Publications by authors named "Shengli Zhou"

35 Publications

MTDH in macrophages promotes the vasculogenic mimicry via VEGFA-165/Flt-1 signaling pathway in head and neck squamous cell carcinoma.

Int Immunopharmacol 2021 Jul 24;96:107776. Epub 2021 May 24.

Department of Otorhinolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Shandong Provincial Key Laboratory of Otology, Jinan, Shandong, China. Electronic address:

Vasculogenic mimicry (VM) refers to vessel-like structures formed by aggressive tumor cells and is closely associated with cancer invasion and metastasis. Here, we investigated the effect of macrophage-derived MTDH on VM formation in head and neck squamous cell carcinoma (HNSCC) and its underlying mechanism. Macrophages with MTDH overexpression (Mac-MTDH) promoted cancer cell VM formation, migration, and invasion in vitro. Moreover, MTDH overexpression triggered macrophage polarization into M2 type tumor-associated macrophages. Analysis of HNSCC clinical samples revealed that MTDH macrophages were predominantly located in the tumor-stromal region in proximity to VM and correlated with lymph node metastasis. Mechanistically, Mac-MTDH enhanced the expression and secretion of VEGFA-165 rather than other VEGFA isoforms via ß-catenin. The VEGFA-165/Flt-1 axis was responsible for Mac-MTDH's effects in cancer cells through p-STAT3/Twist1/VE-cadherin pathway. Using mouse model, we further confirmed that Mac-MTDH increased VM formation and cancer metastasis in vivo. Furthermore, in subcutaneous xenograft mouse model, HN6 + Mac-MTDH tumor exhibited elevated expression of p-STAT3 and Twist1 than HN6 + Mac-NC tumors. This study revealed that Mac-MTDH promoted VM formation, cancer cell migration and invasion, and cancer metastasis through VEGFA-165/Flt-1 axis, and that macrophage-derived MTDH could be a potential therapeutic target in HNSCC.
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http://dx.doi.org/10.1016/j.intimp.2021.107776DOI Listing
July 2021

PHF20 inhibition promotes apoptosis and cisplatin chemosensitivity via the OCT4‑p‑STAT3‑MCL1 signaling pathway in hypopharyngeal squamous cell carcinoma.

Int J Oncol 2021 07 13;59(1). Epub 2021 May 13.

Department of Otorhinolaryngology, Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.

Cisplatin is a widely used platinum‑based chemotherapeutic agent for hypopharyngeal squamous cell carcinoma (HSCC). However, resistance to cisplatin limits its use for the treatment of HSCC, and the underlying molecular mechanism requires further investigation. The present study performed functional assays to determine whether the expression of plant homeodomain finger protein 20 (PHF20) may be involved in the apoptosis and cisplatin resistance of HSCC. The expression levels of PHF20 were higher in cisplatin‑resistant HSCC cells compared with those in cisplatin‑sensitive cells. The inhibition of PHF20 suppressed cell viability but did not affect the migratory and invasive abilities of HSCC cells compared with those of negative control‑transfected cells. Furthermore, PHF20 inhibition reduced cell viability by enhancing apoptosis compared with those in the control cells . Notably, the inhibition of PHF20 sensitized HSCC cells to cisplatin, thus increasing apoptosis via the signal transducer and activator of transcription 3 (STAT3)‑myeloid cell leukemia‑1 (MCL1) pathway. Octamer‑binding transcription factor 4 (OCT4) overexpression restored phosphorylated STAT3‑MCL1‑mediated apoptosis induced by PHF20 inhibition. experiments confirmed that PHF20 silencing induced tumor growth and increased apoptosis in HSCC cells compared with those in the control cells. Thus, PHF20 inhibition may promote apoptosis and improve cisplatin chemosensitivity via the OCT4‑p‑STAT3‑MCL1 signaling pathway in HSCC.
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http://dx.doi.org/10.3892/ijo.2021.5218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121096PMC
July 2021

Minimization of apoptosis-inducing CPP-Bim peptide.

Bioorg Med Chem Lett 2021 03 21;36:127811. Epub 2021 Jan 21.

Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, Japan. Electronic address:

Pro-apoptotic peptides may be promising agents for cancer therapy owing to their ability to induce apoptosis in cancer cells. TatBim, a fusion peptide of Tat cell-penetrating peptide (CPP) and the BH3 domain derived from Bim apoptosis-inducing protein, is a pro-apoptotic peptide. In this study, based on the TatBim sequence, we attempted to minimize the CPP-Bim peptide while retaining apoptosis-inducing activity. The CPP and Bim parts were systematically shortened, and the pro-apoptotic activities of the shortened peptides were examined. We obtained TatBim-N1C2 and R8Bim-N1C2 as minimized peptides with efficient apoptotic activity. These peptides may have potential applications in future biomedical studies, such as cancer therapeutics.
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http://dx.doi.org/10.1016/j.bmcl.2021.127811DOI Listing
March 2021

DCLK1 inhibition attenuates tumorigenesis and improves chemosensitivity in esophageal squamous cell carcinoma by inhibiting β-catenin/c-Myc signaling.

Pflugers Arch 2020 08 12;472(8):1041-1049. Epub 2020 Jun 12.

Department of Gastroenterology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China.

Doublecortin-like kinase 1 (DCLK1) is involved in tumorigenesis, tumor growth and metastasis, and epithelial-to-mesenchymal transition in many digestive tract tumors. It is reportedly highly expressed in Barrett's esophagus and esophageal adenocarcinoma, but its effects on the occurrence and progression of esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, real-time PCR and western blot analysis confirmed significant upregulation of DCLK1 expression in human ESCC tissues and cell lines. CCK-8 assay showed that transfection with siRNA against DCLK1 (si-DCLK1) markedly inhibited cell proliferation and colony formation in the ESCC cell lines Eca109 and TE1. Transwell assay revealed that si-DCLK1 transfection inhibited the migratory and invasive capacities of Eca109 and TE1 cells. Moreover, si-DCLK1 increased the chemosensitivity of these cells to cisplatin, as indicated by inhibited cell viability and colony formation, and increased ROS and apoptosis in cisplatin-treated cells. Western blot assay revealed that expression of nuclear β-catenin and c-Myc was significantly increased in ESCC tissues and that si-DCLK1 markedly downregulated nuclear β-catenin and c-Myc in Eca109 cells. Treatment with lithium chloride, an activator of β-catenin signaling, partially abolished the si-DCLK1-induced inhibition of proliferation, migration, invasion, and chemoresistance of ESCC cells. These findings suggest that knockdown of DCLK1 may inhibit the progression of ESCC by regulating proliferation, migration, invasion, and chemosensitivity via suppressing the β-catenin/c-Myc pathway, supporting a promising therapeutic target against ESCC.
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http://dx.doi.org/10.1007/s00424-020-02415-zDOI Listing
August 2020

Diagnostic Value of Pleural Effusion Mononuclear Cells Count and Adenosine Deaminase for Tuberculous Pleurisy Patients in China: A Case-Control Study.

Front Med (Lausanne) 2019 17;6:301. Epub 2019 Dec 17.

Department of Clinical-Research Service Center, Henan Provincial People's Hospital, Henan University People's Hospital, Zhengzhou, China.

The diagnostic value of pleural effusion mononuclear cells count for tuberculous pleurisy (TBP) is unclear. We aimed to evaluate the diagnostic value of pleural effusion mononuclear cells count and its combination with adenosine deaminase (ADA) in TBP patients. We initially analyzed 296 patients with unknown pleural effusion from the Department of Respiratory Medicine at Provincial People's Hospital during January 2014 to February 2018. Ultimately, 100 tuberculous pleurisy (TBP) patients and 105 non-tuberculous pleurisy (non-TBP) patients with pleural effusion were investigated in the current study. Meanwhile, pleural effusion mononuclear cells count and ADA test were performed to evaluate the diagnostic value for TBP. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), negative likelihood ratio (LR-), accuracy and area under the receiver operating characteristic (ROC) curve (AUC) of pleural effusion mononuclear cells count only and its combination with ADA for TBP diagnosis were investigated. (i) The best cut-off value of pleural effusion mononuclear cells count for TBP diagnosis was 969.6 × 10/L, with the sensitivity, specificity and accuracy of 76, 57, and 66%, respectively. (ii) Combination of pleural effusion mononuclear cells count and ADA test suggested diagnostic value for TBP. Specifically, serial test showed the sensitivity, specificity, accuracy of 65, 90, 78%, respectively, whereas parallel test revealed the sensitivity, specificity, accuracy of 92, 45, 68%, respectively. The sensitivity of parallel test (92%) was significantly higher than pleural effusion mononuclear cells count alone (76%) (X = 23.19, < 0.001). (iii) The area under the ROC of pleural effusion mononuclear cells count and it combined with ADA were 0.66 (95% CI, 0.59-0.72) and 0.83 (95% CI, 0.78-0.89), respectively, with statistically significant difference (Z = 3.46, < 0.001). This retrospective case-control study demonstrated that pleural effusion mononuclear cells count is relatively useful for TBP diagnosis. Furthermore, the pleural effusion mononuclear cells count in combination with ADA can further improve the diagnostic accuracy of TBP.
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http://dx.doi.org/10.3389/fmed.2019.00301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927933PMC
December 2019

PDK1 promotes metastasis by inducing epithelial-mesenchymal transition in hypopharyngeal carcinoma via the Notch1 signaling pathway.

Exp Cell Res 2020 01 25;386(2):111746. Epub 2019 Nov 25.

Shandong Provincial ENT Hospital Affiliated to Shandong University, Shandong Provincial ENT Hospital, Jinan, China; Shandong Provincial Key Laboratory of Otology, Jinan, China. Electronic address:

Hypopharyngeal squamous cell carcinoma (HSCC) is a relatively rare malignancy and has the worst prognosis among head and neck cancer. Metastasis is the major cause of poor prognosis in HSCC patients. In this study, we found that 3-phosphoinositide-dependent protein kinase 1 (PDK1 or PDPK1) was overexpressed in HSCC. The overexpression was positively correlated lymph node metastasis, clinical stage, and distant metastasis and indicated poor outcome. Loss and gain-of-function revealed that PDK1 increased cell proliferation, migration and invasion in vitro as well as tumor growth and metastasis in vivo. Mechanically, PDK1 induced epithelial-mesenchymal transition and promoted metastasis by activating the Notch1 signaling pathway. We further illustrated that PDK1 bound with the Notch1 intracellular domain, thereby inhibiting its ubiquitin-mediated degradation in a protein kinase B (Akt-) independent manner. In summary, PDK1/Notch1 axis played an important role in HSCC metastasis, and this investigation provided a new perspective on potential therapeutic targets for HSCC.
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http://dx.doi.org/10.1016/j.yexcr.2019.111746DOI Listing
January 2020

Iatrogenic subglottic tracheal stenosis after tracheostomy and endotracheal intubation: A cohort observational study of more severity in keloid phenotype.

Acta Anaesthesiol Scand 2019 08 14;63(7):905-912. Epub 2019 Apr 14.

Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, Chelsea & Westminster Hospital, London, UK.

Background: Tracheostomy and endotracheal intubation can result in subglottic tracheal stenosis, and predisposition to keloid scar formation can increase stenosis risk after tracheal injury. This study aims to compare the incidence and severity of subglottic tracheal stenosis in keloid and non-keloid patients following iatrogenic tracheal injury, in particular tracheostomy.

Methods: From 2012 to 2017, 218 573 patients were intubated for surgery; 2276 patients received tracheostomy in People's Hospital of Zhengzhou University, China. Among these patients, 133 patients, who developed tracheal stenosis after intubation and/or tracheostomy, were divided into keloid or non-keloid groups; their Myer and Cotton grading of tracheal stenosis, time-to-onset of airway stenosis, and treatment outcome were assessed and compared.

Results: The percentages of high grade (Myer and Cotton grading III/IV) tracheal stenosis were higher among keloid patients than non-keloid patients (intubation: 83.3% vs 25.7%; tracheostomy: 77.7% vs 33.3%). Time-to-onset of airway stenosis following intubation (tracheostomy) was 27 ± 5 (38 ± 13) and 41 ± 7 (82 ± 14) days for keloid and non-keloid patients, respectively (P < 0.01). The incidence of tracheal stenosis is higher in keloid than non-keloid subjects (19.4% vs 1.82%, P < 0.001). Keloid patients also required more frequent treatment (P < 0.01) of longer duration, yet cure rate was significantly lower (P < 0.01).

Conclusions: Our study suggests that tracheostomized patients with keloid phenotype are more susceptibility to develop iatrogenic tracheal stenosis of greater severity and with poorer treatment outcome. Greater cautions may be required when performing tracheostomy in keloid subjects. More substantive analysis is warranted to establish keloid phenotype as a risk factor for tracheal stenosis.
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http://dx.doi.org/10.1111/aas.13371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619028PMC
August 2019

Triazophos-induced toxicity in zebrafish: inhibits .

Toxicol Res (Camb) 2018 Sep 31;7(5):913-922. Epub 2018 May 31.

College of Life Sciences , Zhejiang Sci-Tech University , Hangzhou , 310018 , China . Email:

Triazophos is a highly toxic organophosphorus pesticide, causing acute toxicity to brain tissue, and neurotoxicity and embryotoxicity to animals. Therefore, triazophos is considered as a public health problem due to its acute hazard index. MicroRNAs (miRNAs), a class of endogenous noncoding RNAs, can regulate the expression of target gene(s) by mediating mRNA cleavage or translational repression in organisms exposed to environmental chemicals. We found that is targeted by , which was significantly regulated in adult zebrafish () exposed to triazophos (phenyl-1,2,4-triazolyl-3-(,-diethyl thionophosphate)). The expression of in both mRNA and protein levels was downregulated in a dose-dependent manner upon stimulation with triazophos. A dual luciferase reporter assay demonstrated that interacted with the 3'-untranslated regions (3'-UTR) of . The expression of in both mRNA and protein level was reduced in ZF4 cells when transfected with an mimic, but increased when transfected with an inhibitor. As a result, is targeted by upon triazophos exposure. We suggest that could be a potential toxicological biomarker for triazophos.
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http://dx.doi.org/10.1039/c8tx00065dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116809PMC
September 2018

Transcriptomic analysis of zebrafish (Danio rerio) embryos to assess integrated biotoxicity of Xitiaoxi River waters.

Environ Pollut 2018 Nov 21;242(Pt A):42-53. Epub 2018 Jun 21.

Institute of Pesticide and Environmental Toxicology, Zhejiang University, Hangzhou, 310058, PR China. Electronic address:

Assessing the toxicity posed by mixtures of unknown chemicals to aquatic organisms is challenging. In this study, water samples from six cross-sections along the Xitiaoxi River Basin (XRB) were monthly or bimonthly collected in 2014. The year-period physiochemical parameters as well as one-month-water sample based acute biotoxicity tests showed that the river water quality of the year was generally in a good status. High performance liquid chromatography (HPLC) screening based on one-month-water samples suggested that the organic pollutants might be non-to-moderately-polar chemicals in very low concentrations. One-month-water sample based RNA-seq was performed to measure the mRNA differential expression profile of zebrafish larvae to furtherly explore the potential bioeffect and the spatial water quality change of the river. Result indicated that the number of deferentially expressed genes (DEGs) tended to increase along the downstream direction of the river. Gene ontology (GO) enrichment analysis implied that the key pollutants might mainly be the function disruptors of biological processes. Principle components analysis (PCA) combining with transcripts and one-month-water sample based physiochemical parameters indicated that the pollution might be similar at TP, DP and CTB sites while pollution homology existed on some extent between YBQ and JW sites. Although the water quality of the river had a complex time-space alternation during the year, and the one-month-data based RNA-seq could not reflex the whole year-water quality of a watershed, the gene expression profile via RNA-seq provided an alternative way for assessing integrated biotoxicity of surface water, and it was relatively fit for early-warning of water quality of a watershed with unobservable acute toxicity. However, the identification of detail toxicants and the links between DEGs and pollution level as well as physiological-biochemical toxicity needed further investigation.
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http://dx.doi.org/10.1016/j.envpol.2018.06.060DOI Listing
November 2018

Receiver design for spread-spectrum communications with a small spread in underwater clustered multipath channels.

J Acoust Soc Am 2017 03;141(3):1627

Key Laboratory of Underwater Acoustic Communication and Marine Information Technology (School of Information Science and Engineering, Xiamen University), Ministry of Education, Xiamen 361005, China.

This paper studies a direct-sequence spread-spectrum communication system with a small spreading factor (e.g., a single digit) in underwater acoustic multipath channels. Exploiting the channel characteristics that the propagation paths can be grouped into distinct clusters, a receiver with a set of parallel branches is proposed, where per-survivor processing (PSP) is applied on each branch to deal with the signal from one cluster while explicitly treating the signals from other clusters as structured interference. As such, it overcomes a major limitation of an existing PSP based receiver [Zhou, Morozov, and Preisig, J. Acoust. Soc. Am. 133, 2746-2754 (2013)], avoiding exponential complexity increase when the spreading factor decreases. On the first branch, joint channel estimation and interference cancellation are performed based solely on the survivor paths. On the other branches, joint channel estimation and interference cancellation are carried out based on the survivor paths and the tentatively decoded data. The bit log-likelihood ratios from different branches are combined for channel decoding. Performance results based on simulations and collected data sets validate the superior performance of the proposed receiver over the conventional RAKE receiver, which is effective only when the spreading factor is large.
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http://dx.doi.org/10.1121/1.4977747DOI Listing
March 2017

Dynamic modeling and characteristics analysis of a modal-independent linear ultrasonic motor.

Ultrasonics 2016 12 30;72:117-27. Epub 2016 Jul 30.

State Key Laboratory of Mechanics and Control of Mechanical Structures, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China.

In this paper, an integrated model is developed to analyze the fundamental characteristics of a modal-independent linear ultrasonic motor with double piezoelectric vibrators. The energy method is used to model the dynamics of the two piezoelectric vibrators. The interface forces are coupled into the dynamic equations of the two vibrators and the moving platform, forming a whole machine model of the motor. The behavior of the force transmission of the motor is analyzed via the resulting model to understand the drive mechanism. In particular, the relative contact length is proposed to describe the intermittent contact characteristic between the stator and the mover, and its role in evaluating motor performance is discussed. The relations between the output speed and various inputs to the motor and the start-stop transients of the motor are analyzed by numerical simulations, which are validated by experiments. Furthermore, the dead-zone behavior is predicted and clarified analytically using the proposed model, which is also observed in experiments. These results are useful for designing servo control scheme for the motor.
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http://dx.doi.org/10.1016/j.ultras.2016.07.018DOI Listing
December 2016

Recruitment of small synergistic movement makes a good pianist.

Annu Int Conf IEEE Eng Med Biol Soc 2015 ;2015:242-5

Time-varying synergies from kinematic data can be used to discern fundamental patterns of movement. We show through simultaneous extraction of synergies from both novice and experienced pianists that movement common to both groups can be identified. The extracted synergies successfully allow for the majority of the variability of the data to be accounted for by a limited number of components. Furthermore, classification of the weightings representing the recruitment of each of the synergies accurately distinguishes between the piano playing of the two groups of subjects. However, the major differences between the two groups lie not in the synergies representing the majority of the variance of the data but in the recruitment of smaller synergies.
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http://dx.doi.org/10.1109/EMBC.2015.7318345DOI Listing
October 2016

Facilitated long chain fatty acid uptake by adipocytes remains upregulated relative to BMI for more than a year after major bariatric surgical weight loss.

Obesity (Silver Spring) 2016 Jan 20;24(1):113-22. Epub 2015 Nov 20.

Department of Medicine, Divisions of Digestive & Liver Disease and Preventive Medicine, Columbia University Medical Center, New York, New York, USA.

Objective: This study examined whether changes in adipocyte long chain fatty acid (LCFA) uptake kinetics explain the weight regain increasingly observed following bariatric surgery.

Methods: Three groups (10 patients each) were studied: patients without obesity (NO: BMI 24.2 ± 2.3 kg m(-2) ); patients with obesity (O: BMI 49.8 ± 11.9); and patients classified as super-obese (SO: BMI 62.6 ± 2.8). NO patients underwent omental and subcutaneous fat biopsies during clinically indicated abdominal surgeries; O were biopsied during bariatric surgery, and SO during both a sleeve gastrectomy and at another bariatric operation 16 ± 2 months later, after losing 113 ± 13 lbs. Adipocyte sizes and [(3) H]-LCFA uptake kinetics were determined in all biopsies.

Results: Vmax for facilitated LCFA uptake by omental adipocytes increased exponentially from 5.1 ± 0.95 to 21.3 ± 3.20 to 68.7 ± 9.45 pmol/sec/50,000 cells in NO, O, and SO patients, respectively, correlating with BMI (r = 0.99, P < 0.001). Subcutaneous results were virtually identical. By the second operation, the mean BMI (SO patients) fell significantly (P < 0.01) to 44.4 ± 2.4 kg m(-2) , similar to the O group. However, Vmax (40.6 ± 11.5) in this weight-reduced group remained ~2X that predicted from the BMI:Vmax regression among NO, O, and SO patients.

Conclusions: Facilitated adipocyte LCFA uptake remains significantly upregulated ≥1 year after bariatric surgery, possibly contributing to weight regain.
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http://dx.doi.org/10.1002/oby.21249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699588PMC
January 2016

Hand-writing motion tracking with vision-inertial sensor fusion: calibration and error correction.

Sensors (Basel) 2014 Aug 25;14(9):15641-57. Epub 2014 Aug 25.

Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong, China.

The purpose of this study was to improve the accuracy of real-time ego-motion tracking through inertial sensor and vision sensor fusion. Due to low sampling rates supported by web-based vision sensor and accumulation of errors in inertial sensors, ego-motion tracking with vision sensors is commonly afflicted by slow updating rates, while motion tracking with inertial sensor suffers from rapid deterioration in accuracy with time. This paper starts with a discussion of developed algorithms for calibrating two relative rotations of the system using only one reference image. Next, stochastic noises associated with the inertial sensor are identified using Allan Variance analysis, and modeled according to their characteristics. Finally, the proposed models are incorporated into an extended Kalman filter for inertial sensor and vision sensor fusion. Compared with results from conventional sensor fusion models, we have shown that ego-motion tracking can be greatly enhanced using the proposed error correction model.
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http://dx.doi.org/10.3390/s140915641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208137PMC
August 2014

Design and optimization of a modal- independent linear ultrasonic motor.

IEEE Trans Ultrason Ferroelectr Freq Control 2014 Mar;61(3):535-46

To simplify the design of the linear ultrasonic motor (LUSM) and improve its output performance, a method of modal decoupling for LUSMs is proposed in this paper. The specific embodiment of this method is decoupling of the traditional LUSM stator's complex vibration into two simple vibrations, with each vibration implemented by one vibrator. Because the two vibrators are designed independently, their frequencies can be tuned independently and frequency consistency is easy to achieve. Thus, the method can simplify the design of the LUSM. Based on this method, a prototype modal- independent LUSM is designed and fabricated. The motor reaches its maximum thrust force of 47 N, maximum unloaded speed of 0.43 m/s, and maximum power of 7.85 W at applied voltage of 200 Vpp. The motor's structure is then optimized by controlling the difference between the two vibrators' resonance frequencies to reach larger output speed, thrust, and power. The optimized results show that when the frequency difference is 73 Hz, the output force, speed, and power reach their maximum values. At the input voltage of 200 Vpp, the motor reaches its maximum thrust force of 64.2 N, maximum unloaded speed of 0.76 m/s, maximum power of 17.4 W, maximum thrust-weight ratio of 23.7, and maximum efficiency of 39.6%.
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http://dx.doi.org/10.1109/TUFFC.2014.2937DOI Listing
March 2014

Per-survivor processing for underwater acoustic communications with direct-sequence spread spectrum.

J Acoust Soc Am 2013 May;133(5):2746-54

Department of Electrical and Computer Engineering, University of Connecticut, 371 Fairfield Road Unit 2157, Storrs, Connecticut 06269, USA.

This paper proposes a receiver for direct-sequence spread spectrum transmissions in underwater acoustic channels, which combines a per-survivor processing (PSP) structure with sparse channel estimation. Specifically, the PSP structure establishes the trellis on the symbol level to render a small to moderate number of states, thus reducing the computational complexity. Meanwhile, the sparse channel estimation is performed on the chip level, where the orthogonal matching pursuit algorithm is used and a two-dimensional grid of path delay and Doppler scaling factor is incorporated in the dictionary construction. The effective combination of the PSP detection and sparse channel estimation achieves a good tradeoff between performance and complexity. Simulation and experiment results show that the proposed receiver outperforms the conventional RAKE receiver considerably, and most importantly, the proposed PSP receiver with an exact wideband dictionary maintains an excellent performance even for challenging underwater acoustic channels with large Doppler disparities on different paths.
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http://dx.doi.org/10.1121/1.4796130DOI Listing
May 2013

Chronic ethanol consumption increases cardiomyocyte fatty acid uptake and decreases ventricular contractile function in C57BL/6J mice.

J Mol Cell Cardiol 2013 Jun 16;59:30-40. Epub 2013 Feb 16.

The Department of Medicine, Division of Digestive & Liver Disease, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.

Alcohol, a major cause of human cardiomyopathy, decreases cardiac contractility in both animals and man. However, key features of alcohol-related human heart disease are not consistently reproduced in animal models. Accordingly, we studied cardiac histology, contractile function, cardiomyocyte long chain fatty acid (LCFA) uptake, and gene expression in male C57BL/6J mice consuming 0, 10, 14, or 18% ethanol in drinking water for 3months. At sacrifice, all EtOH groups had mildly decreased body and increased heart weights, dose-dependent increases in cardiac triglycerides and a marked increase in cardiac fatty acid ethyl esters. [(3)H]-oleic acid uptake kinetics demonstrated increased facilitated cardiomyocyte LCFA uptake, associated with increased expression of genes encoding the LCFA transporters CD36 and Slc27a1 (FATP1) in EtOH-fed animals. Although SCD-1 expression was increased, lipidomic analysis did not indicate significantly increased de novo LCFA synthesis. By echocardiography, ejection fraction (EF) and the related fractional shortening (FS) of left ventricular diameter during systole were reduced and negatively correlated with cardiac triglycerides. Expression of myocardial PGC-1α and multiple downstream target genes in the oxidative phosphorylation pathway, including several in the electron transport and ATP synthase complexes of the inner mitochondrial membrane, were down-regulated. Cardiac ATP was correspondingly reduced. The data suggest that decreased expression of PGC-1α and its target genes result in decreased cardiac ATP levels, which may explain the decrease in myocardial contractile function caused by chronic EtOH intake. This model recapitulates important features of human alcoholic cardiomyopathy and illustrates a potentially important pathophysiologic link between cardiac lipid metabolism and function.
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http://dx.doi.org/10.1016/j.yjmcc.2013.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3647020PMC
June 2013

Parameterizing both path amplitude and delay variations of underwater acoustic channels for block decoding of orthogonal frequency division multiplexing.

J Acoust Soc Am 2012 Jun;131(6):4672-9

Department of Electrical and Computer Engineering, University of Connecticut, 371 Fairfield Road, Unit 2157, Storrs, Connecticut 06269, USA.

There are no commonly-agreed mathematical models for the input-output relationship of underwater acoustic channels. For each path in a time-varying multipath channel within a short period of time (e.g., one short data block), this paper proposes to use one polynomial to approximate the amplitude variation and another polynomial up to the first order to approximate the delay variation within a block duration. Under such a channel parameterization, the discrete-time channel input- output relationship tailored to zero-padded orthogonal-frequency-division-multiplexing (OFDM) transmissions is then derived, based on which an OFDM receiver is validated using experimental data collected during the 2008 Surface Processes and Acoustic Communications Experiment. For channels with a short coherence time, the numerical results show that incorporating both the amplitude and delay variations improves the system performance.
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http://dx.doi.org/10.1121/1.4707460DOI Listing
June 2012

Cardiomyocyte triglyceride accumulation and reduced ventricular function in mice with obesity reflect increased long chain Fatty Acid uptake and de novo Fatty Acid synthesis.

J Obes 2012 2;2012:205648. Epub 2011 Nov 2.

Division of Digestive and Liver Diseases, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

A nonarteriosclerotic cardiomyopathy is increasingly seen in obese patients. Seeking a rodent model, we studied cardiac histology, function, cardiomyocyte fatty acid uptake, and transporter gene expression in male C57BL/6J control mice and three obesity groups: similar mice fed a high-fat diet (HFD) and db/db and ob/ob mice. At sacrifice, all obesity groups had increased body and heart weights and fatty livers. By echocardiography, ejection fraction (EF) and fractional shortening (FS) of left ventricular diameter during systole were significantly reduced. The V(max) for saturable fatty acid uptake was increased and significantly correlated with cardiac triglycerides and insulin concentrations. V(max) also correlated with expression of genes for the cardiac fatty acid transporters Cd36 and Slc27a1. Genes for de novo fatty acid synthesis (Fasn, Scd1) were also upregulated. Ten oxidative phosphorylation pathway genes were downregulated, suggesting that a decrease in cardiomyocyte ATP synthesis might explain the decreased contractile function in obese hearts.
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http://dx.doi.org/10.1155/2012/205648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216284PMC
August 2012

Characterization and inference of gene gain/loss along burkholderia evolutionary history.

Evol Bioinform Online 2011 18;7:191-200. Epub 2011 Oct 18.

State Key Laboratory of Rice Biology and Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Ministry of Agriculture, Institute of Biotechnology, Zhejiang University, Hangzhou 310029, China.

A comparative analysis of 60 complete Burkholderia genomes was conducted to obtain insight in the evolutionary history behind the diversity and pathogenicity at species level. A concatenated multiprotein phyletic pattern and a dataset with Burkholderia clusters of orthologous genes (BuCOGs) were constructed. The extent of horizontal gene transfer (HGT) was assessed using a Markov based probabilistic method. A reconstruction of the gene gains and losses history shows that more than half of the Burkholderia genes families are inferred to have experienced HGT at least once during their evolution. Further analysis revealed that the number of gene gain and loss was correlated with the branch length. Genomic islands (GEIs) analysis based on evolutionary history reconstruction not only revealed that most genes in ancient GEIs were gained but also suggested that the fraction of the genome located in GEIs in the small chromosomes is higher than in the large chromosomes in Burkholderia. The mapping of coexpressed genes onto biological pathway schemes revealed that pathogenicity of Burkholderia strains is probably mainly determined by the gained genes in its ancestor. Taken together, our results strongly support that gene gain and loss especially in ancient evolutionary history play an important role in strain divergence, pathogenicity determinants of Burkholderia and GEIs formation.
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http://dx.doi.org/10.4137/EBO.S7510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210638PMC
November 2011

Effects of butachlor on reproduction and hormone levels in adult zebrafish (Danio rerio).

Exp Toxicol Pathol 2013 Jan 15;65(1-2):205-9. Epub 2011 Sep 15.

Department of Pesticide Science, College of Plant Protection, Nanjing Agricultural University, Key Laboratory of Monitoring and Management of Crop Diseases and Pest Insects, Ministry of Agriculture, Nanjing 210095, China.

Butachlor, a chloracetamide herbicide, is widely used in China. In the present study, paired adult male and female zebrafish (Danio rerio) were exposed to various concentrations of butachlor (0, 25, 50 and 100 μg/L) for 30 days, and the effects on reproduction and endocrine disruption were evaluated using fecundity, condition factor (CF), gonadosomatic index (GSI), liver somatic index (LSI), plasma vitellogenin (VTG), sex steroids and thyroid hormone levels as endpoints. Our results showed that the mean fecundity rates were significantly decreased at 50 and 100 μg/L butachlor during the 30-day exposure period. At the end of the exposure period, no significant changes were observed in CF and LSI in both females and males, while GSI was significantly reduced in males at 50 and 100 μg/L butachlor. At 100 μg/L butachlor, plasma testosterone (T) and 17β-estradiol (E2) levels were significantly decreased in females, while plasma VTG level was significantly increased in males. Plasma thyroxine (T4) and triiodothyronine (T3) levels were significantly increased at 50 and 100 μg/L butachlor in males, and at 100 μg/L in females. This work demonstrated that butachlor adversely affected the normal reproductive success of zebrafish, and disrupted the thyroid and sex steroid endocrine systems, which provides the basis for the estimated ecological risk during butachlor exposure.
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http://dx.doi.org/10.1016/j.etp.2011.08.007DOI Listing
January 2013

Waterborne exposure to clodinafop-propargyl disrupts the posterior and ventral development of zebrafish embryos.

Environ Toxicol Chem 2011 Jul 7;30(7):1576-81. Epub 2011 May 7.

Zhejiang University, Hangzhou, Zhejiang, Peoples Republic of China.

Clodinafop-propargyl, an aryloxyphenoxypropionate herbicide, is widely used for the control of annual grasses. However, research focusing on the ecotoxicity of this herbicide is limited. The present study employed zebrafish (Danio rerio) as a model to investigate its developmental toxicity. Embryos were exposed to a range of concentrations from 0.2 µM to 5 µM starting at late cleavage stage (2 h postfertilization, [hpf]) or late gastrulation stage (10 hpf). The results showed that the two exposure strategies had the same minimum teratogenic concentration of 0.6 µM but caused different groups of morphogenetic malformations. When exposure was initiated at 2 hpf, clodinafop-propargyl caused various embryonic phenotypes, including embryos with a fin gap in the ventral tail and embryos with coiled tail. When exposure was initiated at 10 hpf, clodinafop-propargyl resulted in failure of the tail to detach, in which the ventral tissues failed to grow out but instead adhered to the yolk extension, and the defect differed to various degrees among embryos. Similar effects were observed for embryos exposed to clodinafop, the metabolite of clodinafop-propargyl. Because these defects were mainly confined to the posterior and ventral region that derived from ventral blastoderm cells, we have evaluated the expression of the ventral mesoderm marker gene gata-1 and ventral ectoderm marker gene gata-3. No significant alteration was seen in gata-1 expression except for the expanded blood islands, whereas the expression of gata-3 was significantly reduced. Our findings showed that clodinafop-propargyl exposure disturbed embryonic patterning and fate specification of ventrally derived gastrula ectoderm cells.
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http://dx.doi.org/10.1002/etc.549DOI Listing
July 2011

Digital analysis of hepatic sections in mice accurately quantitates triglycerides and selected properties of lipid droplets.

Exp Biol Med (Maywood) 2010 Nov 13;235(11):1282-6. Epub 2010 Oct 13.

The Department of Medicine, Divisions of Digestive & Liver Disease, Columbia University Medical Center, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.

We describe a method for the histologic evaluation of lipid accumulation in the livers of various mouse models of hepatic steatosis based on quantitative digital analysis of Oil Red O (ORO) accumulation in fresh-frozen hepatic sections. The process involves two principal steps: identification and digital photographic imaging of areas appropriate for analysis, followed by digital determination of the fraction of the identified area (Area Fraction) exhibiting ORO staining. The Area Fraction, designated the Digital Steatosis Score, is a valuable aspect of the histologic assessment of the liver, especially in various forms of alcoholic and non-alcoholic liver diseases. The method is rapid, requiring ∼3 min per specimen, and highly reproducible, avoiding the inevitably subjective, semi-quantitative evaluation of lipid content inherent in visual steatosis scoring systems. In normal mice and in six different mouse models of fatty liver, the Area Fraction was highly correlated with hepatic triglyceride content (P < 0.01). The coefficient of variation of repeated determinations of the Area Fraction by two different observers was ±6.4%. If made available in clinical settings, rapid, accurate quantitation of liver triglycerides by this method could be very useful in specific conditions such as assessment of donor livers for transplantation.
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http://dx.doi.org/10.1258/ebm.2010.010095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965558PMC
November 2010

Effect of triazophos, fipronil and their mixture on miRNA expression in adult zebrafish.

J Environ Sci Health B 2010 Oct;45(7):648-57

Institute of Bioengineering, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, PR China.

MicroRNA (miRNA) plays a crucial role in gene expression regulation. However, no data are available on change of miRNA expression of zebrafish (Danio rerio) after treatment with pesticides. We evaluated the effect of fipronil (5-amino-1-[2, 6-dichloro-4-(trifluoromethyl) phenyl]-4-[(trifluoromethyl) sulfinyl]-1H-pyrazole-3-carbonitrile) and triazophos (3-(O, O-diethyl)-1-phenyl thiophosphoryl-1, 2, 4-triazol) and their mixture on miRNA expression in zebrafish.MiRNA expression profiles in zebrafish were altered after treatment with these chemicals. An association between these chemicals and the expression of 21 miRNAs was found 96 h after treatment. Among them, 14 miRNAs were differentially expressed due to the treatments with fipronil, triazophos and their mixture; 5 miRNAs showed altered expression level after treatment with formulations of these chemicals; miR-29b and miR-738 were differentially expressed after treatment with adjuvants. MiRNAs might present a novel toxicological response that could be used as a toxicological biomarker and have a different direction for future investigations of their association with miRNAs involved in chemical related diseases.
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http://dx.doi.org/10.1080/03601234.2010.502435DOI Listing
October 2010

Insulin- and leptin-regulated fatty acid uptake plays a key causal role in hepatic steatosis in mice with intact leptin signaling but not in ob/ob or db/db mice.

Am J Physiol Gastrointest Liver Physiol 2010 Oct 1;299(4):G855-66. Epub 2010 Jul 1.

Department of Medicine, Columbia University Medical Center, New York, New York, USA.

Hepatic steatosis results from several processes. To assess their relative roles, hepatocellular long-chain fatty acid (LCFA) uptake was assayed in hepatocytes from C57BL/6J control mice, mice with steatosis from a high-fat diet (HFD) or 10%, 14%, or 18% ethanol (EtOH) in drinking water [functioning leptin-signaling groups (FLSGs)], and ob/ob and db/db mice. V(max) for uptake was increased vs. controls (P < 0.001) and correlated significantly with liver weight and triglycerides (TGs) in all FLSG mice but was minimally or not increased in ob/ob and db/db mice, in which liver weights and TGs greatly exceeded projections from regressions in FLSG animals. Coefficients of determination (R(2)) for these FLSG regressions suggest that increased LCFA uptake accounts for ∼80% of the increase in hepatic TGs within these groups, but increased lipogenic gene expression data suggest that enhanced LCFA synthesis is the major contributor in ob/ob and db/db. Got2, Cd36, Slc27a2, and Slc27a5 gene expression ratios were significantly upregulated in the EtOH groups, correlating with sterol regulatory element binding protein 1c (SREBP1c) and V(max), but only Cd36 expression was increased in HFD, ob/ob, and db/db mice. Comparison of V(max) with serum insulin and leptin suggests that both hormones contribute to upregulation of uptake in the FLSG animals. Thus, increased LCFA uptake, reflecting SREBP1c-mediated upregulation of four distinct transporters, is the dominant cause of steatosis in EtOH-fed mice. In ob/ob and db/db mice, increased LCFA synthesis appears more important. In FLSG animals, insulin upregulates hepatocellular LCFA uptake. Leptin appears to upregulate LCFA uptake or to be essential for full expression of upregulation by insulin.
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http://dx.doi.org/10.1152/ajpgi.00434.2009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2957339PMC
October 2010

Identification of RANBP16 and RANBP17 as novel interaction partners for the bHLH transcription factor E12.

J Cell Biochem 2010 Sep;111(1):195-206

Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Toledo, Ohio 43614, USA.

The ubiquitously expressed basic helix-loop-helix (bHLH) transcription factors E12 and E47, products of alternative splicing of the E2A/TCF3 gene, regulate diverse biological processes including cell growth, differentiation and development. To search for novel protein interactions for E12, we utilized the bHLH domain of E12 as a bait in yeast two-hybrid screening. Yeast two-hybrid, mammalian two-hybrid, and co-immunoprecipitation analyses demonstrate specific interaction of E12 with RANBP17, a novel member of the importin-beta superfamily; this interaction maps to the CRM1 homology region of RANBP17. Ectopic expression of RANBP17 leads to a approximately 3-fold increase in E2A/MyoD mediated transactivation of an E-box regulated luciferase reporter gene. Interaction and transactivation studies also revealed similar functions for RANBP16/XPO7. Furthermore, ectopic expression of either RANBP16 or RANBP17 resulted in increased level of endogenous transcript for the cyclin-dependent kinase inhibitor, p21(Waf1/Cip1), a well-characterized E2A target gene. Together, these biochemical and functional data reveal RANBP16 and RANBP17 as novel regulators of E2A protein action.
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http://dx.doi.org/10.1002/jcb.22689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930062PMC
September 2010

A simple and effective noise whitening method for underwater acoustic orthogonal frequency division multiplexing.

J Acoust Soc Am 2010 Apr;127(4):2358-67

Department of Electrical and Computer Engineering, Carnegie Mellon University, 5000 Forbes Avenue HH D201, Pittsburgh, Pennsylvania 15213, USA.

Underwater acoustic orthogonal frequency division multiplexing (OFDM) enables simple frequency domain equalization, but its performance is often limited by intercarrier interference (ICI) that is induced by channel variation, in addition to the ambient noise. As the signal itself, the variance of the ICI is frequency dependent as (i) the transmitter often has a nonideal transmit voltage response (TVR) and (ii) underwater acoustic propagation introduces frequency dependent attenuation. In this paper, a simple method to account for the frequency dependent spectrum of the ICI plus noise is proposed. Specifically, the power spectrum of the ICI plus noise is approximated using a low-order polynomial in the log domain, by fitting the measurements on the null subcarriers embedded in each OFDM symbol. Prewhitening is then applied to each OFDM symbol before channel estimation and data demodulation. The proposed method is tested using experimental data collected from the SPACE08 and RACE08 experiments, where signals with and without transmitter precompensation are compared side by side in the former. Impressive performance gains are found whenever the signal is significantly colored. This is the case when either the TVR is not compensated or the transmission distance and bandwidth are large.
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http://dx.doi.org/10.1121/1.3309452DOI Listing
April 2010

Downregulated expression of the secreted glycoprotein follistatin-like 1 (Fstl1) is a robust hallmark of preadipocyte to adipocyte conversion.

Mech Dev 2010 Apr 4;127(3-4):183-202. Epub 2010 Jan 4.

Department of Biochemistry and Cancer Biology, Center for Diabetes and Endocrine Research, University of Toledo College of Medicine, Toledo, OH 43614, USA.

Obesity is a public health crisis in the United States. Targeting preadipocyte to adipocyte conversion may be an effective approach to regulate adipose mass. Using differential screening we identified Fstl1, a secreted glycoprotein with roles in immunomodulation, cell growth, cardioprotection, and vascularization, as a "preadipokine". Fstl1 is highly expressed in 3T3-L1 preadipocytes and dramatically downregulated early in their differentiation to adipocytes. Northern blot analysis of murine tissues reveals white adipose tissue (WAT), lung and heart as primary sites of Fstl1 transcript expression. In WAT, Fstl1 transcript is restricted to the preadipocyte-containing stromal-vascular cell population. Time course studies in multiple adipogenesis models reveal downregulation of Fstl1 is a hallmark of white and brown adipocyte conversion. By Western blot, we show culture media of 3T3-L1 preadipocytes contains high levels of Fstl1 protein that rapidly decline in adipocyte conversion. Moreover, we observe a correlation between preadipocyte phenotype and Fstl1 expression in that TNFalpha-mediated de-differentiation of 3T3-L1 adipocytes is accompanied by re-expression of Fstl1 transcript and protein. Treatment of 3T3-L1 preadipocytes with a panel of 18 hormones and other agents revealed the demethylating agent 5-aza-cytidine decreases Fstl1 transcript and protein levels by approximately 90%. Furthermore, of 10 additional preadipocyte-expressed genes analyzed we find Pref-1, Col1A1, Sca-1/Ly6a, Lox and Thbs2, are also downregulated by 5-aza-cytidine. Using luciferase reporter constructs containing 791 or 3922 bp of the Fstl1 5' flanking region, we determine negative transcriptional regulation by Kruppel-like factor 15. Together, our data suggest downregulation of Fstl1 expression may be an important feature of preadipocyte to adipocyte conversion.
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http://dx.doi.org/10.1016/j.mod.2009.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849861PMC
April 2010

Developmental toxicity of cartap on zebrafish embryos.

Aquat Toxicol 2009 Dec 1;95(4):339-46. Epub 2009 Nov 1.

Institute of Pesticide and Environmental Toxicology, Zhejiang University, Kaixuan Road 172, Hangzhou, Zhejiang 310029, PR China.

Cartap is a widely used insecticide which belongs to a member of nereistoxin derivatives and acts on nicotinic acetylcholine receptor site. Its effects on aquatic species are of grave concern. To explore the potential developmental toxicity of cartap, zebrafish embryos were continually exposed, from 0.5 to 144h post-fertilization, to a range of concentrations of 25-1000microg/l. Results of the experiment indicated that cartap concentrations of 100microg/l and above negatively affected embryo survival and hatching success. Morphological analysis uncovered a large suite of abnormalities such as less melanin pigmentation, wavy notochord, crooked trunk, fuzzy somites, neurogenesis defects and vasculature defects. The most sensitive organ was proved to be the notochord which displayed defects at concentrations as low as 25microg/l. Both sensitivity towards exposure and localization of the defect were stage specific. To elucidate mechanisms concerning notochord, pigmentation, and hatching defects, enzyme assay, RT Q-PCR, and different exposure strategies were performed. For embryos with hatching failure, chorion was verified not to be digested, while removing cartap from exposure at early pre-hatching stage could significantly increase the hatching success. However, cartap was proved, via vitro assay, to have no effect on proteolytic activity of hatching enzyme. These findings implied that the secretion of hatching enzyme might be blocked. We also revealed that cartap inhibited the activity of melanogenic enzyme tyrosinase and matrix enzyme lysyl oxidase and induced expression of their genes. These suggested that cartap could impaired melanin pigmentation of zebrafish embryos through inhibiting tyrosinase activity, while inhibition of lysyl oxidase activity was responsible for notochord undulation, which subsequently caused somite defect, and at least partially responsible for defects in vasculature and neurogenesis.
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http://dx.doi.org/10.1016/j.aquatox.2009.10.006DOI Listing
December 2009

Functional analysis of FSP27 protein regions for lipid droplet localization, caspase-dependent apoptosis, and dimerization with CIDEA.

Am J Physiol Endocrinol Metab 2009 Dec 20;297(6):E1395-413. Epub 2009 Oct 20.

Department of Biochemistry and Cancer Biology and Center for Diabetes and Endocrine Research, The University of Toledo College of Medicine, Toledo, Ohio 43614, USA.

The adipocyte-specific protein FSP27, also known as CIDEC, is one of three cell death-inducing DFF45-like effector (CIDE) proteins. The first known function for CIDEs was promotion of apoptosis upon ectopic expression in mammalian cells. Recent studies in endogenous settings demonstrated key roles for CIDEs in energy metabolism. FSP27 is a lipid droplet-associated protein whose heterologous expression enhances formation of enlarged lipid droplets and is required for unilocular lipid droplets typical of white adipocytes in vivo. Here, we delineate relationships between apoptotic function and lipid droplet localization of FSP27. We demonstrate that ectopic expression of FSP27 induces enlarged lipid droplets in multiple human cell lines, which is indicative that its mechanism involves ubiquitously present, rather than adipocyte-specific, cellular machinery. Furthermore, promotion of lipid droplet formation in HeLa cells via culture in exogenous oleic acid offsets FSP27-mediated apoptosis. Using transient cotransfections and analysis of lipid droplets in HeLa cells stably expressing FSP27, we show that FSP27 does not protect lipid droplets from action of ATGL lipase. Domain mapping with eGFP-FSP27 deletion constructs indicates that lipid droplet localization of FSP27 requires amino acids 174-192 of its CIDE C domain. The apoptotic mechanism of FSP27, which we show involves caspase-9 and mitochondrial cytochrome c, also requires this 19-amino acid region. Interaction assays determine the FSP27 CIDE C domain complexes with CIDEA, and Western blot reveals that FSP27 protein levels are reduced by coexpression of CIDEA. Overall, our findings demonstrate the function of the FSP27 CIDE C domain and/or regions thereof for apoptosis, lipid droplet localization, and CIDEA interaction.
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http://dx.doi.org/10.1152/ajpendo.00188.2009DOI Listing
December 2009