Publications by authors named "Haitao Song"

22 Publications

  • Page 1 of 1

Rapid identification of papillary thyroid carcinoma and papillary microcarcinoma based on serum Raman spectroscopy combined with machine learning models.

Photodiagnosis Photodyn Ther 2021 Nov 21:102647. Epub 2021 Nov 21.

College of Software, Xinjiang University, Urumqi, 830046, China.; Key Laboratory of Signal Detection and Processing, Xinjiang University, Urumqi, 830046, China.; College of Information Science and Engineering, Xinjiang University, Urumqi, 830046, China.

Thyroid carcinoma is one kind of cancer with the highest diagnosis rate in the endocrine system, and its main histological subtype is papillary thyroid carcinoma (PTC) accounting for 80% of thyroid malignancies. In recent years, the incidence of thyroid cancer has increased exponentially, and its substantial increase was closely related to the overdiagnosis of papillary microcarcinoma (PMC). Therefore, early and accurate identification of PTC and PMC can prevent patients from being irreversibly damaged. This study aimed to identify PTC and PMC using Raman spectroscopy. We collected serum Raman spectra from 16 patients with PTC and 31 patients with PMC. Firstly, the collected imbalance data were preprocessed using the synthetic minority over-sampling technique (SMOTE). Then, the equalized data were dimensionality reduced by principal component analysis (PCA). Finally, the processed data were fed into the single decision tree (DT) classifier, as well as the random forest (RF) built on the idea of Boosting ensemble and the Adaptive Boosting (Adaboost) model built on the idea of Bagging ensemble for classification. The classification accuracy of the three models in the testing set were 75.38%, 81.54%, and 84.61%, respectively. Compared with the DT classifier, the accuracy of the models introducing the idea of ensemble learning was enhanced by 6.16% and 9.23%, respectively. The best model was the Adaboost. This result demonstrates that serum Raman spectroscopy combined with an ensemble learning algorithm was feasible in rapidly identifying PTC and PMC. At the same time, the method has great potential for application in the field of clinical diagnosis.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102647DOI Listing
November 2021

Forecast of the COVID-19 trend in India: A simple modelling approach.

Math Biosci Eng 2021 11;18(6):9775-9786

Department of Applied Mathematics, Hong Kong Polytechnic University, Hong Kong, China.

By February 2021, the overall impact of the COVID-19 pandemic in India had been relatively mild in terms of total reported cases and deaths. Surprisingly, the second wave in early April becomes devastating and attracts worldwide attention. Multiple factors (e.g., Delta variants with increased transmissibility) could have driven the rapid growth of the epidemic in India and led to a large number of deaths within a short period. We aim to reconstruct the transmission rate, estimate the infection fatality rate and forecast the epidemic size. We download the reported COVID-19 mortality data in India and formulate a simple mathematical model with a flexible transmission rate. We use iterated filtering to fit our model to deaths data. We forecast the infection attack rate in a month ahead. Our model simulation matched the reported deaths well and is reasonably close to the results of the serological study. We forecast that the infection attack rate (IAR) could have reached 43% by July 24, 2021, under the current trend. Our estimated infection fatality rate is about 0.07%. Under the current trend, the IAR will likely reach a level of 43% by July 24, 2021. Our estimated infection fatality rate appears unusually low, which could be due to a low case to infection ratio reported in previous study. Our approach is readily applicable in other countries and with other types of data (e.g., excess deaths).
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http://dx.doi.org/10.3934/mbe.2021479DOI Listing
November 2021

NHBS-Net: A Feature Fusion Attention Network for Ultrasound Neonatal Hip Bone Segmentation.

IEEE Trans Med Imaging 2021 12 30;40(12):3446-3458. Epub 2021 Nov 30.

Ultrasound is a widely used technology for diagnosing developmental dysplasia of the hip (DDH) because it does not use radiation. Due to its low cost and convenience, 2-D ultrasound is still the most common examination in DDH diagnosis. In clinical usage, the complexity of both ultrasound image standardization and measurement leads to a high error rate for sonographers. The automatic segmentation results of key structures in the hip joint can be used to develop a standard plane detection method that helps sonographers decrease the error rate. However, current automatic segmentation methods still face challenges in robustness and accuracy. Thus, we propose a neonatal hip bone segmentation network (NHBS-Net) for the first time for the segmentation of seven key structures. We design three improvements, an enhanced dual attention module, a two-class feature fusion module, and a coordinate convolution output head, to help segment different structures. Compared with current state-of-the-art networks, NHBS-Net gains outstanding performance accuracy and generalizability, as shown in the experiments. Additionally, image standardization is a common need in ultrasonography. The ability of segmentation-based standard plane detection is tested on a 50-image standard dataset. The experiments show that our method can help healthcare workers decrease their error rate from 6%-10% to 2%. In addition, the segmentation performance in another ultrasound dataset (fetal heart) demonstrates the ability of our network.
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http://dx.doi.org/10.1109/TMI.2021.3087857DOI Listing
December 2021

Research on Hazardous Waste Removal Management: Identification of the Hazardous Characteristics of Fluid Catalytic Cracking Spent Catalysts.

Molecules 2021 Apr 15;26(8). Epub 2021 Apr 15.

Sinopec Research Institute of Petroleum Processing, Beijing 100083, China.

Fluid catalytic cracking (FCC) spent catalysts are the most common catalysts produced by the petroleum refining industry in China. The National Hazardous Waste List (2016 edition) lists FCC spent catalysts as hazardous waste, but this listing is very controversial in the petroleum refining industry. This study collects samples of waste catalysts from seven domestic catalytic cracking units without antimony-based passivation agents and identifies their hazardous characteristics. FCC spent catalysts do not have the characteristics of flammability, corrosiveness, reactivity, or infectivity. Based on our analysis of the components and production process of the FCC spent catalysts, we focused on the hazardous characteristic of toxicity. Our results show that the leaching toxicity of the heavy metal pollutants nickel, copper, lead, and zinc in the FCC spent catalyst samples did not exceed the hazardous waste identification standards. Assuming that the standards for antimony and vanadium leachate are 100 times higher than that of the surface water and groundwater environmental quality standards, the leaching concentration of antimony and vanadium in the FCC spent catalyst of the G set of installations exceeds the standard, which may affect the environmental quality of surface water or groundwater. The quantities of toxic substances in all spent FCC catalysts, except those from G2, does not exceed the standard. The acute toxicity of FCC spent catalysts in all installations does not exceed the standard. Therefore, we exclude "waste catalysts from catalytic cracking units without antimony-based passivating agent passivation nickel agent" from the "National Hazardous Waste List."
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http://dx.doi.org/10.3390/molecules26082289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071287PMC
April 2021

Estimation of COVID-19 outbreak size in Harbin, China.

Nonlinear Dyn 2021 Apr 10:1-9. Epub 2021 Apr 10.

School of Mathematical Sciences, Tiangong University, Tianjin, 300387 China.

Since the first level response to public health emergencies was launched on January 25, 2020, in Heilongjiang province, China, the outbreak of COVID-19 seems to be under control. However, an outbreak of COVID-19 caused by imported cases developed in Harbin during April 2020. A mathematical model is established to investigate the transmission of COVID-19 in Harbin. Based on the dynamical analysis and data fitting, the research investigates the outbreak of COVID-19 in Harbin and estimates the outbreak size of COVID-19 in Harbin. The outbreak size estimated of COVID-19 in Harbin reaches 174, where 54% of infected cases were identified while 46% of infected cases were not found out. We should maintain vigilance against unfound infected people. Our findings suggest that the effective reproduction number decreased drastically in contrast with the value of 3.6 on April 9; after that the effective interventions were implemented by the Heilongjiang province government. Finally, the effective reproduction number arrived at the value of 0.04 which is immensely below the threshold value 1, which means that the Heilongjiang province government got the outbreak of COVID-19 in Harbin under control.
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http://dx.doi.org/10.1007/s11071-021-06406-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035889PMC
April 2021

Using traveller-derived cases in Henan Province to quantify the spread of COVID-19 in Wuhan, China.

Nonlinear Dyn 2020 Aug 4:1-11. Epub 2020 Aug 4.

School of Mathematical Sciences, Tiangong University, Tianjin, 300387 China.

Wuhan shutdown was implemented on January 23 and the first level response to public health emergencies (FLRPHE) was launched over the country, and then China got the outbreak of COVID-19 under control. A mathematical model is established to study the transmission of COVID-19 in Wuhan. This research investigates the spread of COVID-19 in Wuhan and assesses the effectiveness of control measures including the Wuhan city travel ban and FLRPHE. Based on the dynamical analysis and data fitting, the transmission of COVID-19 in Wuhan is estimated and the effects of control measures including Wuhan city travel ban and FLRPHE are investigated. According to the assumptions, the basic reproduction number for COVID-19 estimated that for Wuhan equal to 7.53 and there are infectious people in Wuhan as of January 23. The interventions including the Wuhan city travel ban and FLRPHE reduce the size of peak and the cumulative number of confirmed cases of COVID-19 in Wuhan by 99%. The extraordinary efforts implemented by China effectively contain the transmission of COVID-19 and protect public health in China.
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http://dx.doi.org/10.1007/s11071-020-05859-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398862PMC
August 2020

Quercetin attenuates reduced uterine perfusion pressure -induced hypertension in pregnant rats through regulation of endothelin-1 and endothelin-1 type A receptor.

Lipids Health Dis 2020 Aug 5;19(1):180. Epub 2020 Aug 5.

Department of obstetrics, Qingdao Municipal Hospital, No. 5 Donghai Road, Qingdao, 266071, Shandong, China.

Background: Quercetin was reported to be crucial for a broad range of activities, including attenuating inflammation, platelet aggregation, capillary permeability, and lipid peroxidation. However, the effect of quercetin in hypertension during pregnancy, was not fully understood.

Methods: The model of hypertension in pregnancy was established in rats by reduced uterine perfusion pressure (RUPP). Quercetin was administrated by gavage. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using the CODA 6 BP system. Plasma concentrations of Endothelin-1 (ET-1), soluble fms-like tyrosine kinase-1 (sFlt-1), and vascular endothelial growth factor (VEGF) were detected using enzyme-linked immunosorbent assay kits. The mRNA and protein levels of ET-1 and endothelin-1 type A receptor (ETR) were determined by RT-PCR and Western blotting. The ETR antagonist BQ-123 was performed by osmotic minipumps.

Results: In RUPP induced rats, quercetin treatment decreased SBP and DBP, fetal resorptions percentage, plasma ET-1 and sFlt-1 concentrations, ET-1 and ETR levels, but increased fetal body weight and VEGF expression. BQ-123 administration attenuated SBP and DBP, suppressed fatal resorptions percentage, and increased fetal body weight of RUPP rats.

Conclusion: Quercetin attenuates RUPP induced hypertension in pregnant rats through the regulation of ET-1 and ETR.
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http://dx.doi.org/10.1186/s12944-020-01357-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409636PMC
August 2020

MicroRNA‑613 inhibits proliferation and invasion of renal cell carcinoma cells through targeting FZD7.

Mol Med Rep 2017 Oct 24;16(4):4279-4286. Epub 2017 Jul 24.

Department of Urinary Surgery, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China.

MicroRNAs (miRNAs) have emerged as critical regulators in cancer progression. miR‑613 has been reported as a tumor suppressor gene in many types of human cancers. However, the function of miR‑613 in renal cell carcinoma (RCC) remains unclear. In the present study, the authors aimed to detect the expression of miR‑613 and its function in RCC cell lines. miR‑613 was reported to be significantly downregulated RCC cell lines. Functional analyses demonstrated that overexpression of miR‑613 significantly decreased RCC cell proliferation and invasion. Bioinformatics analysis showed that Frizzled7 (FZD7) was a predicted target of miR‑613, which was verified by dual‑luciferase reporter assay, reverse transcription quantitative‑polymerase chain reaction and western blot analysis. Restoration of FZD7 significantly reversed the suppressive effects of miR‑613 on RCC cell proliferation and invasion. Taken together, the results of the present study indicated that miR‑613 functions as a tumor suppressor that inhibits RCC cell proliferation and invasion by targeting and inhibiting FZD7, providing novel insight into RCC pathogenesis and a potential therapeutic target for RCC.
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http://dx.doi.org/10.3892/mmr.2017.7076DOI Listing
October 2017

MicroRNA-384 Inhibits the Growth and Invasion of Renal Cell Carcinoma Cells by Targeting Astrocyte Elevated Gene 1.

Oncol Res 2018 Apr 25;26(3):457-466. Epub 2017 Aug 25.

Department of Urinary Surgery, ChinaJapan Union Hospital, Jilin UniversityChangchunP.R. China.

MicroRNAs (miRNAs) are emerging as pivotal regulators in the development and progression of various cancers, including renal cell carcinoma (RCC). MicroRNA-384 (miR-384) has been found to be an important cancer-related miRNA in several types of cancers. However, the role of miR-384 in RCC remains unclear. In this study, we aimed to investigate the potential function of miR-384 in regulating tumorigenesis in RCC. Here we found that miR-384 was significantly downregulated in RCC tissues and cell lines. Overexpression of miR-384 significantly inhibited the growth and invasion of RCC cells, whereas inhibition of miR-384 had the opposite effects. Bioinformatic analysis and luciferase reporter assay showed that miR-384 directly targeted the 3'-untranslated region of astrocyte elevated gene 1 (AEG-1). Further data showed that miR-384 could negatively regulate the expression of AEG-1 in RCC cells. Importantly, miR-384 expression was inversely correlated with AEG-1 expression in clinical RCC specimens. Moreover, miR-384 regulates the activation of Wnt signaling. Overexpression of AEG-1 significantly reversed the antitumor effects of miR-384. Overall, these findings suggest that miR-384 suppresses the growth and invasion of RCC cells via downregulation of AEG-1, providing a potential therapeutic target for the treatment of RCC.
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http://dx.doi.org/10.3727/096504017X15035025554553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844631PMC
April 2018

A series of population models for Hyphantria cunea with delay and seasonality.

Math Biosci 2017 10 19;292:57-66. Epub 2017 Jul 19.

Laboratory of Mathematical Parallel Systems (Lamps), Department of Mathematics and Statistics, York University, Toronto, Ontario, M3J 1P3, Canada. Electronic address:

In this paper, we establish and study a basic stage-structured model for the population of Hyphantria cunea, a delay differential equation model and a model incorporating the resource and seasonality. By introducing the population reproduction number R, we show that R acts as a threshold parameter for the existence and stability of equilibria. The trivial equilibria of the above models are all globally asymptotically stable when R<1; the basic model and the delay-differential model have a unique positive equilibrium respectively, and they are both locally asymptotically stable when R>1; the model with periodic season is uniformly persistent and admits a positive periodic solution if R>1. Numerical simulations are carried out to illustrate the theoretical results. In addition, we consider the effect of temperature and season on the population of Hyphantria cunea.
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http://dx.doi.org/10.1016/j.mbs.2017.07.010DOI Listing
October 2017

Aminoalcohol-Induced Activation of Organophosphorus Hydrolase (OPH) towards Diisopropylfluorophosphate (DFP).

PLoS One 2017 13;12(1):e0169937. Epub 2017 Jan 13.

Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, Hubei, P. R. China.

Aminoalcohols have been addressed as activating buffers for alkaline phosphatase. However, there is no record on the buffer activation regarding organophosphorus hydrolase (OPH). Here we reported the activating effects of aminoalcohols on OPH-catalyzed hydrolysis of diisopropylfluorophosphate (DFP), an analog molecule of G-type warfare agents. The kinetic parametors kcat, Vmax and kcat/Km in the OPH reaction were remarkably increased in the buffers (pH 8.0, 25°C) containing aminoalcohols with C2 between nitrogen (N) and oxygen (O) in their structures, including triethanolamine (TEA), diethanolamine, monoethanolamine, 1-amino-2-propanol, 2-amino-2-methyl-1-propanol, and triisopropanolamine. In contrast, much lower or no rate-enhancing effects were observed in the adding of amines, alcohols, amine/alcohol mixtures, or 3-amino-1-propanol (C3 between N and O). The 300 mM TEA further increased DFP-degrading activities of OPH mutants F132Y and L140Y, the previously reported OPH mutants with desirable activities towards DFP. However, the treatment of ethylenediaminetetraacetate (EDTA) markedly abolished the TEA-induced activation of OPH. The product fluoride effectively inhibited OPH-catalyzed hydrolysis of DFP by a linear mixed inhibition (inhibition constant Ki ~ 3.21 mM), which was partially released by TEA adding at initial or later reaction stage. The obtained results indicate the activation of OPH by aminoalcohol buffers could be attributed to the reduction of fluoride inhibition, which would be beneficial to the hydrolase-based detoxification of organophosphofluoridate.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169937PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5234802PMC
August 2017

MicroRNA-200a-3p suppresses tumor proliferation and induces apoptosis by targeting SPAG9 in renal cell carcinoma.

Biochem Biophys Res Commun 2016 Feb 23;470(3):620-626. Epub 2016 Jan 23.

Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, China. Electronic address:

Sperm-associated antigen 9(SPAG9), as a well-recognized oncogene protein, has a critical effect on renal cell carcinoma (RCC) progression. Our study tried to explore the mediator of miR-200a-3p, a tumor suppressing miRNA on SPAG9 expression and renal cell proliferation and apoptosis. We found the expression of miR-200a-3p was significantly lower in RCC specimens. Based on in vitro assays, we found miR-200a-3p significantly inhibit cancer cell proliferation by inducing apoptosis. In addition, our study uncovered that miR-200a-3p directly regulates oncogenic SPAG9 in 786-O and ACHN cells. Silencing of SPAG9 resulted in significantly decreased in the growth and the cell cycle of the renal cancer cell lines. Understanding of oncogenic SPAG9 regulated by miR-200a-3p might be beneficial to reveal new therapeutic targets for RCC.
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http://dx.doi.org/10.1016/j.bbrc.2016.01.095DOI Listing
February 2016

Virus dynamics model with intracellular delays and immune response.

Math Biosci Eng 2015 Feb;12(1):185-208

Department of Mathematics, Harbin Institute of Technology, Harbin, 150001, China.

In this paper, we incorporate an extra logistic growth term for uninfected CD4+ T-cells into an HIV-1 infection model with both intracellular delay and immune response delay which was studied by Pawelek et al. in [26]. First, we proved that if the basic reproduction number R0 < 1, then the infection-free steady state is globally asymptotically stable. Second, when R0 > 1, then the system is uniformly persistent, suggesting that the clearance or the uniform persistence of the virus is completely determined by R0. Furthermore, given both the two delays are zero, then the infected steady state is asymptotically stable when the intrinsic growth rate of the extra logistic term is sufficiently small. When the two delays are not zero, we showed that both the immune response delay and the intracellular delay may destabilize the infected steady state by leading to Hopf bifurcation and stable periodic oscillations, on which we analyzed the direction of the Hopf bifurcation as well as the stability of the bifurcating periodic orbits by normal form and center manifold theory introduced by Hassard et al. Third, we engaged numerical simulations to explore the rich dynamics like chaotic oscillations, complicated bifurcation diagram of viral load due to the logistic term of target cells and the two time delays.
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http://dx.doi.org/10.3934/mbe.2015.12.185DOI Listing
February 2015

Noninvasive intratympanic dexamethasone treatment for sudden sensorineural hearing loss.

Acta Otolaryngol 2012 Jun 19;132(6):583-9. Epub 2012 Feb 19.

Department of Otolaryngology, Beijing Hospital, Beijing, China.

Conclusion: Noninvasive intratympanic dexamethasone perfusion (IDP) through the eustachian tube is an effective and safe therapy in cases of sudden sensorineural hearing loss (SSNHL).

Objective: To investigate the effectiveness and safety of noninvasive IDP through the eustachian tube in patients with SSNHL.

Methods: In this prospective study, 74 consecutive patients with SSNHL treated between September 2007 and March 2011 were enrolled: 35 patients fitted the criteria for initial treatment in the study (group I), while 39 patients, who had failed systemic therapy, received salvage treatment (group S). IDP through the eustachian tube was applied four times at 2-day intervals. Pure-tone test and tympanometry were performed before starting treatment, and 24 h and 1 week afterwards.

Results: All patients tolerated the procedure well. No perforation or infection was noticed in any of the patients at their last visit. With regard to the 74 patients who received intratympanic treatment, 80.0% (28 of 35) of the patients in group I and 64.1% (25 of 39) patients in group S had improvement in their hearing ability. Patients with simultaneous symptoms reported that the symptoms were relieved as follows: tinnitus, 73.3% (44/60); vertigo, 76.2% (16/21); and stuffy ear, 81.1% (30/37).
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http://dx.doi.org/10.3109/00016489.2011.649145DOI Listing
June 2012

[Application of vestibular autorotation test in diagnosis of benign paroxysmal positional vertigo].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2010 Oct;24(19):865-9

Department of Otorhinolaryngology, Beijing Hospital, Ministry of Public Health, Beijing, 100073, China.

Objective: The objective of this study was to evaluate the utility of vestibular autorotation test in the diagnosis of BPPV.

Method: VAT and caloric test were performed on 41 patients with BPPV. VAT results were analyzed according to the affected semicircular canal.

Result: Results of VAT were abnormal in 34 (82.93%) patients with BPPV. Fourteen cases were found with abnormal vertical phase, 1 case with abnormal vertical gain in a total of 21 vertical semicircular canal BPPV patients. Six cases with abnormal horizontal phase lead, 5 cases with abnormal horizontal gain, 2 cases with asymmetry were found in 12 patients with horizontal semicircular canal BPPV. Phase lead was abnormal in all frequencies in 4 patients, and in 2-3 Hz in 21 patients. 24 (58.54%) patients showed abnormal canal paresis (CP) and direction preference (DP) in caloric test.

Conclusion: VAT can indicate information of vestibular function in both vertical and horizontal semicircular canal. Phase of VAT is constantly enhanced in BPPV, especially in 2-3 Hz. As the supplement of caloric test, VAT may prove helpful in assessment of semicircular canal function.
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October 2010

Release and elementary mechanisms of nitric oxide in hair cells.

J Neurophysiol 2010 May 10;103(5):2494-505. Epub 2010 Mar 10.

Center for Neuroscience, Department of Anesthesiology and Pain Medicine, Program in Communication Sciences, University of California, Davis, Davis, CA 95616, USA.

The enzyme nitric oxide (NO) synthase, that produces the signaling molecule NO, has been identified in several cell types in the inner ear. However, it is unclear whether a measurable quantity of NO is released in the inner ear to confer specific functions. Indeed, the functional significance of NO and the elementary cellular mechanism thereof are most uncertain. Here, we demonstrate that the sensory epithelia of the frog saccule release NO and explore its release mechanisms by using self-referencing NO-selective electrodes. Additionally, we investigated the functional effects of NO on electrical properties of hair cells and determined their underlying cellular mechanism. We show detectable amounts of NO are released by hair cells (>50 nM). Furthermore, a hair-cell efferent modulator acetylcholine produces at least a threefold increase in NO release. NO not only attenuated the baseline membrane oscillations but it also increased the magnitude of current required to generate the characteristic membrane potential oscillations. This resulted in a rightward shift in the frequency-current relationship and altered the excitability of hair cells. Our data suggest that these effects ensue because NO reduces whole cell Ca(2+) current and drastically decreases the open probability of single-channel events of the L-type and non L-type Ca(2+) channels in hair cells, an effect that is mediated through direct nitrosylation of the channel and activation of protein kinase G. Finally, NO increases the magnitude of Ca(2+)-activated K(+) currents via direct NO nitrosylation. We conclude that NO-mediated inhibition serves as a component of efferent nerve modulation of hair cells.
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http://dx.doi.org/10.1152/jn.00017.2010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867581PMC
May 2010

[Mice lacking of voltage-gated L-type calcium channel alpha1D subunit have impaired sinoatrial node function and caused deafness].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2007 May;21(10):468-72

Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Objective: L-type voltage-gated calcium channel subunit alpha1D-/- mice (homozygous mutant, knockout), alpha1D+/- (heterozygous) and alpha1D+/+ (wild-type) have played role in L-type voltage-gated calcium channel alpha1D subunit in auditory function of inner ear as well as sinoatrial node function of the mice.

Method: Hearing threshold and endocochlear potential (EP) were measured in the alpha1D knockout mice, heterozygous mice and wild-type mice by auditory brainstem response(ABR), EP recordings and Electrocardiograph (ECG) respectively. To assessment of the vestibular function of the mice, the ability of Balancing was performed by a swim test and a horizontal cylinder test.

Result: The auditory function of alD+/+ mice were normal, the mean value for ABR thresholds in response to click sound stimulus was (34.8 +/- 5.7) dB SPL,EP was (105.3 +/- 3.1) mV. The mean value for ABR thresholds in response to click sound stimulus was elevated in alpha1D+/- mice was (54.4 +/- 12.4) dB SPL, relative to that observed in alpha1D+/+ mice significantly increased (P < 0.05); EP of alpha1D+/- mice was about (75.8 +/- 9.9) mV. alpha1D-/- mice were completely deaf, the ABR wave form was not observed for even 100 dB SPL sound stimuli used and EP was still remain in (48.6 +/- 19.3) mV. alpha1D knockout mice were deaf and demonstrated no vestibular defect. alpha1D+/- and alpha1D-/- mice show significant sinus bradycardia with significant prolongation of the RR interval (146 +/- 1.4 and 244 +/- 2.9, respectively) comparing to the alpha1D+/+ wild-type mice (117 +/- 0.4) in the same littermates. In addition, the homozygous alpha1D-/- show a significant prolongation of the PR interval (53 +/- 0.5) compared to that of the a1D+/+ wild-type mice (38 +/- 0.3).

Conclusion: L-type voltage-gated calcium channel alpha1D subunit plays a critical role in calcium homeostasis in the inner ear. Mice lacking of alpha1D calcium channel gene would lead to influence auditory function and sinoatrial node dysfunction subsequently.
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May 2007

Cloning and characterization of porcine Fc gamma receptor II (FcgammaRII).

Vet Immunol Immunopathol 2006 Nov 22;114(1-2):178-84. Epub 2006 Aug 22.

College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, China.

Receptors for the Fc region (FcgammaRs) of IgG play a crucial role in the immune system and host protection against infection. In the present study, we describe the cloning, sequencing and characterization of porcine FcgammaRII. By screening a translated EST database with the protein sequence of the human FcgammaRII (CD32) we identified a putative porcine homologue. Using rapid amplification of cDNA ends (RACE), we isolated the full-length cDNA encoding porcine FcgammaRII from peripheral blood leucocyte RNA. The porcine FcgammaRII cDNA was 1488bp long, encoding a 297 amino acid trans-membrane glycoprotein composed of two immunoglobulin-like extracelluar domains, a trans-membrane region and a cytoplasmic tail with an immunoreceptor tyrosine-based inhibitory motif (ITIM). The predicted amino acid sequence was found to be 67% and 52% identitical with human and mouse FcgammaRIIB. RT-PCR indicated porcine FcgammaRII transcripts expressed in liver, alveolar, mesenteric lymph node and PBLs. COS-7 cells transfected with the pig FcgammaRII cDNA were able to bind chicken erythrocytes sensitized with porcine IgG. Identification of porcine FcgammaRII will aid in the understanding IgG-FcgammaR interactions, and may help in developing new immunization protocols.
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http://dx.doi.org/10.1016/j.vetimm.2006.06.012DOI Listing
November 2006

Cloning and expression of a small-conductance Ca(2+)-activated K+ channel from the mouse cochlea: coexpression with alpha9/alpha10 acetylcholine receptors.

J Neurophysiol 2004 Apr 3;91(4):1536-44. Epub 2003 Dec 3.

Department of Otolaryngology, University of California, Davis, California 95616, USA.

Functional interactions between ligand-gated, voltage-, and Ca(2+)-activated ion channels are essential to the properties of excitable cells and thus to the working of the nervous system. The outer hair cells in the mammalian cochlea receive efferent inputs from the brain stem through cholinergic nerve fibers that form synapses at their base. The acetylcholine released from these efferent fibers activates fast inhibitory postsynaptic currents mediated, to some extent, by small-conductance Ca(2+)-activated K+ channels (SK) that had not been cloned. Here we report the cloning, characterization, and expression of a complete SK2 cDNA from the mouse cochlea. The cDNAs of the mouse cochlea alpha9 and alpha10 acetylcholine receptors were also obtained, sequenced, and coexpressed with the SK2 channels. Human cultured cell lines transfected with SK2 yielded Ca(2+)-sensitive K+ current that was blocked by dequalinium chloride and apamin, known blockers of SK channels. Xenopus oocytes injected with SK2 in vitro transcribed RNA, under conditions where only outward K+ currents could be recorded, expressed an outward current that was sensitive to EGTA, dequalinium chloride, and apamin. In HEK-293 cells cotransfected with cochlear SK2 plus alpha9/alpha10 receptors, acetylcholine induced an inward current followed by a robust outward current. The results indicate that SK2 and the alpha9/alpha10 acetylcholine receptors are sufficient to partly recapitulate the native hair cell efferent synaptic response.
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http://dx.doi.org/10.1152/jn.00630.2003DOI Listing
April 2004

Protein kinase A mediates voltage-dependent facilitation of Ca2+ current in presynaptic hair cells in Hermissenda crassicornis.

J Neurophysiol 2003 Mar;89(3):1718-26

Center for Neuroscience, Department of Otolaryngology, University of California, Davis, California 95616, USA.

The simplest cellular model for classical conditioning in the nudibranch mollusk, Hermissenda crassicornis, involves the presynaptic hair cells and postsynaptic photoreceptors. Whereas the cellular mechanisms for postsynaptic photoreceptors have been studied extensively, the presynaptic mechanisms remain uncertain. Here, we determined the phenotype of the voltage-dependent Ca(2+) current in the presynaptic hair cells that may be directly involved in changes in synaptic efficacy during classical conditioning. The Ca(2+) current can be classified as a P-type current because its activation voltage under seawater recording conditions is approximately -30 mV, it showed slow inactivation, and it is reversibly blocked by omega-agatoxin-IVA. The steady-state activation and inactivation curves revealed a window current, and the single-channel conductance is approximately 20 pS. The P-type current was enhanced by cAMP analogs (approximately 1.3-fold), and by forskolin, an activator of adenylyl cyclase (approximately 1.25-fold). In addition, the P-type current showed voltage-dependent facilitation, which is mediated by protein kinase A (PKA). Specifically, the PKA inhibitor peptide [PKI(6-22)amide] blocked the enhancement of the Ca(2+) current produced by conditioning depolarization prepulses. Because neurotransmitter release is mediated by Ca(2+) influx via voltage-gated Ca(2+) channels, and because of the nonlinear relationship between the Ca(2+) influx and neurotransmitter release, we propose that voltage-dependent facilitation of the P-type current in hair cells would produce a robust change in synaptic efficacy.
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http://dx.doi.org/10.1152/jn.00766.2002DOI Listing
March 2003

Functional interaction of auxiliary subunits and synaptic proteins with Ca(v)1.3 may impart hair cell Ca2+ current properties.

J Neurophysiol 2003 Feb;89(2):1143-9

Center for Neuroscience, Department of Otolaryngology, University of California, Davis, California 95616, USA.

We assessed the functional determinants of the properties of L-type Ca(2+) currents in hair cells by co-expressing the pore-forming Ca(V)1.3alpha(1) subunit with the auxiliary subunits beta(1A) and/or alpha(2delta). Because Ca(2+) channels in hair cells are poised to interact with synaptic proteins, we also co-expressed the Ca(V)1.3alpha(1) subunit with syntaxin, vesicle-associated membrane protein (VAMP), and synaptosome associated protein of 25 kDa (SNAP25). Expression of the Ca(V)1.3alpha(1) subunit in human embryonic kidney cells (HEK 293) produced a dihydropyridine (DHP)-sensitive Ca(2+) current (peak current density -2.0 +/- 0.2 pA/pF; n = 11). Co-expression with beta(1A) and alpha(2delta) subunits enhanced the magnitude of the current (peak current density: Ca(V)1.3alpha(1) + beta(1A) = -4.3 +/- 0.8 pA/pF, n = 10; Ca(V)1.3alpha(1) + beta(1A) + alpha(2delta) = -4.1 +/- 0.6 pA/pF, n = 9) and produced a leftward shift of approximately 9 mV in the voltage-dependent activation of the currents. Furthermore, co-expression of Ca(V)1.3alpha(1) with syntaxin/VAMP/SNAP resulted in at least a twofold increase in the peak current density (-4.7 +/- 0.2 pA/pF; n = 11) and reduced the extent of inactivation of the Ca(2+) currents. Botulinum toxin, an inhibitor of syntaxin, accelerated the inactivation profile of Ca(2+) currents in hair cells. Immunocytochemical data also indicated that the Ca(2+) channels and syntaxin are co-localized in hair cells, suggesting there is functional interaction of the Ca(V)1.3alpha(1) with auxiliary subunits and synaptic proteins, that may contribute to the distinct properties of the DHP-sensitive channels in hair cells.
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http://dx.doi.org/10.1152/jn.00482.2002DOI Listing
February 2003

Functional Roles of Ca(v)1.3 (alpha(1D)) calcium channel in sinoatrial nodes: insight gained using gene-targeted null mutant mice.

Circ Res 2002 May;90(9):981-7

Department of Internal Medicine, University of California, Davis 95616, USA.

We directly examined the role of the Ca(v)1.3 (alpha(1D)) Ca(2+) channel in the sinoatrial (SA) node by using Ca(v)1.3 Ca(2+) channel-deficient mice. A previous report has shown that the null mutant (Ca(v)1.3(-/-)) mice have sinus bradycardia with a prolonged PR interval. In the present study, we show that spontaneous action potentials recorded from the SA nodes show a significant decrease in the beating frequency and rate of diastolic depolarization in Ca(v)1.3(-/-) mice compared with their heterozygous (Ca(v)1.3(+/-)) or wild-type (WT, Ca(v)1.3(+/+)) littermates, suggesting that the deficit is intrinsic to the SA node. Whole-cell L-type Ca(2+) currents (I(Ca,L)s) recorded in single isolated SA node cells from Ca(v)1.3(-/-) mice show a significant depolarization shift in the activation threshold. The voltage-dependent activation of Ca(v)1.2 (alpha(1C)) versus Ca(v)1.3 Ca(2+) channel subunits was directly compared by using a heterologous expression system without beta coexpression. Similar to the I(Ca,L) recorded in the SA node of Ca(v)1.3(-/-) mutant mice, the Ca(v)1.2 Ca(2+) channel shows a depolarization shift in the voltage-dependent activation compared with that in the Ca(v)1.3 Ca(2+) channel. In summary, using gene-targeted deletion of the Ca(v)1.3 Ca(2+) channel, we were able to establish a role for Ca(v)1.3 Ca(2+) channels in the generation of the spontaneous action potential in SA node cells.
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http://dx.doi.org/10.1161/01.res.0000018003.14304.e2DOI Listing
May 2002
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