Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
1.
Proc Natl Acad Sci U S A ; 121(10): e2309656121, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38408254

RESUMO

Inner ear hair cells are characterized by the F-actin-based stereocilia that are arranged into a staircase-like pattern on the apical surface of each hair cell. The tips of shorter-row stereocilia are connected with the shafts of their neighboring taller-row stereocilia through extracellular links named tip links, which gate mechano-electrical transduction (MET) channels in hair cells. Cadherin 23 (CDH23) forms the upper part of tip links, and its cytoplasmic tail is inserted into the so-called upper tip-link density (UTLD) that contains other proteins such as harmonin. The Cdh23 gene is composed of 69 exons, and we show here that exon 68 is subjected to hair cell-specific alternative splicing. Tip-link formation is not affected in genetically modified mutant mice lacking Cdh23 exon 68. Instead, the stability of tip links is compromised in the mutants, which also suffer from progressive and noise-induced hearing loss. Moreover, we show that the cytoplasmic tail of CDH23(+68) but not CDH23(-68) cooperates with harmonin in phase separation-mediated condensate formation. In conclusion, our work provides evidence that inclusion of Cdh23 exon 68 is critical for the stability of tip links through regulating condensate formation of UTLD components.


Assuntos
Surdez , Perda Auditiva , Camundongos , Animais , Perda Auditiva/genética , Perda Auditiva/metabolismo , Células Ciliadas Auditivas/fisiologia , Surdez/genética , Células Ciliadas Auditivas Internas/metabolismo , Caderinas/metabolismo , Éxons/genética
2.
Hum Mol Genet ; 32(10): 1622-1633, 2023 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-36617157

RESUMO

As the auditory and balance receptor cells in the inner ear, hair cells are responsible for converting mechanical stimuli into electrical signals, a process referred to as mechano-electrical transduction. Hair cell development and function are tightly regulated, and hair cell deficits are the main reasons for hearing loss and balance disorders. TMCC2 is an endoplasmic reticulum (ER)-residing transmembrane protein whose physiological function largely remains unknown. In the present work, we show that Tmcc2 is specifically expressed in the auditory hair cells of mouse inner ear. Tmcc2 knockout mice were then established to investigate its physiological role in hearing. Auditory brainstem responses measurements show that Tmcc2 knockout mice suffer from congenital hearing loss. Further investigations reveal progressive auditory hair cell loss in the Tmcc2 knockout mice. The general morphology and function of ER are unaffected in Tmcc2 knockout hair cells. However, increased ER stress was observed in Tmcc2 knockout mice and knockdown cells, suggesting that loss of TMCC2 leads to auditory hair cell death through elevated ER stress.


Assuntos
Surdez , Perda Auditiva , Animais , Camundongos , Surdez/metabolismo , Estresse do Retículo Endoplasmático/genética , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas Internas , Audição , Perda Auditiva/metabolismo , Camundongos Knockout
3.
J Neurosci ; 43(18): 3219-3231, 2023 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-37001993

RESUMO

The mechanoelectrical transduction (MET) protein complex in the inner-ear hair cells is essential for hearing and balance perception. Calcium and integrin-binding protein 2 (CIB2) has been reported to be a component of MET complex, and loss of CIB2 completely abolishes MET currents in auditory hair cells, causing profound congenital hearing loss. However, loss of CIB2 does not affect MET currents in vestibular hair cells (VHCs) as well as general balance function. Here, we show that CIB2 and CIB3 act redundantly to regulate MET in VHCs, as MET currents are completely abolished in the VHCs of Cib2/Cib3 double knock-out mice of either sex. Furthermore, we show that Cib2 and Cib3 transcripts have complementary expression patterns in the vestibular maculae, and that they play different roles in stereocilia maintenance in VHCs. Cib2 transcripts are highly expressed in the striolar region, and knock-out of Cib2 affects stereocilia maintenance in striolar VHCs. In contrast, Cib3 transcripts are highly expressed in the extrastriolar region, and knock-out of Cib3 mainly affects stereocilia maintenance in extrastriolar VHCs. Simultaneous knock-out of Cib2 and Cib3 affects stereocilia maintenance in all VHCs and leads to severe balance deficits. Taken together, our present work reveals that CIB2 and CIB3 are important for stereocilia maintenance as well as MET in mouse VHCs.SIGNIFICANCE STATEMENT Calcium and integrin-binding protein 2 (CIB2) is an important component of mechanoelectrical transduction (MET) complex, and loss of CIB2 completely abolishes MET in auditory hair cells. However, MET is unaffected in Cib2 knock-out vestibular hair cells (VHCs). In the present work, we show that CIB3 could compensate for the loss of CIB2 in VHCs, and Cib2/Cib3 double knock-out completely abolishes MET in VHCs. Interestingly, CIB2 and CIB3 could also regulate VHC stereocilia maintenance in a nonredundant way. Cib2 and Cib3 transcripts are highly expressed in the striolar and extrastriolar regions, respectively. Stereocilia maintenance and balance function are differently affected in Cib2 or Cib3 knock-out mice. In conclusion, our data suggest that CIB2 and CIB3 are important for stereocilia maintenance and MET in mouse VHCs.


Assuntos
Células Ciliadas Vestibulares , Animais , Camundongos , Cálcio/metabolismo , Células Ciliadas Vestibulares/metabolismo , Integrinas , Camundongos Knockout , Estereocílios/metabolismo
4.
J Cell Sci ; 135(16)2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35892293

RESUMO

Stereocilia are F-actin-based protrusions on the apical surface of inner-ear hair cells and are indispensable for hearing and balance perception. The stereocilia of each hair cell are organized into rows of increasing heights, forming a staircase-like pattern. The development and maintenance of stereocilia are tightly regulated, and deficits in these processes lead to stereocilia disorganization and hearing loss. Previously, we showed that the F-BAR protein FCHSD2 is localized along the stereocilia of cochlear hair cells and cooperates with CDC42 to regulate F-actin polymerization and cell protrusion formation in cultured COS-7 cells. In the present work, Fchsd2 knockout mice were established to investigate the role of FCHSD2 in hearing. Our data show that stereocilia maintenance is severely affected in cochlear hair cells of Fchsd2 knockout mice, which leads to progressive hearing loss. Moreover, Fchsd2 knockout mice show increased acoustic vulnerability. Noise exposure causes robust stereocilia degeneration as well as enhanced hearing threshold elevation in Fchsd2 knockout mice. Lastly, Fchsd2/Cdc42 double knockout mice show more severe stereocilia deficits and hearing loss, suggesting that FCHSD2 and CDC42 cooperatively regulate stereocilia maintenance.


Assuntos
Proteínas de Transporte , Perda Auditiva , Proteínas de Membrana , Estereocílios , Animais , Camundongos , Actinas/metabolismo , Proteínas de Transporte/metabolismo , Células Ciliadas Auditivas/metabolismo , Perda Auditiva/metabolismo , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estereocílios/metabolismo
5.
Sensors (Basel) ; 24(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38203131

RESUMO

In order to achieve the automatic planning of power transmission lines, a key step is to precisely recognize the feature information of remote sensing images. Considering that the feature information has different depths and the feature distribution is not uniform, a semantic segmentation method based on a new AS-Unet++ is proposed in this paper. First, the atrous spatial pyramid pooling (ASPP) and the squeeze-and-excitation (SE) module are added to traditional Unet, such that the sensing field can be expanded and the important features can be enhanced, which is called AS-Unet. Second, an AS-Unet++ structure is built by using different layers of AS-Unet, such that the feature extraction parts of each layer of AS-Unet are stacked together. Compared with Unet, the proposed AS-Unet++ automatically learns features at different depths and determines a depth with optimal performance. Once the optimal number of network layers is determined, the excess layers can be pruned, which will greatly reduce the number of trained parameters. The experimental results show that the overall recognition accuracy of AS-Unet++ is significantly improved compared to Unet.

6.
J Cell Physiol ; 238(5): 1095-1110, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36947695

RESUMO

As the sensory receptor cells in vertebrate inner ear and lateral lines, hair cells are characterized by the hair bundle that consists of one tubulin-based kinocilium and dozens of actin-based stereocilia on the apical surface of each hair cell. Hair cell development is tightly regulated, and deficits in this process usually lead to hearing loss and/or balance dysfunctions. RNA-binding motif protein 24 (RBM24) is an RNA-binding protein that is specifically expressed in the hair cells in the inner ear. Previously, we showed that RBM24 affects hair cell development in zebrafish by regulating messenger RNA (mRNA) stability. In the present work, we further investigate the role of RBM24 in hearing and balance using conditional knockout mice. Our results show that Rbm24 knockout results in severe hearing and balance deficits. Hair cell development is significantly affected in Rbm24 knockout cochlea, as the hair bundles are poorly developed and eventually degenerated. Hair bundle disorganization is also observed in Rbm24 knockout vestibular hair cells, although to a lesser extent. Consistently, significant hair cell loss is observed in the cochlea but not vestibule. RNAseq analysis identified several genes whose mRNA stability or pre-mRNA alternative splicing is affected by Rbm24 knockout. Among them are Cdh23, Pcdh15, and Myo7a, which have been shown to play important roles in stereocilia development as well as mechano-electrical transduction. Taken together, our present work suggests that RBM24 is required for mouse hair cell development through regulating pre-mRNA alternative splicing as well as mRNA stability.


Assuntos
Processamento Alternativo , Células Ciliadas Auditivas , Precursores de RNA , Animais , Camundongos , Processamento Alternativo/genética , Caderinas/genética , Camundongos Knockout , Precursores de RNA/genética , Precursores de RNA/metabolismo , Estabilidade de RNA/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Peixe-Zebra , Células Ciliadas Auditivas/fisiologia
7.
Theor Appl Genet ; 136(12): 246, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37973669

RESUMO

KEY MESSAGE: qSB12YSB, a major quantitative sheath blight resistance gene originated from rice variety YSBR1 with good breeding potential, was mapped to a 289-Kb region on chromosome 12. Sheath blight (ShB), caused by Rhizoctonia solani kühn, is one of the most serious global rice diseases. Rice resistance to ShB is a typical of quantitative trait controlled by multiple quantitative trait loci (QTLs). Many QTLs for ShB resistance have been reported while only few of them were fine-mapped. In this study, we identified a QTL on chromosome 12, in which the qSB12YSB resistant allele shows significant ShB resistance, by using 150 BC4 backcross inbred lines employing the resistant rice variety YSBR1 as the donor and the susceptible variety Lemont (LE) as the recurrent parent. We further fine-mapped qSB12YSB to a 289-kb region by generating 34 chromosomal segment substitution lines and identified a total of 18 annotated genes as the most likely candidates for qSB12YSB after analyzing resequencing and transcriptomic data. KEGG analysis suggested that qSB12YSB might activate secondary metabolites biosynthesis and ROS scavenging system to improve ShB resistance. qSB12YSB conferred significantly stable resistance in three commercial rice cultivars (NJ9108, NJ5055 and NJ44) in field trials when introduced through marker assisted selection. Under severe ShB disease conditions, qSB12YSB significantly reduced yield losses by up to 13.5% in the LE background, indicating its great breeding potential. Our results will accelerate the isolation of qSB12YSB and its utilization in rice breeding programs against ShB.


Assuntos
Oryza , Oryza/genética , Melhoramento Vegetal , Locos de Características Quantitativas , Fenótipo , Estudos de Associação Genética
8.
Biochem J ; 479(12): 1393-1405, 2022 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-35695292

RESUMO

In cochlea, deafness-related protein PDZD7 is an indispensable component of the ankle link complex, which is critical for the maturation of inner-ear hair cell for sound perception. Ankle links, connecting the different rows of cochlear stereocilia, are essential for the staircase-like development of stereocilia. However, the molecular mechanism of how PDZD7 governs stereociliary development remains unknown. Here, we reported a novel PDZD7-binding partner, FCHSD2, identified by yeast two-hybrid screening. FCHSD2 was reported to be expressed in hair cell, where it co-operated with CDC42 and N-WASP to regulate the formation of cell protrusion. The association between FCHSD2 and PDZD7 was further confirmed in COS-7 cells. More importantly, we solved the complex structure of FCHSD2 tail with PDZD7 PDZ3 domain at 2.0 Šresolution. The crystal structure shows that PDZD7 PDZ3 adopts a typical PDZ domain topology, comprising five ß strands and two α helixes. The PDZ-binding motif of FCHSD2 tail stretches through the αB/ßB groove of PDZD7 PDZ3. Our study not only uncovers the interaction between FCHSD2 tail and PDZD7 PDZ3 at the atomic level, but also provides clues of connecting the ankle link complex with cytoskeleton dynamics for exploiting the molecular mechanism of stereociliary development.


Assuntos
Proteínas de Transporte , Surdez , Proteínas de Transporte/metabolismo , Surdez/genética , Células Ciliadas Auditivas/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Domínios PDZ , Estereocílios/química , Estereocílios/metabolismo
9.
Sensors (Basel) ; 23(13)2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37448061

RESUMO

An improved Dijkstra algorithm based on adaptive resolution grid (ARG) is proposed to assist manual transmission line planning, shorten the construction period and achieve lower cost and higher efficiency of line selection. Firstly, the semantic segmentation network is used to change the remote sensing image into a ground object-identification image and the grayscale image of the ground object-identification image is rasterized. The ARG map model is introduced to greatly reduce the number of redundant grids, which can effectively reduce the time required to traverse the grids. Then, the Dijkstra algorithm is combined with the ARG and the neighborhood structure of the grid is a multi-center neighborhood. An improved method of bidirectional search mechanism based on ARG and inflection point-correction is adopted to greatly increase the running speed. The inflection point-correction reduces the number of inflection points and reduces the cost. Finally, according to the results of the search, the lowest-cost transmission line is determined. The experimental results show that this method aids manual planning by providing a route for reference, improving planning efficiency while shortening the duration, and reducing the time spent on algorithm debugging. Compared with the comparison algorithm, this method is faster in running speed and better in cost saving and has a broader application prospect.


Assuntos
Algoritmos , Espalhamento de Radiação
10.
Sensors (Basel) ; 23(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36617045

RESUMO

The merging of environmental maps constructed by individual UAVs alone and the sharing of information are key to improving the efficiency of distributed multi-UAVexploration. This paper investigates the raster map-merging problem in the absence of a common reference coordinate system and the relative position information of UAVs, and proposes a raster map-merging method with a directed crossover multidimensional perturbation variational genetic algorithm (DCPGA). The algorithm uses an optimization function reflecting the degree of dissimilarity between the overlapping regions of two raster maps as the fitness function, with each possible rotation translation transformation corresponding to a chromosome, and the binary encoding of the coordinates as the gene string. The experimental results show that the algorithm could converge quickly and had a strong global search capability to search for the optimal overlap area of the two raster maps, thus achieving map merging.


Assuntos
Algoritmos
11.
Int J Mol Sci ; 24(5)2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36902415

RESUMO

Rice is one of the staple foods for the majority of the global population that depends directly or indirectly on it. The yield of this important crop is constantly challenged by various biotic stresses. Rice blast, caused by Magnaporthe oryzae (M. oryzae), is a devastating rice disease causing severe yield losses annually and threatening rice production globally. The development of a resistant variety is one of the most effective and economical approaches to control rice blast. Researchers in the past few decades have witnessed the characterization of several qualitative resistance (R) and quantitative resistance (qR) genes to blast disease as well as several avirulence (Avr) genes from the pathogen. These provide great help for either breeders to develop a resistant variety or pathologists to monitor the dynamics of pathogenic isolates, and ultimately to control the disease. Here, we summarize the current status of the isolation of R, qR and Avr genes in the rice-M. oryzae interaction system, and review the progresses and problems of these genes utilized in practice for reducing rice blast disease. Research perspectives towards better managing blast disease by developing a broad-spectrum and durable blast resistance variety and new fungicides are also discussed.


Assuntos
Magnaporthe , Oryza , Resistência à Doença/genética , Virulência/genética , Magnaporthe/genética , Oryza/genética , Doenças das Plantas/genética
12.
Int J Mol Sci ; 24(4)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36835399

RESUMO

Rice blast, caused by the Magnaporthe oryzae fungus, is one of the most devastating rice diseases worldwide. Developing resistant varieties by pyramiding different blast resistance (R) genes is an effective approach to control the disease. However, due to complex interactions among R genes and crop genetic backgrounds, different R-gene combinations may have varying effects on resistance. Here, we report the identification of two core R-gene combinations that will benefit the improvement of Geng (Japonica) rice blast resistance. We first evaluated 68 Geng rice cultivars at seedling stage by challenging with 58 M. oryzae isolates. To evaluate panicle blast resistance, we inoculated 190 Geng rice cultivars at boosting stage with five groups of mixed conidial suspensions (MCSs), with each containing 5-6 isolates. More than 60% cultivars displayed moderate or lower levels of susceptibility to panicle blast against the five MCSs. Most cultivars contained two to six R genes detected by the functional markers corresponding to 18 known R genes. Through multinomial logistics regression analysis, we found that Pi-zt, Pita, Pi3/5/I, and Pikh loci contributed significantly to seedling blast resistance, and Pita, Pi3/5/i, Pia, and Pit contributed significantly to panicle blast resistance. For gene combinations, Pita+Pi3/5/i and Pita+Pia yielded more stable pyramiding effects on panicle blast resistance against all five MCSs and were designated as core R-gene combinations. Up to 51.6% Geng cultivars in the Jiangsu area contained Pita, but less than 30% harbored either Pia or Pi3/5/i, leading to less cultivars containing Pita+Pia (15.8%) or Pita+Pi3/5/i (5.8%). Only a few varieties simultaneously contained Pia and Pi3/5/i, implying the opportunity to use hybrid breeding procedures to efficiently generate varieties with either Pita+Pia or Pita+Pi3/5/i. This study provides valuable information for breeders to develop Geng rice cultivars with high resistance to blast, especially panicle blast.


Assuntos
Magnaporthe , Oryza , Magnaporthe/genética , Genes vpr , Oryza/genética , Doenças das Plantas/microbiologia , Melhoramento Vegetal , Resistência à Doença/genética
13.
Environ Monit Assess ; 195(3): 401, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36790550

RESUMO

As the Earth's population continuously increase with the passage of time, the demand for agricultural raw material for human need increases. It is critical to maintaining updated and accurate information about the dynamics and properties of the world agricultural systems. As cash crop, the updated information of the spatial distribution of cotton field is necessary to monitor the crop area and growth changes at regional level. We used 8-day enhanced vegetation index (EVI) time series to detect cotton crop area and binomial probabilistic approach to obtain the probability distribution of cotton crop occurrence. We used Gaussian kriging to derive cotton yield inside the detected cotton crop areas through crop reporting data. We also used field data from farmers to validate the cotton yield results. A strong correlation between the MODIS-derived cotton cultivated area and statistical data at the tehsil level were achieved (R2 = 0.84) for all study years (2004-2019). The total accuracy for the cotton crop area detection was 84.6% and yield prediction was 92.1%. Our study presents new approaches to map cotton area and yield, which are applicable to other regions through machine learning.


Assuntos
Tecnologia de Sensoriamento Remoto , Rios , Humanos , Paquistão , Monitoramento Ambiental/métodos , Agricultura/métodos
14.
J Cell Physiol ; 237(1): 774-788, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34346063

RESUMO

Stereocilia are actin-based cell protrusions of inner ear hair cells that play an essential role in mechano-electrical transduction (MET). Stereocilia are organized into several rows of increasing heights with the MET protein complex localized at the tips of shorter row stereocilia. At the tips of shorter row mechanotransducing stereocilia also resides a so-called "row 2 protein complex" whose dysfunction causes degeneration of the mechanotransducing stereocilia. In the present work, we show that BAIAP2L2 is localized at the tips of shorter row stereocilia in neonatal and adult mouse cochlear hair cells. Baiap2l2 inactivation causes degeneration of the mechanotransducing stereocilia, which eventually leads to profound hearing loss in mice of either sex. Consistently, electrophysiology and FM 1-43FX dye uptake results confirm that MET currents are compromised in Baiap2l2 knockout mice. Moreover, BAIAP2L2 binds to known row 2 complex components EPS8L2, TWF2, and CAPZB2, and the stereociliary tip localization of CAPZB2 is dependent on functional BAIAP2L2. Interestingly, BAIAP2L2 also binds to CIB2, a known MET complex component, and the stereociliary tip localization of BAIAP2L2 is abolished in Cib2 knockout mice. In conclusion, our present data suggest that BAIAP2L2 is a row 2 complex component, and is required for the maintenance of mechanotransducing stereocilia. Meanwhile, specific MET components such as CIB2 might play a direct role in stereocilia maintenance through binding to BAIAP2L2.


Assuntos
Células Ciliadas Auditivas , Proteínas de Membrana/metabolismo , Estereocílios , Actinas/metabolismo , Animais , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas Internas , Camundongos , Camundongos Knockout , Estereocílios/metabolismo
15.
Sensors (Basel) ; 22(19)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36236386

RESUMO

With the development of robot technology and the extensive application of robots, the research on special robots for some complex working environments has gradually become a hot topic. As a special robot applied to transmission towers, the climbing robot can replace humans to work at high altitudes to complete bolt tightening, detection, and other tasks, which improves the efficiency of transmission tower maintenance and ensures personal safety. However, it is mostly the ability to autonomously locate in the complex environment of the transmission tower that limits the industrial applications of the transmission tower climbing robot. This paper proposes an intelligent positioning method that integrates the three-dimensional information model of transmission tower and visual sensor data, which can assist the robot in climbing and adjusting to the designated working area to guarantee the working accuracy of the climbing robots. The experimental results show that the positioning accuracy of the method is within 1 cm.


Assuntos
Robótica , Humanos
16.
Int Heart J ; 63(3): 578-590, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35650158

RESUMO

Myocardial ischemia-reperfusion (I/R) injury is a serious complication of acute myocardial infarction. Long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) can regulate I/R-induced cardiomyocyte apoptosis. Here, we investigated the mechanism of SNHG15 activity in I/R-induced cardiomyocyte injury.SNHG15, microRNA (miR)-335-3p, and toll-like receptor 4 (TLR4) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell viability, proliferation, and apoptosis were gauged by Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2´-deoxyuridine (EDU) assay, and flow cytometry, respectively. The direct relationship between miR-335-3p and SNHG15 or TLR4 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays.SNHG15 was overexpressed in the infarcted area tissues of I/R mice and I/R-stimulated AC16 cells. SNHG15 knockdown alleviated I/R injury in AC16 cells. Mechanistically, SNHG15 directly targeted miR-335-3p, and miR-335-3p was a functional mediator of SNHG15. MiR-335-3p inhibited TLR4 expression by targeting TLR4, and miR-335-3p-mediated inhibition of TLR4 alleviated I/R-induced injury in AC16 cells. Moreover, SNHG15 regulated the TLR4/nuclear factor-κB (NF-κB) signaling pathway through miR-335-3p.Our findings identify a novel mechanism, the miR-335-3p/TLR4/NF-κB pathway, for the regulation of SNHG15 in myocardial I/R injury.


Assuntos
MicroRNAs , Traumatismo por Reperfusão Miocárdica , RNA Longo não Codificante , Animais , Humanos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
17.
FASEB J ; 34(1): 1136-1149, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914662

RESUMO

Usher syndrome (USH) is the most frequent form of combined hereditary deafness-blindness, characterized by hearing loss and retinitis pigmentosa, with or without vestibular dysfunction. PDZD7 is a PDZ domain-containing scaffold protein that was suggested to be a USH modifier and a contributor to digenic USH. In the inner ear hair cells, PDZD7 localizes at the ankle region of the stereocilia and constitutes the so-called ankle-link complex together with three other USH proteins Usherin, WHRN, and ADGRV1. PDZD7 gene is subjected to alternative splicing, which gives rise to two types of PDZD7 isoforms, namely the long and short isoforms. At present, little is known which specific isoform is involved in ankle-link formation and stereocilia development. In this work, we showed that PDZD7 long isoform, but not short isoforms, localizes at the ankle region of the stereocilia. Moreover, we established Pdzd7 mutant mice by introducing deletions into exon 14 of the Pdzd7 gene, which causes potential premature translational stop in the long isoform but leaves short isoforms unaffected. We found that lack of PDZD7 long isoform affects the localization of other ankle-link complex components in the stereocilia. Consequently, Pdzd7 mutant mice showed stereocilia development deficits and hearing loss as well as reduced mechanotransduction (MET) currents, suggesting that PDZD7 long isoform is indispensable for hair cells. Furthermore, by performing yeast two-hybrid screening, we identified a PDZD7 long isoform-specific binding partner PIP5K1C, which has been shown to play important roles in hearing and might participate in the function and/or transportation of PDZD7.


Assuntos
Proteínas de Transporte/química , Proteínas de Transporte/genética , Perda Auditiva/genética , Síndromes de Usher/genética , Processamento Alternativo , Animais , Cóclea/metabolismo , Modelos Animais de Doenças , Éxons , Feminino , Deleção de Genes , Células HEK293 , Células Ciliadas Auditivas , Humanos , Masculino , Mecanotransdução Celular , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura , Mutação , Isoformas de Proteínas , Estereocílios/química
18.
Oecologia ; 195(1): 131-144, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33491109

RESUMO

The trade-offs between sexual reproduction and clonal propagation are of great significance in terms of ecology and evolution for clonal plants, and they vary with environmental change. Nitrogen (N) deposition can increase litter accumulation in grassland and promote litter decomposition and consequently increase nutrient availability. However, the response of plant reproduction to N and litter addition in grasslands remains unclear. We examined the combined effects of N addition and litter manipulation (i.e. initial litter, removal, addition) on sexual reproduction and clonal propagation of a perennial clonal grass, Leymus chinensis, at the population (total number) and individual (number per ramet) levels in an 11-year field experiment. Nitrogen addition and litter additionally decreased spike and seed number at the population level, and N addition reduced those at the individual level. Nitrogen addition and litter interactively affected bud number at the two levels, and N addition decreased bud number in the litter removal treatments and increased that in the litter addition treatments. The increased soil available N, rather than light and soil water content, explained the change in sexual reproduction and clonal propagation. The positive effects of litter addition on bud number in the treatments with N addition, suggested that the N deposition increased litter accumulation could intensify clonal propagation of perennial grasses and increase their dominance in grasslands. Grassland management that reduces litter accumulation, such as grazing and mowing, can therefore, help alleviate the negative effects of N deposition on plant diversity through decreasing clonal propagation of the dominant species.


Assuntos
Pradaria , Nitrogênio , Poaceae , Reprodução , Solo
19.
Neural Plast ; 2020: 8898811, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774357

RESUMO

Alternative splicing plays a pivotal role in modulating the function of eukaryotic proteins. In the inner ear, many genes undergo alternative splicing, and errors in this process lead to hearing loss. Cadherin 23 (CDH23) forms part of the so-called tip links, which are indispensable for mechanoelectrical transduction (MET) in the hair cells. Cdh23 gene contains 69 exons, and exon 68 is subjected to alternative splicing. Exon 68 of the Cdh23 gene is spliced into its mRNA only in a few cell types including hair cells. The mechanism responsible for the alternative splicing of Cdh23 exon 68 remains elusive. In the present work, we performed a cell-based screening to look for splicing factors that regulate the splicing of Cdh23 exon 68. RBM24 and RBM38 were identified to enhance the inclusion of Cdh23 exon 68. The splicing of Cdh23 exon 68 is affected in Rbm24 knockdown or knockout cells. Moreover, we also found that PTBP1 inhibits the inclusion of Cdh23 exon 68. Taken together, we show here that alternative splicing of Cdh23 exon 68 is regulated by RBM24, RBM38, and PTBP1.


Assuntos
Processamento Alternativo , Caderinas/genética , Orelha Interna/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Proteínas de Ligação a RNA/genética , Animais , Linhagem Celular , Chlorocebus aethiops , Éxons , Camundongos
20.
Glob Chang Biol ; 24(3): 1256-1266, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29080270

RESUMO

Treeline responses to environmental changes describe an important phenomenon in global change research. Often conflicting results and generally too short observations are, however, still challenging our understanding of climate-induced treeline dynamics. Here, we use a state-of-the-art dendroecological approach to reconstruct long-term changes in the position of the alpine treeline in relation to air temperature at two sides in the Changbai Mountains in northeast China. Over the past 160 years, the treeline increased by around 80 m, a process that can be divided into three phases of different rates and drives. The first phase was mainly influenced by vegetation recovery after an eruption of the Tianchi volcano in 1702. The slowly upward shift in the second phase was consistent with the slowly increasing temperature. The last phase coincided with rapid warming since 1985, and shows with 33 m per 1°C, the most intense upward shift. The spatial distribution and age structure of trees beyond the current treeline confirm the latest, warming-induced upward shift. Our results suggest that the alpine treeline will continue to rise, and that the alpine tundra may disappear if temperatures will increase further. This study not only enhances mechanistic understanding of long-term treeline dynamics, but also highlights the effects of rising temperatures on high-elevation vegetation dynamics.


Assuntos
Mudança Climática , Árvores , Tundra , Altitude , China , Ecossistema , Temperatura
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa