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1.
Proc Biol Sci ; 290(2013): 20230983, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38087923

RESUMO

Faculty at research institutions play a central role in advancing knowledge and careers, as well as promoting the well-being of students and colleagues in research environments. Mentorship from experienced peers has been touted as critical for enabling these myriad roles to allow faculty development, career progression, and satisfaction. However, there is little information available on who supports faculty and best ways to structure a faculty mentorship programme for early- and mid-career academics. In the interest of advocating for increased and enhanced faculty mentoring and mentoring programmes, we surveyed faculty around the world to gather data on whether and how they receive mentoring. We received responses from 457 early- and mid-career faculty and found that a substantial portion of respondents either reported having no mentor or a lack of a formal mentoring scheme. Qualitative responses on the quality of mentorship revealed that the most common complaints regarding mentorship included lack of mentor availability, unsatisfactory commitment to mentorship, and non-specific or non-actionable advice. On these suggestions, we identify a need for training for faculty mentors as well as strategies for individual mentors, departments, and institutions for funding and design of more intentional and supportive mentorship programmes for early- and mid-career faculty.


Assuntos
Tutoria , Mentores , Humanos , Mentores/educação , Docentes , Estudantes , Inquéritos e Questionários
2.
J Neurosci ; 39(2): 321-332, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30446530

RESUMO

Some people are more willing to make immediate, risky, or costly reward-focused choices than others, which has been hypothesized to be associated with individual differences in dopamine (DA) function. In two studies using PET imaging, one empirical (Study 1: N = 144 males and females across 3 samples) and one meta-analytic (Study 2: N = 307 across 12 samples), we sought to characterize associations between individual differences in DA and time, probability, and physical effort discounting in human adults. Study 1 demonstrated that individual differences in DA D2-like receptors were not associated with time or probability discounting of monetary rewards in healthy humans, and associations with physical effort discounting were inconsistent across adults of different ages. Meta-analytic results for temporal discounting corroborated our empirical finding for minimal effect of DA measures on discounting in healthy individuals but suggested that associations between individual differences in DA and reward discounting depend on clinical features. Addictions were characterized by negative correlations between DA and discounting, but other clinical conditions, such as Parkinson's disease, obesity, and attention-deficit/hyperactivity disorder, were characterized by positive correlations between DA and discounting. Together, the results suggest that trait differences in discounting in healthy adults do not appear to be strongly associated with individual differences in D2-like receptors. The difference in meta-analytic correlation effects between healthy controls and individuals with psychopathology suggests that individual difference findings related to DA and reward discounting in clinical samples may not be reliably generalized to healthy controls, and vice versa.SIGNIFICANCE STATEMENT Decisions to forgo large rewards for smaller ones due to increasing time delays, uncertainty, or physical effort have been linked to differences in dopamine (DA) function, which is disrupted in some forms of psychopathology. It remains unclear whether alterations in DA function associated with psychopathology also extend to explaining associations between DA function and decision making in healthy individuals. We show that individual differences in DA D2 receptor availability are not consistently related to monetary discounting of time, probability, or physical effort in healthy individuals across a broad age range. By contrast, we suggest that psychopathology accounts for observed inconsistencies in the relationship between measures of DA function and reward discounting behavior.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Desvalorização pelo Atraso , Dopamina/metabolismo , Transtornos Mentais/psicologia , Recompensa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Comportamento Aditivo/diagnóstico por imagem , Comportamento Aditivo/psicologia , Mapeamento Encefálico , Feminino , Humanos , Individualidade , Masculino , Transtornos Mentais/diagnóstico por imagem , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo , Adulto Jovem
3.
J Neurosci ; 38(13): 3230-3239, 2018 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-29483278

RESUMO

The nigrostriatal and mesocorticolimbic dopamine networks regulate reward-driven behavior. Regional alterations to mesolimbic dopamine D2/3 receptor expression are described in drug-seeking and addiction disorders. Parkinson's disease (PD) patients are frequently prescribed D2-like dopamine agonist (DAgonist) therapy for motor symptoms, yet a proportion develop clinically significant behavioral addictions characterized by impulsive and compulsive behaviors (ICBs). Until now, changes in D2/3 receptor binding in both striatal and extrastriatal regions have not been concurrently quantified in this population. We identified 35 human PD patients (both male and female) receiving DAgonist therapy, with (n = 17) and without (n = 18) ICBs, matched for age, disease duration, disease severity, and dose of dopamine therapy. In the off-dopamine state, all completed PET imaging with [18F]fallypride, a high affinity D2-like receptor ligand that can measure striatal and extrastriatal D2/3 nondisplaceable binding potential (BPND). Striatal differences between ICB+/ICB- patients localized to the ventral striatum and putamen, where ICB+ subjects had reduced BPND In this group, self-reported severity of ICB symptoms positively correlated with midbrain D2/3 receptor BPND Group differences in regional D2/3 BPND relationships were also notable: ICB+ (but not ICB-) patients expressed positive correlations between midbrain and caudate, putamen, globus pallidus, and amygdala BPNDs. These findings support the hypothesis that compulsive behaviors in PD are associated with reduced ventral and dorsal striatal D2/3 expression, similar to changes in comparable behavioral disorders. The data also suggest that relatively preserved ventral midbrain dopaminergic projections throughout nigrostriatal and mesolimbic networks are characteristic of ICB+ patients, and may account for differential DAgonist therapeutic response.SIGNIFICANCE STATEMENT The biologic determinants of compulsive reward-based behaviors have broad clinical relevance, from addiction to neurodegenerative disorders. Here, we address biomolecular distinctions in Parkinson's disease patients with impulsive compulsive behaviors (ICBs). This is the first study to image a large cohort of ICB+ patients using positron emission tomography with [18F]fallypride, allowing quantification of D2/3 receptors throughout the mesocorticolimbic network. We demonstrate widespread differences in dopaminergic networks, including (1) D2-like receptor distinctions in the ventral striatum and putamen, and (2) a preservation of widespread dopaminergic projections emerging from the midbrain, which is associated with the severity of compulsive behaviors. This clearly illustrates the roles of D2/3 receptors and medication effects in maladaptive behaviors, and localizes them specifically to nigrostriatal and extrastriatal regions.


Assuntos
Comportamento Compulsivo/diagnóstico por imagem , Sistema Límbico/metabolismo , Doença de Parkinson/diagnóstico por imagem , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Substância Negra/metabolismo , Idoso , Benzamidas , Comportamento Compulsivo/etiologia , Comportamento Compulsivo/metabolismo , Agonistas de Dopamina/farmacologia , Antagonistas dos Receptores de Dopamina D2/farmacologia , Feminino , Humanos , Sistema Límbico/diagnóstico por imagem , Sistema Límbico/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/metabolismo , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Recompensa , Substância Negra/diagnóstico por imagem , Substância Negra/efeitos dos fármacos
4.
Hum Brain Mapp ; 40(10): 3125-3138, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30932295

RESUMO

Theories of adult brain development, based on neuropsychological test results and structural neuroimaging, suggest differential rates of age-related change in function across cortical and subcortical sub-regions. However, it remains unclear if these trends also extend to the aging dopamine system. Here we examined cross-sectional adult age differences in estimates of D2-like receptor binding potential across several cortical and subcortical brain regions using PET imaging and the radiotracer [18 F]Fallypride in two samples of healthy human adults (combined N = 132). After accounting for regional differences in overall radioligand binding, estimated percent difference in receptor binding potential by decade (linear effects) were highest in most temporal and frontal cortical regions (~6-16% per decade), moderate in parahippocampal gyrus, pregenual frontal cortex, fusiform gyrus, caudate, putamen, thalamus, and amygdala (~3-5%), and weakest in subcallosal frontal cortex, ventral striatum, pallidum, and hippocampus (~0-2%). Some regions showed linear effects of age while many showed curvilinear effects such that binding potential declined from young adulthood to middle age and then was relatively stable until old age. Overall, these data indicate that the rate and pattern of decline in D2 receptor availability is regionally heterogeneous. However, the differences across regions were challenging to organize within existing theories of brain development and did not show the same pattern of regional change that has been observed in gray matter volume, white matter integrity, or cognitive performance. This variation suggests that existing theories of adult brain development may need to be modified to better account for the spatial dynamics of dopaminergic system aging.


Assuntos
Envelhecimento/metabolismo , Encéfalo/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Tomografia por Emissão de Pósitrons , Adulto Jovem
5.
J Cogn Neurosci ; 29(3): 467-479, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27779911

RESUMO

Excessively choosing immediate over larger future rewards, or delay discounting (DD), associates with multiple clinical conditions. Individual differences in DD likely depend on variations in the activation of and functional interactions between networks, representing possible endophenotypes for associated disorders, including alcohol use disorders (AUDs). Numerous fMRI studies have probed the neural bases of DD, but investigations of large-scale networks remain scant. We addressed this gap by testing whether activation within large-scale networks during Now/Later decision-making predicts individual differences in DD. To do so, we scanned 95 social drinkers (18-40 years old; 50 women) using fMRI during hypothetical choices between small monetary amounts available "today" or larger amounts available later. We identified neural networks engaged during Now/Later choice using independent component analysis and tested the relationship between component activation and degree of DD. The activity of two components during Now/Later choice correlated with individual DD rates: A temporal lobe network positively correlated with DD, whereas a frontoparietal-striatal network negatively correlated with DD. Activation differences between these networks predicted individual differences in DD, and their negative correlation during Now/Later choice suggests functional competition. A generalized psychophysiological interactions analysis confirmed a decrease in their functional connectivity during decision-making. The functional connectivity of these two networks negatively correlates with alcohol-related harm, potentially implicating these networks in AUDs. These findings provide novel insight into the neural underpinnings of individual differences in impulsive decision-making with potential implications for addiction and related disorders in which impulsivity is a defining feature.


Assuntos
Encéfalo/fisiologia , Desvalorização pelo Atraso/fisiologia , Individualidade , Adolescente , Adulto , Transtornos Relacionados ao Uso de Álcool , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Feminino , Humanos , Comportamento Impulsivo/fisiologia , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Testes Neuropsicológicos , Adulto Jovem
6.
J Neurophysiol ; 115(3): 1146-56, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26683066

RESUMO

Converging evidence links individual differences in mesolimbic and mesocortical dopamine (DA) to variation in the tendency to choose immediate rewards ("Now") over larger, delayed rewards ("Later"), or "Now bias." However, to date, no study of healthy young adults has evaluated the relationship between Now bias and DA with positron emission tomography (PET). Sixteen healthy adults (ages 24-34 yr; 50% women) completed a delay-discounting task that quantified aspects of intertemporal reward choice, including Now bias and reward magnitude sensitivity. Participants also underwent PET scanning with 6-[(18)F]fluoro-l-m-tyrosine (FMT), a radiotracer that measures DA synthesis capacity. Lower putamen FMT signal predicted elevated Now bias, a more rapidly declining discount rate with increasing delay time, and reduced willingness to accept low-interest-rate delayed rewards. In contrast, lower FMT signal in the midbrain predicted greater sensitivity to increasing magnitude of the Later reward. These data demonstrate that intertemporal reward choice in healthy humans varies with region-specific measures of DA processing, with regionally distinct associations with sensitivity to delay and to reward magnitude.


Assuntos
Comportamento de Escolha , Dopamina/metabolismo , Comportamento Impulsivo , Mesencéfalo/fisiologia , Putamen/fisiologia , Recompensa , Adulto , Feminino , Humanos , Masculino , Mesencéfalo/diagnóstico por imagem , Mesencéfalo/metabolismo , Tomografia por Emissão de Pósitrons , Putamen/diagnóstico por imagem , Putamen/metabolismo , Compostos Radiofarmacêuticos , Tempo de Reação , Tirosina/análogos & derivados
7.
J Neurosci ; 34(16): 5468-76, 2014 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-24741037

RESUMO

A variety of evidence suggests that, among humans, the individual tendency to choose immediate rewards ("Now") over larger, delayed rewards ("Later"), or Now bias, varies with frontal dopamine (DA) levels. As cyclic elevations in estradiol (E+) modulate other frontal DA-dependent behaviors, we tested ovarian cycle effects on Now bias, and whether any such effects are E+ mediated. To do so, we quantified Now/Later choice behavior in naturally cycling adult females (n = 87; ages 18-40 years) during both the menstrual phase (MP; cycle day 1-2; low E+), and the follicular phase (FP; cycle day 11-12; high E+). Now bias decreased an average of 3.6% from MP to FP (p = 0.006). Measures of salivary E+ levels at each visit were available in a subsample of participants (n = 34). Participants with a verified E+ rise from MP to FP showed significantly greater decreases in Now bias at mid-cycle (n = 23) than those without a rise (n = 11; p = 0.03); Now bias decreased an average of 10.2% in the E+ rise group but increased an average of 7.9% in the no E+ rise group. The change in Now bias from MP to FP inversely correlated with the change in E+ (ρ = -0.39; p = 0.023), an effect driven by individuals with putatively lower frontal DA based on genotype at the Val(158)Met polymorphism in the COMT gene. This is the first demonstration that intertemporal choice varies across the ovarian cycle, with Now bias declining at mid-cycle, when fertility peaks. Moreover, our data suggest that the interacting effects of estradiol and frontal DA mediate this cycle effect on decision making.


Assuntos
Tomada de Decisões/fisiologia , Estradiol/metabolismo , Ciclo Menstrual/fisiologia , Recompensa , Viés de Seleção , Adolescente , Adulto , Análise de Variância , Catecol O-Metiltransferase/genética , Dopamina/metabolismo , Feminino , Genótipo , Humanos , Ciclo Menstrual/genética , Polimorfismo de Nucleotídeo Único/genética , Psicometria , Saliva/metabolismo , Adulto Jovem
8.
J Cogn Neurosci ; 26(2): 395-407, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24144248

RESUMO

Frontal-dependent task performance is typically modulated by dopamine (DA) according to an inverted-U pattern, whereby intermediate levels of DA signaling optimizes performance. Numerous studies implicate trait differences in DA signaling based on differences in the catechol-O-methyltransferase (COMT) gene in executive function task performance. However, little work has investigated genetic variations in DA signaling downstream from COMT. One candidate is the DA- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32), which mediates signaling through the D1-type DA receptor, the dominant DA receptor in the frontal cortex. Using an n-back task, we used signal detection theory to measure performance in a healthy adult population (n = 97) genotyped for single nucleotide polymorphisms in the COMT (rs4680) and DARPP-32 (rs907094) genes. Correct target detection (hits) and false alarms were used to calculate d' measures for each working memory load (0-, 2-, and 3-back). At the highest load (3-back) only, we observed a significant COMT × DARPP-32 interaction, such that the DARPP-32 T/T genotype enhanced target detection in COMT(ValVal) individuals, but impaired target detection in COMT(Met) carriers. These findings suggest that enhanced dopaminergic signaling via the DARPP-32 T allele aids target detection in individuals with presumed low frontal DA (COMT(ValVal)) but impairs target detection in those with putatively higher frontal DA levels (COMT(Met) carriers). Moreover, these data support an inverted-U model with intermediate levels of DA signaling optimizing performance on tasks requiring maintenance of mental representations in working memory.


Assuntos
Dopamina/fisiologia , Memória de Curto Prazo/fisiologia , Polimorfismo Genético/fisiologia , Córtex Pré-Frontal/fisiologia , Desempenho Psicomotor/fisiologia , Transdução de Sinais/genética , Adulto , População Negra , Catecol O-Metiltransferase/genética , DNA/genética , Interpretação Estatística de Dados , Discriminação Psicológica/fisiologia , Fosfoproteína 32 Regulada por cAMP e Dopamina/genética , Fosfoproteína 32 Regulada por cAMP e Dopamina/fisiologia , Escolaridade , Função Executiva/fisiologia , Feminino , Genótipo , Humanos , Masculino , Repetições Minissatélites , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D1/genética , Receptores de Dopamina D1/fisiologia , População Branca , Adulto Jovem
9.
Bipolar Disord ; 16(7): 703-12, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24990479

RESUMO

OBJECTIVES: Despite different treatments and courses of illness, depressive symptoms appear similar in major depressive disorder (MDD) and bipolar I disorder (BP-I). This similarity of depressive symptoms suggests significant overlap in brain pathways underlying neurovegetative, mood, and cognitive symptoms of depression. These shared brain regions might be expected to exhibit similar activation in individuals with MDD and BP-I during functional magnetic resonance imaging (fMRI). METHODS: fMRI was used to compare regional brain activation in participants with BP-I (n = 25) and MDD (n = 25) during a depressive episode as well as 25 healthy comparison (HC) participants. During the scans, participants performed an attentional task that incorporated emotional pictures. RESULTS: During the viewing of emotional images, subjects with BP-I showed decreased activation in the middle occipital gyrus, lingual gyrus, and middle temporal gyrus compared to both subjects with MDD and HC participants. During attentional processing, participants with MDD had increased activation in the parahippocampus, parietal lobe, and postcentral gyrus. However, among these regions, only the postcentral gyrus also showed differences between MDD and HC participants. CONCLUSIONS: No differences in cortico-limbic regions were found between participants with BP-I and MDD during depression. Instead, the major differences occurred in primary and secondary visual processing regions, with decreased activation in these regions in BP-I compared to major depression. These differences were driven by abnormal decreases in activation seen in the participants with BP-I. Posterior activation changes are a common finding in studies across mood states in participants with BP-I.


Assuntos
Transtorno Bipolar/complicações , Encéfalo/fisiopatologia , Depressão/etiologia , Depressão/patologia , Transtorno Depressivo Maior/complicações , Adulto , Atenção/fisiologia , Encéfalo/irrigação sanguínea , Mapeamento Encefálico , Cognição/fisiologia , Emoções/fisiologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Adulto Jovem
10.
Sci Adv ; 9(11): eadd6947, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36930711

RESUMO

Future space travel needs ultra-lightweight and robust structural materials that can withstand extreme conditions with multiple entry points to orbit to ensure mission reliability. This is unattainable with current inorganic materials. Ultra-highly stable carbon fiber reinforced polymers (CFRPs) have shown susceptibility to environmental instabilities and electrostatic discharge, thereby limiting the full lightweight potential of CFRP. A more robust and improved CFRP is needed in order to improve space travel and structural engineering further. Here, we address these challenges and present a superlattice nano-barrier-enhanced CFRP with a density of ~3.18 g/cm3 that blends within the mechanical properties of the CFRP, thus becoming part of the composite itself. We demonstrate composites with enhanced radiation resistance coupled with electrical conductivity (3.2 × 10-8 ohm⋅m), while ensuring ultra-dimensionally stable physical properties even after temperature cycles from 77 to 573 K.

11.
iScience ; 24(6): 102692, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34195569

RESUMO

The endeavors to develop manufacturing methods that can enhance polymer and composite structures in spacecraft have led to much research and innovation over many decades. However, the thermal stability, intrinsic material stress, and anisotropic substrate properties pose significant challenges and inhibit the use of previously proposed solutions under extreme space environment. Here, we overcome these issues by developing a custom-designed, plasma-enhanced cross-linked poly(p-xylylene):diamond-like carbon superlattice material that enables enhanced mechanical coupling with the soft polymeric and composite materials, which in turn can be applied to large 3D engineering structures. The superlattice structure developed forms an integral part with the substrate and results in a space qualifiable carbon-fiber-reinforced polymer featuring 10-20 times greater resistance to cracking without affecting the stiffness of dimensionally stable structures. This innovation paves the way for the next generation of advanced ultra-stable composites for upcoming optical and radar instrument space programs and advanced engineering applications.

12.
ACS Appl Mater Interfaces ; 13(5): 6670-6677, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33523644

RESUMO

With the realization of larger and more complex space installations, an increase in the surface area exposed to atomic oxygen (AO) and ultraviolet (UV) effects is expected, making structural integrity of space structures essential for future development. In a low Earth orbit (LEO), the effects of AO and UV degradation can have devastating consequences for polymer and composite structures in satellites and space installations. Composite materials such as carbon fiber-reinforced polymer (CFRP) or polymer materials such as polyetherimide and polystyrene are widely used in satellite construction for various applications including structural components, thermal insulation, and importantly radio frequency (RF) assemblies. In this paper, we present a multilayered material protection solution, a multilayered protection barrier, that mitigates the effects of AO and UV without disrupting the functional performance of tested assemblies. This multilayered protection barrier deposited via a custom-built plasma-enhanced chemical vapor deposition (PECVD) system is designed so as to deposit all necessary layers without breaking vacuum to maximize the adhesion to the surface of the substrate and to ensure no pinhole erosion is present. In the multilayer solution, a moisture and outgassing barrier (MOB) is coupled with an AO and UV capping layer to provide complete protection.

13.
Elife ; 92020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32530420

RESUMO

Many postdoctoral researchers apply for faculty positions knowing relatively little about the hiring process or what is needed to secure a job offer. To address this lack of knowledge about the hiring process we conducted a survey of applicants for faculty positions: the survey ran between May 2018 and May 2019, and received 317 responses. We analyzed the responses to explore the interplay between various scholarly metrics and hiring outcomes. We concluded that, above a certain threshold, the benchmarks traditionally used to measure research success - including funding, number of publications or journals published in - were unable to completely differentiate applicants with and without job offers. Respondents also reported that the hiring process was unnecessarily stressful, time-consuming, and lacking in feedback, irrespective of outcome. Our findings suggest that there is considerable scope to improve the transparency of the hiring process.


Assuntos
Mobilidade Ocupacional , Docentes/estatística & dados numéricos , Pesquisadores/estatística & dados numéricos , Logro , Feminino , Humanos , Candidatura a Emprego , Conhecimento , Masculino , Editoração , Pesquisa , Inquéritos e Questionários , Universidades
14.
J Cereb Blood Flow Metab ; 39(5): 822-833, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-29090626

RESUMO

The relatively modest spatial resolution of positron emission tomography (PET) increases the likelihood of partial volume effects such that binding potential (BPND) may be underestimated. Given structural grey matter losses across adulthood, partial volume effects may be even more problematic in older age leading to overestimation of adult age differences. Here we examined the effects of partial volume correction (PVC) in two studies from different sites using different high-affinity D2-like radioligands (18 F-Fallypride, 11C-FLB457) and different PET camera resolutions (∼5 mm, 2.5 mm). Results across both data sets revealed that PVC increased estimated BPND and reduced, though did not eliminate, age effects on BPND. As expected, the effects of PVC were smaller in higher compared to lower resolution data. Analyses using uncorrected data that controlled for grey matter volume in each region of interest approximated PVC corrected data for some but not all regions. Overall, the findings suggest that PVC increases estimated BPND in general and reduces adult age differences especially when using lower resolution cameras. The findings suggest that the past 30 years of research on dopamine receptor availability, for which very few studies use PVC, may overestimate effects of aging on dopamine receptor availability.


Assuntos
Envelhecimento , Encéfalo/fisiologia , Receptores de Dopamina D2/metabolismo , Adulto , Idoso , Dopamina/metabolismo , Feminino , Substância Cinzenta/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Ligação Proteica
15.
Nanoscale ; 11(31): 14734-14741, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31348471

RESUMO

Graphene-based carbon sponges can be used in different applications in a large number of fields including microelectronics, energy harvesting and storage, antimicrobial activity and environmental remediation. The functionality and scope of their applications can be broadened considerably by the introduction of metallic nanoparticles into the carbon matrix during preparation or post-synthesis. Here, we report on the use of X-ray micro-computed tomography (CT) as a method of imaging graphene sponges after the uptake of metal (silver and iron) nanoparticles. The technique can be used to visualize the inner structure of the graphene sponge in 3D in a non-destructive fashion by providing information on the nanoparticles deposited on the sponge surfaces, both internal and external. Other deposited materials can be imaged in a similar manner providing they return a high enough contrast to the carbon microstructure, which is facilitated by the low atomic mass of carbon.

16.
Psychol Aging ; 34(7): 921-932, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31589058

RESUMO

The evidence that dopamine function mediates the association between aging and cognition is one of the most cited findings in the cognitive neuroscience of aging. However, few and relatively small studies have directly examined these associations. Here we examined correlations among adult age, dopamine D2-like receptor (D2R) availability, and cognition in two cross-sectional studies of healthy human adults. Participants completed a short cognitive test battery and, on a separate day, a PET scan with either the high-affinity D2R tracer [18F]Fallypride (Study 1) or [11C]FLB457 (Study 2). Digit span, a measure of short-term memory maintenance and working memory, was the only cognitive test for which dopamine D2R availability partially mediated the age effect on cognition. In Study 1, age was negatively correlated with digit span. Striatal D2R availability was positively correlated with digit span controlling for age. The age effect on digit span was smaller when controlling for striatal D2R availability. Although other cognitive measures used here have individually been associated with age and D2R availability in prior studies, we found no consistent evidence for significant associations between low D2R availability and low cognitive performance on these measures. These results at best only partially supported the correlative triad of age, dopamine D2R availability, and cognition. While a wealth of other research in human and nonhuman animals demonstrates that dopamine makes critical contributions to cognition, the present studies suggest caution in interpreting PET findings as evidence that dopamine D2R loss is a primary cause of broad age-related declines in fluid cognition. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Envelhecimento/fisiologia , Cognição/fisiologia , Receptores de Dopamina D2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Adulto Jovem
17.
Psychopharmacology (Berl) ; 236(2): 581-590, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30350220

RESUMO

RATIONALE: Sex differences in the dopaminergic response to psychostimulants could have implications for drug abuse risk and other psychopathology involving the dopamine system, but human data are limited and mixed. OBJECTIVES: Here, we sought to investigate sex differences in dopamine release after oral D-amphetamine administration. METHODS: We used [18F]fallypride positron emission tomography (PET) to measure the change in dopamine D2/3 receptor availability (%ΔBPND, an index of dopamine release) between placebo and D-amphetamine sessions in two independent datasets containing a total of 39 females (on either hormonal birth control n = 18, postmenopausal n = 10, or studied in the first 10 days of their menstrual cycle n = 11) and 37 males. RESULTS: Using both a priori anatomical regions of interest based on previous findings and voxelwise analyses, we failed to consistently detect broad sex differences in D-amphetamine-induced dopamine release. Nevertheless, there was limited evidence for greater right ventral striatal dopamine release in young adult males relative to similarly aged females, but this was not consistently observed across samples. Plasma estradiol did not correlate with dopamine release and this measure did not differ in females on and off hormonal birth control. CONCLUSIONS: While our finding in young adults from one dataset of greater %ΔBPND in males is partially consistent with a previously published study on sex differences in D-amphetamine-induced dopamine release, our data do not support the presence of consistent widespread sex differences in this measure of dopamine release.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Dextroanfetamina/farmacologia , Dopamina/metabolismo , Receptores de Dopamina D2/efeitos dos fármacos , Receptores de Dopamina D3/efeitos dos fármacos , Estriado Ventral/efeitos dos fármacos , Adulto , Idoso , Benzamidas , Feminino , Radioisótopos de Flúor , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Caracteres Sexuais , Fatores Sexuais , Estriado Ventral/diagnóstico por imagem , Estriado Ventral/metabolismo , Adulto Jovem
18.
Neuroimage Clin ; 18: 433-442, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29541577

RESUMO

Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D2/3 receptor binding in both striatal and extrastriatal regions in PD are limited. We studied 35 PD patients off-medication and 31 age- and sex-matched healthy controls (HCs) using PET imaging with [18F]fallypride, a high affinity D2/3 receptor ligand, to measure striatal and extrastriatal D2/3 nondisplaceable binding potential (BPND). PD patients completed PET imaging in the off medication state, and motor severity was concurrently assessed. Voxel-wise evaluation between groups revealed significant BPND reductions in PD patients in striatal and several extrastriatal regions, including the locus coeruleus and mesotemporal cortex. A region-of-interest (ROI) based approach quantified differences in dopamine D2/3 receptors, where reduced BPND was noted in the globus pallidus, caudate, amygdala, hippocampus, ventral midbrain, and thalamus of PD patients relative to HC subjects. Motor severity positively correlated with D2/3 receptor density in the putamen and globus pallidus. These findings support the hypothesis that abnormal D2/3 expression occurs in regions related to both the motor and non-motor symptoms of PD, including areas richly invested with noradrenergic neurons.


Assuntos
Benzamidas/farmacocinética , Corpo Estriado/diagnóstico por imagem , Antagonistas dos Receptores de Dopamina D2/farmacocinética , Doença de Parkinson/diagnóstico por imagem , Receptores de Dopamina D2/metabolismo , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Corpo Estriado/efeitos dos fármacos , Feminino , Fluordesoxiglucose F18/farmacocinética , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia por Emissão de Pósitrons
19.
Physiol Behav ; 192: 188-193, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29233619

RESUMO

The fat mass and obesity associated gene (FTO) was the first gene identified by genome-wide association studies to correlate with higher body mass index (BMI) and increased odds of obesity. FTO remains the locus with the largest and most replicated effect on body weight, but the mechanism whereby FTO affects body weight and the development of obesity is not fully understood. Here we tested whether FTO is associated with differences in food cravings and a key aspect of dopamine function that has been hypothesized to influence food reward mechanisms. Moreover, as food cravings and dopamine function are known to decline with age, we explored effects of age on relations between FTO and food cravings and dopamine function. Seven-eight healthy subjects between 22 and 83years old completed the Food Cravings Questionnaire and underwent genotyping for FTO rs9939609, the first FTO single nucleotide polymorphism associated with obesity. Compared to TT homozygotes, individuals carrying the obesity-susceptible A allele had higher total food cravings, which correlated with higher BMI. Additionally, food cravings declined with age, but this age effect differed across variants of FTO rs9939609: while TT homozygotes showed the typical age-related decline in food cravings, there was no such decline among A carriers. All subjects were scanned with [18F]fallypride PET to assess a recent proposal that at the neurochemical level FTO alters dopamine D2-like receptor (DRD2) function to influence food reward related mechanisms. However, we observed no evidence of FTO effects on DRD2 availability.


Assuntos
Envelhecimento/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Fissura , Comportamento Alimentar , Alimentos , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Benzamidas , Índice de Massa Corporal , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Fissura/fisiologia , Comportamento Alimentar/fisiologia , Comportamento Alimentar/psicologia , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Tomografia por Emissão de Pósitrons , Pirrolidinas , Compostos Radiofarmacêuticos , Receptores de Dopamina D2/metabolismo , Adulto Jovem
20.
RSC Adv ; 8(65): 37540-37549, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35557804

RESUMO

Graphene is a desirable material for next generation technology. However, producing high yields of single-layer flakes with industrially applicable methods is currently limited. We introduce a combined process for the reduction of graphene oxide (GO) via vitamin C (ascorbic acid) and thermal annealing at temperatures of <150 °C for times of <10 minutes, resulting in electrically conducting thin films with sheet resistances reducing by 8 orders of magnitude to as low as ∼1.3 kΩ â–¡-1, suitable for microelectronics, display technology and optoelectronic applications. The in-depth physicochemical characterisation of the products at different stages of GO preparation and reduction allows for further understanding of the process and demonstrates the suitability for industrial production methodologies due to an environmentally-friendly reducing agent, solution processability and no requirement for high temperatures. The presence of the vitamin C lowers the temperature required to thermally reduce the GO into an electrically conducting thin film, making the technique suitable for thermally sensitive substrates, such as low melting point polymers. Simultaneous spray coating and reduction of GO allows for large area deposition of conductive coatings without sacrificing solution processability, often lost through particle agglomeration, making it compatible with industrial processes, and applicable to, for example, the production of sensors, energy devices and flexible conductive electrodes for touchscreens.

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