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1.
Cereb Cortex ; 34(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38652554

RESUMO

Indole is often associated with a sweet and floral odor typical of jasmine flowers at low concentrations and an unpleasant, animal-like odor at high concentrations. However, the mechanism whereby the brain processes this opposite valence of indole is not fully understood yet. In this study, we aimed to investigate the neural mechanisms underlying indole valence encoding in conversion and nonconversion groups using the smelling task to arouse pleasantness. For this purpose, 12 conversion individuals and 15 nonconversion individuals participated in an event-related functional magnetic resonance imaging paradigm with low (low-indole) and high (high-indole) indole concentrations in which valence was manipulated independent of intensity. The results of this experiment showed that neural activity in the right amygdala, orbitofrontal cortex and insula was associated with valence independent of intensity. Furthermore, activation in the right orbitofrontal cortex in response to low-indole was positively associated with subjective pleasantness ratings. Conversely, activation in the right insula and amygdala in response to low-indole was positively correlated with anticipatory hedonic traits. Interestingly, while amygdala activation in response to high-indole also showed a positive correlation with these hedonic traits, such correlation was observed solely with right insula activation in response to high-indole. Additionally, activation in the right amygdala in response to low-indole was positively correlated with consummatory pleasure and hedonic traits. Regarding olfactory function, only activation in the right orbitofrontal cortex in response to high-indole was positively correlated with olfactory identification, whereas activation in the insula in response to low-indole was negatively correlated with the level of self-reported olfactory dysfunction. Based on these findings, valence transformation of indole processing in the right orbitofrontal cortex, insula, and amygdala may be associated with individual hedonic traits and perceptual differences.


Assuntos
Mapeamento Encefálico , Indóis , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Odorantes , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Percepção Olfatória/fisiologia , Emoções/fisiologia , Olfato/fisiologia
2.
Neuroimage ; 297: 120761, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39069226

RESUMO

Flexible cognitive functions, such as working memory (WM), usually require a balance between localized and distributed information processing. However, it is challenging to uncover how local and distributed processing specifically contributes to task-induced activity in a region. Although the recently proposed activity flow mapping approach revealed the relative contribution of distributed processing, few studies have explored the adaptive and plastic changes that underlie cognitive manipulation. In this study, we recruited 51 healthy volunteers (31 females) and investigated how the activity flow and brain activation of the frontoparietal systems was modulated by WM load and training. While the activation of both executive control network (ECN) and dorsal attention network (DAN) increased linearly with memory load at baseline, the relative contribution of distributed processing showed a linear response only in the DAN, which was prominently attributed to within-network activity flow. Importantly, adaptive training selectively induced an increase in the relative contribution of distributed processing in the ECN and also a linear response to memory load, which were predominantly due to between-network activity flow. Furthermore, we demonstrated a causal effect of activity flow prediction through training manipulation on connectivity and activity. In contrast with classic brain activation estimation, our findings suggest that the relative contribution of distributed processing revealed by activity flow prediction provides unique insights into neural processing of frontoparietal systems under the manipulation of cognitive load and training. This study offers a new methodological framework for exploring information integration versus segregation underlying cognitive processing.


Assuntos
Função Executiva , Imageamento por Ressonância Magnética , Memória de Curto Prazo , Humanos , Feminino , Masculino , Adulto Jovem , Adulto , Memória de Curto Prazo/fisiologia , Função Executiva/fisiologia , Mapeamento Encefálico , Atenção/fisiologia , Cognição/fisiologia , Encéfalo/fisiologia , Rede Nervosa/fisiologia , Rede Nervosa/diagnóstico por imagem , Lobo Parietal/fisiologia
3.
Genetica ; 152(2-3): 119-132, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38789817

RESUMO

The Universal Stress Protein (USP) primarily participates in cellular responses to biotic and abiotic stressors, playing a pivotal role in plant growth, development, and Stress responses to adverse environmental conditions. Totals of 23, 26 and 26 USP genes were recognized in Arabidopsis thaliana, Zea mays, and Oryza sativa, respectively. According to USP genes physicochemical properties, proteins from USP I class were identified as hydrophilic proteins with high stability. Based on phylogenetic analysis, USP genes family were classified into nine groups, USP II were rich in motifs. Additionally, members of the same subgroup exhibited similar numbers of introns/exons, and shared conserved domains, indicating close evolutionary relationships. Motif analysis results demonstrated a high degree of conservation among USP genes. Chromosomal distribution suggested that USP genes might have undergone gene expansion through segmental duplication in Arabidopsis thaliana, Zea mays, and Oryza sativa. Most Ka/Ks ratios were found to be less than 1, suggesting that USP genes in Arabidopsis thaliana, Zea mays, and Oryza sativa have experienced purifying selection. Expression profile analysis revealed that USP genes primarily respond to drought stress in Oryza sativa, temperature, and drought stress in Zea mays, and cold stress in Arabidopsis thaliana. Gene collinearity analysis can reveal correlations between genes, aiding subsequent in-depth investigations. This study sheds new light on the evolution of USP genes in monocots and dicots and lays the foundation for a better understanding of the biological functions of the USP genes family.


Assuntos
Arabidopsis , Regulação da Expressão Gênica de Plantas , Família Multigênica , Oryza , Filogenia , Proteínas de Plantas , Estresse Fisiológico , Zea mays , Oryza/genética , Zea mays/genética , Arabidopsis/genética , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Genoma de Planta , Evolução Molecular , Cromossomos de Plantas/genética
4.
Neuroendocrinology ; 114(4): 331-347, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38147832

RESUMO

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown neuroprotective effects in obese mice. However, whether SGLT2i can ameliorate high-fat diet (HFD)-related ovulation disorders remains unknown. The aim of this research was to investigate whether dapagliflozin improves HFD-induced ovulatory dysfunction by attenuating microglia-mediated hypothalamic inflammation. METHODS: C57BL/6J female mice fed HFD were treated with dapagliflozin (1 mg/kg) for 22 weeks. Plasma insulin, leptin, luteinizing hormone (LH), estradiol (E2), and IL-1ß levels were also tested. Microglial morphology, cell numbers, and SGLT2 expression were evaluated using immunofluorescence. The expression of IL-1ß, NLRP3, kisspeptin, gonadotropin-releasing hormone (GnRH), SGLT2, insulin, and leptin receptors in the hypothalamus was determined using immunohistochemical staining. We also examined the effects of dapagliflozin on glucose metabolism and the release of inflammatory factor in palmitic acid (PA)-treated HMC3 cells. RESULTS: As expected, dapagliflozin improved HFD-induced metabolic disturbances, peripheral versus central insulin and leptin resistance and also restored the regular estrous cycle. Furthermore, dapagliflozin blunted microglia activation, NLRP3 inflammasome priming, hypothalamic inflammation, and increased the expression of GnRH and kisspeptin at proestrus in the hypothalamus. Additionally, dapagliflozin markedly reduced IL-6 and NO release and fat accumulation, decreased lactic acid production and glucose consumption, and inhibited mammalian target of rapamycin (mTOR) and hexokinase 2 (HK2) expression in PA-treated HMC3 cells. These effects suggest that dapagliflozin reduced the mTOR/HK2-mediated aerobic glycolysis. CONCLUSIONS: Dapagliflozin improved HFD-related ovulation disorders by regulating glucose metabolism through mTOR/HK2 signaling and attenuating microglia-mediated hypothalamic inflammation. These results validate the novel role for the neuroprotection of SGLT2i in HFD-induced obesity and ovulation disorders.


Assuntos
Compostos Benzidrílicos , Dieta Hiperlipídica , Glucosídeos , Leptina , Camundongos , Feminino , Animais , Dieta Hiperlipídica/efeitos adversos , Leptina/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Kisspeptinas/metabolismo , Microglia , Camundongos Endogâmicos C57BL , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Hipotálamo/metabolismo , Insulina/metabolismo , Glucose/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Ovulação , Mamíferos/metabolismo
5.
Cereb Cortex ; 33(16): 9504-9513, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37376787

RESUMO

The efficacy of motor imagery training for motor recovery is well acknowledged, but with substantial inter-individual variability in stroke patients. To help optimize motor imagery training therapy plans and screen suitable patients, this study aimed to explore neuroimaging biomarkers explaining variability in treatment response. Thirty-nine stroke patients were randomized to a motor imagery training group (n = 22, received a combination of conventional rehabilitation therapy and motor imagery training) and a control group (n = 17, received conventional rehabilitation therapy and health education) for 4 weeks of interventions. Their demography and clinical information, brain lesion from structural MRI, spontaneous brain activity and connectivity from rest fMRI, and sensorimotor brain activation from passive motor task fMRI were acquired to identify prognostic factors. We found that the variability of outcomes from sole conventional rehabilitation therapy could be explained by the reserved sensorimotor neural function, whereas the variability of outcomes from motor imagery training + conventional rehabilitation therapy was related to the spontaneous activity in the ipsilesional inferior parietal lobule and the local connectivity in the contralesional supplementary motor area. The results suggest that additional motor imagery training treatment is also efficient for severe patients with damaged sensorimotor neural function, but might be more effective for patients with impaired motor planning and reserved motor imagery.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Prognóstico , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/patologia , Neuroimagem , Imageamento por Ressonância Magnética/métodos
6.
Dev Psychopathol ; : 1-11, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38179683

RESUMO

Childhood maltreatment is an established risk factor for psychopathology. However, it remains unclear how childhood traumatic events relate to mental health problems and how the brain is involved. This study examined the serial mediation effect of brain morphological alterations and emotion-/reward-related functions on linking the relationship from maltreatment to depression. We recruited 156 healthy adolescents and young adults and an additional sample of 31 adolescents with major depressive disorder for assessment of childhood maltreatment, depressive symptoms, cognitive reappraisal and anticipatory/consummatory pleasure. Structural MRI data were acquired to identify maltreatment-related cortical and subcortical morphological differences. The mediation models suggested that emotional maltreatment of abuse and neglect, was respectively associated with increased gray matter volume in the ventral striatum and greater thickness in the middle cingulate cortex. These structural alterations were further related to reduced anticipatory pleasure and disrupted cognitive reappraisal, which contributed to more severe depressive symptoms among healthy individuals. The above mediating effects were not replicated in our clinical group partly due to the small sample size. Preventative interventions can target emotional and reward systems to foster resilience and reduce the likelihood of future psychiatric disorders among individuals with a history of maltreatment.

7.
Hum Brain Mapp ; 44(2): 341-361, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36647263

RESUMO

Emerging evidence indicates that activity flow over resting-state network topology allows the prediction of task activations. However, previous studies have mainly adopted static, linear functional connectivity (FC) estimates as activity flow routes. It is unclear whether an intrinsic network topology that captures the dynamic nature of FC can be a better representation of activity flow routes. Moreover, the effects of between- versus within-network connections and tight versus loose (using rest baseline) task contrasts on the prediction of task-evoked activity across brain systems remain largely unknown. In this study, we first propose a probabilistic FC estimation derived from a dynamic framework as a new activity flow route. Subsequently, activity flow mapping was tested using between- and within-network connections separately for each region as well as using a set of tight task contrasts. Our results showed that probabilistic FC routes substantially improved individual-level activity flow prediction. Although it provided better group-level prediction, the multiple regression approach was more dependent on the length of data points at the individual-level prediction. Regardless of FC type, we consistently observed that between-network connections showed a relatively higher prediction performance in higher-order cognitive control than in primary sensorimotor systems. Furthermore, cognitive control systems exhibit a remarkable increase in prediction accuracy with tight task contrasts and a decrease in sensorimotor systems. This work demonstrates that probabilistic FC estimates are promising routes for activity flow mapping and also uncovers divergent influences of connectional topology and task contrasts on activity flow prediction across brain systems with different functional hierarchies.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Humanos , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Vias Neurais/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Descanso/fisiologia
8.
New Phytol ; 239(5): 1754-1770, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37337822

RESUMO

Ubiquitination is a fundamental mechanism regulating the stability of target proteins in eukaryotes; however, the regulatory mechanism in seed longevity remains unknown. Here, we report that an uncharacterized E3 ligase, ARABIDOPSIS TÓXICOS EN LEVADURA 5 (ATL5), positively regulates seed longevity by mediating the degradation of ACTIVATOR OF BASAL TRANSCRIPTION 1 (ABT1) in Arabidopsis. Seeds in which ATL5 was disrupted showed faster accelerated aging than the wild-type, while expressing ATL5 in atl5-2 basically restored the defective phenotype. ATL5 was highly expressed in the embryos of seeds, and its expression could be induced by accelerated aging. A yeast two-hybrid screen identified ABT1 as an ATL5 interacting protein, which was further confirmed by bimolecular fluorescence complementary assay and co-immunoprecipitation analysis. In vitro and in vivo assays showed that ATL5 functions as an E3 ligase and mediates the polyubiquitination and degradation of ABT1. Disruption of ATL5 diminished the degradation of translated ABT1, and the degradation could be induced by seed ageing and occurred in a proteasome-dependent manner. Furthermore, disruption of ABT1 enhanced seed longevity. Taken together, our study reveals that ATL5 promotes the polyubiquitination and degradation of the ABT1 protein posttranslationally and positively regulates seed longevity in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Longevidade , Ubiquitinação , Sementes/genética , Regulação da Expressão Gênica de Plantas
9.
BMC Neurol ; 22(1): 125, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35365121

RESUMO

BACKGROUND: Previous studies have revealed that low frequency repeated transcranial magnetic stimulation (rTMS) on the contralesional primary motor cortex (cM1) is less effective in severe stroke patients with poor neural structural reserve than in patients with highly reserved descending motor pathway. This may be attributed to the fact that secondary motor cortex, especially contralesional dorsal premotor cortex (cPMd), might play an important compensatory role in the motor function recovery of severely affected upper extremity. The main purpose of this study is to compare the effectiveness of low frequency rTMS on cM1 and high frequency rTMS on cPMd in subcortical chronic stroke patients with severe hemiplegia. By longitudinal analysis of multimodal neuroimaging data, we hope to elucidate the possible mechanism of brain reorganization following different treatment regimens of rTMS therapy, and to determine the cut-off of stimulation strategy selection based on the degree of neural structural reserve. METHODS/DESIGN: The study will be a single-blinded randomized controlled trial involving a total of 60 subcortical chronic stroke patients with severe upper limb motor impairments. All patients will receive 3 weeks of conventional rehabilitation treatment, while they will be divided into three groups and receive different rTMS treatments: cM1 low frequency rTMS (n = 20), cPMd high frequency rTMS (n = 20), and sham stimulation group (n = 20). Clinical functional assessment, multimodal functional MRI (fMRI) scanning, and electrophysiological measurement will be performed before intervention, 3 weeks after intervention, and 4 weeks after the treatment, respectively. DISCUSSION: This will be the first study to compare the effects of low-frequency rTMS of cM1 and high-frequency rTMS of cPMd. The outcome of this study will provide a theoretical basis for clarifying the bimodal balance-recovery model of stroke, and provide a strategy for individualized rTMS treatment for stroke in future studies and clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027399. Registered on 12 Nov 2019, http://www.chictr.org.cn/showproj.aspx?proj=43686 .


Assuntos
Córtex Motor , Acidente Vascular Cerebral , Humanos , Córtex Motor/diagnóstico por imagem , Neuroimagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Estimulação Magnética Transcraniana/métodos , Resultado do Tratamento
10.
Ear Hear ; 43(4): 1222-1227, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35044995

RESUMO

OBJECTIVE: HIV positive (HIV+) individuals with otherwise normal hearing ability show central auditory processing deficits as evidenced by worse performance in speech-in-noise perception compared with HIV negative (HIV-) controls. HIV infection and treatment are also associated with lower neurocognitive screening test scores, suggesting underlying central nervous system damage. To determine how central auditory processing deficits in HIV+ individuals relate to brain alterations in the cortex involved with auditory processing, we compared auditory network (AN) functional connectivity between HIV+ adults with or without speech-in-noise perception difficulties and age-matched HIV- controls using resting-state fMRI. DESIGN: Based on the speech recognition threshold of the hearing-in-noise test, twenty-seven HIV+ individuals were divided into a group with speech-in-noise perception abnormalities (HIV+SPabnl, 38.2 ± 6.8 years; 11 males and 2 females) and one without (HIV+SPnl 34.4 ± 8.8 years; 14 males). An HIV- group with normal speech-in-noise perception (HIV-, 31.3 ± 5.2 years; 9 males and 3 females) was also enrolled. All of these younger and middle-aged adults had normal peripheral hearing determined by audiometry. Participants were studied using resting-state fMRI. Independent component analysis was applied to identify the AN. Group differences in the AN were identified using statistical parametric mapping. RESULTS: Both HIV+ groups had increased functional connectivity (FC) in parts of the AN including the superior temporal gyrus, middle temporal gyrus, supramarginal gyrus, and Rolandic operculum compared to the HIV- group. Compared with the HIV+SPnl group, the HIV+SPabnl group showed greater FC in parts of the AN including the middle frontal and inferior frontal gyri. CONCLUSIONS: The classical auditory areas in the temporal lobe are affected by HIV regardless of speech perception ability. Increased temporal FC in HIV+ individuals might reflect functional compensation to achieve normal primary auditory perception. Furthermore, increased frontal FC in the HIV+SPabnl group compared with the HIV+SPnl group suggest that speech-in-noise perception difficulties in HIV-infected adults also affect areas involved in higher-level cognition, providing imaging evidence consistent with the hypothesis that HIV-related neurocognitive deficits can include central auditory processing deficits.


Assuntos
Córtex Auditivo , Infecções por HIV , Percepção da Fala , Adulto , Audiometria , Limiar Auditivo/fisiologia , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Ruído , Percepção da Fala/fisiologia
11.
Neuroimage ; 233: 117929, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33675996

RESUMO

Mate choice copying refers to an agent copying the choice for a potential sexual/romantic partner made by a relevant model and has been observed across many species. This study investigated the neural profiles of two copying strategies in humans - acceptance and rejection copying - using functional magnetic resonance imaging (fMRI). Female participants observed female models accepting, rejecting, or being undecided about (control), males as potential romantic partners before and after rating their own willingness to choose the same males. We found that observing acceptance shifted participants' own choices towards acceptance, while observing rejection shifted participants' choices towards rejection. A network of motivation-, conflict- and reinforcement learning related brain regions was activated for observing the models' decisions. The rostral anterior cingulate gyrus (rACCg) and the caudate in particular were activated more strongly when observing acceptance. Activation in the inferior parietal lobe directly scaled with the magnitude of changes in choices after observing acceptance, while activation in the ACCg also scaled with changes after observing rejection. These findings point to partly dissociable neural profiles for copying strategies that might be linked to different contributions of incentive-driven and vicarious motivation, potentially reflecting the presence or absence of internalised reward experiences.


Assuntos
Comportamento de Escolha/fisiologia , Giro do Cíngulo/fisiologia , Motivação/fisiologia , Distância Psicológica , Rejeição em Psicologia , Parceiros Sexuais , Adulto , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Estimulação Luminosa/métodos , Recompensa , Parceiros Sexuais/psicologia , Adulto Jovem
12.
Neurobiol Dis ; 148: 105218, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33296726

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease. Pathologically, PD is characterized by the formation of Lewy bodies (LBs) in the brain, which mainly comprises phosphorylated and aggregated α-synuclein (α-syn). The aberrant aggregation of α-syn is believed to play a key role in the pathogenesis of PD. While α-syn expression can be reduced by antisense oligonucleotides (ASOs), the challenge to deliver ASOs safely and effectively into the neurons remains unresolved. Here, we developed a safe and highly effective ASO delivery method by using exosomes. We first identified the ASO sequence that selectively reduced α-syn expression: ASO4. Exosome-mediated delivery of ASO4 (exo-ASO4) showed high cellular uptake and low toxicity in primary neuronal cultures. Exo-ASO4 also significantly attenuated α-syn aggregation induced by pre-formed α-syn fibrils in vitro. Exo-ASO4 intracerebroventricular injection into the brains of α-syn A53T mice, a transgenic model of PD, significantly decreased the expression of α-syn and attenuated its aggregation. Furthermore, exo-ASO4 ameliorated the degeneration of dopaminergic neurons in these mice. Finally, the α-syn A53T mice showed significantly improved locomotor functions after exo-ASO4 injection. Overall, this study demonstrates that exosome-mediated ASO4 delivery may be an effective treatment option for PD.


Assuntos
Neurônios Dopaminérgicos/efeitos dos fármacos , Exossomos , Locomoção/efeitos dos fármacos , Oligonucleotídeos Antissenso/farmacologia , Doença de Parkinson/metabolismo , alfa-Sinucleína/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Portadores de Fármacos , Humanos , Injeções Intraventriculares , Camundongos , Camundongos Transgênicos , Doença de Parkinson/genética , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
13.
Sheng Li Xue Bao ; 73(3): 459-470, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34230947

RESUMO

Cardiac hypertrophy is a common pathological process of various cardiovascular diseases and eventually develops into heart failure. This paper was aimed to study the different pathological characteristics exhibited by different mouse strains after hypertrophy stimulation. Two mouse strains, A/J and FVB/nJ, were treated with isoproterenol (ISO) by osmotic pump to induce cardiac hypertrophy. Echocardiography was performed to monitor heart morphology and function. Mitochondria were isolated from hearts in each group, and oxidative phosphorylation function was assayed in vitro. The results showed that both strains showed a compensatory enhancement of heart contractile function after 1-week ISO treatment. The A/J mice, but not the FVB/nJ mice, developed significant cardiac hypertrophy after 3-week ISO treatment as evidenced by increases in left ventricular posterior wall thickness, heart weight/body weight ratio, cross sectional area of cardiomyocytes and cardiac hypertrophic markers. Interestingly, the heart from A/J mice contained higher mitochondrial DNA copy number compared with that from FVB/nJ mice. Functionally, the mitochondria from A/J mice displayed faster O2 consumption at state III with either complex I substrates or complex II substrate, compared with those from FVB/nJ mice. ISO treatment did not affect mitochondrial respiratory control rate (RCR), but significantly suppressed the ADP/O ratio generated from the complex II substrate in both strains. The ADP/O ratio generated from the complex I substrates in A/J mice declined by 50% after ISO treatment, whereas FVB/nJ mice were not affected. These results suggest that, compared with FVB/nJ mice, A/J mice possesses a poor integrity of mitochondrial respiratory chain that might contribute to its vulnerability to ISO-induced cardiac hypertrophy.


Assuntos
Cardiomegalia , Insuficiência Cardíaca , Animais , Cardiomegalia/induzido quimicamente , Isoproterenol/metabolismo , Isoproterenol/toxicidade , Camundongos , Mitocôndrias , Miócitos Cardíacos/metabolismo
14.
Biomed Chromatogr ; 34(10): e4927, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32562289

RESUMO

A sensitive and selective high-performance liquid chromatography-tandam mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of sildenafil and its metabolite N-desmethyl sildenafil in human plasma. Sildenafil-d8 was used as an internal standard. The analytes were extracted by precipitation extraction and chromatographed on a C18 column using mobile phase A of water (containing 0.1% formic acid) and mobile phase B of acetonitrile (containing 0.1% formic acid) with gradient elution. Quantification was done using multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 475.4 → m/z 283.3 for sildenafil, m/z 461.4 → m/z 283.2 for N-desmethyl sildenafil and m/z 483.3 → m/z 108.1 for IS in positive ionization mode. The calibration curve was established over the range of 2.00-1,000 ng/ml and the correlation coefficient was >0.99. The intra-day and inter-day relative standard deviations were <6.5% for sildenafil and 6.3% for N-desmethyl sildenafil respectively. Accuracy determinaed at four concentrations was 86.50-105.67% for sildenafil and 96.83-114.40% for N-desmethyl sildenafil. This method was successfully applied to a pharmacokinetic description of sildenafil and the effect of food intake on the pharmacokinetics of sildenafil was also demonstrated in healthy Chinese volunteers.


Assuntos
Cromatografia Líquida/métodos , Citrato de Sildenafila/sangue , Espectrometria de Massas em Tandem/métodos , Adulto , Humanos , Limite de Detecção , Modelos Lineares , Masculino , Reprodutibilidade dos Testes , Citrato de Sildenafila/análogos & derivados , Citrato de Sildenafila/farmacocinética , Adulto Jovem
15.
J Dairy Res ; 87(2): 170-174, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32482199

RESUMO

In this research communication we describe the DGAT1 sequence and promoter region in dairy cows and buffalo and compare the activities of DGAT1 between the two species in order to increase knowledge of the cause of milk fat variation. pGL-3 basic vectors were used to construct the reporter gene. Based on the predicted promoter region, 4 truncated plasmid vectors were constructed in cow-DGAT1 and 3 plasmid vectors in buffalo-DGAT1. Each reporter plasmid was transfected into the bovine mammary epithelial cell (BMEC), 293T cell, and CHO cells to analyze the activity using Dual-Luciferase Reporter Assay System. The results show that the region between -93 to -556 bp was essential for cow promoter activity while -84 to -590 bp was essential for buffalo promoter activity revealing these regions contain core promoter. The buffalo has higher promoter activity than cow yet it was not statistically significant. Comparison of candidate mutation K232A between cow and buffalo population revealed the presence of both the allelic population in dairy cows (lysine and alanine) however, only K (lysine) allelic amino acid was found in buffalo population. The absence of the alanine allelic population from buffalo explains the higher fat content of buffalo milk.


Assuntos
Búfalos/genética , Bovinos/genética , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Lipídeos/biossíntese , Leite/metabolismo , Animais , Células CHO , Cricetulus , Células Epiteliais/enzimologia , Feminino , Células HEK293 , Humanos , Lipídeos/análise , Glândulas Mamárias Animais/enzimologia , Leite/química , Regiões Promotoras Genéticas/genética , Especificidade da Espécie , Transfecção
16.
Hum Brain Mapp ; 39(11): 4373-4384, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29972261

RESUMO

Emerging evidence has suggested that abnormalities in regional spontaneous brain activity following stroke may be detected by intrinsic low-frequency oscillations (LFO) in resting-state functional MRI (R-fMRI). However, the relationship between hand function outcomes following stroke and local LFO synchronization in different frequency bands is poorly understood. In this study, we performed R-fMRI to examine the regional homogeneity (ReHo) at three different frequency bands (slow-5: .01-.027 Hz; slow-4: .027-.08 Hz; and typical band: .01-.1 Hz) in 26 stroke patients with completely paralyzed hands (CPH) and 26 matched patients with partially paralyzed hands (PPH). Compared to the PPH group, decreased ReHo in the bilateral cerebellum posterior lobes and the contralesional cerebellum anterior lobe was observed in the slow-5 band and the slow-4 band in the CPH group, respectively. The mean ReHo values in these regions were positively correlated with the Fugl-Meyer assessment (FMA) scores. In contrast, increased ReHo in the contralesional supplementary motor area and the contralesional superior temporal gyrus was observed in the slow-4 band and the slow-5 band, respectively. The mean ReHo values in these regions were negatively correlated with the FMA scores. Importantly, significant interactions were identified between the frequency bands and the subgroups of patients in the contralesional precentral gyrus and middle frontal gyrus. These findings indicate that frequency-dependent R-fMRI patterns may serve as potential biomarkers of the neural substrates associated with hand function outcomes following stroke.


Assuntos
Encéfalo/fisiopatologia , Mãos/fisiopatologia , Paresia/fisiopatologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Paresia/diagnóstico por imagem , Paresia/etiologia , Descanso , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia
17.
Hum Brain Mapp ; 39(8): 3388-3397, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29691945

RESUMO

Motor functions are supported through functional integration across the extended motor system network. Individuals following stroke often show deficits on motor performance requiring coordination of multiple brain networks; however, the assessment of connectivity patterns after stroke was still unclear. This study aimed to investigate the changes in intra- and inter-network functional connectivity (FC) of multiple networks following stroke and further correlate FC with motor performance. Thirty-three left subcortical chronic stroke patients and 34 healthy controls underwent resting-state functional magnetic resonance imaging. Eleven resting-state networks were identified via independent component analysis (ICA). Compared with healthy controls, the stroke group showed abnormal FC within the motor network (MN), visual network (VN), dorsal attention network (DAN), and executive control network (ECN). Additionally, the FC values of the ipsilesional inferior parietal lobule (IPL) within the ECN were negatively correlated with the Fugl-Meyer Assessment (FMA) scores (hand + wrist). With respect to inter-network interactions, the ipsilesional frontoparietal network (FPN) decreased FC with the MN and DAN; the contralesional FPN decreased FC with the ECN, but it increased FC with the default mode network (DMN); and the posterior DMN decreased FC with the VN. In sum, this study demonstrated the coexistence of intra- and inter-network alterations associated with motor-visual attention and high-order cognitive control function in chronic stroke, which might provide insights into brain network plasticity following stroke.


Assuntos
Encéfalo/fisiopatologia , Transtornos dos Movimentos/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/diagnóstico por imagem , Transtornos dos Movimentos/etiologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Descanso , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem
18.
Plant Biotechnol J ; 16(8): 1402-1414, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29327510

RESUMO

Pollen germination and pollen tube growth are important physiological processes of sexual reproduction of plants and also are involved in signal transduction. Our previous study reveals that ZmSTK1 and ZmSTK2 are two receptor-like cytoplasmic kinases (RLCK) homologs in Zea mays as members of receptor-like protein kinase (RLK) subfamily, sharing 86% identity at the amino acid level. Here, we report that ZmSTK1 and ZmSTK2, expressed at late stages of pollen development, regulate maize pollen development with additive effect. ZmSTK1 or ZmSTK2 mutation exhibited severe pollen transmission deficiency, which thus influenced pollen fertility. Moreover, the kinase domains of ZmSTKs were cross-interacted with C-terminus of enolases detected by co-immunoprecipitation (Co-IP) and yeast two-hybrid system (Y2H), respectively. Further, the detective ZmSTK1 or ZmSTK2 was associated with decreased activity of enolases and also reduced downstream metabolite contents, which enolases are involved in glycolytic pathway, such as phosphoenolpyruvate (PEP), pyruvate, ADP/ATP, starch, glucose, sucrose and fructose. This study reveals that ZmSTK1 and ZmSTK2 regulate maize pollen development and indirectly participate in glycolytic pathway.


Assuntos
Proteínas de Plantas/metabolismo , Pólen/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Zea mays/metabolismo , Proteínas de Plantas/genética , Pólen/genética , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Zea mays/genética
19.
J Magn Reson Imaging ; 48(4): 1112-1119, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29603826

RESUMO

BACKGROUND: The automatic segmentation of cerebral nuclei in the quantitative susceptibility mapping (QSM) images can provide assistance for surgical treatment and pathological mechanism studies. However, as the most frequently used segmentation method, the atlas method provides unsatisfactory results when segmenting the substantia nigra (SN) and the red nucleus (RN). PURPOSE: To propose and evaluate an improved automatic method based on seed points-discontinuity for segmentations of the SN and the RN in QSM images. STUDY TYPE: Prospective. SUBJECTS: In all, 22 subjects, 11 patients with Parkinson's disease (PD), and 11 healthy subjects (mean age of 68.0 ± 6.9 years) underwent MR scans. FIELD STRENGTH/SEQUENCE: 3T system and a 3D multiecho gradient echo sequence with monopolar readout gradient. ASSESSMENT: Manual segmentations by two radiologists (both with over 10 years of experience in neuroimaging) were used to establish a baseline for assessment. The Dice coefficient and the center-of-gravity distance was employed to evaluate the segmentation accuracy. STATISTICAL TESTS: The mean value and standard deviation of the Dice coefficient and center-of-gravity distance were calculated separately to compare segmentation results from the proposed method, the level set method, the atlas method (including the single-atlas method and the multi-atlas majority voting method). RESULTS: The statistical results of Dice coefficient of the SN and the RN between the ground truth and the segmentation were 0.79 ± 0.14 and 0.77 ± 0.06 for the proposed method, 0.40 ± 0.10 and 0.65 ± 0.09 for the level set method, 0.68 ± 0.09 and 0.64 ± 0.07 for the single-atlas method, 0.70 ± 0.06 and 0.68 ± 0.05 for the multi-atlas majority voting method, respectively. The proposed method also provides the lowest center-of-gravity distance value (1.05 ± 0.71 for the SN and 0.74 ± 0.35 for the RN). DATA CONCLUSION: The segmentation results of the proposed method performed well on the in vivo data and were closer to the manual segmentation than the atlas method. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;48:1112-1119.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico por imagem , Núcleo Rubro/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Idoso , Algoritmos , Mapeamento Encefálico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Variações Dependentes do Observador , Estudos Prospectivos , Radiologia , Reprodutibilidade dos Testes
20.
Int J Mol Sci ; 19(11)2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30469332

RESUMO

Receptor-like cytoplasmic protein kinases (RLCKs) are involved in various activities in plant growth and development. We have totally identified 162, 160, and 402 RLCK genes in maize, rice, and Arabidopsis genomes, respectively. Phylogenetic analyses divided 724 RLCK genes into 15 subfamilies and similar structural patterns of kinase activity sites and functional sites were observed within the subfamilies. Furthermore, the structural patterns of intron/exon in the same subfamilies were similar, implicating their close evolutionary relationship. Chromosome distribution indicated that segmental duplication of RLCK genes might be a major mechanism contributing to the expansion of the RLCK superfamilies in maize, rice, and Arabidopsis, respectively. The analysis of the synteny relationship and gene structure indicated that the evolution of most RLCKs in maize were prior to rice and Arabidopsis. Most of the ratio of Ka/Ks is inferior to one, suggesting that RLCK genes have experienced the negative selection in maize, rice and Arabidopsis. Duplication time revealed that the maize was the earliest emergence among these three species. The expression profiles showed that there are some specifically expressed RLCK genes in maize root, leaf, ear, and tassel. These specific expression genes may participate in the developmental regulation of these maize tissues. Our results will be useful in providing new insights into evolution of RLCKs and revealing the regulatory network of maize, rice, and Arabidopsis development.


Assuntos
Evolução Molecular , Proteínas de Plantas/genética , Proteínas Quinases/genética , Arabidopsis/enzimologia , Arabidopsis/genética , Duplicação Gênica , Íntrons , Oryza/enzimologia , Oryza/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismo , Proteínas Quinases/química , Proteínas Quinases/metabolismo , Seleção Genética , Zea mays/enzimologia , Zea mays/genética
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