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1.
Hum Mol Genet ; 32(5): 720-731, 2023 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-36048850

RESUMO

Hereditary hearing loss has a genetic and phenotypic heterogeneity. However, it is still difficult to explain this heterogeneity perfectly with known deafness genes. Here, we report a novel causative gene EPHA10 as well as its non-coding variant in 5' untranslated region identified in a family with post-lingual autosomal dominant non-syndromic hearing loss from southern China. One affected member of this family had an ideal hearing restoration after cochlear implantation. We speculated that there were probable deafness-causing abnormalities in the cochlea according to clinical imaging and auditory evaluations. A heterozygous variant c.-81_-73delinsAGC was found co-segregating with hearing loss. Epha10 was expressed in mouse cochlea at both transcription and translation levels. The variant caused upregulation of EPHA10 which may result from promoter activity enhancement after sequence change. Overexpression of Eph (the homolog of human EPHA10) exerted effects on the structure and function of chordotonal organ in fly model. In summary, our study linked pseudo-kinase EPHA10 to hearing loss in humans for the first time.


Assuntos
Surdez , Perda Auditiva Neurossensorial , Perda Auditiva , Animais , Camundongos , Humanos , Regulação para Cima , Regiões 5' não Traduzidas , Mutação , Surdez/genética , Perda Auditiva Neurossensorial/genética , Perda Auditiva/genética , Linhagem , Receptores da Família Eph/genética
2.
Proc Natl Acad Sci U S A ; 118(22)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34050020

RESUMO

Genes that are primarily expressed in cochlear glia-like supporting cells (GLSs) have not been clearly associated with progressive deafness. Herein, we present a deafness locus mapped to chromosome 3p25.1 and an auditory neuropathy spectrum disorder (ANSD) gene, TMEM43, mainly expressed in GLSs. We identify p.(Arg372Ter) of TMEM43 by linkage analysis and exome sequencing in two large Asian families segregating ANSD, which is characterized by inability to discriminate speech despite preserved sensitivity to sound. The knock-in mouse with the p.(Arg372Ter) variant recapitulates a progressive hearing loss with histological abnormalities in GLSs. Mechanistically, TMEM43 interacts with the Connexin26 and Connexin30 gap junction channels, disrupting the passive conductance current in GLSs in a dominant-negative fashion when the p.(Arg372Ter) variant is introduced. Based on these mechanistic insights, cochlear implant was performed on three subjects, and speech discrimination was successfully restored. Our study highlights a pathological role of cochlear GLSs by identifying a deafness gene and its causal relationship with ANSD.


Assuntos
Códon sem Sentido , Conexinas/metabolismo , Genes Dominantes , Perda Auditiva Central/genética , Proteínas de Membrana/genética , Animais , Implante Coclear , Feminino , Perda Auditiva Central/metabolismo , Perda Auditiva Central/fisiopatologia , Perda Auditiva Central/cirurgia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Linhagem , Percepção da Fala
3.
BMC Psychiatry ; 23(1): 811, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37936082

RESUMO

OBJECTIVES: Olfactory function, serum tumor necrosis factor-α (TNF-α) and cognitive function were compared between bipolar disorder (BD) and schizophrenia (SP) patients in the remission stage combined with correlation analysis, with the aim of identifying new indicators for the auxiliary diagnosis of these psychiatric illnesses. METHODS: A total of 46 euthymic BD patients, 42 clinically stable SP patients and 42 healthy controls (HC) were included in this study. Olfactory sensitivity (OS) and olfactory identification (OI) were assessed using Sniffin' Sticks test, and serum TNF-α levels were measured by ELISA. Clinical symptoms were evaluated with the Hamilton Rating Scale for Depression, Young Mania Rating Scale, Hamilton anxiety scale, and the Positive and Negative Syndrome Scale (PANSS). Social function was evaluated with the Global Assessment Function (GAF) scale. Cognitive function was evaluated using the Trail Making Test-A (TMT-A) and Digit Cancellation Test (DCT). RESULTS: OI and cognitive function scores and serum TNF-α levels were significantly lower in the BD and SP patients compared with the HC participants. There was no significant difference between the BD and SP groups, and there were no significant differences in OS among the three groups. OI score was positively correlated with years of education in both the BD and SP groups. OI score in the SP group was negatively correlated with age and PANSS score, and positively correlated with GAF score. In the BD group, OS was positively correlated with DCT II and DCT III. In the SP group, OS and OI scores were positively correlated with DCT III, and negatively correlated with TMT-A time. Furthermore, there was a positive correlation between TNF-α and DCT II in the BD group. There was no significant linear correlation between olfactory function and TNF-α in the BD or SP group. CONCLUSION: OI may be a trait marker for BD and SP. Some cognitive functions may be correlated not only with TNF-α in BD patients in remission, but also with olfactory function in BD and SP patients in remission.


Assuntos
Transtorno Bipolar , Esquizofrenia , Humanos , Transtorno Bipolar/psicologia , Cognição , Transtorno Ciclotímico , Esquizofrenia/diagnóstico , Fator de Necrose Tumoral alfa
4.
Hum Mol Genet ; 28(24): 4103-4112, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31628468

RESUMO

ELMOD3, an ARL2 GTPase-activating protein, is implicated in causing hearing impairment in humans. However, the specific role of ELMOD3 in auditory function is still far from being elucidated. In the present study, we used the CRISPR/Cas9 technology to establish an Elmod3 knockout mice line in the C57BL/6 background (hereinafter referred to as Elmod3-/- mice) and investigated the role of Elmod3 in the cochlea and auditory function. Elmod3-/- mice started to exhibit hearing loss from 2 months of age, and the deafness progressed with aging, while the vestibular function of Elmod3-/- mice was normal. We also observed that Elmod3-/- mice showed thinning and receding hair cells in the organ of Corti and much lower expression of F-actin cytoskeleton in the cochlea compared with wild-type mice. The deafness associated with the mutation may be caused by cochlear hair cells dysfunction, which manifests with shortening and fusion of inner hair cells stereocilia and progressive degeneration of outer hair cells stereocilia. Our finding associates Elmod3 deficiencies with stereocilia dysmorphologies and reveals that they might play roles in the actin cytoskeleton dynamics in cochlear hair cells, and thus relate to hearing impairment.


Assuntos
Surdez/enzimologia , Proteínas Ativadoras de GTPase/deficiência , Proteínas Ativadoras de GTPase/metabolismo , Perda Auditiva/enzimologia , Estereocílios/metabolismo , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Animais , Cóclea/enzimologia , Cóclea/metabolismo , Citoesqueleto/metabolismo , Surdez/genética , Feminino , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Proteínas Ativadoras de GTPase/genética , Células Ciliadas Auditivas Internas/metabolismo , Células Ciliadas Auditivas Externas/metabolismo , Células Ciliadas Auditivas Externas/fisiologia , Perda Auditiva/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , Estereocílios/enzimologia
5.
Opt Express ; 28(7): 10705-10713, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32225648

RESUMO

We demonstrate an approach for the realization of coupled-mode induced transparency (CMIT) in a hybrid polydimethylsiloxane (PDMS)-coated silica microbubble resonator, with an Au microwire inserted in the hollow channel. Owing to the large negative thermo-optics coefficient of PDMS, different radial order modes with opposite thermal sensitivities can coexist in this hybrid microcavity. By applying a current through the Au microwire, which acts as a microheater, the generated Ohmic heating could thermally tune the resonance frequencies and the frequency detuning of the coupled mode to achieve controllable CMIT. This platform offers an efficient and convenient way to obtain controllable CMIT for applications, such as label-free biosensing and quantum information processing.

6.
Opt Express ; 28(2): 2201-2209, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32121915

RESUMO

This study introduces design and coupling techniques, which bridge an opaque liquid metal, optical WGM mode, and mechanical mode into an opto-mechano-fluidic microbubble resonator (MBR) consisting of a dielectric silica shell and liquid metal core. Benefiting from the conductivity of the liquid metal, Ohmic heating was carried out for the MBR by applying current to the liquid metal to change the temperature of the MBR by more than 300 °C. The optical mode was thermally tuned (>3 nm) over a full free spectral range because the Ohmic heating changed the refractive index of the silica and dimeter of the MBR. The mechanical mode was thermally tuned with a relative tuning range of 9% because the Ohmic heating changed the velocity and density of the liquid metal.

7.
Sensors (Basel) ; 19(22)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752221

RESUMO

Accurate road information is important for applications involving road maintenance, intelligent transportation, and road network updates. Mobile laser scanning (MLS) can effectively extract road information. However, accurately extracting road edges based on large-scale data for complex road conditions, including both structural and non-structural road types, remains difficult. In this study, a robust method to automatically extract structural and non-structural road edges based on a topological network of laser points between adjacent scan lines and auxiliary surfaces is proposed. The extraction of road and curb points was achieved mainly from the roughness of the extracted surface, without considering traditional thresholds (e.g., height jump, slope, and density). Five large-scale road datasets, containing different types of road curbs and complex road scenes, were used to evaluate the practicality, stability, and validity of the proposed method via qualitative and quantitative analyses. Measured values of the correctness, completeness, and quality of extracted road edges were over 95.5%, 91.7%, and 90.9%, respectively. These results confirm that the proposed method can extract road edges from large-scale MLS datasets without the need for auxiliary information on intensity, image, or geographic data. The proposed method is effective regardless of whether the road width is fixed, the road is regular, and the existence of pedestrians and vehicles. Most importantly, the proposed method provides a valuable solution for road edge extraction that is useful for road authorities when developing intelligent transportation systems, such as those required by self-driving vehicles.

8.
Front Psychiatry ; 15: 1348895, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38651009

RESUMO

Introduction: Research has indicated that individuals diagnosed with bipolar disorder (BD) might experience alterations in their olfaction or levels of serum tumor necrosis factor-α (TNF-α), but no studies have investigated olfactory function and serum TNF-α in BD patients simultaneously. Moreover, there is a lack of existing research that compares the longitudinal olfactory function between individuals with manic and euthymic BD I. Methods: Patients with manic BD I (BDM, n=44) and healthy controls (HCs, n=32) were evaluated symptoms (measured via the Young Manic Rating Scale, YRMS), social function (measured via the Global Assessment Function, GAF), serum TNF-α, and olfactory function (via the Sniffin' Sticks test) including olfactory sensitivity (OS) and olfactory identification (OI). The BDM patients were followed up to the remission period and re-evaluated again. We compared OS, OI and serum TNF-α in manic and euthymic patients with BD I and HCs. We examined the correlation between olfactory function and symptoms, social function, and serum TNF-α in patients with BD I. Results: The BDM patients exhibited significantly lower OS and OI compared to the HCs (Z = -2.235, P = 0.025; t = -6.005, P < 0.001), while a positive correlation was observed between OS and GAF score (r = 0.313, P = 0.039). The OS in the BD I remission group (n=25) exhibited significantly superior performance compared to the BDM group (t = -4.056, P < 0.001), and the same as that in the HCs (P = 0.503). The change in OS showed a positive correlation with the decrease in YMRS score (r = 0.445, P = 0.026), and a negative correlation with the course of disease (r = -0.594, P = 0.002). The TNF-α in BD I patients was significantly lower compared to HCs (P < 0.001), and not significantly correlated with olfactory function (all P > 0.05). Conclusion: The findings suggest that OS and OI are impaired in BDM patients, and the impaired OS in those patients can be recovered in the remission stage. OI may serve as a potential characteristic marker of BD. OS might be useful as an index for BDM treatment efficacy and prognosis.

9.
Redox Biol ; 74: 103218, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38870779

RESUMO

The ABCC1 gene belongs to the ATP-binding cassette membrane transporter superfamily, which plays a crucial role in the efflux of various endogenous and exogenous substances. Mutations in ABCC1 can result in autosomal dominant hearing loss. However, the specific roles of ABCC1 in auditory function are not fully understood. Through immunofluorescence, we found that ABCC1 was expressed in microvascular endothelial cells (ECs) of the stria vascularis (StV) in the murine cochlea. Then, an Abcc1 knockout mouse model was established by using CRISPR/Cas9 technology to elucidate the role of ABCC1 in the inner ear. The ABR threshold did not significantly differ between WT and Abcc1-/- mice at any age studied. After noise exposure, the ABR thresholds of the WT and Abcc1-/- mice were significantly elevated. Interestingly, after 14 days of noise exposure, ABR thresholds largely returned to pre-exposure levels in WT mice but not in Abcc1-/- mice. Our subsequent experiments showed that microvascular integrity in the StV was compromised and that the number of outer hair cells and the number of ribbons were significantly decreased in the cochleae of Abcc1-/- mice post-exposure. Besides, the production of ROS and the accumulation of 4-HNE significantly increased. Furthermore, StV microvascular ECs were cultured to elucidate the role of ABCC1 in these cells under glucose oxidase challenge. Notably, 30 U/L glucose oxidase (GO) induced severe oxidative stress damage in Abcc1-/- cells. Compared with WT cells, the ROS and 4-HNE levels and the apoptotic rate were significantly elevated in Abcc1-/- cells. In addition, the reduced GSH/GSSG ratio was significantly decreased in Abcc1-/- cells after GO treatment. Taken together, Abcc1-/- mice are more susceptible to noise-induced hearing loss, possibly because ABCC1 knockdown compromises the GSH antioxidant system of StV ECs. The exogenous antioxidant N-acetylcysteine (NAC) may protect against oxidative damage in Abcc1-/- murine cochleae and ECs.


Assuntos
Antioxidantes , Cóclea , Perda Auditiva Provocada por Ruído , Camundongos Knockout , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Estresse Oxidativo , Animais , Camundongos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Cóclea/metabolismo , Cóclea/patologia , Perda Auditiva Provocada por Ruído/metabolismo , Perda Auditiva Provocada por Ruído/genética , Antioxidantes/metabolismo , Modelos Animais de Doenças , Espécies Reativas de Oxigênio/metabolismo , Células Endoteliais/metabolismo
10.
Front Psychiatry ; 14: 1284567, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965355

RESUMO

Background: The aim of this study was to analyze whether the presence of psychotic symptoms affects olfactory function in patients with bipolar disorder (BD). We also compared olfactory function between the period of episode and remission in patients with BD. Methods: BD patients in the acute phase were tracked to the remission stage. The psychiatric symptoms and social function of the enrolled subjects were assessed using the Hamilton Rating Scale for Depression (HAMD), the Young Mania Rating Scale (YMRS), the Hamilton Rating Scale for Anxiety (HAMA), the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment Function (GAF). Olfactory sensitivity (OS) and olfactory identification (OI) was assessed using the Sniffin' Sticks test. Differences in OS and OI among the episodic group, the euthymic group, and the healthy control (HC) group were compared. According to whether BD is accompanied by psychotic symptoms, the OS and OI in the BD with psychotic symptoms group (P-BD), the BD without psychotic symptoms group (NP-BD), and the HC group were compared. Results: The P-BD and NP-BD groups exhibited impaired OI compared with the HC group, but there was no significant difference in OI between the P-BD and NP-BD groups, or in OS among all three groups. All patients with episodic BD had significantly lower OS and OI compared with the HC group. OI in euthymic BD patients was still impaired; however, OS recovered, showing no significant difference compared with that in the HC group. Conclusion: The results indicate that patients with episodic BD have impaired OS and OI, regardless of psychotic symptoms. OI may be a characteristic marker of BD, and OS may be a state marker that can be used to distinguish between episodic and euthymic BD.

11.
PLoS One ; 18(9): e0288640, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37708136

RESUMO

The ELMOD3 gene is implicated in causing autosomal recessive/dominant non-syndromic hearing loss in humans. However, the etiology has yet to be completely elucidated. In this study, we generated a patient-derived iPSC line carrying ELMOD3 c.512A>G mutation. In addition, the patient-derived iPSC line was corrected by CRISPR/Cas9 genome editing system. Then we applied RNA sequencing profiling to compare the patient-derived iPSC line with different controls, respectively (the healthy sibling-derived iPSCs and the CRISPR/Cas9 corrected iPSCs). Functional enrichment and PPI network analysis revealed that differentially expressed genes (DEGs) were enriched in the gene ontology, such as sensory epithelial development, intermediate filament cytoskeleton organization, and the regulation of ion transmembrane transport. Our current work provided a new tool for studying how disruption of ELMOD3 mechanistically drives hearing loss.


Assuntos
Surdez , Perda Auditiva , Células-Tronco Pluripotentes Induzidas , Humanos , Perda Auditiva/genética , Regulação da Expressão Gênica , Mutação , Proteínas Ativadoras de GTPase
12.
Clin Exp Otorhinolaryngol ; 16(4): 342-358, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37817567

RESUMO

OBJECTIVES: Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient's hearing. METHODS: We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. RESULTS: A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. CONCLUSION: We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

13.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue ; 24(5): 286-9, 2012 May.
Artigo em Zh | MEDLINE | ID: mdl-22587924

RESUMO

OBJECTIVE: To investigate the protective effect of combined pretreatment of edaravone and propofol on cerebral cortex with ischemia/reperfusion (I/R) injury and its therapeutic window. METHODS: Sprague Dawley (SD) rat brain cortex cells harvested within 24 hours of birth were cultured in vitro for 7 days. The cells were then divided into blank control group, glutamate injury group, 24-hour drug precondition control group, and 24-, 2-, 0-hour drug precondition groups according to random number table. The nerve cells in each pretreatment group were cultured in medium containing 100 µmol/L of edaravone and 3 mg/L of propofol 24, 2, or 0 hour before glutamate damage (200 µmol/L for 0.5 hour). Nerve cell survival or damage was determined by methyl thiazolyl tetrazolium (MTT), lactate dehydrogenase (LDH) leakage rate, and nerve cell Na+-K+-ATPase activity. The oxidation and anti-oxidation ability of nerve cells was observed by determining superoxide dismutase (SOD) activity (xanthine oxidase), malondialdehyde (MDA) content (thiobarbituric acid). Nerve apoptosis was detected by flow cytometry. RESULTS: Compared with blank control group, in the glutamate injury group, nerve cell survival rate [(62.2±23.4)% vs. (90.5±14.8)%], the activity of SOD (U/ml: 6.864±2.872 vs. 29.569±3.684), Na+-K+-ATPase activity [U×mg(-1)×h(-1): 0.318±0.146 vs. 0.636±0.168] were significantly decreased, and rate of neuronal apoptosis [(9.4±0.7)% vs. (6.1±0.2)%], the content of MDA (nmol/ml: 0.515±0.101 vs. 0.294±0.105), LDH leakage rate [(41.2±1.6)% vs. (36.8±4.6)%] were significantly increased (P<0.05 or P<0.01). Compared with glutamate injury group, the cell survival rate and the activity of SOD and Na+-K+-ATPase were significantly increased in the drug pretreatment groups, and apoptosis rate, MDA content, and LDH leakage rate were significantly decreased with time-department, and effect in the 24-hour pretreatment group was most significant [survival rate of cell: (89.2±30.3)% vs. (62.2±23.4)%, SOD activity (U/ml): 17.780±4.514 vs. 6.864±2.872, Na+-K+-ATPase activity [U×mg(-1)×h(-1)]: 0.541±0.052 vs. 0.318±0.146, the rate of cell apoptosis: (6.7±0.4)% vs. (9.4±0.7)%, the content of MDA (nmol/ml): 0.319±0.101 vs. 0.515±0.101, LDH leakage rate: (37.2±1.4)% vs. (41.2±1.6)%, all P<0.01]. CONCLUSION: The synergistic protective effect of pretreatment with edaravone combined with propofol on neonatal rat brain cortex cells with I/R injury in vitro was evident; and 24-hour pretreatment is the best time window of protection for the cerebral neurons.


Assuntos
Antipirina/análogos & derivados , Córtex Cerebral/citologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Propofol/farmacologia , Animais , Antipirina/farmacologia , Antipirina/uso terapêutico , Apoptose , Isquemia Encefálica/prevenção & controle , Sobrevivência Celular , Células Cultivadas , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/efeitos dos fármacos , Edaravone , Fármacos Neuroprotetores/uso terapêutico , Propofol/uso terapêutico , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controle
14.
Artigo em Zh | MEDLINE | ID: mdl-23484277

RESUMO

Five integral and active plerocercoids collected from naturally infected frogs were fixed by glutaraldehyde-osmic acid, dehydrated in graded series of ethanol, dried via vacuum freeze and coated with carbon gold. They were then observed by scanning electron microscopy. The results showed that the anterior and posterior ends of the plerocercoids were slightly swell and without segmentation. Annular furrows ran irregularly along the body surface. The anterior end was drawn inside and had a deep dorsoventral hollow, around which, the plasma membrane displayed a lip bulge. The posterior end was similar to the anterior one in the shape, but a fissure in its central part was comparatively narrower and shallower than the hollow in the anterior end. There were thousands of pits and grooves on the body surface, unequal in size. The whole body surface of the plerocercoid was densely covered by sharp spine-like microtriches.


Assuntos
Microscopia Eletrônica de Varredura , Ranidae/parasitologia , Plerocercoide/anatomia & histologia , Animais , Plerocercoide/ultraestrutura
15.
Stem Cell Res ; 64: 102916, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36126472

RESUMO

The human induced pluripotent stem cell (iPSC) lines, CSUXHEi001-A and CSUXHEi002-A, were generated from peripheral blood mononuclear cells (PBMCs). The donors were couple and each of them has a heterozygous mutation in the SLC26A4 gene. It manifests in their children as Enlarged vestibular aqueduct (EVA). The use of iPSC will allow describing the early stages of hearing loss, which is undoubtedly relevant for identifying key stages of development at which phenotypic manifestations of mutations in the SLC26A4 gene are found.


Assuntos
Células-Tronco Pluripotentes Induzidas , Aqueduto Vestibular , Criança , Humanos , Transportadores de Sulfato/genética , Leucócitos Mononucleares , Proteínas de Membrana Transportadoras/genética , Mutação/genética
16.
Artigo em Inglês | MEDLINE | ID: mdl-33802442

RESUMO

The ecological system is the basis of human survival and global environmental protection. In the process of development, countries will pay close attention to the changing state of the ecosystem. Taking the ecosystem pattern as the research object, a three-layer analysis method was proposed. The transfer matrix and landscape index were used as the first layer to analyze the basic changes. Grey correlation, range-coupling coordination and relative priority were used as the second layer to analyze the reasons of the change. The interval-entropy weight, TOPSIS (Technique for Order Preference by Similarity to an Ideal Solution), was used as the third layer to evaluate the quality of the change. The ten counties in the worst-hit areas of the Wenchuan earthquake were analyzed from different angles, with county region, intensity zone and ecosystem as the objects, and the following results were obtained: (1) Taking Mianzhu City as an example, from 2000 to 2010 and 2018, the conversion ratio of forest, grassland and farmland is 54.24, 59.19, 17.21, 20.06, 37.39 and 52.86%, which were distributed in the north, central and southern parts, respectively. (2) Taking the ninth intensity zone as an example, the forest landscape fragmentation increased, disturbance decreased, and species diversity increased. There is a high influence and restriction relationship between ecosystem and landscape pattern in the total landscape area change. Additionally, the relationship between them tends to develop in a benign way. As of 2018, it is in the change state of moderate imbalance-ecosystem lag. (3) Taking the county ecosystem change as an example, urban type is the best in the counties of ecosystem change, of which Shifang is the best and Pingwu is the worst. The results show that this method can effectively compare and analyze the changes in the multi-regional ecosystem pattern, which has the characteristics of universality and can also be applied to the research of ecosystem pattern change in special regions.


Assuntos
Desastres , Terremotos , China , Cidades , Conservação dos Recursos Naturais , Ecossistema , Humanos
17.
Stem Cell Res ; 53: 102300, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33774334

RESUMO

Waardenburg Syndrome (WS) is a common autosomal dominant syndrome associated with hearing loss. Its clinical manifestations include hearing impairment and pigmentation anomalies. In this study, we generated an induced pluripotent stem cell (iPSC) line from the Epstein-Barr virus-immortalized B lymphocytes of a 6-year-old boy affected with WS type I, caused by a heterozygous splice site mutation in the PAIRED BOX GENE 3 (PAX3) (NM_181457.3: c.452-2A > G). The patient-specific iPSC line (CSUXHi004-A) carrying the same PAX3 mutation showed a normal karyotype, expressed pluripotent markers, and presented differentiation capacity in vitro. This method may be a useful tool for the in vitro modeling of WS.


Assuntos
Infecções por Vírus Epstein-Barr , Células-Tronco Pluripotentes Induzidas , Síndrome de Waardenburg , Criança , Herpesvirus Humano 4 , Humanos , Masculino , Mutação , Fator de Transcrição PAX3/genética , Linhagem , Síndrome de Waardenburg/genética
18.
Artigo em Zh | MEDLINE | ID: mdl-21137322

RESUMO

Plerocercoids of Spirometra mansoni were collected from muscles of the frogs. Specimens were treated following the routine procedure, embedded, sliced and stained. The ultrastructure of plerocercoid was observed with transmission electron microscopy. It was found that the wall of plerocercoid consisted of tegument and parenchyma. Thornshape microtriches distributed over the outer surface of the tegument. Matrix zone had a lot of granular discoidal bodies, vesicles, mitochondria and endoplasmic reticulum. Most of the mitochondria were near the basal membrane. Parenchyma zone consisted of muscular layer, tegument cells, parenchymal cells, excretory system, and so on. Many cytoplasmic pathways of tegumentary cells stretch into muscular layer, suggesting that the tegument may be the absorptive site of nutrients.


Assuntos
Spirometra/ultraestrutura , Animais , Microscopia Eletrônica de Transmissão
19.
Talanta ; 213: 120815, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32200920

RESUMO

Lead ions are deleterious pollutants that often reach drinking water, and can cause significant harm to humans (particularly children). An ultra-sensitive lead ion detection method using a whispering gallery mode (WGM) optofluidic microbubble resonator and the classic GR-5 DNAzyme is proposed in this paper. With the auxiliary piranha and Ploy-l-lysine solution, GR-5 DNAzyme was successfully modified on the inner wall of a microbubble. The mode field distribution of the microbubble was analysed, and the optofluidic sensor with thin wall exhibited a maximum bulk refractive index sensitivity of 265.2 nm/RIU. Lead ions at concentrations ranging from 0.1 pM to 100 pM were tested using the proposed WGM optofluidic sensor. The noise was decreased to 2.43 fM using the self-referenced differential method. Thus, a limit of approximately 15 fM was obtained for the detection of lead ions using the WGM optofluidic biosensor. Eight competing metal ions were also used to evaluate the selectivity of the proposed sensor, with results indicating that it has high selectivity for lead ions. Finally, the sensor performance is verified using real samples.


Assuntos
Técnicas Biossensoriais/instrumentação , DNA Catalítico/química , Chumbo/análise , Poluição Química da Água/análise , Desenho de Equipamento , Íons/análise , Limite de Detecção , Refratometria/instrumentação , Rios/química
20.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 10): m1224-5, 2009 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-21577746

RESUMO

In the title compound, [Dy(C(5)H(2.5)N(2)O(4))(2)(C(12)H(8)N(2))(2)]·2H(2)O, the Dy(III) ion is located on a twofold rotation axis and is coordinated in a square-anti-prismatic geometry by two chelating 1,10-phenanthroline mol-ecules as well as two 4-oxido-2-oxo-2,3-di-hydro-pyrimidin-1-ium-5-carboxyl-ato(1.5-) anions. N-H⋯O and O-H⋯O hydrogen bonds help to stabilize the crystal structure. The H atom involved in an N-H⋯N hydrogen bond is disordered around a twofold rotation axis.

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