72 results on '"Jiefu Zheng"'
Search Results
2. Structural and mechanistic insights into the MCM8/9 helicase complex
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Zhuangfeng Weng, Jiefu Zheng, Yiyi Zhou, Zuer Lu, Yixi Wu, Dongyi Xu, Huanhuan Li, Huanhuan Liang, and Yingfang Liu
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MCM8/9 ,helicase ,homologous recombination ,HROB ,cryo-electron microscopy ,DNA unwinding ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
MCM8 and MCM9 form a functional helicase complex (MCM8/9) that plays an essential role in DNA homologous recombination repair for DNA double-strand break. However, the structural characterization of MCM8/9 for DNA binding/unwinding remains unclear. Here, we report structures of the MCM8/9 complex using cryo-electron microscopy single particle analysis. The structures reveal that MCM8/9 is arranged into a heterohexamer through a threefold symmetry axis, creating a central channel that accommodates DNA. Multiple characteristic hairpins from the N-terminal oligosaccharide/oligonucleotide (OB) domains of MCM8/9 protrude into the central channel and serve to unwind the duplex DNA. When activated by HROB, the structure of MCM8/9’s N-tier ring converts its symmetry from C3 to C1 with a conformational change that expands the MCM8/9’s trimer interface. Moreover, our structural dynamic analyses revealed that the flexible C-tier ring exhibited rotary motions relative to the N-tier ring, which is required for the unwinding ability of MCM8/9. In summary, our structural and biochemistry study provides a basis for understanding the DNA unwinding mechanism of MCM8/9 helicase in homologous recombination.
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- 2023
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3. Encounter complexes and dimensionality reduction in protein–protein association
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Dima Kozakov, Keyong Li, David R Hall, Dmitri Beglov, Jiefu Zheng, Pirooz Vakili, Ora Schueler-Furman, Ioannis Ch Paschalidis, G Marius Clore, and Sandor Vajda
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encounter landscapes ,FFT sampling ,protein-protein interaction ,Medicine ,Science ,Biology (General) ,QH301-705.5 - Abstract
An outstanding challenge has been to understand the mechanism whereby proteins associate. We report here the results of exhaustively sampling the conformational space in protein–protein association using a physics-based energy function. The agreement between experimental intermolecular paramagnetic relaxation enhancement (PRE) data and the PRE profiles calculated from the docked structures shows that the method captures both specific and non-specific encounter complexes. To explore the energy landscape in the vicinity of the native structure, the nonlinear manifold describing the relative orientation of two solid bodies is projected onto a Euclidean space in which the shape of low energy regions is studied by principal component analysis. Results show that the energy surface is canyon-like, with a smooth funnel within a two dimensional subspace capturing over 75% of the total motion. Thus, proteins tend to associate along preferred pathways, similar to sliding of a protein along DNA in the process of protein-DNA recognition.
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- 2014
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4. Cyborg Botany: Augmented Plants as Sensors, Displays and Actuators.
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Harpreet Sareen, Jiefu Zheng, and Pattie Maes
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- 2019
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5. Decomposition techniques for Markov zero-sum games with nested information.
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Jiefu Zheng and David A. Castañón
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- 2013
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6. Stochastic dynamic network interdiction games.
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Jiefu Zheng and David A. Castañón
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- 2012
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7. Dynamic network interdiction games with imperfect information and deception.
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Jiefu Zheng and David A. Castañón
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- 2012
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8. 99mTc-Leukocyte Scintigraphy Revealed Viral Pulmonary Infection in a COVID-19 Patient
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Yiyan Liu and Jiefu Zheng
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Thorax ,Adult ,Pathology ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,chemistry.chemical_element ,Pulmonary infection ,Scintigraphy ,Technetium ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Superior vena cava ,medicine ,99mTc-leukocyte scintigraphy ,pneumonia ,Humans ,Radiology, Nuclear Medicine and imaging ,Radionuclide Imaging ,Lung ,Pandemics ,medicine.diagnostic_test ,business.industry ,COVID-19 ,General Medicine ,medicine.disease ,Interesting Images ,SARS-CoV-2 RNA ,Pneumonia ,chemistry ,Radiology Nuclear Medicine and imaging ,030220 oncology & carcinogenesis ,Female ,Radiopharmaceuticals ,business ,Coronavirus Infections - Abstract
99mTc-leukocyte scintigraphy was performed on a 40-year-old woman with spiking fevers. A focus of intense uptake in the right upper thorax was identified, concerning for infection along the central line in the superior vena cava. Additionally, heterogeneously increased uptake in both lungs was noted, which suggested pulmonary infection. CT images of the chest showed patchy ground-glass changes in both lungs and a large consolidation in the right lower lobe, which were consistent with changes for COVID-19 (coronavirus disease 2019). Severe acute respiratory syndrome coronavirus 2 RNA test was positive. This case demonstrates that leukocyte uptake in bilateral lungs could reveal viral pulmonary infection in COVID-19.
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- 2020
9. A low-density lipoprotein receptor (LDLR) class A domain-containing C-type lectin from Litopenaeus vannamei plays opposite roles in antibacterial and antiviral responses
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Hongliang Zuo, Zhiwei Liang, Jiefu Zheng, Jianguo He, Xiaopeng Xu, Shaoping Weng, and Linwei Yang
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0301 basic medicine ,Hemocytes ,Immunology ,White spot syndrome ,Arthropod Proteins ,Microbiology ,03 medical and health sciences ,White spot syndrome virus 1 ,Immune system ,Penaeidae ,Phagocytosis ,Protein Domains ,C-type lectin ,Animals ,RNA, Small Interfering ,Receptor ,Innate immune system ,biology ,Pattern recognition receptor ,04 agricultural and veterinary sciences ,biology.organism_classification ,DNA Virus Infections ,Immunity, Innate ,Shrimp ,030104 developmental biology ,Receptors, LDL ,Receptors, Pattern Recognition ,Vibrio Infections ,LDL receptor ,040102 fisheries ,0401 agriculture, forestry, and fisheries ,Vibrio parahaemolyticus ,Sequence Alignment ,Developmental Biology - Abstract
C-type lectins (CTLs) are a group of pattern recognition receptors (PRRs) that contain carbohydrate recognition domains and play important roles in innate immunity. CTLs that contain an additional low-density lipoprotein receptor (LDLR) class A domain (LdlrCTL) have been identified in many crustaceans, but their functions in immune responses are mostly unknown. In this study, a novel LdlrCTL was identified from pacific white shrimp Litopenaeus vannamei (LvLdlrCTL), which showed high homology with previously reported crustacean LdlrCTLs. LvLdlrCTL was highly expressed in hemocytes and its expression was up-regulated after immune stimulations. Silencing of LdlrCTL significantly promoted infection of shrimp by Vibrio parahaemolyticus but inhibited infection by white spot syndrome virus (WSSV), suggesting that LdlrCTL could play opposite roles in antibacterial and antiviral responses. LdlrCTL exhibited agglutination activity against bacteria and fungi and could potentiate the phagocytosis of hemocytes. Moreover, the expression of many immune effector genes and signalling pathway components was significantly changed in LdlrCTL-silenced shrimp, indicating that LdlrCTL could be involved in immune regulation.
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- 2019
10. A single C4 Zinc finger-containing protein from Litopenaeus vannamei involved in antibacterial responses
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Jiefu Zheng, Ziqi Su, Linwei Yang, Xiaopeng Xu, Shaoping Weng, Hongliang Zuo, and Jianguo He
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Gills ,0301 basic medicine ,Antimicrobial peptides ,White spot syndrome ,Aquatic Science ,Arthropod Proteins ,03 medical and health sciences ,White spot syndrome virus 1 ,Penaeidae ,RNA interference ,In vivo ,Animals ,Environmental Chemistry ,Zinc finger ,030102 biochemistry & molecular biology ,biology ,Muscles ,RNA ,Zinc Fingers ,General Medicine ,biology.organism_classification ,Shrimp ,Cell biology ,030104 developmental biology ,Cytoplasm ,RNA Interference ,Vibrio parahaemolyticus - Abstract
The Zinc finger domains (ZnFs), which contain finger-like protrusions stabilized by zinc ions and function to bind DNA, RNA, protein and lipid substrates, are ubiquitously present in a large number of proteins. In this study, a novel protein containing a single C4 type Znf domain (SZnf) was identified from Pacific white shrimp, Litopenaeus vannamei and its role in immunity was further investigated. The ZnF domain of SZnF but not other regions shared high homology with those of fushi tarazu-factor 1 (FTZ-F1) proteins. The SZnF protein was mainly localized in the cytoplasm and was also present in the nucleus at a small level. SZnF was high expressed in the scape and muscle tissues of healthy shrimp and its expression in gill and heptopancreas was strongly up-regulated during bacterial infection. Silencing of SZnf in vivo could strongly increase the susceptibility of shrimp to infection with Vibrio parahaemolyticus but not white spot syndrome virus (WSSV), suggesting that SZnf could be mainly involved in antibacterial responses. Both dual luciferase reporter assays and real-time PCR analysis demonstrated that SZnf could positively regulate the expression of various antimicrobial peptides in vitro and in vivo, which could be part of the mechanism underlying its antibacterial effects. In summary, the current study could help learn more about the function of ZnF-containing proteins and the regulatory mechanisms of immune responses against pathogen infection in crustaceans.
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- 2018
11. Wnt11 positively regulates immune defense against Vibrio parahaemolyticus but promotes white spot syndrome virus infection in Litopenaeus vannamei
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Hongliang Zuo, Linwei Yang, Jiefu Zheng, Jianguo He, Shaoping Weng, Shengwen Niu, Xiaopeng Xu, and Zi-ang Wang
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0303 health sciences ,Vibrio parahaemolyticus ,fungi ,White spot syndrome ,Context (language use) ,04 agricultural and veterinary sciences ,biochemical phenomena, metabolism, and nutrition ,Aquatic Science ,Biology ,biology.organism_classification ,Shrimp ,Microbiology ,03 medical and health sciences ,Immune system ,040102 fisheries ,bacteria ,0401 agriculture, forestry, and fisheries ,Gene silencing ,Immediate early gene ,Transcription factor ,030304 developmental biology - Abstract
Vibrio parahaemolyticus and white spot syndrome virus (WSSV) are major threats for shrimp aquaculture. The Wnt family genes are well known to be involved in development and growth. In this study, the role of the Wnt11 gene from Pacific white shrimp Litopenaeus vannamei (LvWnt11) was investigated in the context of immune responses against V. parahaemolyticus and WSSV infection. We demonstrated that expression of LvWnt11 was regulated by Relish, Dorsal and STAT signaling pathways and changed after infection with various pathogens. Silencing of LvWnt11 in vivo significantly attenuated the immune defense against V. parahaemolyticus infection but enhanced that against WSSV infection. Although not affecting hemocyte phagocytosis, LvWnt11 regulated expression of immune related transcription factors Relish, Dorsal and STAT and a series of immune function proteins. Besides regulating promoters of target genes, LvWnt11 cooperated with Relish and Dorsal to improve their transcription regulatory activities. Moreover, LvWnt11 activated immediate early gene ie1 of WSSV, which could contribute to its promoting effect on WSSV infection. Therefore, the current study demonstrated that LvWnt11 played opposite roles in V. parahaemolyticus and WSSV infection, which may help to reveal the immune mechanisms in crustaceans and provide support for the prevention of diseases in cultured shrimp.
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- 2021
12. An Overview of Electrically Evoked Otoacoustic Emissions in the Mammalian Cochlea
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Jiefu, Zheng, Yuan, Zou, Tianying, Ren, and Nuttall, Alfred L.
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- 2006
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13. Cyborg Botany
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Pattie Maes, Harpreet Sareen, and Jiefu Zheng
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Computer science ,05 social sciences ,Botany ,0202 electrical engineering, electronic engineering, information engineering ,Xylem ,ComputerApplications_COMPUTERSINOTHERSYSTEMS ,020207 software engineering ,0501 psychology and cognitive sciences ,02 engineering and technology ,Interaction design ,Actuator ,050107 human factors - Abstract
The nature has myriad plant organisms, many of them carrying unique sensing and expression abilities. Plants can sense the environment, other living entities and regenerate, actuate or grow in response. Our interaction mechanisms and communication channels with such organisms in nature are subtle, unlike our interaction with digital devices. We propose a new convergent view of interaction design in nature by merging and powering our electronic functionalities with existing biological functions of plants. Cyborg Botany is a design exploration of deep technological integration within plants. Each desired synthetic function is grown, injected or carefully placed in conjunction with a plant's natural functions. With a nanowire grown inside the xylem of a plant [1, 2, 3, 4], we demonstrate its use as a touch sensor, motion sensor, antenna and more. We also demonstrate a software through which a user clicks on a plant's leaves to individual control their movement [6], and explore the use of plants as a display [5]. Our goal is to make use of a plant's own sensing and expressive abilities of nature for our interaction devices. Merging synthetic circuitry with plant's own physiology could pave a way to make these lifeforms responsive to our interactions and their ubiquitous sustainable deployment.
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- 2019
14. Identification of the thioredoxin-related protein of 14 kDa (TRP14) from Litopenaeus vannamei and its role in immunity
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Jiefu Zheng, Hongliang Zuo, Linwei Yang, Xiaopeng Xu, Jia Yuan, Shaoping Weng, and Jianguo He
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0301 basic medicine ,Staphylococcus aureus ,animal structures ,DNA, Complementary ,White spot syndrome ,Antimicrobial peptides ,Hepatopancreas ,Aquatic Science ,Arthropod Proteins ,03 medical and health sciences ,0302 clinical medicine ,Thioredoxins ,White spot syndrome virus 1 ,Penaeidae ,RNA interference ,Environmental Chemistry ,Gene silencing ,Animals ,Amino Acid Sequence ,RNA, Messenger ,Intestinal Mucosa ,Transcription factor ,Gene knockdown ,biology ,Base Sequence ,fungi ,NF-kappa B ,General Medicine ,Staphylococcal Infections ,biology.organism_classification ,DNA Virus Infections ,Shrimp ,Cell biology ,030104 developmental biology ,030220 oncology & carcinogenesis ,Vibrio Infections ,Vibrio parahaemolyticus ,Thioredoxin - Abstract
The thioredoxin system plays essential roles in maintenance and regulation of the redox state of cysteine residues in cellular proteins. The thioredoxin-related protein of 14 kDa (TRP14) is an important member of the TRX superfamily which acts on various substrate proteins, some of which are not overlapped with those of thioredoxin. The knowledge on the function of TRP14 in invertebrates is limited to date. In this study, a TRP14 gene was identified from Pacific white shrimp Litopenaeus vannamei (LvTRP14) and its role in immune responses was investigated. We demonstrated that the expression level of LvTRP14 was high in hepatopancreas and intestine, low in eyestalk, and medium in other tissues of healthy shrimp. The transcription of LvTRP14 in vivo was significantly down-regulated in Relish-silencing shrimp but up-regulated in STAT-silencing shrimp, indicating a complex regulation of LvTRP14 expression. Although the LvTRP14 expression showed little change after immune stimulation with different type of pathogens, knockdown of LvTRP14 expression using RNAi strategy could significantly facilitate the infection of white spot syndrome virus (WSSV) and Vibrio parahaemolyticus in shrimp. Dual luciferase reporter assays demonstrated that LvTRP14 enhanced the transcription factor activity of Relish but attenuated that of Dorsal. Furthermore, silencing of LvTRP14 in vivo had opposite effects on expression of different type of antimicrobial peptides. These suggested that LvTRP14 could play a complex role in shrimp immunity.
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- 2018
15. A chitinase from pacific white shrimp Litopenaeus vannamei involved in immune regulation
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Jiefu Zheng, Jianguo He, Hongliang Zuo, Xiaopeng Xu, Shengwen Niu, Shaoping Weng, and Linwei Yang
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0301 basic medicine ,Hemocytes ,Immunology ,Antimicrobial peptides ,White spot syndrome ,Microbiology ,Arthropod Proteins ,03 medical and health sciences ,chemistry.chemical_compound ,Immune system ,White spot syndrome virus 1 ,Chitin ,Penaeidae ,Immunity ,Chitin binding ,Animals ,Immunologic Factors ,Amino Acid Sequence ,Immunity, Cellular ,030102 biochemistry & molecular biology ,biology ,Base Sequence ,fungi ,Chitinases ,biology.organism_classification ,Shrimp ,Immunity, Humoral ,Up-Regulation ,030104 developmental biology ,chemistry ,Chitinase ,biology.protein ,Vibrio parahaemolyticus ,Sequence Alignment ,Developmental Biology - Abstract
Chitinases are a group of hydrolytic enzymes that hydrolyze chitin and widely exist in organisms. Studies in mammals have demonstrated that chitinases play important roles in regulation of humoral and cellular immune responses. In arthropods, although it is well known that chitinases are involved in growth, molting and development, the current knowledge on the role of chitinases in immunity, especially in immune regulation, remains largely unknown. In this study, a chitinase (LvChi5) from Litopenaeus vannamei was representatively selected for studying its immune function. The start codon of LvChi5 was corrected by 5′RACE analysis and its protein sequence was reanalyzed. LvChi5 contains a catalytic domain and a chitin binding domain and shows no inhibitory effect on growth of bacteria in vitro. However, in vivo experiments demonstrated that silencing of LvChi5 increased the mortality of shrimp infected with white spot syndrome virus (WSSV) and Vibro parahaemolyticus and significantly upregulated the load of pathogens in tissues. The expression of various immune related genes, including transcription factors, antimicrobial peptides and other functional proteins with antibacterial and antiviral activities, was widely changed in LvChi5 silencing shrimp. Moreover, the recombinant LvChi5 protein could enhance the phagocytic activity of hemocytes against bacteria. These suggested that shrimp chitinase could play a role in regulation of both humoral and cellular immune responses in shrimp.
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- 2018
16. Identification and characterization of an interleukin-16-like gene from pacific white shrimp Litopenaeus vannamei
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Xiaopeng Xu, Chaozheng Li, Jiefu Zheng, Jianguo He, Shengwen Niu, Hongliang Zuo, Shaoping Weng, Linwei Yang, Muting Yan, and Qianhui Liang
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0301 basic medicine ,Immunology ,Litopenaeus ,PDZ Domains ,Biology ,Microbiology ,Arthropod Proteins ,03 medical and health sciences ,Immune system ,White spot syndrome virus 1 ,Penaeidae ,RNA interference ,Animals ,Cloning, Molecular ,RNA, Small Interfering ,Gene ,Gene knockdown ,Interleukin-16 ,Caspase 3 ,fungi ,Interleukin ,04 agricultural and veterinary sciences ,biology.organism_classification ,Molecular biology ,DNA Virus Infections ,Immunity, Innate ,Shrimp ,Up-Regulation ,030104 developmental biology ,Vibrio Infections ,040102 fisheries ,Mutagenesis, Site-Directed ,0401 agriculture, forestry, and fisheries ,Vibrio parahaemolyticus ,Interleukin 16 ,Developmental Biology - Abstract
Interleukins are a group of cytokines that play essential roles in immune regulation. Almost all interleukin genes are only found in vertebrates. In this study, an interleukin-16-like gene (LvIL-16L) was identified from Pacific white shrimp, Litopenaeus vannamei. LvIL-16L was predicted to encode a precursor (pro-LvIL-16L) with 1378 amino acids, sharing similarities with predicted pro-IL-16-like proteins from insects. The C-terminus of pro-LvIL-16L protein contained two PDZ domains homologous to the mature IL-16 cytokine of vertebrates. In tissues, LvIL-16L could be processed into a ∼36 kDa mature peptide through a caspase-3 cleavage site, which was verified by in vitro site mutation analysis and in vivo RNA interference (RNAi) experiments. The LvIL-16L mRNA could be detected in all the analyzed tissues and the expression of LvIL-16L was significantly up-regulated after immune stimulation. Using RNAi strategy, the role of LvIL-16L in immune responses was initially investigated. Interestingly, knockdown of LvIL-16L could significantly increase the mortality of the Vibro parahaemolyticus infected shrimps but reduce that of the WSSV infected shrimps, suggesting that LvIL-16L could have opposite effects on the antiviral and antibacterial immune responses in shrimp. To our knowledge, this is the first study of an IL-16-like gene in invertebrates, which could help to elucidate interleukin evolution and regulatory mechanisms of shrimp immune responses.
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- 2016
17. A differentially amplified motion in the ear for near-threshold sound detection
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Xiaorui Shi, Jiefu Zheng, Ruikang K. Wang, Alfred L. Nuttall, Niloy Choudhury, Fangyi Chen, Dingjun Zha, Steven L. Jacques, and Anders Fridberger
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Acoustics ,Guinea Pigs ,Stimulus (physiology) ,Vibration ,Article ,03 medical and health sciences ,Motion ,0302 clinical medicine ,Optical coherence tomography ,Hair Cells, Auditory ,otorhinolaryngologic diseases ,medicine ,Auditory system ,Animals ,Sound pressure ,Cochlea ,030304 developmental biology ,Physics ,0303 health sciences ,medicine.diagnostic_test ,General Neuroscience ,Sound detection ,Auditory Threshold ,Anatomy ,Basilar Membrane ,Basilar membrane ,medicine.anatomical_structure ,Sound ,Acoustic Stimulation ,sense organs ,Neuroscience ,030217 neurology & neurosurgery ,Tomography, Optical Coherence - Abstract
The ear is a remarkably sensitive pressure fluctuation detector. In guinea pigs, behavioral measurements indicate a minimum detectable sound pressure of ∼20 μPa at 16 kHz. Such faint sounds produce 0.1-nm basilar membrane displacements, a distance smaller than conformational transitions in ion channels. It seems that noise within the auditory system would swamp such tiny motions, making weak sounds imperceptible. Here we propose a new mechanism contributing to a resolution of this problem and validate it through direct measurement. We hypothesized that vibration at the apical side of hair cells is enhanced compared with that at the commonly measured basilar membrane side. Using in vivo optical coherence tomography, we demonstrated that apical-side vibrations peaked at a higher frequency, had different timing and were enhanced compared with those at the basilar membrane. These effects depend nonlinearly on the stimulus sound pressure level. The timing difference and enhancement of vibrations are important for explaining how the noise problem is circumvented.
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- 2011
18. Achieving reliability and high accuracy in automated protein docking: Cluspro, PIPER, SDU, and stability analysis in CAPRI rounds 13-19
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Keyong Li, Stephen R. Comeau, Jiefu Zheng, Pirooz Vakili, Yang Shen, Ryan Brenke, David R. Hall, Sandor Vajda, Ioannis Ch. Paschalidis, Dmitri Beglov, and Dima Kozakov
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Computer science ,Monte Carlo method ,Fast Fourier transform ,Biochemistry ,Structural Biology ,Docking (molecular) ,Macromolecular docking ,Pairwise comparison ,Homology modeling ,Cluster analysis ,Molecular Biology ,Global optimization ,Algorithm ,Simulation - Abstract
Our approach to protein-protein docking includes three main steps. First, we run PIPER, a rigid body docking program based on the Fast Fourier Transform (FFT) correlation approach, extended to use pairwise interactions potentials. Second, the 1000 best energy conformations are clustered, and the 30 largest clusters are retained for refinement. Third, the stability of the clusters is analyzed by short Monte Carlo simulations, and the structures are refined by the medium-range optimization method SDU. The first two steps of this approach are implemented in the ClusPro 2.0 protein-protein docking server. Despite being fully automated, the last step is computationally too expensive to be included in the server. When comparing the models obtained in CAPRI rounds 13-19 by ClusPro, by the refinement of the ClusPro predictions and by all predictor groups, we arrived at three conclusions. First, for the first time in the CAPRI history, our automated ClusPro server was able to compete with the best human predictor groups. Second, selecting the top ranked models, our current protocol reliably generates high-quality structures of protein-protein complexes from the structures of separately crystallized proteins, even in the absence of biological information, provided that there is limited backbone conformational change. Third, despite occasional successes, homology modeling requires further improvement to achieve reliable docking results.
- Published
- 2010
19. Inverted direction of wave propagation (IDWP) in the cochlea
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Alfred L. Nuttall, Jiefu Zheng, Edward Porsov, and Egbert de Boer
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Physics ,Classical theory ,Tympanic Membrane ,Fourier Analysis ,Acoustics and Ultrasonics ,Wave propagation ,Acoustics ,Mathematical analysis ,Article ,Basilar Membrane ,Stapes ,Cochlea ,Basilar membrane ,symbols.namesake ,medicine.anatomical_structure ,Arts and Humanities (miscellaneous) ,Fourier analysis ,medicine ,symbols ,Humans ,Constant frequency ,Inner ear ,Forward wave - Abstract
The "classical" view on wave propagation is that propagating waves are possible in both directions along the length of the basilar membrane and that they have identical properties. Results of several recently executed experiments [T. Ren, Nat. Neurosci. 2, 333-334 (2004) and W. X. He, A. L. Nuttall, and T. Ren, Hear. Res., 228, 112-122 (2007)] appear to contradict this view. In the current work measurements were made of the velocity of the guinea-pig basilar membrane (BM). Distortion products (DPs) were produced by presenting two primary tones, with frequencies below the characteristic frequency f(0) of the BM location at which the BM measurements were made, with a constant frequency ratio. In each experiment the phase of the principal DP, with frequency 2f(1)-f(2), was recorded as a function of the DP frequency. The results indicate that the DP wave going from the two-tone interaction region toward the stapes is not everywhere traveling in the reverse direction, but also in the forward direction. The extent of the region in which the forward wave occurs appears larger than is accounted for by classical theory. This property has been termed "inverted direction of wave propagation." The results of this study confirm the wave propagation findings of other authors. The experimental data are compared to theoretical predictions for a classical three-dimensional model of the cochlea that is based on noise-response data of the same animal. Possible physical mechanisms underlying the findings are discussed.
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- 2008
20. The Allen-Fahey experiment extended
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Yuan Zou, Alfred L. Nuttall, Egbert de Boer, Jiefu Zheng, Ning Hu, and Faculteit der Geneeskunde
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Cochlear amplifier ,Time Factors ,Acoustics and Ultrasonics ,Distortion product ,Gain measurement ,Acoustics ,Guinea Pigs ,Otoacoustic Emissions, Spontaneous ,Basilar Membrane ,Cochlea ,Basilar membrane ,medicine.anatomical_structure ,Arts and Humanities (miscellaneous) ,otorhinolaryngologic diseases ,Outer ear ,medicine ,Animals ,sense organs ,Cochlear Nerve ,Mathematics ,Stapes - Abstract
An ingenious experiment has been performed by Allen and Fahey [J. Acoust. Soc. Am. 92, 178-188 (1992)], in which they attempted to estimate the gain of the cochlear amplifier by comparing responses to the 2 f1-f2 distortion product (DP) in the outer ear canal (otoacoustic emissions) and from an auditory-nerve fiber. Results were essentially negative: no evidence of cochlear amplification was found in that experiment. A variation of that experiment is reported here, where DP responses in the outer ear canal are compared with mechanical responses of the basilar membrane. This variation does not suffer from the major limitation in the original experiment in the choice of possible frequency ratios. Results confirm and extend those of Allen and Fahey entirely. Apparently, the gain of the cochlear amplifier cannot be measured in this way. It is argued that the retrograde wave going to the stapes is most likely reduced in magnitude by wave interference when the two primary frequencies approach each other. Such a reduction does not take place in the forward-going wave to the location tuned to the DP frequency. This explanation is illustrated on the basis of results of earlier experiments on the movements of the basilar membrane.
- Published
- 2005
21. Organ of Corti Potentials and the Motion of the Basilar Membrane
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Ning Hu, Tianying Ren, Alfred L. Nuttall, Jiefu Zheng, Jacques Boutet de Monvel, Anders Fridberger, and Yuan Zou
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Guinea Pigs ,Receptor potential ,Behavioral/Systems/Cognitive ,Stimulus (physiology) ,Models, Biological ,Membrane Potentials ,Motion ,otorhinolaryngologic diseases ,medicine ,Animals ,Prestin ,Organ of Corti ,Cochlea ,Membrane potential ,biology ,Chemistry ,General Neuroscience ,Electric Conductivity ,Anatomy ,Basilar Membrane ,Hair Cells, Auditory, Outer ,Basilar membrane ,medicine.anatomical_structure ,Acoustic Stimulation ,biology.protein ,Biophysics ,sense organs ,Hair cell ,Microelectrodes - Abstract
During sound stimulation, receptor potentials are generated within the sensory hair cells of the cochlea. Prevailing theory states that outer hair cells use the potential-sensitive motor protein prestin to convert receptor potentials into fast alterations of cellular length or stiffness that boost hearing sensitivity almost 1000-fold. However, receptor potentials are attenuated by the filter formed by the capacitance and resistance of the membrane of the cell. This attenuation would limit cellular motility at high stimulus frequencies, rendering the above scheme ineffective. Therefore, Dallos and Evans (1995a) proposed that extracellular potential changes within the organ of Corti could drive cellular motor proteins. These extracellular potentials are not filtered by the membrane. To test this theory, both electric potentials inside the organ of Corti and basilar membrane vibration were measured in response to acoustic stimulation. Vibrations were measured at sites very close to those interrogated by the recording electrode using laser interferometry. Close comparison of the measured electrical and mechanical tuning curves and time waveforms and their phase relationships revealed that those extracellular potentials indeed could drive outer hair cell motors. However, to achieve the sharp frequency tuning that characterizes the basilar membrane, additional mechanical processing must occur inside the organ of Corti.
- Published
- 2004
22. High-frequency electromotile responses in the cochlea
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Yuan Zou, Jiefu Zheng, Egbert de Boer, Karl Grosh, Alfred L. Nuttall, and Faculteit der Geneeskunde
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Acoustics and Ultrasonics ,Chemistry ,Acoustics ,Guinea Pigs ,Stimulation ,Basilar Membrane ,Electric Stimulation ,Cochlea ,Electrophysiology ,Pitch Discrimination ,Sensory epithelium ,Guinea pig ,Hair Cells, Auditory, Outer ,Basilar membrane ,Acoustic Stimulation ,Arts and Humanities (miscellaneous) ,In vivo ,otorhinolaryngologic diseases ,Biophysics ,Animals ,sense organs ,Pitch Perception ,Guinea pig cochlea ,Outer hair cells - Abstract
Mammalian outer hair cells (OHCs) convert electrical energy into mechanical energy. The significance of this electromotility rests in the ability of the OHCs to modulate the vibrations of the cochlear partition in vivo. While high-frequency electromotility of isolated OHCs has been demonstrated at frequencies up to 100 kHz, a similar measure of the effect of OHC electromotility on motion of the sensory epithelium has not been made in vivo. In this study, in vivo electrical stimulation of the guinea pig cochlea is found to induce a mechanical response of the basilar membrane for frequencies to at least 100 kHz, nearly twice the upper limit of hearing for the guinea pig. The perfusion of salicylate in the cochlea reversibly reduces the electromotile response, indicating that an OHC-mediated process is the key contributor.
- Published
- 2004
23. Vanilloid Receptors in Hearing: Altered Cochlear Sensitivity by Vanilloids and Expression of TRPV1 in the Organ of Corti
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Chunfu Dai, Young Ki Kim, Alfred L. Nuttall, Jiefu Zheng, Peter S. Steyger, Tianying Ren, and Zoltan Vass
- Subjects
medicine.medical_specialty ,Physiology ,Endocochlear potential ,Receptors, Drug ,Guinea Pigs ,TRPV1 ,Resiniferatoxin ,Article ,chemistry.chemical_compound ,Hearing ,Internal medicine ,Laser-Doppler Flowmetry ,otorhinolaryngologic diseases ,medicine ,Animals ,Inner ear ,Organ of Corti ,Cochlea ,Spiral ganglion ,General Neuroscience ,Immunohistochemistry ,Electric Stimulation ,Electrophysiology ,Endocrinology ,medicine.anatomical_structure ,Acoustic Stimulation ,chemistry ,sense organs ,Capsaicin ,Capsazepine - Abstract
Capsaicin, the vanilloid that selectively activates vanilloid receptors (VRs) on sensory neurons for noxious perception, has been reported to increase cochlear blood flow (CBF). VR-related receptors have also been found in the inner ear. This study aims to address the question as to whether VRs exist in the organ of Corti and play a role in cochlear physiology. Capsaicin or the more potent VR agonist, resiniferatoxin (RTX), was infused into the scala tympani of guinea pig cochlea, and their effects on cochlear sensitivity were investigated. Capsaicin (20 μM) elevated the threshold of auditory nerve compound action potential and reduced the magnitude of cochlear microphonic and electrically evoked otoacoustic emissions. These effects were reversible and could be blocked by a competitive antagonist, capsazepine. Application of 2 μM RTX resulted in cochlear sensitivity alterations similar to that by capsaicin, which could also be blocked by capsazepine. A desensitization phenomenon was observed in the case of prolonged perfusion with either capsaicin or RTX. Brief increase of CBF by capsaicin was confirmed, and the endocochlear potential was not decreased. Basilar membrane velocity (BM) growth functions near the best frequency and BM tuning were altered by capsaicin. Immunohistochemistry study revealed the presence of vanilloid receptor type 1 of the transient receptor potential channel family in the hair cells and supporting cells of the organ of Corti and the spiral ganglion cells of the cochlea. The results indicate that the main action of capsaicin is on outer hair cells and suggest that VRs in the cochlea play a role in cochlear homeostasis.
- Published
- 2003
24. Alterations of basilar membrane response phase and velocity after acoustic overstimulation
- Author
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Jiefu Zheng, Alfred L. Nuttall, and Anders Fridberger
- Subjects
Materials science ,Acoustics ,Guinea Pigs ,Stimulus (physiology) ,medicine.disease ,Vibration ,Basilar Membrane ,Sensory Systems ,Disease Models, Animal ,Basilar membrane ,Sound exposure ,medicine.anatomical_structure ,Amplitude ,Acoustic Stimulation ,Hearing Loss, Noise-Induced ,Laser-Doppler Flowmetry ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,Inner ear ,sense organs ,Auditory fatigue ,Cochlea ,Noise-induced hearing loss - Abstract
To investigate the physiology of noise-induced hearing loss, the sound-induced vibrations of the basilar membrane (BM) of the inner ear were measured in living anesthetized guinea pigs before and after intense sound exposure. The vibrations were measured using a laser Doppler velocimeter after placing reflective glass beads on the BM. Pseudo-random noise waveforms containing frequencies between 4 and 24 kHz were used to generate velocity tuning curves. Before overstimulation, sharp response peaks were seen at stimulus frequencies between 15 and 17 kHz, consistent with the expected best frequency of the recording location. The response to low level stimuli lagged the high level ones by up to 90 degrees at the characteristic frequency. Following exposure to loud sound, the BM vibrations showed a pronounced reduction in amplitude, primarily at low stimulus levels, and the best frequency moved to approximately 12 kHz. At higher levels, the reduction was either absent or much smaller. In addition to the amplitude changes, increased phase lags were seen at frequencies near the characteristic frequency. In animals with more severe exposures, response phases were altered also at frequencies showing no change of the amplitude. The phase was independent of stimulus level after severe exposures.
- Published
- 2002
25. In vivo Micromechanical Measurements of the Organ of Corti in the Basal Cochlear Turn
- Author
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Anand Parthasarathi, Menghe Guo, Karl Grosh, Jiefu Zheng, Tianying Ren, Egbert de Boer, Alfred L. Nuttall, and David F. Dolan
- Subjects
Physiology ,Tectorial membrane ,Guinea Pigs ,Biology ,Synaptic Transmission ,Vibration ,Speech and Hearing ,Basal (phylogenetics) ,Hearing ,otorhinolaryngologic diseases ,medicine ,Animals ,Inner ear ,Organ of Corti ,Cochlea ,Anatomy ,Basilar Membrane ,Sensory Systems ,Biomechanical Phenomena ,Apex (geometry) ,Basilar membrane ,medicine.anatomical_structure ,Otorhinolaryngology ,Reticular connective tissue ,Biophysics ,sense organs ,Gerbillinae ,Signal Transduction - Abstract
Cochlear mechanical measurements of organ of Corti motion are generally accomplished in the apical or basal turn as in vivo or in vitro studies. In the apex it is possible to observe and measure tectorial membrane vibration as well as vibrations of structures such as the reticular lamina or the basilar membrane (BM). However, compared to the basal turn, cochlear amplification and nonlinearity are not strong in the apex. Basal turn studies have typically been limited to point location measurements of the BM but improved technology for laser interferometry is now making possible the spatial mapping of BM motion. The ‘complexity’ of BM motion in the radial direction (particularly the phase variation) is important to new models of cochlear wave amplification. In future work it may be possible to learn about vibration of structures within the organ of Corti.
- Published
- 2002
26. Encounter complexes and dimensionality reduction in protein–protein association
- Author
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Dmitri Beglov, Sandor Vajda, Jiefu Zheng, David R. Hall, Dima Kozakov, Ioannis Ch. Paschalidis, Keyong Li, Ora Schueler-Furman, Pirooz Vakili, and G. Marius Clore
- Subjects
Surface (mathematics) ,Protein Conformation ,none ,QH301-705.5 ,Science ,protein–protein interactions ,Biology ,Bioinformatics ,General Biochemistry, Genetics and Molecular Biology ,protein-protein interaction ,Protein structure ,Biology (General) ,General Immunology and Microbiology ,Euclidean space ,encounter landscapes ,General Neuroscience ,Dimensionality reduction ,Intermolecular force ,Energy landscape ,Proteins ,General Medicine ,FFT sampling ,Biophysics and Structural Biology ,Orientation (vector space) ,Molecular Docking Simulation ,Principal component analysis ,Thermodynamics ,Medicine ,Biological system ,Protein Binding ,Research Article - Abstract
An outstanding challenge has been to understand the mechanism whereby proteins associate. We report here the results of exhaustively sampling the conformational space in protein–protein association using a physics-based energy function. The agreement between experimental intermolecular paramagnetic relaxation enhancement (PRE) data and the PRE profiles calculated from the docked structures shows that the method captures both specific and non-specific encounter complexes. To explore the energy landscape in the vicinity of the native structure, the nonlinear manifold describing the relative orientation of two solid bodies is projected onto a Euclidean space in which the shape of low energy regions is studied by principal component analysis. Results show that the energy surface is canyon-like, with a smooth funnel within a two dimensional subspace capturing over 75% of the total motion. Thus, proteins tend to associate along preferred pathways, similar to sliding of a protein along DNA in the process of protein-DNA recognition. DOI: http://dx.doi.org/10.7554/eLife.01370.001, eLife digest Proteins rarely act alone. Instead, they tend to bind to other proteins to form structures known as complexes. When two proteins come together to form a complex, they twist and turn through a series of intermediate states before they form the actual complex. These intermediate states are difficult to study because they don’t last for very long, which means that our knowledge of how complexes are formed remains incomplete. One promising approach for studying the formation of complexes is called paramagnetic relaxation enhancement. In this technique certain areas in one of the proteins are labelled with magnetic particles, which produce signals when the two proteins are close to each other. Repeating the measurement several times with the magnetic particles in different positions provides information about the overall structure of the complex. Computational modelling can then be used to work out the fine details of the structure, including the shapes of the intermediate structures made by the proteins as they interact. A computer method called docking can be used to predict the most favourable positions that the proteins can take, relative to one another, in a complex. This involves calculating the energy contained in the system, with the correct structure having the lowest energy. Docking methods also predict protein models with slightly higher energies, but with structures that are radically different. Modellers usually ignore these structures, but comparing the docking results to paramagnetic relaxation enhancement data, Kozakov et al. found that these structures actually represent the intermediate states. Analysing the structure of the intermediate states revealed that the movement of the two proteins relative to one another is severely restricted as they form the final complex. Kozakov et al. found that proteins associate along preferred pathways, similar to the way a protein slides along DNA in the process of protein-DNA recognition. Knowing that the movement of the proteins is restricted in this way will enable researchers to improve the efficiency of docking calculations. DOI: http://dx.doi.org/10.7554/eLife.01370.002
- Published
- 2014
27. Author response: Encounter complexes and dimensionality reduction in protein–protein association
- Author
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Ora Schueler-Furman, G. Marius Clore, Keyong Li, Pirooz Vakili, David R. Hall, Jiefu Zheng, Dmitri Beglov, Dima Kozakov, Ioannis Ch. Paschalidis, and Sandor Vajda
- Subjects
Chemistry ,Protein protein ,Association (object-oriented programming) ,Dimensionality reduction ,Computational biology - Published
- 2014
28. Quinine-induced alterations of electrically evoked otoacoustic emissions and cochlear potentials in guinea pigs
- Author
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Alfred L. Nuttall, Jiefu Zheng, Anand Parthasarathi, and Tianying Ren
- Subjects
Cochlear amplifier ,medicine.medical_specialty ,Guinea Pigs ,Otoacoustic Emissions, Spontaneous ,Otoacoustic emission ,Action Potentials ,Audiology ,Ototoxicity ,otorhinolaryngologic diseases ,medicine ,Animals ,Spiral ganglion ,Cochlea ,Round window ,Quinine ,Chemistry ,medicine.disease ,Electric Stimulation ,Sensory Systems ,Compound muscle action potential ,Hair Cells, Auditory, Outer ,Basilar membrane ,medicine.anatomical_structure ,Cochlear Microphonic Potentials ,Biophysics ,sense organs - Abstract
Quinine is a well-known ototoxic drug which may affect portions of the auditory system with different biochemical effects, causing reversible hearing loss and tinnitus. Recent investigations indicate that quinine at high concentrations can act directly on cochlear outer hair cells to affect their motility and the mechanical response of the basilar membrane. This study aimed to investigate the effect of quinine on the electromotility of outer hair cells in vivo by means of measuring the electrically evoked otoacoustic emissions (EEOAEs), and the relationship between EEOAE and hearing sensitivity alterations in guinea pigs. Quinine was infused into the scala tympani with concentrations between 0.05 and 5 mM. An alternating current (35 microA RMS) swept from 400 Hz to 40 kHz was applied to the round window to evoke the EEOAE. The compound action potential (CAP), cochlear microphonic (CM) and summating potential (SP) were also measured. Results show that quinine affects the EEOAE in a dose-dependent manner and that its effects are reversible. Two aspects of the EEOAE were affected by quinine, depending on concentration: (1) the 'fine structure' only for concentrations below 0.1 mM and (2) the overall amplitude and the 'fine structure' for concentrations above 0.1 mM. At 5 mM the fine structure was completely absent and the mean amplitude of the EEOAE greatly decreased. Multiple component analysis shows the short delay component of the EEOAE is related to the mean value of the amplitude spectrum while the long delay component is related to the fine structure. The alterations of the EEOAE are roughly comparable to that of the cochlear potentials. A 'threshold concentration' for quinine's effects was found at 25 microM. CAP was significantly affected at 25 microM while EEOAE, CM and SP were not. Enhancement of the EEOAE amplitude was noticed in five out of 20 animals in the current study. The enhancement appears only related to the EEOAE mean level or short delay component. The results suggest that quinine can affect in vivo electromotility of outer hair cells at low concentration and therefore change the cochlear amplifier performance via an effect on electro-mechanical transduction. Its effects on the cochlear spiral ganglion neurons and/or their presynaptic process are also suggested, and these are speculated to be the primary sites for quinine's effects on the auditory system.
- Published
- 2001
29. Decomposition techniques for Markov zero-sum games with nested information
- Author
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David A. Castanon and Jiefu Zheng
- Subjects
Computer Science::Computer Science and Game Theory ,Mathematical optimization ,Markov chain ,Sequential game ,Computer science ,Stochastic game ,Normal-form game ,ComputingMilieux_PERSONALCOMPUTING ,Markov process ,Minimax ,symbols.namesake ,Bayesian game ,Zero-sum game ,Example of a game without a value ,Backward induction ,symbols ,Markov decision process ,Game tree ,Game theory - Abstract
Markov zero-sum games arise in applications such as network interdiction, where an informed defender protects a network against attacks. This problem has received significant attention in recent years due to its relevance to military problems and network security. In this paper, we focus on finite games where the attacker knows imperfectly the network state, and formulate this as a Markov game with nested information. By exploiting the nested information structure, we decompose the multistage game into a sequence of one-stage subgames and develop an algorithm that computes the value of the game and the saddle point strategies for the game. This decomposition method computes the value of the game using backward induction as in stochastic dynamic programming, then identifies saddle-point strategies that achieve this value. Using the Markov structure of the game, we show that the value of the game can be computed efficiently in terms of a single value function of an information state at each stage. The resulting single stage optimization problems are much smaller than the original multistage game. We illustrate our results with an example of multistage network interdiction where the attacker may not be able to observe outcomes of the attacks.
- Published
- 2013
30. MEASUREMENT OF AMPLITUDE AND DELAY OF STIMULUS FREQUENCY OTOACOUSTIC EMISSIONS
- Author
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Tianying Ren, Alfred L. Nuttall, Jiefu Zheng, and Wenxuan He
- Subjects
Physics ,medicine.medical_specialty ,Signal processing ,Human ear ,Cochlear mechanics ,Audiology ,01 natural sciences ,Article ,03 medical and health sciences ,Tone (musical instrument) ,0302 clinical medicine ,Amplitude ,medicine.anatomical_structure ,Otorhinolaryngology ,0103 physical sciences ,medicine ,otorhinolaryngologic diseases ,Stimulus frequency ,Ear canal ,sense organs ,Sound pressure ,010301 acoustics ,030217 neurology & neurosurgery - Abstract
Although stimulus frequency otoacoustic emissions (SFOAEs) have been used as a non-invasive measure of cochlear mechanics, clinical and experimental application of SFOAEs has been limited by difficulties in accurately deriving quantitative information from sound pressure measured in the ear canal. In this study, a novel signal processing method for multicomponent analysis (MCA) was used to measure the amplitude and delay of the SFOAE. This report shows the delay-frequency distribution of the SFOAE measured from the human ear. A low level acoustical suppressor near the probe tone significantly suppressed the SFOAE, strongly indicating that the SFOAE was generated at characteristic frequency locations. Information derived from this method may reveal more details of cochlear mechanics in the human ear.
- Published
- 2013
31. Stochastic dynamic network interdiction games
- Author
-
David A. Castanon and Jiefu Zheng
- Subjects
Mathematical optimization ,Dynamic network analysis ,Intelligent Network ,Network security ,business.industry ,Computer science ,business ,Interdiction ,Stochastic neural network ,Game theory ,Network operations center - Abstract
Network interdiction problems consist of games between an attacker and an intelligent network, where the attacker seeks to degrade network operations while the network adapts its operations to counteract the effects of the attacker. This problem has received significant attention in recent years due to its relevance to military problems and network security. When the attacker's actions achieve uncertain effects, the resulting problems become stochastic network interdiction problems, and allow the players to adapt to new information collected during the game. In this paper, we study stochastic network interdiction games where the attacker has one or two stages to attack the network, and can collect information on the outcomes of previous attacks. For the single stage problem, we develop a new solution algorithm, based on parsimonious integration of branch and bound techniques with increasingly accurate lower bounds, that obtains solutions significantly faster than previous approaches in the literature. We extend the single stage formulation to a two stage formulation, and develop a new set of performance bounds for this problem. We integrate these bounds into a modified branch and bound procedure that extends the single stage approach to two stages. The efficacy of the new algorithms is shown using simulated experiments with networks studied in previous papers.
- Published
- 2012
32. In vivo measurement of amplifying motion within the organ of Corti under sound stimulation using optical coherence tomography
- Author
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Jiefu Zheng, Fangyi Chen, Niloy Choudhury, Anders Fridberger, Ruikang K. Wang, Alfred L. Nuttall, Dingjun Zha, and Steven L. Jacques
- Subjects
Physics ,medicine.diagnostic_test ,Acoustics ,Stimulus (physiology) ,Vibration ,Basilar membrane ,Amplitude ,medicine.anatomical_structure ,Optical coherence tomography ,Organ of Corti ,Reticular connective tissue ,otorhinolaryngologic diseases ,medicine ,sense organs ,Cochlea - Abstract
Hearing in mammals, depend on an amplifying motion which hypothetically uses force from outer hair cells (OHC) motility to enhance sound induced vibration of the organ of Corti of cochlea. In this hypothesis the differential motion among key structures in this organ and the timing of the OHC force generation is essential for cochlear amplification to occur. Using a time domain optical coherence tomography system which allows us to make vibration measurements we were able to measure differential motion of two functionally important surfaces, namely, basilar membrane and reticular lamina. The reticular lamina vibrates at higher amplitude than the basilar membrane and has significant phase lead over basilar membrane vibration. The differential motion, that is, different amplitude and phase of vibration, become less as the energy of the sound stimulus is increased and the amplification processes in the organ of Corti are quenched.
- Published
- 2012
33. In vivo measurement of differential motion inside the organ of Corti using a low coherence interferometer system
- Author
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Alfred L. Nuttall, Jiefu Zheng, Niloy Choudhury, Dingjun Zha, Steven L. Jacques, Anders Fridberger, Ruikang K. Wang, and Fangyi Chen
- Subjects
Physics ,Cochlear amplifier ,medicine.diagnostic_test ,Acoustics ,Vibration ,Basilar membrane ,medicine.anatomical_structure ,Optical coherence tomography ,Organ of Corti ,otorhinolaryngologic diseases ,medicine ,Coherence (signal processing) ,sense organs ,Hair cell ,Cochlea - Abstract
The differential motion of the organ of Corti has been expected as a result of the outer hair cell force, believed to be necessary for the cochlear amplifier. In vitro experiments have been performed to demonstrate this motion but the in vivo data was unavailable due to the technical difficulties. Using a specially-designed time-domain optical coherence tomography system, we performed in vivo imaging and vibration measurement at the sensitive base of the guinea pig cochlea. This technique, for the first time, provides in vivo information about the internal vibration of the organ of Corti. At low sound level, when the cochlea is more sensitive, top surface of the organ of Corti, the reticular lamina (RL) showed tuning at a higher frequency than of the bottom surface, basilar membrane (BM) and its vibration amplitude is 2-3 times of that of the BM. Corresponding to the frequency difference, the phase of RL vibration is lead to that of the BM. Both the amplitude gain and the phase lead on RL is level dependent. This suggests that they are related to the cochlear amplification. The amplitude gain at the RL is an enhancement of the BM motion for stimulating the stereocillia. The advance in time of RL vibration can prepare proper timing of stereocillia stimulation for the cochlear amplification.
- Published
- 2012
34. ORGAN OF CORTI MICROMECHANICS WITH LOCAL ELECTRICAL STIMULATION
- Author
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Niloy Choudhury, Alfred L. Nuttall, Fangyi Chen, Jiefu Zheng, and Steve Jaques
- Subjects
Materials science ,Acoustics ,Laser Doppler velocimetry ,Sweep frequency response analysis ,Basilar membrane ,Interferometry ,medicine.anatomical_structure ,Organ of Corti ,Reticular connective tissue ,otorhinolaryngologic diseases ,medicine ,sense organs ,Coherence (physics) ,Group delay and phase delay ,Biomedical engineering - Abstract
Optical low coherence interferometry is able to both image and measure the vibration of the cellular and non-cellular structures of the organ of Corti in vivo. In this study we applied an electric current to the basal turn from a pair of electrodes, one in scala tympani and the other in scala vestibuli, at the location corresponding to ~17 kHz when interferometry measurements were made. The coherence gate of the interferometer was positioned 1) at the basilar membrane (BM) near the radial location of the outer hair cells (OHCs) (approximately 1⁄2 the width of the BM) and 2) at the reticular lamina (RL) where the OHCs are located. We confirmed that electrical stimulation with a frequency sweep (12 kHz –25 kHz) caused a mechanical BM displacement with a peak and a traveling wave-like phase delay as we reported previously using laser Doppler velocimetry and reflective beads on the BM. Reflective beads were not used in the current study. The vibration of the RL had little or no phase delay that would characterize a traveling wave. These data suggest a very high compliance system for the electrically activated cellular structure of the organ.
- Published
- 2009
35. In vivo imaging and low-coherence interferometry of organ of Corti vibration
- Author
-
Fangyi Chen, Jiefu Zheng, Alfred L. Nutall, Niloy Choudhury, Steven L. Jacques, and Scott Matthews
- Subjects
Male ,Tectorial membrane ,Movement ,Guinea Pigs ,Biomedical Engineering ,Mechanotransduction, Cellular ,Vibration ,Biomaterials ,Optics ,Optical coherence tomography ,Hearing ,Image Interpretation, Computer-Assisted ,otorhinolaryngologic diseases ,medicine ,Animals ,Organ of Corti ,Cochlea ,Physics ,medicine.diagnostic_test ,business.industry ,Image Enhancement ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials ,Interferometry ,Basilar membrane ,medicine.anatomical_structure ,Acoustic Stimulation ,Reticular connective tissue ,Female ,sense organs ,business ,Preclinical imaging ,Tomography, Optical Coherence - Abstract
An optical coherence tomography (OCT) system is built to acquire in vivo both images and vibration measurements of the organ of Corti of the guinea pig. The organ of Corti is viewed through a approximately 300-microm-diam hole in the bony wall of the cochlea at the scala tympani of the first cochlear turn. In imaging mode, the image is acquired as reflectance R(x,z). In vibration mode, the basilar membrane (BM) or reticular lamina (RL) are selected by the investigator interactively from the R(x,z) image. Under software control, the system moves the scanning mirrors to bring the sensing volume of the measurement to the desired membrane location. In vivo images of the organ of Corti are presented, indicating reflectance signals from the BM, RL, tectorial membrane, and Reissner's membrane. The tunnel of Corti and the inner sulcus are also visible in the images. Vibrations of +/-2 and +/-22 nm are recorded in the BM in response to low and high sound levels at 14 kHz above a noise floor of 0.2 nm.
- Published
- 2007
36. MANIPULATIONS OF CHLORIDE ION CONCENTRATION IN THE ORGAN OF CORTI ALTER OUTER HAIR CELL ELECTROMOTILITY AND COCHLEAR AMPLIFICATION
- Author
-
A. L. Nuttall, Jiefu Zheng, Y. Zou, and J. Santos-Sacchi
- Subjects
medicine.anatomical_structure ,Chemistry ,Organ of Corti ,medicine ,Biophysics ,Hair cell ,Chloride ,medicine.drug ,Ion - Published
- 2006
37. COCHLEAR TRANSDUCER OPERATING POINT ADAPTATION
- Author
-
Yuan Zou, Alfred L. Nuttall, Jiefu Zheng, and Tianying Ren
- Subjects
Sound Spectrography ,Acoustics and Ultrasonics ,Loudness Perception ,Acoustics ,Speech recognition ,Guinea Pigs ,Otoacoustic Emissions, Spontaneous ,Perilymph ,Arts and Humanities (miscellaneous) ,otorhinolaryngologic diseases ,medicine ,Animals ,Inner ear ,Cilia ,Ear canal ,Mechanotransduction ,Sound pressure ,Endolymphatic Duct ,Pitch Perception ,Cochlea ,Physics ,Auditory Threshold ,Signal Processing, Computer-Assisted ,Basilar Membrane ,Hair Cells, Auditory, Outer ,medicine.anatomical_structure ,Transducer ,Acoustic Stimulation ,Round Window, Ear ,Organ of Corti ,sense organs ,Hair cell ,Mechanoreceptors ,Transduction (physiology) ,Ear Canal ,DC bias - Abstract
The operating point (OP) of outer hair cell (OHC) mechanotransduction can be defined as any shift away from the center position on the transduction function. It is a dc offset that can be described by percentage of the maximum transduction current or as an equivalent dc pressure in the ear canal. The change of OP can be determined from the changes of the second and third harmonics of the cochlear microphonic (CM) following a calibration of its initial value. We found that the initial OP was dependent on sound level and cochlear sensitivity. From CM generated by a lower sound level at 74 dB SPL to avoid saturation and suppression of basal turn cochlear amplification, the OHC OP was at constant 57% of the maximum transduction current (an ear canal pressure of -0.1 Pa). To perturb the OP, a constant force was applied to the bony shell of the cochlea at the 18 kHz best frequency location using a blunt probe. The force applied over the scala tympani induced an OP change as if the organ of Corti moved toward the scala vestibuli (SV) direction. During an application of the constant force, the second harmonic of the CM partially recovered toward the initial level, which could be described by two time constants. Removing the force induced recovery of the second harmonic to its normal level described by a single time constant. The force applied over the SV caused an opposite result. These data indicate an active mechanism for OHC transduction OP.
- Published
- 2006
38. LOW COHERENCE INTERFEROMETRY OF THE COCHLEAR PARTITION
- Author
-
Steven L. Jacques, Alfred L. Nuttall, Fangyi Chen, S. Mathew, Jiefu Zheng, and Niloy Choudhury
- Subjects
Physics ,Interferometry ,Optics ,Cochlear partition ,business.industry ,Coherence (statistics) ,business - Published
- 2006
39. Control of Mammalian Cochlear Amplification by Chloride Anions
- Author
-
Joseph Santos-Sacchi, Lei Song, Jiefu Zheng, and Alfred L. Nuttall
- Subjects
biology ,Chemistry ,General Neuroscience ,Guinea Pigs ,Anatomy ,Articles ,Chloride ,Transmembrane protein ,Cochlea ,Motor protein ,Basilar membrane ,Hair Cells, Auditory, Outer ,medicine.anatomical_structure ,Chlorides ,Models, Animal ,medicine ,biology.protein ,Biophysics ,Animals ,Hair cell ,sense organs ,Anion binding ,Prestin ,medicine.drug - Abstract
Chloride ions have been hypothesized to interact with the membrane outer hair cell (OHC) motor protein, prestin on its intracellular domain to confer voltage sensitivity (Oliver et al., 2001). Thus, we hypothesized previously that transmembrane chloride movements via the lateral membrane conductance of the cell,GmetL, could serve to underlie cochlear amplification in the mammal. Here, we report on experimental manipulations of chloride-dependent OHC motor activityin vitroandin vivo.In vitro, we focused on the signature electrical characteristic of the motor, the nonlinear capacitance of the cell. Using the well known ototoxicant, salicylate, which competes with the putative anion binding or interaction site of prestin to assess level-dependent interactions of chloride with prestin, we determined that the resting level of chloride in OHCs is near or below 10 mm, whereas perilymphatic levels are known to be ∼140 mm. With this observation, we sought to determine the effects of perilymphatic chloride level manipulations of basilar membrane amplification in the living guinea pig. By either direct basolateral perfusion of the OHC with altered chloride content perilymphatic solutions or by the use of tributyltin, a chloride ionophore, we found alterations in OHC electromechanical activity and cochlear amplification, which are fully reversible. Because these anionic manipulations do not impact on the cation selective stereociliary process or the endolymphatic potential, our data lend additional support to the argument that prestin activity dominates the process of mammalian cochlear amplification.
- Published
- 2006
40. Low coherence interferometry of the cochlear partition
- Author
-
Jiefu Zheng, Tanja Tschinkel, Niloy Choudhury, Alfred L. Nuttall, Fangyi Chen, Guiju Song, Scott Matthews, and Steven L. Jacques
- Subjects
Materials science ,Guinea Pigs ,Vibration ,Optics ,Optical coherence tomography ,medicine ,Animals ,Organ of Corti ,Cochlea ,medicine.diagnostic_test ,business.industry ,Superluminescent diode ,Sensory Systems ,Basilar Membrane ,Numerical aperture ,Coherence length ,Biomechanical Phenomena ,Basilar membrane ,Interferometry ,medicine.anatomical_structure ,sense organs ,business ,Tomography, Optical Coherence ,Signal Transduction - Abstract
Interferometric measurement of the vibration of the organ of Corti in the isolated guinea pig cochlea was conducted using low-coherence light (1310+/-47 nm wavelength) from a superluminescent diode. The short coherence length of the light source localized measurements along the axial direction to within a approximately 10-microm window (in tissue), even when using a low numerical-aperture lens. The ability to accomplish this is important because measurement of the vibration of the basal-turn organ of Corti is generally done via a small hole in the bone of the cochlea, which effectively limits the numerical aperture. The axial localization, combined with the inherent sensitivity of the method, allowed distinct measurements of the basilar membrane (BM) and the putative reticular lamina (RL) vibration using only the native tissue reflectance, that is without requiring the use of reflective particles. The system was first operated in a scanning mode as an optical coherence tomography (OCT) system to yield an image of the organ of Corti. The reflectance of intensity from the BM and RL was 8x10(-5) and 8x10(-6), respectively. The internal structure between the BM and RL presented a variable reflectivity of about 10(-7). A mirror would define a reflectance of 1.00. Then the instrument was operated as a homodyne interferometer to measure the displacement of either the BM or RL. Vibration at 16 kHz was induced by a piezoelectric actuator, causing whole movement of a dissected cochlea. After calibration of the system, we demonstrated clear measurement of mechanically driven vibration for both the BM and RL of 0.30 nm above a noise floor equivalent to 0.03 nm. OCT interferometry, when adapted for in vivo organ of Corti measurements, appears suitable to determine the micromechanical vibration of cells and tissue elements of the organ.
- Published
- 2006
41. Spontaneous Basilar Membrane Oscillation and Otoacoustic Emission at 15 kHz in a Guinea Pig
- Author
-
Jiefu Zheng, Tianying Ren, E. de Boer, Alfred L. Nuttall, Karl Grosh, and Yuan Zou
- Subjects
Materials science ,Acoustics ,Guinea Pigs ,Otoacoustic Emissions, Spontaneous ,Otoacoustic emission ,Action Potentials ,Article ,Nuclear magnetic resonance ,medicine ,otorhinolaryngologic diseases ,Animals ,Ear canal ,Oscillation ,Audiogram ,Sensory Systems ,Basilar Membrane ,Compound muscle action potential ,Electrophysiology ,Basilar membrane ,medicine.anatomical_structure ,Otorhinolaryngology ,Acoustic Stimulation ,Evoked Potentials, Auditory ,sense organs ,Tonotopy ,Ear Canal - Abstract
A spontaneous otoacoustic emission (SOAE) measured in the ear canal of a guinea pig was found to have a counterpart in spontaneous mechanical vibration of the basilar membrane (BM). A spontaneous 15-kHz BM velocity signal was measured from the 18-kHz tonotopic location and had a level close to that evoked by a 14-kHz, 15-dB SPL tone given to the ear. Lower-frequency pure-tone acoustic excitation was found to reduce the spontaneous BM oscillation (SBMO) while higher-frequency sound could entrain the SBMO. Octave-band noise centered near the emission frequency showed an increased narrow-band response in that frequency range. Applied pulses of current enhanced or suppressed the oscillation, depending on polarity of the current. The compound action potential (CAP) audiogram demonstrated a frequency-specific loss at 8 and 12 kHz in this animal. We conclude that a relatively high-frequency spontaneous oscillation of 15 kHz originated near the 15-kHz tonotopic place and appeared at the measured BM location as a mechanical oscillation. The oscillation gave rise to a SOAE in the ear canal. Electric current can modulate level and frequency of the otoacoustic emission in a pattern similar to that for the observed mechanical oscillation of the BM.
- Published
- 2004
42. The sources of electrically evoked otoacoustic emissions
- Author
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Alfred L. Nuttall, Jiefu Zheng, Yuan Zou, and Tianying Ren
- Subjects
Round window ,Materials science ,Acoustics ,Otoacoustic Emissions, Spontaneous ,Otoacoustic emission ,Low frequency ,Sensory Systems ,Basilar Membrane ,Electric Stimulation ,Tone (musical instrument) ,Basilar membrane ,medicine.anatomical_structure ,Acoustic Stimulation ,Round Window, Ear ,Frequency separation ,otorhinolaryngologic diseases ,medicine ,Reaction Time ,Animals ,Inner ear ,sense organs ,Sound pressure ,Gerbillinae - Abstract
It has been hypothesized that electrically evoked otoacoustic emissions (EEOAEs) are generated at a site on the basilar membrane near the stimulating electrode. From this original site, the energy propagates towards the oval window, giving rise to the short time delay component (SDC) of EEOAEs. The energy also propagates towards its characteristic frequency (CF) location, and the emission reflected from the CF location forms a long time delay component (LDC). This hypothesis is directly tested in this study by using an acoustical swept tone to modulate the EEOAEs generated by alternating electric current delivered to the round window niche in gerbils. An acoustical tone with a high sound pressure level or a small frequency separation from the EEOAE frequency induced a strong suppression of the EEOAE LDC, but no obvious suppression of the SDC. When the electrical current frequency was fixed, the swept acoustic tone induced a slight suppression, an enhanced peak, and a strong suppression of EEOAEs as the acoustic frequency was swept from the low to high frequency. These data indicate that the electrical current induced cochlear partition vibration near the stimulating electrode. One part of this energy propagates directly to the ear canal, forming the SDC, and the other part propagates to its CF place and is reflected from there to the ear canal, forming the LDC.
- Published
- 2003
43. MODELING ELECTRICALLY EVOKED OTOACOUSTIC EMISSIONS
- Author
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Anand A. Parthasarathi, Niranjan Deo, Alfred L. Nuttall, Jiefu Zheng, Karl Grosh, and Tianying Ren
- Subjects
Physics ,Basilar membrane ,medicine.anatomical_structure ,Round window ,Acoustics ,Electrode ,medicine ,Traveling wave ,Hair cell ,Spatial extent ,Excitation ,Stapes - Abstract
Electrical evoked otoacoustic emissions (EEOAE) are used to investigate in viwo cochlear electromechanical function. Round window electrical stimulation gives rise to a broad frequency EEOAE response, from 100 Hz or below to 40 kHz in guinea pigs. Placing bipolar electrodes very close to the basilar membrane (in the scala vestibuli and scala tympani) gives rise to a much narrower frequency range of EEOAE, limited to around 20 kHz when the electrodes are placed near the 18 kHz best frequency place. Model predictions using a three dimensional fluid model in conjunction with a simple model for outer hair cell (OHC) activity are used to interpret the experimental results. The model is solved using a 2.5D finiteelement formulation. Predictions show that the high-frequency limit of the excitation is determined by the spatial extent of the current stimulus (also called the current spread). The global peaks in the EEOAE spectra are interpreted as constructive interference between electrically evoked backward traveling waves and forward traveling waves reflected from the stapes. Steady-state response predictions of the model are presented.
- Published
- 2003
44. Effect of current stimulus on in vivo cochlear mechanics
- Author
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Jiefu Zheng, Karl Grosh, Alfred L. Nuttall, and Anand A. Parthasarathi
- Subjects
Sound Spectrography ,Acoustics and Ultrasonics ,Acoustics ,Loudness Perception ,Guinea Pigs ,Stimulus (physiology) ,Synaptic Transmission ,Membrane Potentials ,Arts and Humanities (miscellaneous) ,otorhinolaryngologic diseases ,medicine ,Animals ,Pitch Perception ,Impulse response ,Physics ,Membrane potential ,Direct current ,Scala Tympani ,Basilar Membrane ,Electric Stimulation ,Basilar membrane ,Hair Cells, Auditory, Outer ,Amplitude ,medicine.anatomical_structure ,Acoustic Stimulation ,Biophysics ,Cochlear Microphonic Potentials ,sense organs ,Hair cell ,Excitation - Abstract
In this paper, the influence of direct current stimulation on the acoustic impulse response of the basilar membrane (BM) is studied. A positive current applied in the scala vestibuli relative to a ground electrode in the scala tympani is found to enhance gain and increase the best frequency at a given location on the BM. An opposite effect is found for a negative current. Also, the amplitude of low-frequency cochlear microphonic at high sound levels is found to change with the concurrent application of direct current stimulus. BM vibrations in response to pure tone acoustic excitation are found to possess harmonics whose levels relative to the fundamental increase with the application of positive current and decrease with the application of negative current. A model for outer hair cell activity that couples changes in length and stiffness to transmembrane potential is used to interpret the results of these experiments and others in the literature. The importance of the in vivo mechanical and electrical loading is emphasized. Simulation results show the somewhat paradoxical finding that for outer hair cells under tension, hyperpolarization causes shortening of the cell length due to the dominance of voltage dependent stiffness changes.
- Published
- 2003
45. Electrically evoked otoacoustic emissions from apical and basal perilymphatic electrode positions in the guinea pig cochlea
- Author
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Jiefu Zheng, Alfred L. Nuttall, Tianying Ren, and Egbert de Boer
- Subjects
Materials science ,Round window ,Acoustics ,Guinea Pigs ,Otoacoustic Emissions, Spontaneous ,Otoacoustic emission ,Perilymph ,Sensory Systems ,Cochlear Aqueduct ,Electric Stimulation ,Cochlea ,Basilar membrane ,medicine.anatomical_structure ,Nuclear magnetic resonance ,Round Window, Ear ,Organ of Corti ,otorhinolaryngologic diseases ,medicine ,Cochlear aqueduct ,Animals ,Inner ear ,sense organs ,Electrodes - Abstract
Stimulation of the cochlea with sinusoidal current results in the production of an otoacoustic emission at the primary frequency of the stimulus current. In this study we test the hypothesis that the wide frequency response from round window (RW) stimulation is due to the involvement of a relatively large spatial segment of the organ of Corti. Tonotopically organized group delays would be evident from perilymphatic electrode locations that restrict the spatial extent of hair cell stimulation. Monopolar and bipolar-paired stimulus electrodes were placed in perilymphatic areas of the first or third cochlear turns and the electrically evoked otoacoustic emissions (EEOAE) produced by these electrodes were compared to that from the RW monopolar electrode in the anesthetized guinea pig. Current stimuli of 35 microA RMS were swept across the frequency range between 60 Hz and 100 kHz. The EEOAE was measured using a microphone coupled to the ear canal. It was found that the bandwidth of EEOAEs from RW stimulation extended to at least 40 kHz and was a relatively insensitive to electrode location on the RW. The group delay of the EEOAE from stimulation at the RW membrane (corrected to stapes motion) was about 53 micros. First and third turn stimulations from electrode placements in perilymph near the bony wall of cochlea yielded narrower band EEOAE magnitude spectra but which had the same short group delays as for RW stimulation. A confined current (from a bipolar electrode pair) applied close to the basilar membrane (BM) in the first turn produced the narrowest frequency-band magnitude emissions and a mean corrected group delay of 176 micros for a location approximately 3 mm from the high frequency end of the BM (corresponding to about the 18 kHz best frequency location). Bipolar electrodes in the third turn scala tympani produced low pass EEOAE magnitude functions with corrected group delays ranging between approximately 0.3 and 1 ms. The average phase slopes did not change with altered cochlear sensitivity and postmortem. These data indicate that the EEOAE from RW stimulation is the summed response from a wide-tonotopic distribution of outer hair cells. A preliminary model study indicates that short time delayed emissions are the result of a large spatial distribution of current applied to perilymphatic locations possibly giving rise to "wave-fixed" emissions.
- Published
- 2001
46. ORGAN OF CORTI MICROMECHANICS WITH LOCAL ELECTRICAL STIMULATION.
- Author
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FANGYI CHEN, JIEFU ZHENG, CHOUDHURY, NILOY, JAQUES, STEVE, and NUTTALL, ALFRED L.
- Subjects
CORTI'S organ ,COCHLEA ,MICROMECHANICS ,TYMPANIC membrane ,OPTICAL coherence tomography - Published
- 2009
47. A differentially amplified motion in the ear for near-threshold sound detection.
- Author
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Fangyi Chen, Zha, Dingjun, Fridberger, Anders, Jiefu Zheng, Choudhury, Niloy, Jacques, Steven L., Wang, Ruikang K., Xiaorui Shi, and Nuttall, Alfred L.
- Subjects
BASILAR membrane ,HAIR cells ,TOMOGRAPHY ,SOUNDS ,AUDITORY pathways ,GUINEA pigs as laboratory animals - Abstract
The ear is a remarkably sensitive pressure fluctuation detector. In guinea pigs, behavioral measurements indicate a minimum detectable sound pressure of ∼20 μPa at 16 kHz. Such faint sounds produce 0.1-nm basilar membrane displacements, a distance smaller than conformational transitions in ion channels. It seems that noise within the auditory system would swamp such tiny motions, making weak sounds imperceptible. Here we propose a new mechanism contributing to a resolution of this problem and validate it through direct measurement. We hypothesized that vibration at the apical side of hair cells is enhanced compared with that at the commonly measured basilar membrane side. Using in vivo optical coherence tomography, we demonstrated that apical-side vibrations peaked at a higher frequency, had different timing and were enhanced compared with those at the basilar membrane. These effects depend nonlinearly on the stimulus sound pressure level. The timing difference and enhancement of vibrations are important for explaining how the noise problem is circumvented. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
48. Inverted direction of wave propagation (IDWP) in the cochlea.
- Author
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De Boer, Egbert, Jiefu Zheng, Porsov, Edward, and Nuttall, Alfred L.
- Subjects
- *
COCHLEA , *BASILAR membrane , *EAR , *HEARING , *BIOLOGICAL membranes , *WORK measurement - Abstract
The “classical” view on wave propagation is that propagating waves are possible in both directions along the length of the basilar membrane and that they have identical properties. Results of several recently executed experiments [T. Ren, Nat. Neurosci. 2, 333–334 (2004) and W. X. He, A. L. Nuttall, and T. Ren, Hear. Res., 228, 112–122 (2007)] appear to contradict this view. In the current work measurements were made of the velocity of the guinea-pig basilar membrane (BM). Distortion products (DPs) were produced by presenting two primary tones, with frequencies below the characteristic frequency f0 of the BM location at which the BM measurements were made, with a constant frequency ratio. In each experiment the phase of the principal DP, with frequency 2f1-f2, was recorded as a function of the DP frequency. The results indicate that the DP wave going from the two-tone interaction region toward the stapes is not everywhere traveling in the reverse direction, but also in the forward direction. The extent of the region in which the forward wave occurs appears larger than is accounted for by classical theory. This property has been termed “inverted direction of wave propagation.” The results of this study confirm the wave propagation findings of other authors. The experimental data are compared to theoretical predictions for a classical three-dimensional model of the cochlea that is based on noise-response data of the same animal. Possible physical mechanisms underlying the findings are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
49. Chlorpromazine Alters Cochlear Mechanics and Amplification: In Vivo Evidence for a Role of Stiffness Modulation in the Organ of Corti.
- Author
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Jiefu Zheng
- Subjects
- *
CHLORPROMAZINE , *COCHLEAR nucleus , *HAIR cells , *COCHLEA - Abstract
Although prestin-mediated outer hair cell (OHC) electromotility provides mechanical force for sound amplification in the mammalian cochlea, proper OHC stiffness is required to maintain normal electromotility and to transmit mechanical force to the basilar membrane (BM). To investigate the in vivo role of OHC stiffness in cochlear amplification, chlorpromazine (CPZ), an antipsychotic drug that alters OHC lateral wall biophysics, was infused into the cochleae in living guinea pigs. The effects of CPZ on cochlear amplification and OHC electromotility were observed by measuring the acoustically and electrically evoked BM motions. CPZ significantly reduced cochlear amplification as measured by a decline of the acoustically evoked BM motion near the best frequency (BF) accompanied by a loss of nonlinearity and broadened tuning. It also substantially reduced electrically evoked BM vibration near the BF and at frequencies above BF (≤80 kHz). The high-frequency notch (near 50 kHz) in the electrically evoked BM response shifted toward higher frequency in a CPZ concentration-dependent manner with a corresponding phase change. In contrast, salicylate resulted in a shift in this notch toward lower frequency. These results indicate that CPZ reduces OHC-mediated cochlear amplification probably via its effects on the mechanics of the OHC plasma membrane rather than via a direct effect on the OHC motor, prestin. Through modeling, we propose that with a combined OHC somatic and hair bundle forcing, the upward-shift of the ∼50-kHz notch in the electrically-evoked BM motion may indicate stiffness increase of the OHCs that is responsible for the reduced cochlear amplification. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
50. Control of Mammalian Cochlear Amplification by Chloride Anions.
- Author
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Santos-Sacchi, Joseph, Lei Song, Jiefu Zheng, and Nuttall, Alfred L.
- Subjects
CHLORIDES ,IONS ,HAIR cells ,CHLORINE compounds ,INTERMEDIATES (Chemistry) ,SOLUTION (Chemistry) ,CORTI'S organ ,MECHANORECEPTORS - Abstract
Chloride ions have been hypothesized to interact with the membrane outer hair cell (OHC) motor protein, prestin on its intracellular domain to confer voltage sensitivity (Oliver et al., 2001). Thus, we hypothesized previously that transmembrane chloride movements via the lateral membrane conductance of the cell, G
metL , could serve to underlie cochlear amplification in the mammal. Here, we report on experimental manipulations of chloride-dependent OHC motor activity in vitro and in vivo. In vitro,we focused on the signature electrical characteristic of the motor, the nonlinear capacitance of the cell. Using the well known ototoxicant, salicylate, which competes with the putative anion binding or interaction site of prestin to assess level-dependent interactions of chloride with prestin, we determined that the resting level of chloride in OHCs is near or below 10 mM, whereas perilymphatic levels are known to be ∼140 mM. With this observation, we sought to determine the effects of perilymphatic chloride level manipulations of basilar membrane amplification in the living guinea pig. By either direct basolateral perfusion of the OHC with altered chloride content perilymphatic solutions or by the use of tributyltin, a chloride ionophore, we found alterations in OHC electromechanical activity and cochlear amplification, which are fully reversible. Because these anionic manipulations do not impact on the cation selective stereociliary process or the endolymphatic potential, our data lend additional support to the argument that prestin activity dominates the process of mammalian cochlear amplification. [ABSTRACT FROM AUTHOR]- Published
- 2006
- Full Text
- View/download PDF
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