linker can be a key regulatory element in villin's functions such as its interactions with F-actin. Here we report a calcium-bound solution nuclear magnetic resonance (NMR) structure of V6, which has a gelsolin-like fold with the long α-helix in the extended conformation. Intrinsic tryptophan fluorescence quenching reveals two-Kd calcium binding in V6 (Kd1 of 22 µM and Kd2 of 2.8 mM). According to our NMR data, the conformation of V6 responds the most to micromolar calcium. We show that the long α-helix and the adjacent residues form the calcium-sensitive elements in V6. These observations are consistent with the calcium activation of F-actin severing by villin analogous to the gelsolin helix-straightening mechanism.


Assuntos
Cálcio/química , Gelsolina/química , Proteínas dos Microfilamentos/química , Actinas/química , Actinas/metabolismo , Cromatografia em Gel , Gelsolina/metabolismo , Vetores Genéticos , Humanos , Espectroscopia de Ressonância Magnética , Proteínas dos Microfilamentos/metabolismo , Ligação Proteica
5.
Biol Mood Anxiety Disord ; 3(1): 10, 2013 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-23672953

RESUMO

BACKGROUND: Previous research suggests that individuals with posttraumatic stress disorder (PTSD) preferentially attend to trauma-related emotional stimuli and have difficulty completing unrelated concurrent tasks. Compared to trauma-exposed control groups, individuals with PTSD also exhibit lower rostral anterior cingulate cortex (rACC) activation during tasks involving interference from trauma-related stimuli. However, it is not clear whether relatively diminished rACC activation in PTSD also occurs during interference tasks involving trauma-unrelated emotional stimuli. The present study employed functional magnetic resonance imaging (fMRI) and an interference task that involves emotional facial expressions and elicits rACC activation in healthy participants. FINDINGS: While performing a trauma-unrelated emotional interference task, participants with PTSD (n=17) showed less rACC activation than trauma-exposed non-PTSD (TENP; n=18) participants. In the PTSD group, rACC activation was negatively correlated with the severity of re-experiencing symptoms. The two groups did not significantly differ on behavioral measures (i.e., response times and error rates). CONCLUSIONS: These findings suggest that relatively diminished rACC activation in PTSD can be observed in interference tasks involving trauma-unrelated emotional stimuli, indicating a more general functional brain abnormality in this disorder. Future neuroimaging studies need not employ trauma-related stimuli in order to detect rACC abnormalities in PTSD.

6.
Psychopathology ; 46(3): 176-85, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22906962

RESUMO

BACKGROUND: Reported rates of comorbid anxiety disorders in psychotic and mood disorders vary widely among studies. SAMPLING AND METHODS: We used the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, to examine rates of comorbid anxiety disorders in patients with schizoaffective disorder (SZA; n = 153), bipolar I disorder (BP; n = 304) and schizophrenia (SZ; n = 174). RESULTS: The rates of anxiety disorders in participants with SZA (30.1%), BP (22.4%) and SZ (16.7%) differed significantly [χ²(2) = 8.368, p = 0.015]. Among anxiety disorders, this effect was most pronounced for panic disorder (PD). PD rates were significantly higher in participants with SZA (15.7%) as compared to participants with BP (6.9%) and SZ [6.9%; χ²(2) = 10.879, p = 0.004]. Logistic regression models controlling for demographic and clinical characteristics confirmed that primary diagnosis (SZA, BP or SZ) was a significant predictor of PD comorbidity and approached significance in predicting the comorbidity of any anxiety disorder. CONCLUSIONS: Our findings suggest that patients with SZA have high rates of anxiety disorders. Clinicians treating patients with SZA should evaluate for anxiety disorder comorbidity, especially as anxiety symptoms may not be reported at first presentation.


Assuntos
Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/psicologia , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/psicologia , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/psicologia , Esquizofrenia/epidemiologia , Adulto , Ansiedade , Transtornos de Ansiedade/diagnóstico , Transtorno Bipolar/diagnóstico , Comorbidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Entrevista Psicológica , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/diagnóstico , Transtorno de Pânico/epidemiologia , Transtorno de Pânico/psicologia , Valor Preditivo dos Testes , Transtornos Psicóticos/diagnóstico , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Índice de Gravidade de Doença
7.
Schizophr Res ; 138(2-3): 177-82, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22445668

RESUMO

There is growing evidence that schizophrenia (SZ) and bipolar disorder (BD) overlap significantly in risk factors, neurobiological features, clinical presentations, and outcomes. SZ is characterized by well documented gray matter (GM) abnormalities in multiple frontal, temporal and subcortical structures. Recent voxel-based morphometry (VBM) studies and meta-analyses in BD also report GM reductions in overlapping, albeit less widespread, brain regions. Psychosis, a hallmark of SZ, is also experienced by a significant proportion of BD patients and there is evidence that psychotic BD may be characterized by specific clinical and pathophysiological features. However, there are few studies comparing GM between SZ and psychotic BD. In this study we compared GM volumes in a sample of 58 SZ patients, 28 BD patients experiencing psychotic symptoms and 43 healthy controls using whole-brain voxel-based morphometry. SZ patients had GM reductions in multiple frontal and temporal regions compared to healthy controls and in the subgenual cortex compared to psychotic BD patients. GM volume was increased in the right posterior cerebellum in SZ patients compared to controls. However, psychotic BD patients did not show significant GM deficits compared to healthy controls or SZ patients. We conclude that GM abnormality as measured by VBM analysis is less pronounced in psychotic BD compared to SZ. This may be due to disease-specific factors or medications used more commonly in BD.


Assuntos
Transtorno Bipolar/patologia , Cerebelo/patologia , Córtex Cerebral/patologia , Fibras Nervosas Amielínicas/patologia , Esquizofrenia/patologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão
8.
Compr Psychiatry ; 53(6): 718-26, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22197213

RESUMO

BACKGROUND: Auditory hallucinations (AH) are a cardinal feature of schizophrenia spectrum disorders. They are not disease specific, however, and can occur in other conditions, including affective psychoses. METHODS: In this descriptive, cross-sectional study, we examined AH in relation to other psychotic symptoms, mood symptoms, illness severity, and functional status in 569 patients with psychosis (n = 172 schizophrenia, n = 153 schizoaffective disorder, n = 244 bipolar disorder with psychotic features). RESULTS: A total of 323 (56.7%) patients reported a lifetime history of AH (75.6% of patients with schizophrenia, 71.9% schizoaffective disorder, and 34.0% bipolar disorder). The mean score for the hallucinations item (P3) of the Positive and Negative Syndrome Scale in the AH group was 3.66 ± 1.79, indicating mild to moderate state hallucinations severity. Auditory hallucinations were strongly associated with hallucinations in other sensory modalities and with the first-rank symptoms of delusions of control, thought insertion, and thought broadcasting. Multivariate analysis showed that AH were associated with lower education even after controlling for diagnosis, age, and sex. There was no association between AH and functional status as measured by the Multnomah Community Ability Scale. CONCLUSIONS: Auditory hallucinations are associated with specific clinical features across the continuum of both schizophrenic and affective psychoses independent of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis.


Assuntos
Delusões/complicações , Alucinações/diagnóstico , Transtornos Psicóticos/complicações , Esquizofrenia/complicações , Adulto , Estudos Transversais , Delusões/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Alucinações/complicações , Alucinações/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/psicologia , Psicologia do Esquizofrênico , Índice de Gravidade de Doença
9.
Chemistry ; 16(42): 12650-9, 2010 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-20859962

RESUMO

As part of an ongoing effort to expand the genetic alphabet for in vitro and eventual in vivo applications, we have synthesized a wide variety of predominantly hydrophobic unnatural base pairs and evaluated their replication in DNA. Collectively, the results have led us to propose that these base pairs, which lack stabilizing edge-on interactions, are replicated by means of a unique intercalative mechanism. Here, we report the synthesis and characterization of three novel derivatives of the nucleotide analogue dMMO2, which forms an unnatural base pair with the nucleotide analogue d5SICS. Replacing the para-methyl substituent of dMMO2 with an annulated furan ring (yielding dFMO) has a dramatically negative effect on replication, while replacing it with a methoxy (dDMO) or with a thiomethyl group (dTMO) improves replication in both steady-state assays and during PCR amplification. Thus, dTMO-d5SICS, and especially dDMO-d5SICS, represent significant progress toward the expansion of the genetic alphabet. To elucidate the structure-activity relationships governing unnatural base pair replication, we determined the solution structure of duplex DNA containing the parental dMMO2-d5SICS pair, and also used this structure to generate models of the derivative base pairs. The results strongly support the intercalative mechanism of replication, reveal a surprisingly high level of specificity that may be achieved by optimizing packing interactions, and should prove invaluable for the further optimization of the unnatural base pair.


Assuntos
DNA/química , Modelos Moleculares , Oligorribonucleotídeos Antissenso/química , Oligorribonucleotídeos Antissenso/síntese química , Pareamento de Bases , Replicação do DNA , DNA Polimerase Dirigida por DNA/metabolismo , Dados de Sequência Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Conformação de Ácido Nucleico , Homologia de Sequência do Ácido Nucleico , Relação Estrutura-Atividade
10.
Biol Psychiatry ; 68(11): 1023-30, 2010 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-20855060

RESUMO

BACKGROUND: Posttraumatic stress disorder (PTSD) is marked by intrusive, chronic, and distressing memories of highly emotional events. Previous research has highlighted the role of the amygdala and its interactions with the hippocampus in mediating the effect of enhanced memory for emotional information in healthy individuals. As the functional integrity of these regions may be compromised in PTSD, the current study examined the neural correlates of emotional memory in PTSD. METHODS: We used functional magnetic resonance imaging and an event-related subsequent memory recognition paradigm to study amygdala and hippocampus activation in 18 individuals with PTSD and 18 trauma-exposed non-PTSD control participants. RESULTS: Memory enhancement for negative, relative to neutral, pictures was found across all subjects, without significant differences between groups. Relative to the trauma-exposed non-PTSD group, the PTSD group showed exaggerated amygdala activation during the encoding of negative versus neutral pictures. This effect was even more pronounced when the analysis included data from only pictures that were subsequently remembered 1 week later. In the PTSD group, degree of amygdala activation during the encoding of negative versus neutral pictures was positively correlated with hippocampal activation and current PTSD symptom severity. The PTSD group also showed exaggerated hippocampal activation in response to negative pictures that were remembered versus forgotten. Finally, hippocampal activation associated with the successful encoding of negative relative to neutral pictures was significantly greater in the PTSD group. CONCLUSIONS: Exaggerated amygdala activation during the encoding of emotionally negative stimuli in PTSD is related to symptom severity and to hippocampal activation.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Emoções/fisiologia , Hipocampo/fisiopatologia , Memória/fisiologia , Neurônios/fisiologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adulto , Análise de Variância , Nível de Alerta/fisiologia , Mapeamento Encefálico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Transtornos de Estresse Pós-Traumáticos/psicologia
11.
J Am Chem Soc ; 130(14): 4869-78, 2008 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-18341343

RESUMO

The incorporation of synthetic nucleoside analogues into DNA duplexes provides a unique opportunity to probe both structure and function of nucleic acids. We used 1H and 19F NMR and molecular dynamics calculations to determine the solution structures of two similar DNA decamer duplexes, one containing a central G-T mismatched or "wobble" base pair, and one in which the thymine in this base pair is replaced by difluorotoluene (a thymine isostere) creating a G-F pair. Here, we show that the non-hydrogen-bonding G-F pair stacks relatively well into the helix and that the distortions caused by each non-Watson-Crick G-T or G-F base pair are quite localized to a three base pair site around the mismatch. A detailed structural analysis reveals that the absence of hydrogen bonding introduces more dynamic motion into the G-F pair relative to G-T and permits the G-F pair to exhibit stacking and conformational features characteristic of both a Watson-Crick base pair (on the guanine containing strand) and a wobble base pair (on the strand containing the difluorotoluene). We used these results to posit a rationale for recognition and repair of mismatch sites in DNA.


Assuntos
DNA/química , Guanina/química , Tolueno/análogos & derivados , Pareamento de Bases , Reparo do DNA , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Oligonucleotídeos/síntese química , Oligonucleotídeos/química , Teoria Quântica , Soluções , Tolueno/química
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