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1.
Angew Chem Int Ed Engl ; 59(14): 5756-5764, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-31860759

RESUMO

Magnetic hysteresis is demonstrated for monolayers of the single-molecule magnet (SMM) Dy2 ScN@C80 deposited on Au(111), Ag(100), and MgO|Ag(100) surfaces by vacuum sublimation. The topography and electronic structure of Dy2 ScN@C80 adsorbed on Au(111) were studied by STM. X-ray magnetic CD studies show that the Dy2 ScN@C80 monolayers exhibit similarly broad magnetic hysteresis independent on the substrate used, but the orientation of the Dy2 ScN cluster depends strongly on the surface. DFT calculations show that the extent of the electronic interaction of the fullerene molecules with the surface is increasing dramatically from MgO to Au(111) and Ag(100). However, the charge redistribution at the fullerene-surface interface is fully absorbed by the carbon cage, leaving the state of the endohedral cluster intact. This Faraday cage effect of the fullerene preserves the magnetic bistability of fullerene-SMMs on conducting substrates and facilitates their application in molecular spintronics.

2.
J Biomech ; 93: 226-230, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31387697

RESUMO

The present study quantified the effects of different shear cushion stiffness on the time to peak posterior shear force (TPPSF), peak posterior shear force (PPSF), average posterior loading rate (APLR), and maximum posterior loading rate (MPLR) at different locomotion speeds using a custom-made sliding platform, as well as to identify the optimal stiffness of shear cushion. Twelve male collegiate students (heel-strikers) performed walking at 1.5 m/s, jogging at 2.5 m/s, and running at 3.5 m/s. A custom-made sliding platform was used to provide the different shear cushion conditions. The shear cushion conditions were fixed (a fixed platform; control group), stiff (K = 2746 N/m), medium stiff (K = 2256 N/m), medium soft (K = 1667 N/m), and soft (K = 1079 N/m). The results showed that all cushion conditions produced sliding displacement and delayed the TPPSF during walking, jogging, and running compared with fixed condition. The APLR and MPLR were lowest under medium soft condition during walking, while the PPSF was similar between medium soft and soft conditions. For jogging and running, the PPSF as well as APLR and MPLR were the lowest under medium stiff condition except the maximum PLR was similar among stiff, medium stiff, and medium soft conditions during running. In conclusion, shear cushion produces appropriate sliding displacement and effectively delays the TPPSF to provide the musculoskeletal system additional time to absorb the impact and reduce loading. The present study demonstrates optimal stiffness of shear cushion at different traveling speeds and suggests that a shear cushion system can be applied in future designs of cushion structures.

3.
Acc Chem Res ; 52(7): 1824-1833, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31260256

RESUMO

Fullerene carbon cages can encapsulate a wide variety of atoms, ions, clusters, or small molecules inside, resulting in stable compounds with unusual structures and electronic properties. These compounds are collectively defined as endohedral fullerenes. The most studied endohedral fullerenes are those containing metal atoms or ions inside, and these are referred to as endohedral metallofullerenes (EMFs). For EMFs, the inner isolated space of the fullerene cages can lead to the stabilization of unique clusters, which are otherwise not synthetically accessible. This offers an excellent environment and opportunity for investigating the nature of previously unobserved metal-metal, metal-non-metal, and metal-fullerene interactions, which are of fundamental interest and importance. Up until now, most of the work in this field has been mainly focused on the rare-earth metals and related elements (groups II, III, and IV). The encapsulation of other elements of the periodic table could potentially lead to totally new structures and bonding motifs and to material properties beyond those of the existing EMFs. Actinides were originally explored as encapsulated elements in fullerenes when Smalley et al. ( Science 1992 , 257 , 1661 ) reported mass spectral evidence of actinide endohedral fullerenes back in 1992. However, the full characterization of these actinide endohedral fullerenes, including single crystal X-ray diffractometric analyses, was not reported until very recently, in 2017. In this Account, we highlight some recent advances made in the field of EMF compounds, focusing primarily on the molecular and electronic structures of novel actinide-based EMFs, new evidence for the formation mechanisms of EMFs, and the influence of the entrapped species on the reactivity and regiochemistry of EMF compounds. We recently reported that some monometallic actinide EMFs represent the first examples of tetravalent metals encapsulated inside fullerenes that exhibit considerably stronger host-guest interactions when compared to those observed for the lanthanide EMFs. These unusually strong metal-cage interactions, along with very high mobilities of the actinides inside the fullerene cages at high temperatures, result in the stabilization of unexpected non-IPR (isolated pentagon rule) fullerene cages encapsulating only one metal ion. Strikingly, such covalent stabilization factors had never been previously observed, although Sm@C2v(19138)-C76 was the first reported mono-EMF with a non-IPR cage, see details below. In addition, we showed that a long sought-after actinide-actinide bond was obtained upon encapsulation of U2 inside an Ih(7)-C80 fullerene cage. More interestingly, we demonstrated that actinide multiple bonds, which are very difficult to prepare by conventional synthetic methods, are stabilized when trapped inside fullerene cages. A totally unexpected and previously unreported uranium carbide cluster, U═C═U, was fully characterized inside an EMF, U2C@Ih(7)-C80, which, for the first time, clearly exhibits two unsupported axial U═C double bonds that are ∼2.03 Šlong. We also discovered that synthetic bis-porphyrin nanocapsules exhibit exquisitely selective complexation of some of these uranium endohedral compounds, providing the basis for a nonchromatographic EMF purification method for actinide EMFs. Regarding EMF formation mechanisms, we suggested that novel carbide EMF structures, that is, Sc2C2@Cs(hept)-C88, are likely key intermediates in a bottom-up fullerene growth process. Additionally, the structural correlation between chiral carbon cages during a bottom-up growth process was shown to be enantiomer-dependent. The influence of the encapsulated clusters on the chemical reactivity of EMFs is discussed at the end, which showed that the regioselectivities of multiple additions to the fullerene cages are remarkably controlled by the encapsulated metal clusters.

4.
Sci Rep ; 9(1): 7701, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31097724

RESUMO

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

5.
Sci Rep ; 9(1): 4980, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30899073

RESUMO

Heroin use disorder (HUD) is a complex disease resulting from interactions among genetic and other factors (e.g., environmental factors). The mechanism of HUD development remains unknown. Newly developed network medicine tools provide a platform for exploring complex diseases at the system level. This study proposes that protein-protein interactions (PPIs), particularly those among proteins encoded by casual or susceptibility genes, are extremely crucial for HUD development. The giant component of our constructed PPI network comprised 111 nodes with 553 edges, including 16 proteins with large degree (k) or high betweenness centrality (BC), which were further identified as the backbone of the network. JUN with the largest degree was suggested to be central to the PPI network associated with HUD. Moreover, PCK1 with the highest BC and MAPK14 with the secondary largest degree and 9th highest BC might be involved in the development HUD and other substance diseases.

6.
Nat Commun ; 10(1): 571, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718550

RESUMO

Engineering intramolecular exchange interactions between magnetic metal atoms is a ubiquitous strategy for designing molecular magnets. For lanthanides, the localized nature of 4f electrons usually results in weak exchange coupling. Mediating magnetic interactions between lanthanide ions via radical bridges is a fruitful strategy towards stronger coupling. In this work we explore the limiting case when the role of a radical bridge is played by a single unpaired electron. We synthesize an array of air-stable Ln2@C80(CH2Ph) dimetallofullerenes (Ln2 = Y2, Gd2, Tb2, Dy2, Ho2, Er2, TbY, TbGd) featuring a covalent lanthanide-lanthanide bond. The lanthanide spins are glued together by very strong exchange interactions between 4f moments and a single electron residing on the metal-metal bonding orbital. Tb2@C80(CH2Ph) shows a gigantic coercivity of 8.2 Tesla at 5 K and a high 100-s blocking temperature of magnetization of 25.2 K. The Ln-Ln bonding orbital in Ln2@C80(CH2Ph) is redox active, enabling electrochemical tuning of the magnetism.

7.
Brain Behav ; 8(7): e01016, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29927088

RESUMO

BACKGROUND: Patients with late-life depression may be at the preclinical stage of dementia. However, the neurodegenerative processes in late-life depression are poorly understood. This study aimed to investigate the distribution patterns of amyloid pathology and neurodegeneration in a depressive population without dementia. METHODS: The study recruited 63 middle-aged and elderly patients with major depressive disorder (MDD) and 22 control subjects. The MDD patients were further subdivided into those with mild cognitive impairment (MCI) (n = 24) and non-MCI (n = 39) patients. We used the global standardized uptake value ratio of 18 F-florbetapir (AV-45/Amyvid) positron emission tomography imaging as a biomarker of cerebral amyloidosis and the hippocampal volume as a biomarker for neurodegeneration. Cutoff points of brain amyloid positivity and hippocampal atrophy were determined using independent data obtained from clinically diagnosed Alzheimer's disease (AD) patients in a previous study. RESULTS: Most of the control subjects (81.8%) were biomarker-negative, in contrast to the MCI MDD patients (37.5%). A relatively high proportion of the MCI MDD patients (12.5%) exhibited both amyloid positivity and hippocampal atrophy as compared to the control subjects (4.5%) and non-MCI patients (5.1%). However, a considerable proportion of the MCI MDD patients (29.2%) were categorized into the group with hippocampal atrophy alone, and negative amyloid deposition, as compared to the control subjects (0%) and non-MCI patients (5.1%). CONCLUSIONS: This study highlights the expected heterogeneity of the processes of neurodegeneration in MDD patients. The diverse neurodegenerative processes may have important etiologic and therapeutic implications regarding neurodegenerative pathophysiology in late-life depression.


Assuntos
Amiloidose/complicações , Encefalopatias/complicações , Transtorno Depressivo Maior/etiologia , Hipocampo/patologia , Doenças Neurodegenerativas/etiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/etiologia , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina , Atrofia/diagnóstico por imagem , Biomarcadores/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Transtorno Depressivo Maior/diagnóstico por imagem , Etilenoglicóis , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Lobo Temporal/diagnóstico por imagem
8.
J Sleep Res ; 27(5): e12700, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29845680

RESUMO

Excessively sleepy teenagers and young adults without sleep-disordered breathing are diagnosed with either narcolepsy type 1 or narcolepsy type 2, or hypersomnia, based on the presence/absence of cataplexy and the results of a multiple sleep latency test. However, there is controversy surrounding this nomenclature. We will try to find the differences between different diagnoses of hypersomnia from the results of the long-term follow-up evaluation of a sleep study. We diagnosed teenagers who had developed excessive daytime sleepiness based on the criteria of the International Classification of Sleep Disorders, 3rd edition. Each individual received the same clinical neurophysiologic testing every year for 5 years after the initial diagnosis of narcolepsy type 1 (n = 111) or type 2 (n = 46). The follow-up evaluation demonstrated that narcolepsy type 1 (narcolepsy-cataplexy) is a well-defined clinical entity, with very reproducible clinical neurophysiologic findings over time, whereas patients with narcolepsy type 2 presented clear clinical and test variability. By the fifth year of the follow-up evaluation, 17.6% of subjects did not meet the diagnostic criteria of narcolepsy type 2, and 23.9% didn't show any two sleep-onset rapid eye movement periods in multiple sleep latency during the 5-year follow-up. Therefore narcolepsy type 1 (narcolepsy-cataplexy) is a well-defined syndrome, with the presentation clearly related to the known consequences of destruction of hypocretin/orexin neurons. Narcolepsy type 2 covers patients with clinical and test variability over time, thus bringing into question the usage of the term "narcolepsy" to label these patients.


Assuntos
Narcolepsia/diagnóstico , Latência do Sono/fisiologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Narcolepsia/patologia , Fatores de Tempo , Adulto Jovem
9.
Mol Autism ; 9: 11, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29456827

RESUMO

Background: Impaired social interaction is one of the essential features of autism spectrum disorder (ASD). Our previous copy number variation (CNV) study discovered a novel deleted region associated with ASD. One of the genes included in the deleted region is ARHGEF10. A missense mutation of ARHGEF10 has been reported to be one of the contributing factors in several diseases of the central nervous system. However, the relationship between the loss of ARHGEF10 and the clinical symptoms of ASD is unclear. Methods: We generated Arhgef10 knockout mice as a model of ASD and characterized the social behavior and the biochemical changes in the brains of the knockout mice. Results: Compared with their wild-type littermates, the Arhgef10-depleted mice showed social interaction impairment, hyperactivity, and decreased depression-like and anxiety-like behavior. Behavioral measures of learning in the Morris water maze were not affected by Arhgef10 deficiency. Moreover, neurotransmitters including serotonin, norepinephrine, and dopamine were significantly increased in different brain regions of the Arhgef10 knockout mice. In addition, monoamine oxidase A (MAO-A) decreased in several brain regions. Conclusions: These results suggest that ARHGEF10 is a candidate risk gene for ASD and that the Arhgef10 knockout model could be a tool for studying the mechanisms of neurotransmission in ASD. Trial registration: Animal studies were approved by the Institutional Animal Care and Use Committee of National Taiwan University (IACUC 20150023). Registered 1 August 2015.


Assuntos
Transtorno do Espectro Autista/genética , Fatores de Troca de Nucleotídeo Guanina Rho/genética , Comportamento Social , Animais , Encéfalo/metabolismo , Encéfalo/fisiologia , Aprendizagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monoaminoxidase/metabolismo , Norepinefrina/metabolismo , Fatores de Troca de Nucleotídeo Guanina Rho/deficiência , Serotonina/metabolismo
10.
Sci Rep ; 8(1): 2739, 2018 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-29426824

RESUMO

An increased level of brain amyloid deposition and a decreased level of cerebral spinal fluid (CSF) Aß42 are currently considered reliable biomarkers of Alzheimer's disease (AD); however, the usefulness of plasma Aß levels are not well-established. This study investigated the relationships between plasma Aß levels and cerebral amyloidosis in 36 non-demented patients with major depressive disorder (MDD). All participants underwent 18F-florbetapir PET imaging and provided a blood sample at the same time for immunomagnetic reduction assay to measure the plasma levels of Aß40 and Aß42. We found inverse associations of the plasma Aß42 level and the Aß42/Aß40 ratio, and a positive association of the plasma Aß40 level, with cerebral amyloid deposition in the precuneus, parietal and posterior cingulate cortex. Subgroup analyses in subjects with higher 18F-florbetapir uptake values or MDD with amnestic mild cognitive impairment revealed more pervasive relationships of plasma Aß measures with 18F-florbetapir binding across the brain regions examined. The study suggested that regional brain amyloid deposition in terms of 18F-florbetapir PET uptake had weak-to-moderate associations with plasma Aß42 and Aß40 levels, and the Aß42/Aß40 ratio. Validation in a larger population of subjects of known cerebral amyloidosis status is needed. Careful interpretation of plasma data is warranted.


Assuntos
Peptídeos beta-Amiloides/sangue , Angiopatia Amiloide Cerebral/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/patologia , Fragmentos de Peptídeos/sangue , Idoso , Compostos de Anilina/química , Angiopatia Amiloide Cerebral/patologia , Etilenoglicóis/química , Feminino , Giro do Cíngulo/patologia , Humanos , Separação Imunomagnética/métodos , Masculino , Pessoa de Meia-Idade , Lobo Parietal/patologia , Placa Amiloide/sangue , Placa Amiloide/patologia , Tomografia por Emissão de Pósitrons/métodos
11.
J Vis Exp ; (131)2018 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-29364283

RESUMO

The presence of anti-NMDA receptor autoantibody can cause various neuropsychiatric symptoms in the affected patients, termed anti-NMDA receptor autoimmune encephalitis. Detection of the specific autoantibody against the NMDA receptor in the blood or cerebrospinal fluid (CSF) is essential for the accurate diagnosis of this condition. The NMDA receptor is an ion channel protein complex that contains four subunits, including two mandatory NMDA receptor subunit 1 (NR1) and one or two NMDA receptor subunit 2A (NR2A), NMDA receptor subunit 2B (NR2B), NMDA receptor subunit 2C (NR2C), or NMDA receptor subunit 2D (NR2D). The epitope of anti-NMDA receptor autoantibody was reported to be present at the extracellular N-terminal domain of the NR1 subunit of the NMDA receptor. The goal of this study is to develop a simple cell-based immunofluorescence assay that can be used as a screening test to detect the presence of autoantibodies against NR1 subunit of the NMDA receptor in the blood to facilitate the clinical and basic research of anti-NMDA receptor autoimmune encephalitis.


Assuntos
Autoanticorpos/sangue , Autoanticorpos/imunologia , Imunofluorescência/métodos , Receptores de N-Metil-D-Aspartato/sangue , Receptores de N-Metil-D-Aspartato/imunologia , Células HEK293 , Humanos , Transfecção
12.
Chem Sci ; 8(9): 6451-6465, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29263779

RESUMO

A method for the selective synthesis of sulfide clusterfullerenes Dy2S@C2n is developed. Addition of methane to the reactive atmosphere reduces the formation of empty fullerenes in the arc-discharge synthesis, whereas the use of Dy2S3 as a source of metal and sulfur affords sulfide clusterfullerenes as the main fullerene products along with smaller amounts of carbide clusterfullerenes. Two isomers of Dy2S@C82 with Cs(6) and C3v(8) cage symmetry, Dy2S@C72-Cs(10528), and a carbide clusterfullerene Dy2C2@C82-Cs(6) were isolated. The molecular structure of both Dy2S@C82 isomers was elucidated by single-crystal X-ray diffraction. SQUID magnetometry demonstrates that all of these clusterfullerenes exhibit hysteresis of magnetization, with Dy2S@C82-C3v(8) being the strongest single molecule magnet in the series. DC- and AC-susceptibility measurements were used to determine magnetization relaxation times in the temperature range from 1.6 K to 70 K. Unprecedented magnetization relaxation dynamics with three consequent Orbach processes and energy barriers of 10.5, 48, and 1232 K are determined for Dy2S@C82-C3v(8). Dy2S@C82-Cs(6) exhibits faster relaxation of magnetization with two barriers of 15.2 and 523 K. Ab initio calculations were used to interpret experimental data and compare the Dy-sulfide clusterfullerenes to other Dy-clusterfullerenes. The smallest and largest barriers are ascribed to the exchange/dipolar barrier and relaxation via crystal-field states, respectively, whereas an intermediate energy barrier of 48 K in Dy2S@C82-C3v(8) is assigned to the local phonon mode, corresponding to the librational motion of the Dy2S cluster inside the carbon cage.

13.
Front Psychiatry ; 8: 257, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29230184

RESUMO

Neuroligin 2 (NLGN2) is a postsynaptic adhesion protein that plays an essential role in synaptogenesis and function of inhibitory neuron. We previously identified a missense mutation R215H of the NLGN2 in a patient with schizophrenia. This missense mutation was shown to be pathogenic in several cell-based assays. The objective of this study was to better understand the behavioral consequences of this mutation in vivo. We generated a line of transgenic mice carrying this mutation using a recombinant-based method. The mice were subjected to a battery of behavioral tests including open field locomotor activity assay, prepulse inhibition (PPI) assay, accelerated rotarod test, novel location and novel recognition tests, elevated plus-maze (EPM) test, and Morris water maze test. The transgenic animals were viable and fertile, but the Nlgn2 R215H knock-in (KI) homozygous mice showed growth retardation, anxiety-like behavior, increased PPI, and impaired spatial learning and memory. There was no significant interaction between sex and genotype in most behavioral tests; however, we observed a significant interaction between sex and genotype in EPM test in this study. Also, we found that the Nlgn2 R215H homozygous KI mice did not express the NLGN2 protein, resembling Nlgn2 knockout mice. Our results demonstrate that Nlgn2 R215H KI homozygous mice manifest several behavioral abnormalities similar to those found in psychiatric patients carrying NLGN2 mutations, indicating that dysfunction of NLGN2 contributes to the pathogenesis of certain psychiatric symptoms commonly present in various mental disorders, not limited to schizophrenia.

14.
Sci Rep ; 7(1): 11919, 2017 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-28931914

RESUMO

Rare genomic copy number variations (CNVs) (frequency <1%) contribute a part to the genetic underpinnings of autism spectrum disorders (ASD). The study aimed to understand the scope of rare CNV in Taiwanese patients with ASD. We conducted a genome-wide CNV screening of 335 ASD patients (299 males, 36 females) from Taiwan using Affymetrix Genome-Wide Human SNP Array 6.0 and compared the incidence of rare CNV with that of 1093 control subjects (525 males, 568 females). We found a significantly increased global burden of rare CNVs in the ASD group compared to the controls as a whole or when the rare CNVs were classified by the size and types of CNV. Further analysis confirmed the presence of several rare CNVs at regions strongly associated with ASD as reported in the literature in our sample. Additionally, we detected several new private pathogenic CNVs in our samples and five patients carrying two pathogenic CNVs. Our data indicate that rare genomic CNVs contribute a part to the genetic landscape of our ASD patients. These CNVs are highly heterogeneous, and the clinical interpretation of the pathogenic CNVs of ASD is not straightforward in consideration of the incomplete penetrance, varied expressivity, and individual genetic background.


Assuntos
Transtorno do Espectro Autista/genética , Dosagem de Genes , Predisposição Genética para Doença , Adolescente , Idoso , Criança , Pré-Escolar , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Taiwan
15.
Schizophr Res ; 190: 28-31, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28341002

RESUMO

Autoimmune encephalopathy caused by autoantibodies against neuronal cell-surface proteins in the brain is a newly discovered disease category associated with psychiatric disorders. Correct diagnosis of this condition relies on the detection of specific autoantibodies in the blood or cerebral spinal fluid in addition to the clinical presentations. The study aimed to understand the seroprevalence of selective anti-neuronal autoantibodies in our patients with schizophrenia. First, we screened for six anti-neuronal autoantibodies in an archived blood sample collected from patients with the first-episode schizophrenia. The six autoantibodies including antibodies against N-methyl-d-aspartate (NMDA) receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors 1 and 2, γ-butyric acid receptor type B1 (GABARB1), leucine-rich glioma inactivated-1 (LGI1) protein, and contactin-associated protein-like 2 (CASPR2) protein. A total of 78 plasma samples (46 males and 32 females) were investigated; however, no positive case was identified. In this second study, we screened anti-NMDA receptor autoantibodies in a blood sample of 234 patients with chronic schizophrenia (133 females and 101 males) including 48 patients defined as treatment resistance. None of this sample was detected as positive. The negative findings in this study suggest that the seroprevalence of autoantibodies against neuronal surface proteins might be low in patients diagnosed with schizophrenia.


Assuntos
Autoanticorpos/sangue , Proteínas do Tecido Nervoso/imunologia , Esquizofrenia/epidemiologia , Esquizofrenia/imunologia , Doença Aguda , Adulto , Doença Crônica , Resistência a Medicamentos/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Esquizofrenia/sangue , Estudos Soroepidemiológicos , Adulto Jovem
16.
EJNMMI Res ; 7(1): 24, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28324341

RESUMO

BACKGROUND: Lack of treatment response in patients with late-life depression is common. The role of brain beta-amyloid (Aß) deposition in treatment outcome in subjects with late-life depression remains unclear. The present study aimed to investigate brain Aß deposition in patients with major depressive disorder (MDD) with differing treatment outcomes in vivo using 18F-florbetapir imaging. This study included 62 MDD patients and 18 healthy control subjects (HCs).We first employed the Maudsley staging method (MSM) to categorize MDD patients into two groups according to treatment response: mild treatment resistance (n = 29) and moderate-to-severe treatment resistance (n = 33).The standard uptake value ratio (SUVR) of each volume of interest was analysed, and voxel-wise comparisons were made between the MDD patients and HCs. Vascular risk factors, serum homocysteine level, and apolipoprotein E (ApoE) genotype were also determined. RESULTS: The MDD patients with moderate-to-severe treatment resistance had higher 18F-florbetapir SUVRs than the HCs in the parietal region (P < 0.01). Voxel-wise comparisons further demonstrated elevated SUVRs in MDD patients with moderate-to-severe treatment resistance in the precuneus, parietal, temporal, and occipital regions. The MDD patients with mild treatment resistance were found to have increased 18F-florbetapir uptake mainly in the left frontal and parietal regions as compared with the HCs. In addition, voxel-to-voxel correlation analysis showed that brain Aß deposition was correlated positively with MSM score in the occipital region. 18F-florbetapir SUVRs were correlated negatively with Mini Mental Status Examination (MMSE) score in the sample of all MDD patients (r = -0.355, P = 0.005). CONCLUSIONS: This study provided preliminary evidence that region-specific Aß deposition was present in some (but not all) MDD patients, especially in those with moderate-to-severe treatment resistance, and their depressive symptoms may represent prodromal manifestations of Alzheimer's disease (AD). Depressive symptomatology in old age, particularly in subjects with a poor treatment response, may underscore early changes of AD-related pathophysiology.

17.
Psychiatr Genet ; 27(1): 23-33, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27846046

RESUMO

OBJECTIVES: Chromosome 22q13 is a hot region of genomic rearrangements that may result in deletion, duplication, and translocation, and that may lead to neurodevelopmental disorders in affected patients. MATERIALS AND METHODS: We carried out an array-based comparative genomic hybridization analysis to detect copy number variations (CNVs) of genomic DNA in patients with autism spectrum disorders (ASD) who were consecutively recruited into our molecular genetic study of ASD. Karyotyping, fluorescent in-situ hybridization analysis, and real time-quantitative PCR were used for validation tests. RESULTS: We completed a genome-wide CNV analysis of 335 patients with ASD from Taiwan. Three unrelated male patients were found to carry three different CNVs at 22q13.3, respectively, including a de novo terminal deletion of ∼106 kb at 22q13.33, a de novo interstitial duplication of ∼1.8 Mb at 22q13.32-q13.33, and a microdeletion of ∼147 kb at 22q13.33. These three CNVs all involved the dosage change of the SHANK3 gene. The last patient also carried a genomic duplication of ∼3.86 Mb at 19q13.42-q13.4 in addition to a microdeletion of ∼147 kb at 22q13.33. His younger sister also carried these two CNVs, but she had developmental delay and other neurological deficits without ASD. These two CNVs were transmitted from their unaffected father, who carried a balanced translocation between chromosome 22q and 19q. CONCLUSION: Our data support that recurrent genomic rearrangements at 22q13.3 are part of the genetic landscape of ASD in our patients and changes in SHANK3 dosage are associated with neurodevelopmental disorders. However, the clinical symptoms of patients with 22q13.3 rearrangements can vary depending on other genetic and nongenetic factors, not limited to genes involved in CNVs in this region.


Assuntos
Transtorno do Espectro Autista/genética , Transtornos Cromossômicos/genética , Adolescente , Criança , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 22/genética , Hibridização Genômica Comparativa/métodos , DNA , Variações do Número de Cópias de DNA/genética , Feminino , Genômica , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Proteínas do Tecido Nervoso/genética , Taiwan
18.
J Am Chem Soc ; 138(39): 13030-13037, 2016 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-27592501

RESUMO

A non-isolated pentagon rule metallic carbide clusterfullerene containing a heptagonal ring, Sc2C2@Cs(hept)-C88, was isolated from the raw soot obtained by electric arc vaporization of graphite rods packed with Sc2O3 and graphite powder under a helium atmosphere. The Sc2C2@Cs(hept)-C88 was purified by multistage high-performance liquid chromatography (HPLC), cocrystallized with Ni-(octaethylporphyrin), and characterized by single-crystal X-ray diffraction. The diffraction data revealed a zigzag Sc2C2 unit inside an unprecedented Cs(hept)-C88 carbon cage containing 13 pentagons, 32 hexagons, and 1 heptagon. Calculations suggest that the observed nonclassical fullerene could be a kinetically trapped species derived from the recently reported Sc2C2@C2v(9)-C86 via a direct C2 insertion.

19.
Medicine (Baltimore) ; 95(31): e4473, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27495086

RESUMO

Heroin addiction is a complex psychiatric disorder with a chronic course and a high relapse rate, which results from the interaction between genetic and environmental factors. Heroin addiction has a substantial heritability in its etiology; hence, identification of individuals with a high genetic propensity to heroin addiction may help prevent the occurrence and relapse of heroin addiction and its complications. The study aimed to identify a small set of genetic signatures that may reliably predict the individuals with a high genetic propensity to heroin addiction. We first measured the transcript level of 13 genes (RASA1, PRKCB, PDK1, JUN, CEBPG, CD74, CEBPB, AUTS2, ENO2, IMPDH2, HAT1, MBD1, and RGS3) in lymphoblastoid cell lines in a sample of 124 male heroin addicts and 124 male control subjects using real-time quantitative PCR. Seven genes (PRKCB, PDK1, JUN, CEBPG, CEBPB, ENO2, and HAT1) showed significant differential expression between the 2 groups. Further analysis using 3 statistical methods including logistic regression analysis, support vector machine learning analysis, and a computer software BIASLESS revealed that a set of 4 genes (JUN, CEBPB, PRKCB, ENO2, or CEBPG) could predict the diagnosis of heroin addiction with the accuracy rate around 85% in our dataset. Our findings support the idea that it is possible to identify genetic signatures of heroin addiction using a small set of expressed genes. However, the study can only be considered as a proof-of-concept study. As the establishment of lymphoblastoid cell line is a laborious and lengthy process, it would be more practical in clinical settings to identify genetic signatures for heroin addiction directly from peripheral blood cells in the future study.


Assuntos
Predisposição Genética para Doença , Dependência de Heroína/genética , Adulto , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Estudos de Casos e Controles , Perfilação da Expressão Gênica , Genes jun/genética , Humanos , Modelos Logísticos , Linfócitos/citologia , Masculino , Fosfopiruvato Hidratase/genética , Proteína Quinase C beta/genética , RNA Ribossômico 18S/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Software , Máquina de Vetores de Suporte
20.
Schizophr Res ; 176(2-3): 106-113, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27464451

RESUMO

Activity-regulated cytoskeleton-associated protein (ARC), which interacts with the N-methyl-d-aspartate receptor (NMDAR) complex, is a critical effector molecule downstream of multiple neuronal signaling pathways. Dysregulation of the ARC/NMDAR complex can disrupt learning, memory, and normal brain functions. This study examined the role of ARC in susceptibility to schizophrenia. We used a resequencing strategy to identify the variants of ARC in 1078 subjects, including patients with schizophrenia and normal controls. We identified 16 known SNPs and 27 rare mutations. SNP-based analysis showed no association of ARC with schizophrenia. In addition, the rare mutations did not increase the burden in patients compared with controls. However, one patient-specific allele in the putative ARC promoter region and seven patient-specific mutants in ARC exon regions significantly reduced the reporter gene activity compared with ARC wild-type. Methylation of a putative ARC promoter attenuated reporter activity in vitro, suggesting that ARC expression is regulated by DNA methylation. Pyrosequencing revealed eight hypermethylated CpG sites in the putative ARC promoter region in 64 schizophrenic patients compared with 63 controls. Taken together, our results suggest that both rare variants and epigenetic regulation of ARC contribute to the pathogenesis of schizophrenia in some patients.


Assuntos
Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Metilação de DNA , Mutação , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Esquizofrenia/genética , Esquizofrenia/metabolismo , Grupo com Ancestrais do Continente Asiático/genética , Linhagem Celular Tumoral , Ilhas de CpG , Éxons , Feminino , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Taiwan
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