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1.
J Biol Chem ; 300(3): 105772, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38382674

RESUMO

Pre-mRNA splicing is a precise regulated process and is crucial for system development and homeostasis maintenance. Mutations in spliceosomal components have been found in various hematopoietic malignancies (HMs) and have been considered as oncogenic derivers of HMs. However, the role of spliceosomal components in normal and malignant hematopoiesis remains largely unknown. Pre-mRNA processing factor 31 (PRPF31) is a constitutive spliceosomal component, which mutations are associated with autosomal dominant retinitis pigmentosa. PRPF31 was found to be mutated in several HMs, but the function of PRPF31 in normal hematopoiesis has not been explored. In our previous study, we generated a prpf31 knockout (KO) zebrafish line and reported that Prpf31 regulates the survival and differentiation of retinal progenitor cells by modulating the alternative splicing of genes involved in mitosis and DNA repair. In this study, by using the prpf31 KO zebrafish line, we discovered that prpf31 KO zebrafish exhibited severe defects in hematopoietic stem and progenitor cell (HSPC) expansion and its sequentially differentiated lineages. Immunofluorescence results showed that Prpf31-deficient HSPCs underwent malformed mitosis and M phase arrest during HSPC expansion. Transcriptome analysis and experimental validations revealed that Prpf31 deficiency extensively perturbed the alternative splicing of mitosis-related genes. Collectively, our findings elucidate a previously undescribed role for Prpf31 in HSPC expansion, through regulating the alternative splicing of mitosis-related genes.


Assuntos
Fatores de Processamento de RNA , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Desenvolvimento Embrionário , Mutação , Precursores de RNA/metabolismo , Fatores de Processamento de RNA/metabolismo , Células-Tronco/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
2.
Development ; 149(17)2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35929537

RESUMO

Mutations that occur in RNA-splicing machinery may contribute to hematopoiesis-related diseases. How splicing factor mutations perturb hematopoiesis, especially in the differentiation of erythro-myeloid progenitors (EMPs), remains elusive. Dhx38 is a pre-mRNA splicing-related DEAH box RNA helicase, for which the physiological functions and splicing mechanisms during hematopoiesis currently remain unclear. Here, we report that Dhx38 exerts a broad effect on definitive EMPs as well as the differentiation and maintenance of hematopoietic stem and progenitor cells (HSPCs). In dhx38 knockout zebrafish, EMPs and HSPCs were found to be arrested in mitotic prometaphase, accompanied by a 'grape' karyotype, owing to the defects in chromosome alignment. Abnormal alternatively spliced genes related to chromosome segregation, the microtubule cytoskeleton, cell cycle kinases and DNA damage were present in the dhx38 mutants. Subsequently, EMPs and HSPCs in dhx38 mutants underwent P53-dependent apoptosis. This study provides novel insights into alternative splicing regulated by Dhx38, a process that plays a crucial role in the proliferation and differentiation of fetal EMPs and HSPCs.


Assuntos
Processamento Alternativo , Peixe-Zebra , Processamento Alternativo/genética , Animais , Hematopoese/genética , Células-Tronco Hematopoéticas , Células Progenitoras Mieloides , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
3.
PLoS Genet ; 18(3): e1009841, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35245286

RESUMO

Neural retina leucine zipper (NRL) is an essential gene for the fate determination and differentiation of the precursor cells into rod photoreceptors in mammals. Mutations in NRL are associated with the autosomal recessive enhanced S-cone syndrome and autosomal dominant retinitis pigmentosa. However, the exact role of Nrl in regulating the development and maintenance of photoreceptors in the zebrafish (Danio rerio), a popular animal model used for retinal degeneration and regeneration studies, has not been fully determined. In this study, we generated an nrl knockout zebrafish model via the CRISPR-Cas9 technology and observed a surprising phenotype characterized by a reduced number, but not the total loss, of rods and over-growth of green cones. We discovered two waves of rod genesis, nrl-dependent and -independent at the embryonic and post-embryonic stages, respectively, in zebrafish by monitoring the rod development. Through bulk and single-cell RNA sequencing, we characterized the gene expression profiles of the whole retina and each retinal cell type from the wild type and nrl knockout zebrafish. The over-growth of green cones and mis-expression of green-cone-specific genes in rods in nrl mutants suggested that there are rod/green-cone bipotent precursors, whose fate choice between rod versus green-cone is controlled by nrl. Besides, we identified the mafba gene as a novel regulator of the nrl-independent rod development, based on the cell-type-specific expression patterns and the retinal phenotype of nrl/mafba double-knockout zebrafish. Gene collinearity analysis revealed the evolutionary origin of mafba and suggested that the function of mafba in rod development is specific to modern fishes. Furthermore, the altered photoreceptor composition and abnormal gene expression in nrl mutants caused progressive retinal degeneration and subsequent regeneration. Accordingly, this study revealed a novel function of the mafba gene in rod development and established a working model for the developmental and regulatory mechanisms regarding the rod and green-cone photoreceptors in zebrafish.


Assuntos
Degeneração Retiniana , Peixe-Zebra , Animais , Fatores de Transcrição de Zíper de Leucina Básica/genética , Proteínas do Olho/metabolismo , Mamíferos/metabolismo , Células Fotorreceptoras Retinianas Cones/metabolismo , Degeneração Retiniana/genética , Degeneração Retiniana/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
4.
Small ; : e2312086, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38412409

RESUMO

Rechargeable aqueous aluminum batteries (AABs) are promising energy storage technologies owing to their high safety and ultra-high energy-to-price ratio. However, either the strong electrostatic forces between high-charge-density Al3+ and host lattice, or sluggish large carrier-ion diffusion toward the conventional inorganic cathodes generates inferior cycling stability and low rate-capacity. To overcome these inherent confinements, a series of promising redox-active organic materials (ROMs) are investigated and a π-conjugated structure ROMs with synergistic C═O and C═N groups is optimized as the new cathode in AABs. Benefiting from the joint utilization of multi-redox centers and rich π-π intermolecular interactions, the optimized ROMs with unique ion coordination storage mechanism facilely accommodate complex active ions with mitigated coulombic repulsion and robust lattice structure, which is further validated via theoretical simulations. Thus, the cathode achieves enhanced rate performance (153.9 mAh g-1 at 2.0 A g-1 ) and one of the best long-term stabilities (125.7 mAh g-1 after 4,000 cycles at 1.0 A g-1 ) in AABs. Via molecular exploitation, this work paves the new direction toward high-performance cathode materials in aqueous multivalent-ion battery systems.

5.
Small ; 19(24): e2301086, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36919923

RESUMO

The direct growth of wafer-scale single crystal two-dimensional (2D) hexagonal boron nitride (h-BN) layer with a controllable thickness is highly desirable for 2D-material-based device applications. Here, for the first time, a facile submicron-spacing vapor deposition (SSVD) method is reported to achieve 2-inch single crystal h-BN layers with controllable thickness from monolayer to tens of nanometers on the dielectric sapphire substrates using a boron film as the solid source. In the SSVD growth, the boron film is fully covered by the same-sized sapphire substrate with a submicron spacing, leading to an efficient vapor diffusion transport. The epitaxial h-BN layer exhibits extremely high crystalline quality, as demonstrated by both a sharp Raman E2g vibration mode (12 cm-1 ) and a narrow X-ray rocking curve (0.10°). Furthermore, a deep ultraviolet photodetector and a ZrS2 /h-BN heterostructure fabricated from the h-BN layer demonstrate its fascinating properties and potential applications. This facile method to synthesize wafer-scale single crystal h-BN layers with controllable thickness paves the way to future 2D semiconductor-based electronics and optoelectronics.

6.
Brief Bioinform ; 22(5)2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-33822848

RESUMO

Irregular splicing was associated with tumor formation and progression in renal cell carcinoma (RCC) and many other cancers. By using splicing data in the TCGA SpliceSeq database, RCC subtype classification was performed and splicing features and their correlations with clinical course, genetic variants, splicing factors, pathways activation and immune heterogeneity were systemically analyzed. In this research, alternative splicing was found useful for classifying RCC subtypes. Splicing inefficiency with upregulated intron retention and cassette exon was associated with advanced conditions and unfavorable overall survival of patients with RCC. Splicing characteristics like splice site strength, guanine and cytosine content and exon length may be important factors disrupting splicing balance in RCC. Other than cis-acting and trans-acting regulation, alternative splicing also differed in races and tissue types and is also affected by mutation conditions, pathway settings and the response to environmental changes. Severe irregular splicing in tumor not only indicated terrible intra-cellular homeostasis, but also changed the activity of cancer-associated pathways by different splicing effects including isoforms switching and expression regulation. Moreover, irregular splicing and splicing-associated antigens were involved in immune reprograming and formation of immunosuppressive tumor microenvironment. Overall, we have described several clinical and molecular features in RCC splicing subtypes, which may be important for patient management and targeting treatment.


Assuntos
Processamento Alternativo , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Mutação , Carcinoma de Células Renais/classificação , Análise por Conglomerados , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/classificação , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Microambiente Tumoral/genética
7.
Phys Chem Chem Phys ; 25(15): 10769-10777, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37010260

RESUMO

Due to the excellent electrostatic control, high mobility, large specific surface area, and suitable direct energy gap of two-dimensional (2D) indium arsenide (InAs), it is regarded as one of the most promising alternative channel materials for next-generation electronic and optoelectronic devices. Recently, 2D semiconducting InAs has been successfully prepared. Based on first-principles calculations, we calculate the mechanical, electronic, and interfacial properties of monolayer (ML) fully-hydrogen-passivated InAs (InAsH2) material. The results show that 2D InAsH2 with excellent stability has a suitable logic device band gap (1.59 eV) comparable to silicon (1.14 eV) and 2D MoS2 (1.80 eV), and the electron carrier mobility of ML InAsH2 (490 cm2 V-1 s-1) is twice as large as that of 2D MoS2 (200 cm2 V-1 s-1). In addition, we study the electronic structure of the interfacial contact characteristics of ML half-hydrogen-passivated InAs (InAsH) with seven bulk metals (Ag, Au, Cu, Al, Ni, Pd, Pt) and two 2D metals (ML Ti2C and ML graphene). 2D InAs was metallized after contact with the seven bulk metals and two 2D metals. Based on the above, we insert 2D boron nitride (BN) between ML InAsH and the seven low/high-power function bulk metals to eliminate the interfacial states. Remarkably, the semiconducting properties of 2D InAs with Pd and Pt electrodes are recovered, and 2D InAs achieves p-type ohmic contact with the Pt electrode, which facilitates high on-current and high-frequency operation of the transistor. Hence, this work provides systematic theoretical guidance for the design of next-generation electronic devices.

8.
Nucleic Acids Res ; 49(4): 2027-2043, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33476374

RESUMO

Dysfunction of splicing factors often result in abnormal cell differentiation and apoptosis, especially in neural tissues. Mutations in pre-mRNAs processing factor 31 (PRPF31) cause autosomal dominant retinitis pigmentosa, a progressive retinal degeneration disease. The transcriptome-wide splicing events specifically regulated by PRPF31 and their biological roles in the development and maintenance of retina are still unclear. Here, we showed that the differentiation and viability of retinal progenitor cells (RPCs) are severely perturbed in prpf31 knockout zebrafish when compared with other tissues at an early embryonic stage. At the cellular level, significant mitotic arrest and DNA damage were observed. These defects could be rescued by the wild-type human PRPF31 rather than the disease-associated mutants. Further bioinformatic analysis and experimental verification uncovered that Prpf31 deletion predominantly causes the skipping of exons with a weak 5' splicing site. Moreover, genes necessary for DNA repair and mitotic progression are most enriched among the differentially spliced events, which may explain the cellular and tissular defects in prpf31 mutant retinas. This is the first time that Prpf31 is demonstrated to be essential for the survival and differentiation of RPCs during retinal neurogenesis by specifically modulating the alternative splicing of genes involved in DNA repair and mitosis.


Assuntos
Processamento Alternativo , Células-Tronco Neurais/metabolismo , Neurogênese/genética , Retina/embriologia , Proteínas de Peixe-Zebra/fisiologia , Animais , Apoptose , Sistemas CRISPR-Cas , Sobrevivência Celular , Dano ao DNA , Reparo do DNA , Éxons , Técnicas de Inativação de Genes , Pontos de Checagem da Fase M do Ciclo Celular , Células-Tronco Neurais/citologia , Neurônios Retinianos/citologia , Neurônios Retinianos/metabolismo , Fuso Acromático/ultraestrutura , Proteína Supressora de Tumor p53/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
9.
Opt Express ; 30(23): 42504-42511, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36366703

RESUMO

We prove that the dark solitons can be stable in the purely quintic nonlinear lattices, including the fundamental, tripole and five-pole solitons. These dark soliton families are generated on the periodic nonlinear backgrounds. The propagation constant affects the forms of these solitons, while the number of poles does not lead to the variation of the backgrounds. The dark solitons are stable only when the propagation constant is moderately large.

10.
Opt Express ; 30(15): 27429-27438, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-36236914

RESUMO

High spatial resolution on the image plane (intrinsic spatial resolution) has always been a problem for ultrafast imaging. Single-shot ultrafast imaging methods can achieve high spatial resolution on the object plane through amplification systems but with low intrinsic spatial resolutions. We present frequency domain integration sequential imaging (FISI), which encodes a transient dynamic by an inversed 4f (IFF) system and decodes it using optical spatial frequencies recognition (OFR), which overcomes the limitation of the spatial frequencies recognition algorithm. In an experiment on the process of an air plasma channel, FISI achieved shadow imaging of the channel with a framing rate of 1.26×1013 fps and an intrinsic spatial resolution of 108 lp/mm (the spatial resolution on the image plane). Owing to its excellent framing time and high intrinsic spatial resolution, FISI can probe both repeatable and unrepeatable ultrafast phenomena, such as laser-induced damage, plasma physics, and shockwave interactions in living cells with high quality.

11.
Rep Prog Phys ; 84(5)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33761489

RESUMO

Over the past decade, two-dimensional semiconductors (2DSCs) have aroused wide interest due to their extraordinary electronic, magnetic, optical, mechanical, and thermal properties, which hold potential in electronic, optoelectronic, thermoelectric applications, and so forth. The field-effect transistor (FET), a semiconductor gated with at least three terminals, is pervasively exploited as the device geometry for these applications. For lack of effective and stable substitutional doping techniques, direct metal contact is often used in 2DSC FETs to inject carriers. A Schottky barrier (SB) generally exists in the metal-2DSC junction, which significantly affects and even dominates the performance of most 2DSC FETs. Therefore, low SB or Ohmic contact is highly preferred for approaching the intrinsic characteristics of the 2DSC channel. In this review, we systematically introduce the recent progress made in theoretical prediction of the SB height (SBH) in the 2DSC FETs and the efforts made both in theory and experiments to achieve low SB contacts. From the comparison between the theoretical and experimentally observed SBHs, the emerging first-principles quantum transport simulation turns out to be the most powerful theoretical tool to calculate the SBH of a 2DSC FET. Finally, we conclude this review from the viewpoints of state-of-the-art electrode designs for 2DSC FETs.

12.
Blood ; 133(8): 805-815, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30482793

RESUMO

Hematopoietic stem and progenitor cells (HSPCs) originate from the hemogenic endothelium via the endothelial-to-hematopoietic transition, are self-renewing, and replenish all lineages of blood cells throughout life. BCAS2 (breast carcinoma amplified sequence 2) is a component of the spliceosome and is involved in multiple biological processes. However, its role in hematopoiesis remains unknown. We established a bcas2 knockout zebrafish model by using transcription activator-like effector nucleases. The bcas2 -/- zebrafish showed severe impairment of HSPCs and their derivatives during definitive hematopoiesis. We also observed significant signs of HSPC apoptosis in the caudal hematopoietic tissue of bcas2 -/- zebrafish, which may be rescued by suppression of p53. Furthermore, we show that the bcas2 deletion induces an abnormal alternative splicing of Mdm4 that predisposes cells to undergo p53-mediated apoptosis, which provides a mechanistic explanation of the deficiency observed in HSPCs. Our findings revealed a novel and vital role for BCAS2 during HSPC maintenance in zebrafish.


Assuntos
Embrião não Mamífero/embriologia , Desenvolvimento Embrionário , Células-Tronco Hematopoéticas/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/embriologia , Animais , Animais Geneticamente Modificados/embriologia , Animais Geneticamente Modificados/genética , Técnicas de Silenciamento de Genes , Proteínas de Neoplasias/genética , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética
13.
Opt Express ; 29(17): 27298-27308, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34615148

RESUMO

A novel single-shot ultrafast all-optical photography with raster principle (OPR) that can capture real-time imaging of ultrafast phenomena is proposed and demonstrated. It consists of a sequentially timed module (STM), spectral-shaping module (SSM), and raster framing camera (RFC). STM and SSM are used for linearly encoding frequency-time mapping and system calibration, respectively. The function of the RFC is sampling the target by microlens arrays and framing on the basis of frequency-time-spatial positions conversion. We demonstrated the recording of transient scenes with the spatial resolution of ∼90lp/mm, the frame number of 12 and the frame rate of 2 trillion frames per second (Tfps) in single-shot. Thanks to its high spatial-temporal resolution, high frame rate (maximum up to 10 Tfps or more) and sufficient frame number, our OPR can observe the dynamic processes with complex spatial structure at the atomic time scale (10 fs∼1ps), which is promising for application in plasma physics, shock waves in laser-induced damage, and dynamics of condensed matter materials.

14.
Opt Lett ; 46(9): 2216-2219, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33929457

RESUMO

Dark solitons and localized defect modes against periodic backgrounds are considered in arrays of waveguides with defocusing Kerr nonlinearity, constituting a nonlinear lattice. Bright defect modes are supported by a local increase in nonlinearity, while dark defect modes are supported by a local decrease in nonlinearity. Dark solitons exist for both types of defects, although in the case of weak nonlinearity, they feature side bright humps, making the total energy propagating through the system larger than the energy transferred by the constant background. All considered defect modes are found stable. Dark solitons are characterized by relatively narrow windows of stability. Interactions of unstable dark solitons with bright and dark modes are described.

15.
J Biol Chem ; 294(38): 13953-13963, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31362982

RESUMO

Mutations in human prominin 1 (PROM1), encoding a transmembrane glycoprotein localized mainly to plasma membrane protrusions, have been reported to cause retinitis pigmentosa, macular degeneration, and cone-rod dystrophy. Although the structural role of PROM1 in outer-segment (OS) morphogenesis has been demonstrated in Prom1-knockout mouse, the mechanisms underlying these complex disease phenotypes remain unclear. Here, we utilized a zebrafish model to further investigate PROM1's role in the retina. The Prom1 orthologs in zebrafish include prom1a and prom1b, and our results showed that prom1b, rather than prom1a, plays an important role in zebrafish photoreceptors. Loss of prom1b disrupted OS morphogenesis, with rods and cones exhibiting differences in impairment: cones degenerated at an early age, whereas rods remained viable but with an abnormal OS, even at 9 months postfertilization. Immunofluorescence experiments with WT zebrafish revealed that Prph2, an ortholog of the human transmembrane protein peripherin 2 and also associated with OS formation, is localized to the edge of OS and is more highly expressed in the cone OS than in the rod OS. Moreover, we found that Prom1b deletion causes mislocalization of Prph2 and disrupts its oligomerization. We conclude that the variation in Prph2 levels between cones and rods was one of the reasons for the different PROM1 mutation-induced phenotypes of these retinal structures. These findings expand our understanding of the phenotypes caused by PROM1 mutations and provide critical insights into its function.


Assuntos
Antígeno AC133/metabolismo , Células Fotorreceptoras/metabolismo , Segmento Externo da Célula Bastonete/metabolismo , Antígeno AC133/genética , Animais , Distrofias de Cones e Bastonetes/genética , Modelos Animais de Doenças , Células HeLa , Humanos , Degeneração Macular/metabolismo , Proteínas de Membrana/metabolismo , Morfogênese , Mutação , Periferinas/genética , Retina/metabolismo , Retina/fisiologia , Células Fotorreceptoras Retinianas Cones/metabolismo , Degeneração Retiniana/genética , Degeneração Retiniana/fisiopatologia , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Retinose Pigmentar/genética , Deleção de Sequência , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
16.
Mol Vis ; 26: 670-678, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33088171

RESUMO

Purpose: To identify the genetic cause in a four-generation Chinese family with Axenfeld-Rieger syndrome (ARS). Methods: The family members received clinical examinations of the eye, tooth, periumbilical skin, and heart. Sanger sequencing and whole-exome sequencing (WES) were performed to screen potential mutations. The genomic deletion region around the PITX2 gene was estimated from single nucleotide polymorphism (SNP) data from WES and then confirmed with "quantitative PCR (qPCR) using a set of primers. The DNA breakpoint was further identified with long-range PCR and Sanger sequencing. Results: Symptoms including anterior segment dysplasia of the eye (iris dysplasia, multiple pupils, and posterior embryotoxon), dental dysplasia, and periumbilical skin redundancy were present in all of the affected individuals. Three of them had glaucoma. Corneal abnormalities (inferior sclerocornea, corneal endothelial dystrophy, and central corneal scar) were seen in most of the affected individuals. Cataract, limited eye movement, electrocardiographic abnormalities, intellectual disability, and recurrent miscarriages were observed in some of the affected individuals. No mutations in the coding and exon-intron adjacent regions of the PITX2 and FOXC1 genes were identified with Sanger sequencing. According to the SNP data from WES, we suspected that there might be a deletion region (at most 1.6 Mb) around the PITX2 gene. With the use of qPCR and long-range PCR, we identified a 53,840 bp deletion (chr4: 111,535,454-111,588,933) spanning PITX2 and PANCR. The genomic deletion cosegregated with the major ARS symptoms observed in the family members. Conclusions: With the help of WES, qPCR, and long-range PCR, we identified a genomic deletion encompassing PITX2 and the adjacent noncoding gene PANCR in a Chinese family with ARS. The clinical features of the affected individuals are reported. This work may broaden understanding of the phenotypic and mutational spectrums related to ARS.


Assuntos
Segmento Anterior do Olho/anormalidades , Anormalidades do Olho/genética , Oftalmopatias Hereditárias/genética , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genética , Adulto , Segmento Anterior do Olho/fisiopatologia , Povo Asiático , Eletrocardiografia , Anormalidades do Olho/fisiopatologia , Oftalmopatias Hereditárias/fisiopatologia , Feminino , Fatores de Transcrição Forkhead/genética , Genótipo , Glaucoma/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real , Deleção de Sequência , Sequenciamento do Exoma , Proteína Homeobox PITX2
17.
Phys Chem Chem Phys ; 22(15): 7853-7863, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32227028

RESUMO

Monolayer (ML) MoS2 is one of the most extensively studied two-dimensional (2D) semiconductors. However, it suffers from low carrier mobility and pervasive Schottky contact with metal electrodes. 2D semiconductor Bi2O2S, a sulfur analogue of 2D Bi2O2Se, has been prepared recently. ML fully hydrogen-passivated Bi2O2S2 (Bi2O2S2H2) posseses a comparable band gap (1.92 eV) with ML MoS2 (1.8 eV), but probably has a better device performance than ML MoS2. Based on the density functional theory, the electron and hole mobilities of ML Bi2O2S2H2 at 300 K are calculated to be 16 447-26 699 and 264-968 cm2 V-1 s-1, respectively. Then we firstly characterize the contact properties of ML half hydrogen-passivated Bi2O2S2 (Bi2O2S2H) with four bulk metal electrodes (Ti, Sc, Pd, and Pt) based on ab initio quantum transport simulation. In the lateral direction, a p-type Schottky contact is found in Pd and Pt electrodes, and the corresponding hole Schottky barrier heights (SBHs) are 0.54 and 0.99 eV, respectively. Remarkably, a coveted n-type Ohmic contact appears in Sc and Ti electrodes. Finally, the current on-off ratio of the ML hydrogen-passivated Bi2O2S2 field effect transistor with a Ti electrode reaches 105. Hence, the good intrinsic properties, contact properties, and large switching ability put ML hydrogen-passivated Bi2O2S2 in the rank of potential channel candidates for post-silicon era field effect transistors.

18.
BMC Med Inform Decis Mak ; 19(Suppl 6): 266, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856801

RESUMO

BACKGROUND: Globally, the cases of diabetes mellitus (diabetes) have increased in the past three decades, and it is recorded as one of the leading cause of death. This epidemic is a metabolic condition where the body cannot regulate blood glucose, thereby leading to abnormally high blood sugar. Genetic condition plays a significant role to determine a person susceptibility to the condition, a sedentary lifestyle and an unhealthy diet are behaviour that supports the current global epidemic. The complication that arises from diabetes includes loss of vision, peripheral neuropathy, cardiovascular complications and so on. Victims of this condition require constant monitoring of blood glucose which is done by the pricking of the finger. This procedure is painful, inconvenient and can lead to disease infection. Therefore, it is important to find a way to measure blood glucose non-invasively to minimize or eliminate the disadvantages encountered with the usual monitoring of blood glucose. METHOD: In this paper, we performed two experiments on 16 participants while electrocardiogram (ECG) data was continuously captured. In the first experiment, participants are required to consume 75 g of anhydrous glucose solution (oral glucose tolerance test) and the second experiment, no glucose solution was taken. We explored statistical and spectral analysis on HRV, HR, R-H, P-H, PRQ, QRS, QT, QTC and ST segments derived from ECG signal to investigate which segments should be considered for the possibility of achieving non-invasive blood glucose monitoring. In the statistical analysis, we examined the pattern of the data with the boxplot technique to reveal the change in the statistical properties of the data. Power spectral density estimation was adopted for the spectral analysis to show the frequency distribution of the data. RESULTS: HRV segment obtained a statistical score of 81% for decreasing pattern and HR segment have the same statistical score for increasing pattern among the participants in the first quartile, median and mean properties. While ST segment has a statistical score of 81% for decreasing pattern in the third quartile, QT segment has 81% for increasing pattern for the median. From a total change score of 6, ST, QT, PRQ, P-H, HR and HRV obtained 4, 5, 4, 5 and 6 respectively. For spectral analysis, HRV and HR segment scored 81 and 75% respectively. ST, QT, PRQ have 75, 62 and 68% respectively. CONCLUSIONS: The results obtained demonstrate that HR, HRV, PRQ, QT and ST segments under a normal, healthy condition are affected by glucose and should be considered for modelling a system to achieve the possibility of non-invasive blood glucose measurement with ECG.


Assuntos
Automonitorização da Glicemia/estatística & dados numéricos , Glicemia/metabolismo , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Eletrocardiografia/estatística & dados numéricos , Adulto , Automonitorização da Glicemia/instrumentação , Interpretação Estatística de Dados , Diagnóstico por Computador/instrumentação , Diagnóstico por Computador/métodos , Eletrocardiografia/instrumentação , Eletrodos , Desenho de Equipamento , Feminino , Teste de Tolerância a Glucose/instrumentação , Teste de Tolerância a Glucose/métodos , Frequência Cardíaca/fisiologia , Humanos , Masculino
19.
Hum Genet ; 137(10): 779-794, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30242501

RESUMO

Most cases of Usher syndrome type II (USH2) are due to mutations in the USH2A gene. There are no effective treatments or ideal animal models for this disease, and the pathological mechanisms of USH2 caused by USH2A mutations are still unknown. Here, we constructed a ush2a knockout (ush2a-/-) zebrafish model using TALEN technology to investigate the molecular pathology of USH2. An early onset auditory disorder and abnormal morphology of inner ear stereocilia were identified in the ush2a-/- zebrafish. Consequently, the disruption of Ush2a in zebrafish led to a hearing impairment, like that in mammals. Electroretinography (ERG) test indicated that deletion of Ush2a affected visual function at an early stage, and histological analysis revealed that the photoreceptors progressively degenerated. Rod degeneration occurred prior to cone degeneration in ush2a-/- zebrafish, which is consistent with the classical description of the progression of retinitis pigmentosa (RP). Destruction of the outer segments (OSs) of rods led to the down-regulation of phototransduction cascade proteins at late stage. The expression of Ush1b and Ush1c was up-regulated when Ush2a was null. We also found that disruption of fibronectin assembly at the retinal basement membrane weakened cell adhesion in ush2a-/- mutants. In summary, for the first time, we generated a ush2a knockout zebrafish line with auditory disorder and retinal degeneration which mimicked the symptoms of patients, and revealed that disruption of fibronectin assembly may be one of the factors underlying RP. This model may help us to better understand the pathogenic mechanism and find treatment for USH2 in the future.


Assuntos
Proteínas da Matriz Extracelular , Técnicas de Inativação de Genes , Síndromes de Usher , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Modelos Animais de Doenças , Eletrorretinografia , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Humanos , Síndromes de Usher/genética , Síndromes de Usher/metabolismo , Síndromes de Usher/patologia , Síndromes de Usher/fisiopatologia , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
20.
Opt Lett ; 43(2): 295, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29328263

RESUMO

This publisher's note corrects an error in one of the authors' names and an error in one of the grant numbers in Opt. Lett.42, 4263 (2017).

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