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1.
Cereb Cortex ; 33(14): 9165-9174, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37310142

RESUMO

It has been proved that unilateral hearing loss (UHL) can cause functional connectivity alterations in adults. However, the mechanism of the human brain coping with the challenge of unilateral hearing deprivation at very early developmental phases remains poorly understood. Here, we performed a resting-state functional near-infrared spectroscopy (fNIRS) study on 3- to 10-month-old infants with varying degrees of unilateral hearing loss to investigate the effect of unilateral auditory deprivation in infants. Using network-based statistics, increased functional connectivity was observed in single-sided deafness (SSD) compared with normal hearing infants, and the right middle temporal gyrus was the most involved nodes. In addition, changes in cortical function in infants were related to the degree of hearing loss, with significantly increased functional connectivity in infants with severe to profound unilateral hearing loss compared with the ones with mild to moderate. Moreover, more significant cortical functional recombination changes were found in right-SSD than in left-SSD infants. For the first time, our study provides evidence for the effects of unilateral hearing deprivation on the early cortical development of the human brain, which would also act as a reference for intervention decisions in children with unilateral hearing loss in clinical settings.


Assuntos
Perda Auditiva Unilateral , Perda Auditiva , Adulto , Criança , Humanos , Lactente , Perda Auditiva Unilateral/diagnóstico por imagem , Encéfalo , Mapeamento Encefálico , Tempo
2.
Asia Pac J Clin Nutr ; 33(3): 413-423, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38965729

RESUMO

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) has become a worldwide public health problem. Current evidence on the association between dietary iron intake and the risk of NAFLD is limited. The present study aimed to investigate the associations of animal-derived dietary iron (ADDI) intake, plant-derived dietary iron (PDDI) intake, and the ratio of PDDI:ADDI with NAFLD risk among U.S. adult population. METHODS AND STUDY DESIGN: This was a repeated cross-sectional study. Data were collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. NAFLD was defined as a United States Fatty Lives Index ≥30, and dietary iron intake was assessed through two 24-h dietary recall in-terviews. Logistic regression and restricted cubic spline models were applied to examine the associations between dietary iron intake from different sources and NAFLD risk. RESULTS: A total of 9478 participants aged ≥20 years were enrolled in the present study. After adjustment for multiple confounding factors, relative to the lowest quartile, the odds ratio (OR) and 95% confidence interval (CI) of NAFLD for the highest quartile was 1.01(95% CI, 0.82-1.24) for ADDI intake, 0.82 (95% CI, 0.64-0.99) for PDDI intake, and 1.00 (95% CI, 0.81-1.24) for the PDDI: ADDI intake ratio. In stratified analysis by sex and age, the significantly negative associations of PDDI intake with NAFLD was observed in women and participants older than 45 years. Dose-response analyses indicated that NAFLD was negatively associated with PDDI intake in a non-linear manner. CONCLUSIONS: PDDI intake was negatively associated with NAFLD in U.S. adults.


Assuntos
Ferro da Dieta , Hepatopatia Gordurosa não Alcoólica , Inquéritos Nutricionais , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Masculino , Feminino , Adulto , Estudos Transversais , Ferro da Dieta/administração & dosagem , Pessoa de Meia-Idade , Dieta/métodos , Dieta/estatística & dados numéricos , Adulto Jovem , Estados Unidos/epidemiologia
3.
Anal Chem ; 95(2): 1301-1308, 2023 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-36576392

RESUMO

Rheumatoid arthritis (RA) is well-known as a kind of autoimmune disease, which brings unbearable pain to the patients by multiple organ complications besides arthritis. To date, RA can be hardly cured, but early diagnosis and standard treatment can relieve symptoms and pain. Therefore, an effective tool to assist the early diagnosis of RA deserves considerable attention. On account of the overexpressed ONOO- during the early stage of RA, a near-infrared (NIR) receptor, Lyso-Cy, is proposed in this work by linker chemistry to expand the conjugated rhodamine framework by cyanine groups. Contributed by the pH-sensitive spiral ring in rhodamine, receptor Lyso-Cy has been found to be workable in lysosomes specifically, which was confirmed by the pH-dependent spectra with a narrow responding region and a well-calculated pKa value of 5.81. We presented an excellent ratiometric sensing protocol for ONOO- in an acidic environment, which was also available for targeting ONOO- in lysosomes selectively. This innovative dual-targeting responsive design is expected to be promising for assisting RA diagnosis at an early stage with respect to the joint inflammatory model established in this work at the organism level.


Assuntos
Artrite Reumatoide , Corantes Fluorescentes , Humanos , Corantes Fluorescentes/química , Rodaminas/química , Lisossomos/química , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/metabolismo , Concentração de Íons de Hidrogênio , Estresse Oxidativo
4.
Plant Cell ; 32(4): 1270-1284, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32086364

RESUMO

Male and female gametophytes are generated from micro- or megaspore mother cells through consecutive meiotic and mitotic cell divisions. Defects in these divisions often result in gametophytic lethality. Gametophytic lethality was also reported when genes encoding ribosome-related proteins were mutated. Although numerous ribosomal proteins (RPs) have been identified in plants based on homology with their yeast and metazoan counterparts, how RPs are regulated, e.g., through dynamic subcellular targeting, is unknown. We report here that an Arabidopsis (Arabidopsis thaliana) importin ß, KETCH1 (karyopherin enabling the transport of the cytoplasmic HYL1), is critical for gametogenesis. Karyopherins are molecular chaperones mediating nucleocytoplasmic protein transport. However, the role of KETCH1 during gametogenesis is independent of HYPONASTIC LEAVES 1 (HYL1), a previously reported KETCH1 cargo. Instead, KETCH1 interacts with several RPs and is critical for the nuclear accumulation of RPL27a, whose mutations caused similar gametophytic defects. We further showed that knocking down KETCH1 caused reduced ribosome biogenesis and translational capacity, which may trigger the arrest of mitotic cell cycle progression and lead to gametophytic lethality.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Núcleo Celular/metabolismo , Gametogênese Vegetal , Carioferinas/metabolismo , Proteínas Ribossômicas/metabolismo , Arabidopsis/genética , Arabidopsis/ultraestrutura , Pontos de Checagem do Ciclo Celular , Núcleo Celular/ultraestrutura , Regulação para Baixo , Regulação da Expressão Gênica de Plantas , Mutação com Perda de Função/genética , Óvulo Vegetal/metabolismo , Óvulo Vegetal/ultraestrutura , Pólen/crescimento & desenvolvimento , Pólen/ultraestrutura , Ligação Proteica , Biossíntese de Proteínas , Proteínas de Ligação a RNA/metabolismo , Ribossomos/metabolismo , Sementes/metabolismo , Sementes/ultraestrutura
5.
Plant Cell ; 32(12): 3812-3824, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32989172

RESUMO

Plant roots are sustained through meristem activity at the root tip. Two transcriptional pathways, one mediated by PLETHORAs (PLTs) and the other by SHORTROOT and SCARECROW, play major roles in root meristem development. The role of PLTs during root meristem development requires a concentration gradient, which is not only contributed by posttranslational regulation such as growth dilution and intercellular movement but also likely by a largely unknown fine-tuned transcriptional regulatory mechanism. We report here that Arabidopsis (Arabidopsis thaliana) JANUS positively regulates PLT1 expression in the root meristem by recruiting RNA polymerase II (Pol II) to PLT1 and by interacting with PLT1. JANUS-dependent recruitment of Pol II is inhibited through the competitive binding of JANUS by GRF-INTERACTING FACTOR1 (GIF1)/ANGUSTIFOLIA3, a transcriptional cofactor that negatively regulates PLT1 expression. Finally, GIF1 and JANUS, the antagonistic regulators of PLT1, both depend on Arabidopsis IMPORTIN ß4 for their nuclear accumulation. The combination of an importin and its two antagonistic cargos in PLT1 transcription may have logistic benefits in fine-tuning the transcription of PLT1 in root meristem.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Carioferinas/metabolismo , Fatores de Transcrição/metabolismo , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Carioferinas/genética , Meristema/genética , Meristema/crescimento & desenvolvimento , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Fatores de Transcrição/genética
6.
BMC Psychiatry ; 23(1): 481, 2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37386434

RESUMO

BACKGROUND: Given the serious consequences of depression and the lack of information about it during the crucially developmental period from the National College Entrance Exam (CEE, i.e., Chinese gaokao) to college, this study aimed to estimate the cumulative incidence, prevalence, age of onset, correlates, and service use of depressive disorders (DDs) among youth who passed the CEE and were enrolled at Hunan Normal University in China. METHODS: A two-stage cross-sectional epidemiological survey of DDs was conducted from October to December, 2017 among 6,922 incoming college students (98.5% effective response, N = 6,818, 71.4% female, age range: 16-25 years, mean age = 18.6). Using a stratified sampling method based on the risk of depression, 926 participants (mean age = 18.5, 75.2% female) were selected and subsequently interviewed with the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and lifetime version (K-SADS-PL). RESULTS: The sex-adjusted 9-month (i.e., 3 months pre-CEE, 3 months after CEE, and 3 months post-matriculation) incidence of new-onset DDs was 2.3% (standard error [S.E.] 0.3%), and the sex-adjusted 1-month, 6-month and lifetime prevalence were 0.7 (S.E. 0.3%), 1.7 (S.E. 0.2%) and 7.5% (S.E. 1.3%), respectively. The median age of onset was 17 (interquartile range: 16-18) years. Critically, over one-third (36.5%, S.E. 0.6) of depressed youth had their new onset during the 9-month period. The risk factors for depression included having mothers with higher education, experiencing major life events, being female, and experiencing parental divorce or death. The adjusted lifetime treatment rate was 8.7%. CONCLUSION: The 9-month incidence of new-onset depression from gaokao to college among the youth sample in China is similar to the global annual incidence (3.0%), but the 1-month and lifetime prevalence are significantly lower than the global point (7.2%) and lifetime prevalence (19%). These findings suggest a high proportion of new-onset depression during the CEE to college among the sample youth in China. The risk of depression is associated with familial and stress correlates. Low treatment is a serious concern. Emphasis on early prevention and available treatment for adolescent and young adult depression is a critical need in China.


Assuntos
Transtorno Depressivo , Adulto Jovem , Humanos , Adolescente , Feminino , Adulto , Masculino , Universidades , Estudos Transversais , China/epidemiologia , Transtorno Depressivo/epidemiologia , Inquéritos Epidemiológicos
7.
Psychol Health Med ; 28(6): 1599-1610, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35260012

RESUMO

Compared with their younger counterparts, older adults are inclined to allocate more attentional resources to positive over negative materials. This age-related positivity effect has been reported in various experimental paradigms; however, studies have not investigated the attention stage at which it appears or its potential neural mechanism. Thus, we investigated the time and frequency domain dynamics of younger and older adults during emotional attention processes. We obtained electroencephalography oscillation and event-related potential data for 20 older and 20 younger participants while they performed an emotional dot-probe task. We focused our time and frequency domain dynamics analyses on the posterior regions as a key structure for facial emotion perception and the frontal regions as a crucial structure for cognitive control. In the time domain, older adults showed an initial attentional shift to happy-related stimuli, whereas their younger counterparts did not demonstrate emotional modulation, as reflected by the N2pc component. The time-frequency decomposition was analyzed for the N2pc time window. The results showed that compared with younger adults, older adults showed an increased alpha power for happy faces in the right-posterior regions. Moreover, a parallel pattern was seen in frontal theta activity. The current findings highlight how electrocortical activity of the brain might moderate the tendency to prioritize positive information among healthy older adults. The emergence of an age-related positivity effect may be related to frontal cognitive control processing. These findings provide insight into the prevention and treatment of unsuccessful aging, such as late-life depression and anxiety.


Assuntos
Atenção , Emoções , Humanos , Idoso , Felicidade , Ansiedade/psicologia , Envelhecimento/psicologia , Expressão Facial
8.
Int J Mol Sci ; 24(4)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36835467

RESUMO

Dendritic cells(DCs) play a protective role in the antitumor immunity of most cancers, which can be divided into conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs). Most current studies are only based on either cDCs or pDCs for the study of the relationship between DCs and breast cancer prognosis, without combining the two together. We aimed to select new biomarkers from pDCs and cDCs. In this paper, the xCell algorithm was first used to calculate the cellular abundance of 64 types of immune cells and stromal cells in tumor samples from the TCGA database, and the high-abundance pDC group and cDC group were divided according to the results of a survival analysis. Then, we looked for the co-expressed gene module of highly infiltrating pDC and cDC patients with a weighted correlation network analysis (WGCNA) and screened out the hub genes, including RBBP5, HNRNPU, PEX19, TPR, and BCL9. Finally, we analyzed the biological functions of the hub genes, and the results showed that RBBP5, TPR, and BCL9 were significantly related to the immune cells and prognosis of patients, and RBBP5 and BCL9 were involved in responding to TCF-related instructions of the Wnt pathway. In addition, we also evaluated the response of pDCs and cDCs with different abundances to chemotherapy, and the results showed that the higher the abundance of pDCs and cDCs, the higher their sensitivity to drugs. This paper revealed new biomarkers related to DCs-among them, BCL9, TPR, and RBBP5 were proven to be closely related to dendritic cells in cancer. For the first time, this paper puts forward that HNRNPU and PEX19 are related to the prognosis of dendritic cells in cancer, which also provides new possibilities for finding new targets for breast cancer immunotherapy.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Células Dendríticas , Feminino , Humanos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Células Dendríticas/imunologia , Biomarcadores Tumorais/metabolismo , Prognóstico
9.
Am J Hum Genet ; 105(4): 803-812, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31564438

RESUMO

Concurrent hearing and genetic screening of newborns is expected to play important roles not only in early detection and diagnosis of congenital deafness, which triggers intervention, but also in predicting late-onset and progressive hearing loss and identifying individuals who are at risk of drug-induced HL. Concurrent hearing and genetic screening in the whole newborn population in Beijing was launched in January 2012. This study included 180,469 infants born in Beijing between April 2013 and March 2014, with last follow-up on February 24, 2018. Hearing screening was performed using transiently evoked otoacoustic emission (TEOAE) and automated auditory brainstem response (AABR). For genetic testing, dried blood spots were collected and nine variants in four genes, GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened using a DNA microarray platform. Of the 180,469 infants, 1,915 (1.061%) were referred bilaterally or unilaterally for hearing screening; 8,136 (4.508%) were positive for genetic screening (heterozygote, homozygote, or compound heterozygote and mtDNA homoplasmy or heteroplasmy), among whom 7,896 (4.375%) passed hearing screening. Forty (0.022%) infants carried two variants in GJB2 or SLC26A4 (homozygote or compound heterozygote) and 10 of those infants passed newborn hearing screening. In total, 409 (0.227%) infants carried the mtDNA 12S rRNA variant (m.1555A>G or m.1494C>T), and 405 of them passed newborn hearing screening. In this cohort study, 25% of infants with pathogenic combinations of GJB2 or SLC26A4 variants and 99% of infants with an m.1555A>G or m.1494C>T variant passed routine newborn hearing screening, indicating that concurrent screening provides a more comprehensive approach for management of congenital deafness and prevention of ototoxicity.


Assuntos
Testes Genéticos/métodos , Perda Auditiva/diagnóstico , Pequim , Teste em Amostras de Sangue Seco , Feminino , Predisposição Genética para Doença , Humanos , Recém-Nascido , Masculino
10.
Anal Chem ; 93(32): 11337-11345, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34353021

RESUMO

Alzheimer's disease (AD) has become a global threat to the elderly health with a short survival time after diagnosis. Due to the asymptomatic stage during the early development, patients are usually diagnosed at the middle or late stage. Therefore, an efficient tool for AD early diagnosis deserves considerable attention, which could make a significant contribution to the treatment intervention. A fluorescent probe has been widely applied for detecting and visualizing species of interest in vitro and in vivo, and the proper reaction between the probe and analytes is responsible for the fluorescence change to provide a lighting-on or ratiometric responsive pattern with satisfactory sensing behavior. In this work, we report the first attempt to build up an AND-logic probe P2 for AD accuracy diagnosis taking butyrylcholinesterase (BChE) and reactive oxygen species (ROSs) as dual targets. Upon the co-stimulation by these two factors through enzymatic hydrolysis and redox reaction, the NIR emission could be readily turned on. This AND sensing pattern avoided the false-positive response effectively, and other diseases sharing one biomarker could hardly induce a NIR fluorescence response. The sensing assay has also been confirmed to be feasible in vitro and in vivo with good sensibility and selectivity. It is worth mentioning that the probe structure has been optimized in terms of the linkage length. This study shows that probe P2 with a connecting arm of medium length (one methylene, n = 1) has superior sensing performance, promising to provide a reference for the relative structure design.


Assuntos
Doença de Alzheimer , Corantes Fluorescentes , Idoso , Doença de Alzheimer/diagnóstico , Biomarcadores , Butirilcolinesterase , Humanos , Lógica
11.
New Phytol ; 232(6): 2384-2399, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34559890

RESUMO

Maize kernel weight is influenced by the unloading of nutrients from the maternal placenta and their passage through the transfer tissue of the basal endosperm transfer layer (BETL) and the basal intermediate zone (BIZ) to the upper part of the endosperm. Here, we show that Small kernel 10 (Smk10) encodes a choline transporter-like protein 1 (ZmCTLP1) that facilitates choline uptake and is located in the trans-Golgi network (TGN). Its loss of function results in reduced choline content, leading to smaller kernels with a lower starch content. Mutation of ZmCTLP1 disrupts membrane lipid homeostasis and the normal development of wall in-growths. Expression levels of Mn1 and ZmSWEET4c, two kernel filling-related genes, are downregulated in the smk10, which is likely to be one of the major causes of incompletely differentiated transfer cells. Mutation of ZmCTLP1 also reduces the number of plasmodesmata (PD) in transfer cells, indicating that the smk10 mutant is impaired in PD formation. Intriguingly, we also observed premature cell death in the BETL and BIZ of the smk10 mutant. Together, our results suggest that ZmCTLP1-mediated choline transport affects kernel development, highlighting its important role in lipid homeostasis, wall in-growth formation and PD development in transfer cells.


Assuntos
Endosperma , Zea mays , Homeostase , Lipídeos , Proteínas de Plantas/genética , Zea mays/genética
12.
Neuroimage ; 207: 116372, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31751665

RESUMO

The protracted nature of development makes the cerebellum vulnerable to a broad spectrum of pathologic conditions, especially during the early fetal period. This study aims to characterize normal cerebellar growth in human fetuses during the early second trimester. We manually segmented the fetal cerebellum using 7.0-T high-resolution MR images obtained in 35 specimens with gestational ages ranging from 15 to 22 weeks. Volume measurements and shape analysis were performed to quantitatively evaluate global and regional cerebellar growth. The absolute volume of the fetal cerebellum showed a quadratic growth with increasing gestational age, while the pattern of relative volume changes revealed that the cerebellum grew at a greater pace than the cerebrum after 17 gestational weeks. Shape analysis was used to examine the distinctive development of subregions of the cerebellum. The extreme lateral portions of both cerebellar hemispheres showed the lowest rate of growth. The anterior lobe grew faster than most of the posterior lobe. These findings expand our understanding of the early growth pattern of the human cerebellum and could be further used to assess the developmental conditions of the fetal brain.


Assuntos
Cerebelo/patologia , Desenvolvimento Fetal/fisiologia , Segundo Trimestre da Gravidez/fisiologia , Feminino , Idade Gestacional , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Lactente , Imageamento por Ressonância Magnética/métodos , Gravidez
13.
Plant Physiol ; 179(3): 1080-1092, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30659067

RESUMO

Ovule development is critical for seed development and plant reproduction. Multiple transcription factors (TFs) have been reported to mediate ovule development. However, it is not clear which intracellular components regulate these TFs during ovule development. After their synthesis, TFs are transported into the nucleus a process regulated by karyopherins commonly known as importin alpha and ß. Around half of Arabidopsis (Arabidopsis thaliana) importin ß-coding genes have been functionally characterized but only two with specific cargos have been identified. We report here that Arabidopsis IMPORTIN ß4 (IMB4) regulates ovule development through nucleocytoplasmic transport of transcriptional coactivator growth regulating factors-interacting factors (GIFs). Mutations in IMB4 impaired ovule development by affecting integument growth. imb4 mutants were also defective in embryo sac development, leading to partial female sterility. IMB4 directly interacts with GIFs and is critical for the nucleocytoplasmic transport of GIF1. Finally, functional loss of GIFs resulted in ovule defects similar to those in imb4 mutants, whereas enhanced expression of GIF1 partially restored the fertility of imb4 The results presented here uncover a novel genetic pathway regulating ovule development and reveal the upstream regulator of GIFs.


Assuntos
Proteínas de Arabidopsis/fisiologia , Arabidopsis/metabolismo , Transporte Ativo do Núcleo Celular , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Núcleo Celular/metabolismo , Citocininas/metabolismo , Citoplasma/metabolismo , Ácidos Indolacéticos/metabolismo , Óvulo Vegetal/genética , Óvulo Vegetal/crescimento & desenvolvimento , Óvulo Vegetal/metabolismo , Transativadores/metabolismo
14.
Proc Natl Acad Sci U S A ; 114(24): E4877-E4883, 2017 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-28559348

RESUMO

Double fertilization in angiosperms requires the delivery of immotile sperm through pollen tubes, which enter embryo sacs to initiate synergid degeneration and to discharge. This fascinating process, called pollen tube reception, involves extensive communications between pollen tubes and synergids, within which few intracellular regulators involved have been revealed. Here, we report that vacuolar acidification in synergids mediated by AP1G and V-ATPases might be critical for pollen tube reception. Functional loss of AP1G or VHA-A, encoding the γ subunit of adaptor protein 1 or the shared component of two endomembrane V-ATPases, respectively, impaired synergid-controlled pollen tube reception and caused partial female sterility. AP1G works in parallel to the plasma membrane-associated receptor FERONIA in synergids, suggesting that synergid-mediated pollen tube reception requires proper sorting of vacuolar cargos by AP1G. Although AP1G did not mediate the targeting of V-ATPases, AP1G loss of function or the expression of AP1G-RNAi compromised vacuolar acidification mediated by V-ATPases, implying their genetic interaction. We propose that vacuolar acidification might represent a distinct cell-death mechanism specifically adopted by the plant phylum, which is critical for synergid degeneration during pollen tube reception.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Arabidopsis/metabolismo , Tubo Polínico/metabolismo , ATPases Vacuolares Próton-Translocadoras/metabolismo , Arabidopsis/metabolismo , Morte Celular/fisiologia , Membrana Celular/metabolismo , Fertilização/fisiologia , Magnoliopsida/metabolismo , Polinização/fisiologia
15.
Int J Mol Sci ; 21(4)2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32070036

RESUMO

The tumor suppressor protein p53 is a critical hub in the comprehensive transcriptional network that inhibits the growth of cells after acute stress stimulation. In this paper, an integrated model of the p53 signaling pathway in response to DNA damage is proposed and the p53 stability and oscillatory dynamics are analyzed. Through theoretical analysis and numerical simulation, we find that the delay as a bifurcation parameter can drive the p53-Mdm2 module to undergo a supercritical Hopf bifurcation, thereby producing oscillation behavior. Moreover, we demonstrate how the positive feedback loop formed by p53* and microRNA-34a (miR-34a) with the feature of double-negative regulation produces limit-cycle oscillations. Further, we find that miR-34a can affect the critical value of Hopf bifurcation in delay-induced p53 networks. In addition, we show that ATM, once activated by DNA damage, makes p53* undergo two Hopf bifurcations. These results revealed that both time delay and miR-34a can have tumor suppressing roles by promoting p53 oscillation or high level expression, which will provide a perspective for promoting the development of anti-cancer drugs by targeting miR-34a and time delay.


Assuntos
MicroRNAs/genética , Neoplasias/genética , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteína Supressora de Tumor p53/genética , Proliferação de Células/genética , Dano ao DNA/genética , Retroalimentação Fisiológica , Redes Reguladoras de Genes/genética , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Estabilidade Proteica , Transdução de Sinais/genética
16.
Ear Hear ; 40(3): 605-614, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30063476

RESUMO

OBJECTIVES: The primary aim of this study was to evaluate the health-related quality of life (HRQoL) of children with cochlear implants (CIs) from the parental perspective. The secondary objective was to explore possible relationships between demographic variables (such as age at assessment, gender, age at implantation, and duration of language rehabilitation) and the HRQoL. The third objective was to determine the developmental trajectories of HRQoL. DESIGN: This study included parents of 123 children with CIs (mean age, 40.45 months; mean age of CI implantation, 24.74 months; mean device experience, 16.34 months). The time periods for follow-up were at 0, 1, 2, 3, 6, and 12-month intervals of CI use. The Mandarin Children with Cochlear Implants: Parental Perspectives questionnaire was employed to assess HRQoL. RESULTS: Parents were satisfied with HRQoL, especially with the domain of social relations; however, education received a less positive rating. The duration of CI use was positively correlated with 5 domains, suggesting that children who used CIs for a longer time had higher HRQoL ratings. Children with longer language rehabilitation received more positive ratings in the domains of social relations and education (p < 0.05); children whose mothers had higher education levels received more positive ratings in the domain of general functioning (p < 0.05); children living in cities received more positive ratings in the domains of communication, general functioning and self-reliance (p < 0.05). Girls received more positive rating than boys in the domain of well-being (p < 0.05). No significant correlation was found between age at implantation, age at assessment, only child status, and HRQoL. All domains showed clear increases in the duration of CI use; the majority of the domains showed steeper progress over the first 3 months of CI use. Communication exhibited the most rapid progress, with education progressing at a slower rate. CONCLUSIONS: Parents were satisfied with all domains of HRQoL. Almost all domains exhibited rapid progress over the first 3 months of CI use, with education progressing at a slower rate. This research underscores the importance of language rehabilitation by revealing that strengthening language rehabilitation could be an effective means of improving the HRQoL of children with CIs.


Assuntos
Implante Coclear , Surdez/reabilitação , Qualidade de Vida , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Idioma , Masculino , Pais , Fatores Sexuais
17.
PLoS Genet ; 12(8): e1006269, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27541731

RESUMO

Planar morphogenesis, a distinct feature of multicellular organisms, is crucial for the development of ovule, progenitor of seeds. Both receptor-like kinases (RLKs) such as STRUBBELIG (SUB) and auxin gradient mediated by PIN-FORMED1 (PIN1) play instructive roles in this process. Fine-tuned intercellular communications between different cell layers during ovule development demands dynamic membrane distribution of these cell-surface proteins, presumably through vesicle-mediated sorting. However, the way it's achieved and the trafficking routes involved are obscure. We report that HAPLESS13 (HAP13)-mediated trafficking of SUB is critical for ovule development. HAP13 encodes the µ subunit of adaptor protein 1 (AP1) that mediates protein sorting at the trans-Golgi network/early endosome (TGN/EE). The HAP13 mutant, hap13-1, is defective in outer integument growth, resulting in exposed nucellus accompanied with impaired pollen tube guidance and reception. SUB is mis-targeted in hap13-1. However, unlike that of PIN2, the distribution of PIN1 is independent of HAP13. Genetic interference of exocytic trafficking at the TGN/EE by specifically downregulating HAP13 phenocopied the defects of hap13-1 in SUB targeting and ovule development, supporting a key role of sporophytically expressed SUB in instructing female gametogenesis.


Assuntos
Complexo 1 de Proteínas Adaptadoras/genética , Proteínas de Arabidopsis/genética , Proteínas de Membrana Transportadoras/genética , Óvulo Vegetal/genética , Receptores Proteína Tirosina Quinases/genética , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/biossíntese , Endossomos/genética , Gametogênese Vegetal/genética , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Proteínas de Domínio MADS/biossíntese , Proteínas de Domínio MADS/genética , Proteínas de Membrana Transportadoras/biossíntese , Óvulo Vegetal/crescimento & desenvolvimento , Desenvolvimento Vegetal/genética , Transporte Proteico/genética , Receptores Proteína Tirosina Quinases/biossíntese , Transdução de Sinais
18.
Zhonghua Nan Ke Xue ; 25(6): 529-534, 2019 Jun.
Artigo em Zh | MEDLINE | ID: mdl-32223088

RESUMO

OBJECTIVE: To investigate the correlation of the single nucleotide polymorphisms rs995030 and rs4474514 of the tyrosine kinase receptor-specific ligand (KITLG) gene with the risk of male infertility. METHODS: This study included 360 patients with idiopathic male infertility and 338 healthy fathers as controls, all from the surrounding areas of Nanjing. According to the 5th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, we divided the infertility patients into an azoospermia (n = 143), a severe oligozoospermia (n = 159), and an oligozoospermia group (n = 58). We obtained the basic clinical data on all the subjects, collected genomic DNA from the peripheral blood of the patients, determined the genotypes of the KITLG gene rs995030 and rs4474514 by sequence mass-array, and analyzed the correlation between the two-point gene polymorphism and male infertility by logistic regression analysis. RESULTS: Statistically significant differences were observed between the infertility patients and normal fertile controls in sperm concentration (ï¼»13.23 ± 24.52ï¼½ vs ï¼»78.74 ± 61.25ï¼½ ×106/ml, P < 0.01), the percentage of progressively mobile sperm (ï¼»18.71 ± 15.19ï¼½% vs ï¼»39.36 ± 9.75ï¼½%, P < 0.01), and the level of FSH (ï¼»16.09 ± 17.31ï¼½ vs ï¼»4.56 ± 2.41ï¼½ IU/L, P < 0.01), but not between the genotypes and male infertility, and no correlation was found in subgroup analysis. CONCLUSIONS: The single nucleotide polymorphisms rs995030 and rs4474514 of the KITLG gene were not significantly correlated with male infertility, which is to be further verified by more studies with samples of larger size and expanded selection range.


Assuntos
Infertilidade Masculina/genética , Polimorfismo de Nucleotídeo Único , Fator de Células-Tronco/genética , Azoospermia/genética , Estudos de Casos e Controles , Genótipo , Humanos , Masculino , Oligospermia/genética , Contagem de Espermatozoides
19.
Zhonghua Nan Ke Xue ; 24(8): 708-712, 2018 08.
Artigo em Zh | MEDLINE | ID: mdl-30173430

RESUMO

Objective: To investigate the correlation between the single nucleotide polymorphism (SNP) rs662 of the paraoxonase 1 gene (PON1) and the risk of male infertility. METHODS: This case-control study included 403 male idiopathic infertility patients aged 29.00 ± 4.48 years in the case group and 329 normal fertile men aged 28.28 ± 4.08 years as healthy controls. We obtained DNA from the peripheral venous blood of the subjects, genotyped the SNP rs662 of PON1 by Sequenom MassArray, and analyzed the association between different genotypes of PON1 rs662 and male infertility using the logistic regression model. RESULTS: Compared with the normal controls, the infertility patients showed a significantly increased level of follicle-stimulating hormone (FSH) (ï¼»16.30 ± 17.76ï¼½ vs ï¼»4.72 ± 2.51ï¼½ U/L, P < 0.01) but a decreased percentage of progressively motile sperm (PMS) (ï¼»7.40 ± 14.17ï¼½ % vs ï¼»41.93 ± 9.06ï¼½ %, P < 0.01) and sperm concentration (ï¼»2.74 ± 3.64ï¼½ vs ï¼»75.83 ± 63.66ï¼½ ×106/ml, P < 0.01). Statistically significant differences were not found in the other parameters between the two groups of subjects, nor in the correlation of male infertility with the heterozygous genotype GA versus the wild homozygous genotype GG (OR = 0.98, 95% CI: 0.63-1.53, P = 0.923) or the homozygous genotype AA versus the wild homozygous genotype GG (OR = 0.87, 95% CI: 0.56-1.34, P = 0.525). CONCLUSIONS: The SNP rs662 of PON1 was not correlated with male infertility, which, however, needs to be confirmed by further studies with larger samples from a larger area.


Assuntos
Arildialquilfosfatase/genética , Infertilidade Masculina/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , Hormônio Foliculoestimulante/sangue , Predisposição Genética para Doença , Genótipo , Heterozigoto , Homozigoto , Humanos , Infertilidade Masculina/sangue , Modelos Logísticos , Masculino , Contagem de Espermatozoides , Adulto Jovem
20.
J Magn Reson Imaging ; 45(1): 157-166, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27227967

RESUMO

PURPOSE: To explore the acute effect of betel quid (BQ) use on functional network connectivity by comparing the global functional brain networks and their subsets before and immediately after BQ chewing. MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging (fMRI) was performed in 27 healthy male participants before and just after chewing BQ on a 3.0T scanner with a gradient-echo echo planar imaging sequence. Independent component analysis (ICA) was used to determine components that represent the brain's functional networks and their spatial aspects of functional connectivity. A paired t-test was used for exploring the connectivity differences in each network before and after BQ chewing. RESULTS: Sixteen networks were identified by ICA. Nine of them showed connectivity differences before and after BQ chewing (P < 0.05 false discovery rate corrected): (A) orbitofrontal, (B) left frontoparietal, (C) visual, (D) right frontoparietal, (E) anterior default mode, (F) medial frontal/anterior cingulate (G) frontotemporal, (H) occipital/parietal, (I) occipital/temporal/cerebellum. Moreover, networks A, B, C, D, G, H, and I showed increased connectivity, while networks E and F showed decreased connectivity in participants after BQ chewing compared to before chewing. CONCLUSION: The acute effects of BQ use appear to actively alter functional connectivity of frontal and default networks that are known to play a key role in addictive behavior. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:157-166.


Assuntos
Areca/química , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Extratos Vegetais/efeitos adversos , Tabaco sem Fumaça/efeitos adversos , Adolescente , Adulto , Areca/efeitos adversos , Conectoma/métodos , Lobo Frontal/diagnóstico por imagem , Humanos , Masculino , Mastigação , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/fisiopatologia , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiopatologia , Piper betle/química , Extratos Vegetais/química , Descanso
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