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1.
Artigo em Inglês | MEDLINE | ID: mdl-31927054

RESUMO

The widespread cigarette smoking behavior in schizophrenia is generally attributed to its alleviation of patients' symptomatology by the self-medication hypothesis. The prefrontal cortex (PFC), which predominantly supports orchestrating thoughts and actions, might underlie the biological underpinnings of smoking behavior in schizophrenia. However, few studies have focused on the impact of smoking on the prefrontal function in schizophrenia. This study assumed that smoking-related alterations on the prefrontal dynamics of information integration (chronnectome) were different between healthy control (HC) and schizophrenia patient (SP). We recruited SP smokers (N = 22)/nonsmokers (N = 27) and HC smokers (N = 22)/nonsmokers (N = 21) who underwent resting-state functional magnetic resonance imaging (rsfMRI) with a total of 240 volumes (lasting for 480 s). We employed a chronnectomic density analysis on the rsfMRI signal by using a sliding-window method. We examined the interaction effect between smoking status and diagnosis utilizing two-way analysis of covariance under permutation test. Whereas disease-related reduced effects were found on the bilateral dorsolateral PFC chronnectomic density, no smoking effect was observed. As regards interaction effect, a smoking-related reduced effect was found on the right dorsolateral PFC chronnectomic density in HC, while a smoking-related increased effect was observed in SP. Nevertheless, post-hoc analysis revealed significant group difference between SP smokers and HC nonsmokers. Therefore, these results indicated a smoking-related preservation effect on disrupted prefrontal dynamics in schizophrenia that cannot restore it to normal levels. The novel findings yield a prefrontal-based chronnectome framework to elaborate upon the self-medication hypothesis in schizophrenia.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31962188

RESUMO

During depressive episode, bipolar disorder (BD) patients share indistinguishable depression symptoms with major depressive disorder (MDD).However, whether neural correlates underlying the anhedonia, a core feature of depression, is different between BD and MDD remains unknown. To explore neural correlates underlying the anhedonia in BD and MDD, structural T1-weighted images from 36 depressed BD patients, 40 depressed MDD patients matched for depression severity and 34 health controls (HCs) were scanned. Considering the vital role of nucleus accumbens (NAc) in the anhedonia, we constructed the structural covariance network of NAc for each subject. Then, we explored altered structural covariance network of NAc and its interaction with the anhedonia severity in BD and MDD patients. As a result, BD and MDD patients shared decreased structural covariance of NAc connected to prefrontal gyrus, bilateral striatum extending to bilateral anterior insula. Apart from these regions, BD patients presented specifically increased structural covariance of NAc connected to left hippocampus extending to thalamus. The interaction between structural covariance network of NAc and the anhedonia severity in MDD was mainly associated anterior insula (AIC), amygdala, anterior cingulate cortex (ACC)and caudate while that in BD was mainly located in striatum and prefrontal cortex. Our results found that BD and MDD patients presented commonly and distinctly altered structural covariance network of NAc. What is more, the neural correlates underlying the anhedonia in BD and MDD might be different.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31981719

RESUMO

Abnormalities in the structure of subcortical regions are central to numerous behaviors affected by autism spectrum disorder (ASD), and these regions may undergo atypical coordinated neurodevelopment. However, relatively little is known about morphological correlations among subcortical structures in young children with ASD. In this study, using volumetric-based methodology and structural covariance approach, we investigated structural covariance of subcortical brain volume in 40 young children with ASD (<7.5 years old) and 38 age-, gender-, and handedness-matched typically developing (TD) children. Results showed that compared with TD children, children with ASD exhibited decreased structural covariation between the left and right cerebral hemispheres, specifically between the left and right thalami, right globus pallidus and left nucleus accumbens, and left globus pallidus and right nucleus accumbens. Compared with TD children, children with ASD exhibited increased structural covariation between adjacent regions, such as between the right globus pallidus and right putamen. Additionally, abnormalities in subcortical structural covariance can predict social communication and repetitive and stereotypic behavior in young children with ASD. Overall, these results suggest decreased long-range structural covariation and enhanced local covariation in subcortical structures in children with ASD, highlighting aberrant developmental coordination or synchronized maturation between subcortical regions that play crucial roles in social cognition and behavior in ASD.

4.
Hum Brain Mapp ; 41(2): 419-428, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31600014

RESUMO

Emerging evidence has associated autism spectrum disorder (ASD) with static functional connectivity abnormalities between multiple brain regions. However, the temporal dynamics of intra- and interhemispheric functional connectivity patterns remain unknown in ASD. Resting-state functional magnetic resonance imaging data were analyzed for 105 ASD and 102 demographically matched typically developing control (TC) children (age range: 7-12 years) available from the Autism Brain Imaging Data Exchange database. Whole-brain functional connectivity was decomposed into ipsilateral and contralateral functional connectivity, and sliding-window analysis was utilized to capture the intra- and interhemispheric dynamic functional connectivity density (dFCD) patterns. The temporal variability of the functional connectivity dynamics was further quantified using the standard deviation (SD) of intra- and interhemispheric dFCD across time. Finally, a support vector regression model was constructed to assess the relationship between abnormal dFCD variance and autism symptom severity. Both intra- and interhemispheric comparisons showed increased dFCD variability in the anterior cingulate cortex/medial prefrontal cortex and decreased variability in the fusiform gyrus/inferior temporal gyrus in autistic children compared with TC children. Autistic children additionally showed lower intrahemispheric dFCD variability in sensorimotor regions including the precentral/postcentral gyrus. Moreover, aberrant temporal variability of the contralateral dFCD predicted the severity of social communication impairments in autistic children. These findings demonstrate altered temporal dynamics of the intra- and interhemispheric functional connectivity in brain regions incorporating social brain network of ASD, and highlight the potential role of abnormal interhemispheric communication dynamics in neural substrates underlying impaired social processing in ASD.

5.
Hum Brain Mapp ; 41(1): 230-240, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31571346

RESUMO

Schizophrenia has been conceptualized as a disorder arising from structurally pathological alterations to white-matter fibers in the brain. However, few studies have focused on white-matter functional changes in schizophrenia. Considering that converging evidence suggests that white-matter resting state functional MRI (rsfMRI) signals can effectively depict neuronal activity and psychopathological status, this study examined white-matter network-level interactions in antipsychotic-naive first-episode schizophrenia (FES) to facilitate the interpretation of the psychiatric pathological mechanisms in schizophrenia. We recruited 42 FES patients (FESs) and 38 healthy controls (HCs), all of whom underwent rsfMRI. We identified 11 white-matter functional networks, which could be further classified into deep, middle, and superficial layers of networks. We then examined network-level interactions among these 11 white-matter functional networks using coefficient Granger causality analysis. We employed group comparisons on the influences among 11 networks using network-based statistic. Excitatory influences from the middle superior corona radiate network to the superficial orbitofrontal and deep networks were disrupted in FESs compared with HCs. Additionally, an extra failure of suppression within superficial networks (including the frontoparietal network, temporofrontal network, and the orbitofrontal network) was observed in FESs. We additionally recruited an independent cohort (13 FESs and 13 HCs) from another center to examine the replicability of our findings across centers. Similar replication results further verified the white-matter functional network interaction model of schizophrenia. The novel findings of impaired interactions among white-matter functional networks in schizophrenia indicate that the pathophysiology of schizophrenia may also lie in white-matter functional abnormalities.

6.
Schizophr Res ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31801675

RESUMO

Numerous studies strongly have suggested the significant role of serotonin in the pathomechanism of schizophrenia. However, few studies have directly explored the altered serotonin function in schizophrenia. In the current study, we explored the altered serotonin function in first-episode treatment-naive patients with schizophrenia with resting-state functional magnetic resonance imaging. A total 42 first-episode treatment-naive patients with schizophrenia and carefully matched healthy controls are included in the study. Considering that the raphe nucleus providing a substantial proportion of the serotonin innervation to the forebrain, the raphe nucleus was chosen as the seed to construct voxel-based functional connectivity (FC) maps. In the results, subcortical dopamine-related regions presented decreased FC with the raphe nucleus, such as the bilateral striatum, pallidum, and thalamus, in patients with schizophrenia. Decreased FC in these regions was significantly correlated with the total negative scores in PANSS. Furthermore, these regions presented with decreased FC connection to salience network. Our results presented that the raphe nucleus played an important role in the dysfunction of subcortical DA-related regions, and contributed to the altered salience network in schizophrenia. Our study emphasized the importance of the raphe nucleus in the pathophysiology of schizophrenia.

7.
Immunol Res ; 67(4-5): 398-407, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31773490

RESUMO

Limited protective effects of commercially available vaccines necessitate the development of novel pneumococcal vaccines. We recently reported a pneumococcal systemic vaccine containing two proteins, Pneumococcal surface protein A (PspA of family 1 and 2) and a bacterium-like particle-based pneumococcal mucosal vaccine containing PspA2 and PspA4 fragments, both eliciting broad protective immune responses. We had previously reported that subcutaneous (s.c.+s.c.+s.c.) immunization with the systemic vaccine induced more pronounced humoral serum IgG responses, while intranasal (i.n.+i.n.+i.n.) immunization with the mucosal vaccine elicited a more pronounced mucosal secretory IgA (sIgA) response. We hypothesized that a combinatorial administration of the two vaccines might elicit more pronounced and broader protective immune responses. Therefore, this study aimed to determine the efficacy of combinatorial prime-boost immunization using both systemic and mucosal vaccines for a pneumococcal infection. Combinatorial prime-boost immunization (s.c.+i.n. and i.n.+s.c.) induced not only IgG, but also mucosal sIgA production at high levels. Systemic priming and mucosal boosting immunization (s.c.+i.n.) provided markedly better protection than homologous prime-boost immunization (s.c.+s.c.+s.c. and i.n.+i.n.+i.n.). Moreover, it induced more robust Th1 and Th17 cell-mediated immune responses than mucosal priming and systemic boosting immunization (i.n.+s.c.). These results indicate that combinatorial prime-boost immunization potentially induces a robust systemic and mucosal immune response, making it an optimal alternative for maximum protection against lethal pneumococcal infections.

8.
Eur J Pharmacol ; 863: 172676, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31542488

RESUMO

Myelodysplastic syndromes (MDSs) are a group of clonal disorders of hematopoietic stem cells, resulting in ineffective hematopoiesis. Previous studies have reported that decitabine (DAC) plays an essential role in cell cycle arrest and cell death induction in multiple cell types. Nevertheless, the effect of decitabine on mesenchymal stromal cells derived from bone marrow of patients with MDSs is not completely clarified. Here, we explored the apoptotic and anti-proliferative effect of DAC on MSCs isolated from patients with MDSs. Treatment with DAC inhibited cell growth in a concentration- and time-dependent manner by inducing apoptosis. We found a positive relationship between cell death triggered by DAC in MSCs and the death receptor family members Fas and FasL mRNA and protein levels (***P < 0.00085), cleaved caspase (-3, -8, and -9) activity, and mitochondrial membrane potential reduction. Additionally, DAC-induced apoptosis was inhibited by Kp7-6, a FasL/Fas antagonist, indicating a crucial role of FasL/Fas, a cell death receptor, in mediating the apoptotic effect of DAC. DAC also induced reactive oxygen species (ROS) generation in MSCs derived from MDSs patients (*P = 0.038). Furthermore, N-acetyl-L-cysteine (NAC), a widely accepted ROS scavenger, efficiently reversed DAC-induced apoptosis by inhibiting ROS generation (***P < 0.00051) in mitochondria and restoring mitochondrial membrane potential. Furthermore, ROS production was found to be a consequence of caspase activation via caspases inhibition. Our data imply that DAC triggers ROS production in human MSCs, which serves as a crucial factor for mitochondrial membrane potential reduction, and DAC induces cell death prior to FasL/Fas stimulation.

9.
Hum Brain Mapp ; 40(18): 5354-5369, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31464062

RESUMO

Autism is a neurodevelopmental condition characterized by atypical brain functional organization. Here we investigated the intrinsic indirect (semi-metric) connectivity of the functional connectome associated with autism. Resting-state functional magnetic resonance imaging scans were acquired from 65 neurotypical adults (33 males/32 females) and 61 autistic adults (30 males/31 females). From functional connectivity networks, semi-metric percentages (SMPs) were calculated to assess the proportion of indirect shortest functional pathways at global, hemisphere, network, and node levels. Group comparisons were then conducted to ascertain differences between autism and neurotypical control groups. Finally, the strength and length of edges were examined to explore the patterns of semi-metric connections associated with autism. Compared with neurotypical controls, autistic adults displayed significantly higher SMP at all spatial scales, similar to prior observations in adolescents. Differences were primarily in weaker, longer-distance edges in the majority between networks. However, no significant diagnosis-by-sex interaction effects were observed on global SMP. These findings suggest increased indirect functional connectivity in the autistic brain is persistent from adolescence to adulthood and is indicative of reduced functional network integration.

10.
Food Sci Biotechnol ; 28(4): 1187-1193, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31275719

RESUMO

Glycyrrhetic acid monoglucuronide (GAM) is obtained from the natural sweetener glycyrrhizin through enzymolysis. Its sweetness concentration-response (C-R) behavior in room-temperature in water was determined using two-alternative forced choice discrimination tests. The C-R equation of resultant hyperbolic curve relating sucrose equivalent (SE, %) to GAM concentration ([GAM], mg/L) was SE = 19.6 × [GAM]/(194.8 + [GAM]). From the C-R function, Pw (2) of GAM, relative to a 2% (w/v) sucrose reference, is more than 900, which has much higher potency than its precursor glycyrrhizin. Molecular modeling showed that GAM is finely bound into protein 1EWK through conventional hydrogen bonds, π-Alkyl interactions and Van der Waals bonds, which exhibited better protein inclusion than Glycyrrhizin. Thus, GAM could be developed as a new zero-calorie, naturally high-potency sweetener.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31202912

RESUMO

Major depressive disorder (MDD) has been linked to imbalanced communication among large-scale brain networks. However, the details of altered large-scale coordination of MDD remains unknown. To explore the altered large-scale functional organization in MDD. We used static and dynamic global signal (GS) topography, which are data-driven methods to explore altered relationship between global and local neuronal activities in MDD. Sixty three MDD patients and matched 63 healthy controls (HCs) were recruited in current study. Patients with MDD presented decreased static GS topography in bilateral parahippocampal gyrus and hippocampus gyrus. Meanwhile, patients with MDD presented increased variability of dynamic GS topography in the right ventromedial prefrontal cortex. This result may reflect the decreased and unstable whole brain functional coherence in MDD. The decreased static GS topography in the right parahippocampal gyrus was correlated with psychomotor retardation in patients with MDD. Our results presented that the altered static and dynamic GS topography can provide distinct evidence on the physiological mechanisms of MDD.

12.
Biomed Pharmacother ; 114: 108823, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30965238

RESUMO

We previously developed propranolol-encapsulated liposomes-in-microspheres (PLIM) to realize the sustained propranolol release for the treatment of hemangiomas. However, the liposomes released from the microspheres still lacked specificity for CD133-positive hemangioma-derived stem cells (HemSCs) which are considered to be the seeds of hemangiomas. Therefore, we hereby encapsulated propranolol-loaded CD133 aptamers conjugated liposomes in poly(lactic-co-glycolic acid (PLGA) microspheres to develop propranolol-loaded CD133 aptamers conjugated liposomes-in-microspheres (PCLIM), to realize the aim of the sustained and targeted therapy of hemangiomas. The evaluation of the release of propranolol from PCLIM was carried out, and the cytotoxic effect and angiogenic growth factor expression inhibitory ability of PCLIM were performed in HemSCs. The in vivo hemangioma inhibitory ability of PCLIM was also investigated in nude mice with subcutaneous human hemangiomas. PCLIM possessed a desired size of 29.2 µm, drug encapsulation efficiency (25.3%), and a prolonged drug release for 40 days. Importantly, PCLIM could inhibit HemSCs proliferation and the protein expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF) in HemSCs to a greater extent compared with PLIM. In nude mice bearing hemangioma xenograft, PCLIM showed the best therapeutic efficacy towards hemangiomas, as reflected by remarkably decreased hemangioma volume, weight and microvessel density (MVD). Thus, our results demonstrated that PCLIM realized the sustained and targeted treatment of hemangiomas, resulting in remarkable inhibition of hemangiomas.


Assuntos
Antígeno AC133/química , Aptâmeros de Nucleotídeos/química , Preparações de Ação Retardada/farmacologia , Hemangioma/tratamento farmacológico , Lipossomos/química , Propranolol/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Preparações de Ação Retardada/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/fisiologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Hemangioma/metabolismo , Humanos , Camundongos Nus , Microesferas , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Propranolol/química , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Hum Brain Mapp ; 40(4): 1264-1275, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30367744

RESUMO

Time-invariant resting-state functional connectivity studies have illuminated the crucial role of the right anterior insula (rAI) in prominent social impairments of autism spectrum disorder (ASD). However, a recent dynamic connectivity study demonstrated that rather than being stationary, functional connectivity patterns of the rAI vary significantly across time. The present study aimed to explore the differences in functional connectivity in dynamic states of the rAI between individuals with ASD and typically developing controls (TD). Resting-state functional magnetic resonance imaging data obtained from a publicly available database were analyzed in 209 individuals with ASD and 298 demographically matched controls. A k-means clustering algorithm was utilized to obtain five dynamic states of functional connectivity of the rAI. The temporal properties, frequency properties, and meta-analytic decoding were first identified in TD group to obtain the characteristics of each rAI dynamic state. Multivariate analysis of variance was then performed to compare the functional connectivity patterns of the rAI between ASD and TD groups in obtained states. Significantly impaired connectivity was observed in ASD in the ventral medial prefrontal cortex and posterior cingulate cortex, which are two critical hubs of the default mode network (DMN). States in which ASD showed decreased connectivity between the rAI and these regions were those more relevant to socio-cognitive processing. From a dynamic perspective, these findings demonstrate partially impaired resting-state functional connectivity patterns between the rAI and DMN across states in ASD, and provide novel insights into the neural mechanisms underlying social impairments in individuals with ASD.

14.
Hum Brain Mapp ; 40(2): 628-637, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30251763

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable neuroanatomical heterogeneity. Thus, how and to what extent the brains of individuals with ASD differ from each other is still unclear. In this study, brain structural MRI data from 356 right-handed, male subjects with ASD and 403 right-handed male healthy controls were selected from the Autism Brain Image Data Exchange database (age range 5-35 years old). Voxel-based morphometry preprocessing steps were conducted to compute the gray matter volume maps for each subject. Individual neuroanatomical difference patterns for each ASD individual were calculated. A data-driven clustering method was next utilized to stratify individuals with ASD into several subtypes. Whole-brain functional connectivity and clinical severity were compared among individuals within the ASD subtypes identified. A searchlight analysis was applied to determine whether subtyping ASD could improve the classification accuracy between ASD and healthy controls. Three ASD subtypes with distinct neuroanatomical difference patterns were revealed. Different degrees of clinical severity and atypical brain functional connectivity patterns were observed among these three subtypes. By dividing ASD into three subtypes, the classification accuracy between subjects of two out of the three subtypes and healthy controls was improved. The current study confirms that ASD is not a disorder with a uniform neuroanatomical signature. Understanding neuroanatomical heterogeneity in ASD could help to explain divergent patterns of clinical severity and outcomes.

15.
Brain Imaging Behav ; 13(4): 985-994, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29956102

RESUMO

Converging evidence has shown the link between benign epilepsy with centrotemporal spikes (BECTS) and abnormal functional connectivity among distant brain regions. However, prior research in BECTS has not examined the dynamic changes in functional connectivity as networks form. We combined functional connectivity density (FCD) mapping and sliding windows correlation analyses, to fully capture the functional dynamics in patients with respect to the presence of interictal epileptic discharges (IEDs). Resting-state fMRI was performed in 43 BECTS patients and 28 healthy controls (HC). Patients were further classified into two subgroups, namely, IED (n = 20) and non-IED (n = 23) depending on the simultaneous EEG-fMRI recordings. The global dynamic FCD (dFCD) was measured using sliding window correlation. Then we quantified dFCD variability using their standard deviation. Compared with HC, patients with and without IEDs both showed invariable dFCD (decreased) among the orbital fontal cortex, anterior cingulate cortex and striatum, as well as variable dFCD (increased) in the posterior default mode network (P < 0.05, AlphaSim corrected). Correlation analysis indicated that the variable dFCD in precuneus was related to seizure onset age (P < 0.05, uncorrected). BECTS with IEDs showed variable dFCD in regions related to the typical seizure semiology. The abnormal patterns of fluctuating FCD in BECTS suggest that both active and chronic epileptic state may contribute to altered dynamics of functional connectivity associated with cognitive disturbances and developmental alterations. These findings highlight the importance of considering fluctuating dynamic neural communication among brain systems to deepen our understanding of epilepsy diseases.


Assuntos
Epilepsia do Lobo Frontal/fisiopatologia , Epilepsia Rolândica/fisiopatologia , Vias Neurais/fisiopatologia , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Córtex Cerebral/fisiopatologia , Criança , Corpo Estriado/fisiopatologia , Eletroencefalografia/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Testes Neuropsicológicos , Descanso
16.
Autism Res ; 11(12): 1643-1652, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30475453

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by atypical functional integration of brain regions. The vast majority of neuroimaging studies of ASD have focused on older children, adolescents, and adults with the disorder. Very little work has explored whole-brain functional connectivity of young children with ASD. Here, we collected resting-state functional magnetic resonance imaging data from 58 young children (mean age 4.98 years; 29 with ASD; 29 matched healthy controls [HC]). All children were under sedation during scanning. A functional "connectedness" method was first used to seek for brain regions showing atypical functional connectivity (FC) in children with ASD. Then, a recurrent-seek strategy was applied to reveal atypical FC circuits in ASD children. FC matrices between regions-of-interest (ROIs) were compared between ASD and HC. Finally, a support vector regression (SVR) method was used to assess the relationship between the FC circuits and ASD symptom severity. Two atypical FC circuits comprising 23 ROIs in ASD were revealed: one predominantly comprised brain regions involved with social cognition showing under-connectivity in ASD; the other predominantly comprised sensory-motor and visual brain regions showing over-connectivity in ASD. The SVR analysis showed that the two FC circuits were separately related to social deficits and restricted behavior scores. These findings indicate disrupted FC of neural circuits involved in the social and sensorimotor processes in young children with ASD. The finding of the atypical FC patterns in young children with ASD underscores the utility of studying younger children with the disorder, and highlights nuanced patterns of brain connectivity underlying behavior closer to disorder onset. Autism Research 2018, 11: 1643-1652. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder. Understanding brain functional alterations at early ages is important for understanding biological mechanisms of ASD. Here, we found two atypical brain functional circuits in young children with ASD that were related to social and sensorimotor function. These results show how atypical patterns of brain functional connectivity in young children with of ASD may underlie core symptoms of the disorder.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Imagem por Ressonância Magnética/métodos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Análise de Regressão , Comportamento Social
17.
Autism Res ; 11(11): 1479-1493, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30270547

RESUMO

Accumulating neuroimaging evidence suggests that abnormal functional connectivity of the default mode network (DMN) contributes to the social-cognitive deficits of autism spectrum disorder (ASD). Although most previous studies relied on conventional functional connectivity methods, which assume that connectivity patterns remain constant over time, understanding the temporal dynamics of functional connectivity during rest may provide new insights into the dysfunction of the DMN in ASD. In this work, dynamic functional connectivity analysis based on sliding time window correlation was applied to the resting-state functional magnetic resonance imaging data of 28 young children with ASD (age range: 3-7 years) and 29 matched typically developing controls (TD group). In addition, k-means cluster analysis was performed to identify distinct temporal states based on the spatial similarity of each functional connectivity pattern. Compared with the TD group, young children with ASD showed decreased dynamic functional connectivity variance between the posterior cingulate cortex (PCC) and the right precentral gyrus, which is negatively correlated with social motivation and social relating. Cluster analysis revealed significant differences in functional connectivity patterns between the ASD and TD groups in discrete temporal states. Our findings reveal that atypical dynamic interactions between the PCC and sensorimotor cortex are associated with social deficits in ASD. Results also highlight the critical role of PCC in the social-cognitive deficits of ASD and support the concept that understanding the dynamic neural interactions among brain regions can provide insights into functional abnormalities in ASD. Autism Research 2018, 11: 1479-1493. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Social cognitive dysfunction in autism spectrum disorder (ASD) is associated with dysfunction of the default mode network (DMN), a set of brain areas involved in various domains of social processing. We found that decreases in the dynamic functional connectivity variance between the posterior cingulate cortex and the sensorimotor cortex are associated with deficits in social motivation and social relating in young children with ASD. This result suggests that aberrations in the DMN and its dynamic interactions with other networks contribute to atypical integration of information with respect to self and others.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Imagem por Ressonância Magnética/métodos , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Humanos , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Descanso
18.
Protein Expr Purif ; 151: 56-61, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29908315

RESUMO

Streptococcus pneumoniae is a major pathogen that causes life-threatening diseases, such as pneumonia, otitis media, bacteremia, and meningitis, worldwide and especially in young children and the elderly. Pneumococcal surface protein A (PspA) is a widely studied candidate protein vaccine that represents a promising replacement for current polysaccharide and polysaccharide-conjugate vaccines. In this study, we describe a simple method to produce PspA of clade 4 from an Escherichia coli expression system using hydroxylapatite and ion-exchange chromatography. Using this method, we successfully expressed soluble PspA4 in 10 L of autoinducing culture medium, with a wet-cell yield of 19 g/L and a final PspA4 concentration of 22.8 mg/L. Additionally, we improved PspA4 purity from 17% to 70% in a single step through the use of hydroxylapatite, resulting in acquisition of recombinant PspA4 (>95% purity) at a final yield of 43% from the starting cell-lysis solution. We subsequently verified the secondary structure molecular weight of recombinant PspA4 by circular dichroism and mass spectrometry, respectively. These results demonstrated a highly efficient method for mass producing PspA4 protein and that can also be applied for purification of PspA proteins from other clades.


Assuntos
Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/isolamento & purificação , Durapatita/química , Escherichia coli/metabolismo , Cromatografia por Troca Iônica , Escherichia coli/genética , Fermentação , Expressão Gênica , Estrutura Secundária de Proteína , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação
19.
Appl Opt ; 57(10): 2564-2569, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29714241

RESUMO

An integrated silicon photonic circuit consisting of two silicon microring resonators (MRRs) is proposed and experimentally demonstrated for the purpose of half-subtraction operation. The thermo-optic modulation scheme is employed to modulate the MRRs due to its relatively simple fabrication process. The high and low levels of the electrical pulse signal are utilized to define logic 1 and 0 in the electrical domain, respectively, and the high and low levels of the optical power represent logic 1 and 0 in the optical domain, respectively. Two electrical pulse sequences regarded as the operands are applied to the corresponding micro-heaters fabricated on the top of the MRRs to achieve their dynamic modulations. The final operation results of bit-wise borrow and difference are obtained at their corresponding output ports in the form of light. At last, the subtraction operation of two bits with the operation speed of 10 kbps is demonstrated successfully.

20.
Chem Biol Interact ; 289: 40-46, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29704511

RESUMO

Ischemia/reperfusion (I/R) injury is a main cause of acute kidney injury (AKI), and currently lacks effective therapies. This study is to investigate the level of Neutrophil gelatinase-associated lipocalin (NGAL) and autophagy status during renal I/R injury, so as to determine whether the exogenous NGAL protein could exert a protective effect for I/R injury and explore the potential mechanisms. Forty male Wistar rats were randomly divided into the following four groups: Sham, I/R, pre-treated with NGAL before I/R (I/R + pre-N), treated with NGAL after I/R (I/R + post-N). All rats were subjected to clamping the left renal pedicle for 45 min after right nephrectomy, followed by 24 h of reperfusion. Serum creatinine (SCr) and blood urea nitrogen (BUN) were used for renal function, tubular cell apoptosis and autophagy were measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, histological examination and electron microscope, respectively. The tubular cell proliferation was assessed by the protein expression of proliferating cell nuclear antigen (PCNA). Western blotting was used to quantitate the levels of LC3, Beclin-1, Bcl-2 and Bax in kidney tissues. Exogenous NGAL protein intervention significantly improved renal function, reduced tubular cell apoptosis, increased tubular cell proliferation and promoted autophagy activation after renal I/R injury. Further, the efficacy in pre-N was significantly better than post-N. The mechanisms were involved in the regulation of several autophagy and apoptosis-related genes. Our study demonstrated that exogenous NGAL protein play a protective role during I/R injury, which may offer a novel may for prevention and treatment of renal I/R injury.


Assuntos
Apoptose , Autofagia , Lipocalina-2/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Animais , Nitrogênio da Ureia Sanguínea , Proliferação de Células , Creatinina/sangue , Epitélio/metabolismo , Epitélio/patologia , Marcação In Situ das Extremidades Cortadas , Testes de Função Renal , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Masculino , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia , Vacúolos/metabolismo , Vacúolos/ultraestrutura
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