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The Effect of 5-Fluorouracil with Calcium Leucovorin on the Mammary Cancer Cells

The Effect of 5-Fluorouracil with Calcium Leucovorin on the ...

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“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者： Ying Yang~1,Shao-Hui Cui~2,Shu-Biao Zhang~2,Bing Wang~2,Yi-Hui Xu~1,Wei Zou~(1*) 1 LiaoNing Normal University 2 Dalian university

5-Fluorouracil(Fluorouracil,5-Fu) is a anti-tumor drug,which is in possession of speediness,high efficiency and low toxicity, and has been the first choose drug in malignant cancer *** with the modern medicine biological technology development, 5-Fluorouracil associated with other medicine was used to enhance the drug efficacy successfully. However,some kinds,dose-effect and the mechanisms of 5-Fluorouracil associated with other drugs,are still unknown clearly. Thus,here we adopt the way of MTT,and so on,take 5-Fluorouracil with Calcium Leuco-vorin (CF) on MCF-7 cell line,which is used for different effect of the dose of 5-Fluorouracil Calcium Leucovorin,also to detect the best time and the dose of the drugs with MCF-7 cell *** take doses of 5-Fluorouracil and Calcium Leucovorin,we observe the cell apoptosis with morphological ways,AO/EB staining,DNA ladder and also we use Cyto-Flows to see the change of phases with MCF-7 cell ***,we detect the expression relative protein of Bcl-2,Bax and so *** results showed that:(1) MTT method to find the best medication dosage as well as best medication time,with different dose of 5-Fluorouracil with Calcium Leucovorin(2.5μg/ mL、5μg/mL).5-Fluorouracil,which is used single,is not better than that both used 5- Fluorouracil and Calcium Leucovorin.(2) We see the changes of phases to the cells which are dosed with 5-Fluorouracil and Calcium Leucovorin,with cyto-flows,different period of apoptosis could be *** the early phase of apoptosis cells,we could see some small bodies in cells,late phase of apoptosis cells become red,shapes are similar to the early *** death cells are all red without intact shapes.(3) After dosing with 5-Fluorouracil and Calcium Leucovorin with some time,the expression of Bcl-2 is falling,the expression of Bax is ***:(1) 5- Fluorouracil would get more effect on cancer cells if it is used together with Calcium Leuco- vorin.(2) The cells rise with the doses

关键词： Apoptosis 5-Fluorouracil CF Bcl-2 Bax

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The Single-on and Double-on Responders in the Inferior Colliculus of the Leaf-nosed Bat,Hipposideros Armiger

The Single-on and Double-on Responders in the Inferior Colli...

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“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者：付子英 Philip H.S.Jen College of Life Sciences and Hubei Key Lab of Genetic Regulation & Integrative Biology Central China normal university Division of Biological Sciences University of Missouri-ColumbiaMO 65211USA

For orientation,the leaf-nosed Hipposideros armiger emits multiple constant frequency -frequency modulated(CF-FM) signals with energy mainly distributed at the predominant second harmonic of 66.4 kHz and analyzes the returning echoes to extract information about the ***,the importance of analysis of different prey features from the returning echoes may also vary throughout a target approaching *** present study examines the role of the FM component of CF-FM sounds in shaping the response properties of neurons in the central nucleus of the inferior colliculus(IC) of the CF-FM bat, Hipposideros armiger,using CF,FM and CF-FM sounds as *** recorded 169 IC neurons are tonotopically organized along the dorsoventral axis of the IC(n=169,r=0. 716,P<0.001).Collicular neurons have Vshaped or upper-threshold frequency tuning *** neurons tuned at the predominant second harmonic have extremely sharp frequency tuning curves and low minimum *** neurons typically discharge impulses to both CF and FM sounds. However,when stimulated with CF-FM sounds,most(76%) neurons only discharge impulses to the onset of CF-FM sounds(single -on responders).The remaining neurons (24%) discharge impulses to both the onset of CF and FM components(double-on responders) of CF-FM *** double-on responders have higher minimum threshold(P<0.001) and longer latency(P<0.01) to the FM component than to the CF component of CF-FM *** data show that the FM component of the CF-FM sounds contributes significantly in shaping the discharge pattern, latency and number of impulses of IC neurons. The present study suggests that using CF-FM sounds to study auditory response properties of the CF-FM bat may be essential for better understanding of echo analysis by the CF-FM bat in the real *** the double-on responders have shorter response latency than single-on responders,we speculate that these two types of responders may be best suited for

关键词： CF-FM bat Frequency tuning curve Inferior colliculus Response pattern

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Effects of Medium Intensity White Noise Exposure on Cognitive Ability of Young Mice

Effects of Medium Intensity White Noise Exposure on Cognitiv...

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“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者： Liang Cheng,Shao-Hui Wang,Qi-Cai Chen,Xiao-Mei Liao~* College of Life Sciences,Central China Normal University,Laboratory of Neuro biology,HuBei province Key Laboratory of Genetic Regulation and Integrative biology,Wuhan 430079

To explore the effects of medium intensity white noise exposure on cognitive ability of young mice and its underlying mechanisms.3- weeks-old mice are chosen as experimental animals (n=110).Among the 110 mice,22 young mice were exposed to medium intensity white noise(80dB SPL) for 6 weeks then examined the basic sound response properties of inferior colliculus (IC) including minimal threshold,latency, characterizing *** other 88 young mice were divided into 8 groups(11 in each group):3 days' noise exposure group and its control group,1 week's noise exposure group and its control group,3 weeks' noise exposure group and its control group,6 weeks' noise exposure group and its control *** control groups are fed normally;the noise groups are exposed to 80dB white noise 2 hours per *** exposed to noise for different time,we detected the learning and memory ability by Morris water maze and step down inhibitory avoidance tests;at the same time we also detect the value of Malondialdehyde (MDA) and superoxide dismutase (SOD) of hippocampus,auditory cortex and inferior colliculus of the *** also detect the level of hyperphosphorylated tau of hippocampus of mice by Western *** results were as follows;(1) The mice were scared and fidgety in the early period during noise treatment and in the late period of noise exposure,the mice were primness and moveless.(2) Compared with control, the avoidance latency was prolonged in Morris water maze and in step down inhibitory avoidance tests,the step down avoidance latency was shorten and the number of errors was increased after exposure to medium intensity white noise. All the parameters above was positive association with the exposure time.(3)Compared with control, after 6 weeks' medium intensity white noise exposure,the minimum threshold of neurons in inferior colliculus rise,the latency of neurons in inferior colliculus increase,and the bandwidth of frequency tuning curve at 10dB+MT and 20Db+ MT narrow.(4

关键词： Medium intensity white noise Oxidative stress Tau phosphorylation Sound response properties of IC Cognition

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FKBP12-6 Knockout Increases Ryanodine Receptors Open Probability during b-adrenergic Stimulation in Mice Cardiac Myocytes

FKBP12-6 Knockout Increases Ryanodine Receptors Open Probabi...

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“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者： Yan-Ting Zhao~1,Peng Zhou~1,Zheng Chen~2,Guang-Ju Ji~2,Shi-Qiang Wang~1 1 State Key Laboratory of Biomembrane and Membrane Biotechnology,College of Life Sciences, Peking University 2 Institute of Biophysics,Chinese Academy of Sciences,Beijing 100871

FK506 binding protein 12.6（FK-BP12.6） is the protein in the ryanodine receptor complex,but its function is controversial in different reported *** conclude that FK-BP12.6 stabilizes ryanodine receptors（RyRs） but some conclude that it has no effect on *** published work of FKBP12.6 effect on RyRs is demonstrated by lipid bilayer experiment,which destroys the in situ environment around FKBP12. 6 and ***,we employed two methods to test FKBP12.6 function directly in RyR complex in intact cardiac ***,using loose-seal patch clamp combined with confocal imaging,we gave the cell membrane a local depolarization to～0mV just below the pipette,at the same time recorded the Ca fluorescent signals,as sparklet from L-type calcium channel（LCC） and spark from *** found that the spark amplitude was decreased and the LCC-RyR coupling latency was shortened in FKBP12.6 knockout mice （KO）.Analyzation of spark flux revealed that the quantal nature of RyR Ca release observed in WT was diminished in KO,indicating that the coupled state of RyR Ca release channel was destroyed when FKBP12.6 was dissociated from RyR *** using isoproterenol（ISO）, a b-adrenergic receptors agonist,we found that the LCC-RyR coupling latency in KO myocytes was much shorter,more sparks and Ca waves occurred compared with ISO treated WT myocytes. We also certified the above results in rat cardiac myocytes pharmacologically,using FK506,the drug proved to dissociate FKBP12.6 from RyR ***,using whole cell patch clamp with confocal imaging,we gave cells a high voltage depolarization（+ 160mV） to make sure all the available LCCs were open,then repolarized to different voltages（-70-120 mV） to make different *** found that FK506 with ISO together induced higher Ca transient, whatever i was small（at higher repolarization voltages） or big（at lower repolarization voltages）. Together,we conclude that FKBP12.6 is important to maintain the quantal nature of RyR Ca release channe

关键词： B-adrenergic FKBP12.6 Isoproterenol Ryanodine receptor Spark

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The Dynamic Monitoring Effect of Fluorescent Nissl Stains for Neural Differentiation of hMSCS

The Dynamic Monitoring Effect of Fluorescent Nissl Stains fo...

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“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者： Jing Liu~(1,2),Yang Liu~(2,3),De-Cheng Lv~4,Hua Ye~2,Zhan-Feng Cui~2 1 The Sino-UK Centre of Regenerative Medicine,the First Associated Hospital of Dalian Medical University,Dalian 116011 2 Oxford Centre for Tissue Engineering and Bioprocessing,Department of Engineering Science, University of Oxford,0X1 3PJ 3 Dalian R & D Center for Stem Cell & Tissue Engineering,Dalian University of Technology, Dalian 116024 4 Department of neurology,the First Associated Hospital of Dalian Medical University,Dalian 116011

Currently there is no fast and easy ways of monitoring level of neural differentiation of human mesenchamal stem cells(hMSCs) in real time in cell transplantation therapy. Nissl substance reflects the high protein synthesis capacity of neuronal cells and Nissl stains have long been used to identify mature neuronal cells in *** study aimed to explore whether Nissl stains could be developed as a simple and practical method for monitoring neural differentiation of hMSCs. hMSCs were induced to differentiate towards neural lineage using neural culture media with growth factors(bFGF,human basic fibroblast growth factor;EGF,epidermal growth factor human;PDGF,platelet derived growth factor from human ).Immunofluorescent staining was performed to visualize the expression of neural progenitor marker(nestin) and neuronal specific enolase(NSE,marker for mature neuronal cell).Neuron Trace Fluorescent Nissl Stain and cresyl violet stain were used to stain the Nissl substance at different time points after the *** 24hrs of neural induction,the cells lost the characteristic shape of mesenchamal stem cells and expressed high levels of *** Nissl substance was detected inside these nestin positive *** a small percentage of cells expressed NSE and showed positive fluorescent Nissl ***,traditional cresyl violet stain didn't detect Nissl substance in these *** day 3 to day 15 after neural induction, almost 40-71%of cells presented typical neural cell morphology with axons and dendrites. For these cells,both the expression of NSE and positive fluorescent Nissl stain were observed,but 30%of these cells showed negative when stained with cresyl *** study indicated that Neuron Trace Fluorescent Nissl Stain is more sensitive,much faster and easier to use than immunocytochemistry in detection of level of neural differentiation of hMSCS. This fluorescent Nissl stain could be adopted as an effective method for monitoring the progress

关键词： Nissl stain Neural differentiation hMSC

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Modulation Rate Selectivity to FM Sweeps is Co-shaped by Duration Tuning Features and Sweeps Bandwidth in the Inferior Collicular Neurons

Modulation Rate Selectivity to FM Sweeps is Co-shaped by Dur...

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“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者： Yang Liao~1,Xu-Dong Zang~1,Xiao-Yan Han~1,An-An Li~2,Qi-Cai Chen~1,Fei-Jian Wu~1 1 College of Life Sciences and Hubei Key Lab of Genetic Regulation and Integrative Biology,Central China Normal University,Wuhan 430079 2 Department of Life Sciences and Chemistry,Hubei University of Education,Wuhan 430205

The acoustic signals in nature environment including animal communication sounds and human speech always contain frequency modulations（FM） *** rate selective neurons named according their responding to FM stimulus with different modulation rates have been found in many kinds of animals（bat,mouse,rat,monkey） at different levels of central auditory structures （MGB,IC,AC）,three types rate selectivity units have been classified,they are fast, low,and moderate-rate selectivity that sensitive to fast,low,and moderate modulation rate FM tone,***,The neural mechanism and critical factors of modulation rate selectivity is an old yet still current *** extra-cellular single unit recordings, we examined the neuronal modulation rate selectivity in the inferior colliculus（IC） of Kunming mouse（Mus musculus Km） in the free-field stimulation conditions.19 adult healthy Kunming mice（Mus musculus Km） were used in the present *** anesthesia and operation,the characteristic frequency （CF）,minimal threshold（MT） and excitatory responding frequency band width at MT + 10 dB SPL(RB) of the IC neurons were attained under 40ms pure tone *** the PSTHs（post-stimulus time histogram） recorded after 32 stimuli of pure tone with different durations （4,8,16,32,64,128,256 ms,respectively） and linear FM sweeps with different modulation rates which was leaded by several durations as same as pure tone and a serial of modulation ranges（2,4,8,16,32 kHz as CF in the center frequency）.All the date were analyzed with assistance of origin6.0,excel and sigmaplot10.0. Totally,102 neurons were recorded, and 41.2%（42/102） of them displayed duration tuning under pure tone（PT） *** these neurons,short-pass,band-pass,and long-pass were 22.6%（23/10）,8.8%（9/102）, 9.8%（10/102）,*** 60 neurons （58.8%） didn't show any duration tuning fea- *** FM stimulus,the majority of duration tuning neurons（78.6%,33/42） showed rate selectivity.

关键词： Modulation rate selectivity Modulation range Duration tuning Inferior collicullus Mouse

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The Role of Casein Kinase 1 in Circadian Timing

The Role of Casein Kinase 1 in Circadian Timing

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“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者： Michael H.Hastings Andrew S.I.Loudon MRC Laboratory of Molecular Biology Neurobiology DivisionHills RdCambridge CB2 0QHU.K. Faculty of Life Sciences University of ManchesterA.V.Hill BuildingOxford RoadManchesterM13 9PT

Post-translational modifications of key clock proteins are essential regulators circadian clocks,with phosphorylation by casein kinase 1 as a key step in the degradation pathway of mammalian PER *** the role （s） of theεandδisoforms of CK1 are unclear, not least because CK1εnull mice exhibit near-normal circadian behavioural rhythms. Questions remain,therefore,as to whether both enzymes are active regulators of the circadian clock,and how they interact with specific clock *** using novel pharmacological inhibitors targeting either CK1εor CK1δcombined with gene knock-out,and knock-down,we define their respective roles in the mammalian *** CK1ε-selective drug（PF-4800567） had no significant action on circadian rhythmicity in wild-type and CK1εnull animals,tissues or *** did,however,counteract the acceleration of circadian period of behavioural activity and clock gene oscillation observed in the CK1ε *** contrast,CK1δinhibitor（PF- 670462） dose-dependently lengthened the circadian period of wild-type and CK1εnull mice in terms of in vivo behaviour,as well as clock gene oscillations in the SCN,peripheral tissues and *** gene-specific SiRNA and ShRNA in cell lines and primary cells,we confirmed that CK1εknockdown had little impact on the circadian clockwork,while CK1δknock-down significantly reduced the amplitude of oscillation and lengthened circadian *** determine the mechanism of action of CK1δin setting circadian period,we examined the effects of inhibitor on PER2 protein *** high doses,PF-670462 caused a reversible arrhythmia in cell cultures, which was accompanied by prolonged nuclear retention of *** treatment of SCN slices with PF-670462 caused desynchrony between left and right SCN（splitting） and ultimately cellular dys-rhythmia and sustained PER2 *** suggests that CK1 enzymes are crucial for nuclear clearance of the target PER2 *** retention of PER2 in the nucleus ma

关键词： Casein kinase 1 Circadian Period Inhibitor Suprachiasmatic

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TRP Channels:Structural and Molecular Basis of the Assembly of the TRPP2/PKD1 Complex

TRP Channels:Structural and Molecular Basis of the Assembly ...

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“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者： Maximilian H.Ulbrich Albert C.M.Ong Ehud Y.Isacoff 杨建 Department of Molecular and Cell Biology University of CaliforniaBerkeleyCA 94720USA Kidney Genetics Group Academic Unit of NephrologySheffield Kidney InstituteSchool of Medicine and Biomedical SciencesUniversity of SheffieldSheffieldUK Department of Molecular and Cell Biology University of CaliforniaBerkeleyCA 94720USA Material Sciences & Physics Biosciences DivisionsLawrence Berkeley National LaboratoryBerkeleyCA 94720USA Department of Biological Sciences Columbia UniversityNew YorkNY 10027USA

Autosomal dominant polycystic kidney disease（ADPKD） is one of the most common genetic diseases in *** is caused by mutations in PKD1 or ***1（also known as polycystin-1 or PC1） is a 4302-amino acid,465 kDa integral membrane protein containing 11 putative transmembrane regions. Its large extracellular N terminus contains a number of well recognized repeats and domains,some of which are known to interact with extracellular matrix *** short intracellular C terminus contains a G protein activation ***,PKD1 is generally thought to function as a cell surface receptor for extracellular ligands and matrix proteins that couples extracellular stimuli,including mechanical stimuli,to intracellular signaling. TRPP2（also known as PKD2,polycystin-2 or PC2） is a member of the transient receptor potential （TRP） channel *** is a 968 amino acid,110 kDa integral membrane protein with 6 putative transmembrane segments and a pore-forming *** forms a Ca-permea- ble nonselective cation *** mutations in PKD1 and TRPP2 lead to ADPKD is *** two proteins likely participate in the same molecular and cellular processes in some kidney cells,since mutations in them produce similar pathological manifestations. Although both proteins are widely distributed, they show high levels of expression in kidney cells,where they are present on the plasma membrane and in the Golgi and endoplasmic *** also colocalize in the primary cilia of kidney *** two proteins associate physically and form functional ***,the subunit composition of this heteromeric complex and the molecular mechanism underlying its assembly are *** a combination of biochemistry, x-ray crystallography and a single molecule optical imaging method to determine the subunit composition of proteins in the plasma membrane of live cells,we find that this complex contains 3 TRPP2 and 1 PKD1. We also identified a coiled coil domain in the C terminus of TR

关键词： TRP channels Polycystic kidney disease Subunit stoichiometry Crystal structure Cross-linking Single molecule

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