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1.
Opt Express ; 32(7): 12982-12991, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38571104

RESUMEN

Quantum dense metrology (QDM) performs high-precision measurements by a two-mode entangled state created by an optical parametric amplifier (PA), where one mode is a meter beam and the other is a reference beam. In practical applications, the photon losses of meter beam are unavoidable, resulting in a degradation of the sensitivity. Here, we employ coherent feedback that feeds the reference beam back into the PA by a beam splitter to enhance the sensitivity in a lossy environment. The results show that the sensitivity is enhanced significantly by adjusting the splitting ratio of the beam splitter. This method may find its potential applications in QDM. Furthermore, such a strategy that two non-commuting observables are simultaneous measurements could provide a new way to individually control the noise-induced random drift in phase or amplitude of the light field, which would be significant for stabilizing the system and long-term precision measurement.

2.
Opt Express ; 31(4): 6499-6513, 2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-36823904

RESUMEN

We propose an alternative scheme for phase estimation in a Mach-Zehnder interferometer (MZI) with photon recycling. It is demonstrated that with the same coherent-state input and homodyne detection, our proposal possesses a phase sensitivity beyond the traditional MZI. For instance, it can achieve an enhancement factor of ∼9.32 in the phase sensitivity compared with the conventional scheme even with a photon loss of 10% on the photon-recycled arm. From another point of view, the quantum Cramér-Rao bound (QCRB) is also investigated. It is found that our scheme is able to achieve a lower QCRB than the traditional one. Intriguingly, the QCRB of our scheme is dependent of the phase shift ϕ while the traditional scheme has a constant QCRB regardless of the phase shift. Finally, we present the underlying mechanisms behind the enhanced phase sensitivity. We believe that our results provide another angle from which to enhance the phase sensitivity in a MZI via photon recycling.

3.
Phys Rev Lett ; 130(7): 073601, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36867793

RESUMEN

Interferometers are crucial for precision measurements, including gravitational waves, laser ranging, radar, and imaging. The phase sensitivity, the core parameter, can be quantum-enhanced to break the standard quantum limit (SQL) using quantum states. However, quantum states are highly fragile and quickly degrade with losses. We design and demonstrate a quantum interferometer utilizing a beam splitter with a variable splitting ratio to protect the quantum resource against environmental impacts. The optimal phase sensitivity can reach the quantum Cramér-Rao bound of the system. This quantum interferometer can greatly reduce the quantum source requirements in quantum measurements. In theory, with a 66.6% loss rate, the sensitivity can break the SQL using only a 6.0 dB squeezed quantum resource with the current interferometer rather than a 24 dB squeezed quantum resource with a conventional squeezing-vacuum-injected Mach-Zehnder interferometer. In experiments, when using a 2.0 dB squeezed vacuum state, the sensitivity enhancement remains at ∼1.6 dB via optimizing the first splitting ratio when the loss rate changes from 0% to 90%, indicating that the quantum resource is excellently protected with the existence of losses in practical applications. This strategy could open a way to retain quantum advantages for quantum information processing and quantum precision measurement in lossy environments.

4.
Phys Rev Lett ; 131(15): 150804, 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37897768

RESUMEN

A quantum memory with the performances of low noise, high efficiency, and high bandwidth is of crucial importance for developing practical quantum information technologies. However, the excess noises generated during the highly efficient processing of quantum information inevitably destroy quantum state. Here, we present a quantum memory with built-in excess-noise eraser by integrating a photon-correlated quantum interferometry in quantum memory, where the memory efficiency can be enhanced and the excess noises can be suppressed to the vacuum level via destructive interference. This quantum memory is demonstrated in a rubidium vapor cell with a 10-ns-long photonics signal. We observe ∼80% noise suppression, the write-in efficiency enhancement from 87% to 96.2% without and with interferometry, and the corresponding memory efficiency excluding the noises from 70% to 77%. The fidelity is 93.7% at the single-photon level, significantly exceeding the no-cloning limit. Such interferometry-integrated quantum memory, the first expansion of quantum interference techniques to quantum information processing, simultaneously enables low noise, high bandwidth, high efficiency, and easy operation.

5.
Opt Express ; 30(7): 11514-11523, 2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35473094

RESUMEN

The SU (1,1)-type atom-light hybrid interferometer (SALHI) is a kind of interferometer that is sensitive to both the optical phase and atomic phase. However, the loss has been an unavoidable problem in practical applications and greatly limits the use of interferometers. Visibility is an important parameter to evaluate the performance of interferometers. Here, we experimentally demonstrate the mitigating effect of the loss on visibility of the SALHI via asymmetric gain optimization, where the maximum threshold of loss to visibility close to 100% is increased. Furthermore, we theoretically find that the optimal condition for the largest visibility is the same as that for the enhancement of signal-to-noise ratio (SNR) to the best value with the existence of the losses using the intensity detection, indicating that visibility can act as an experimental operational criterion for SNR improvement in practical applications. Improvement of the interference visibility means achievement of SNR enhancement. Our results provide a significant foundation for practical application of the SALHI in radar and ranging measurements.

6.
Phys Rev Lett ; 128(3): 033601, 2022 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-35119880

RESUMEN

We present experimental and theoretical results on a new interferometer topology that nests a SU(2) interferometer, e.g., a Mach-Zehnder or Michelson interferometer, inside a SU(1,1) interferometer, i.e., a Mach-Zehnder interferometer with parametric amplifiers in place of beam splitters. This SU(2)-in-SU(1,1) nested interferometer (SISNI) simultaneously achieves a high signal-to-noise ratio (SNR), sensitivity beyond the standard quantum limit (SQL) and tolerance to photon losses external to the interferometer, e.g., in detectors. We implement a SISNI using parametric amplification by four-wave mixing (FWM) in Rb vapor and a laser-fed Mach-Zehnder SU(2) interferometer. We observe path-length sensitivity with SNR 2.2 dB beyond the SQL at power levels (and thus SNR) 2 orders of magnitude beyond those of previous loss-tolerant interferometers. We find experimentally the optimal FWM gains and find agreement with a minimal quantum noise model for the FWM process. The results suggest ways to boost the in-practice sensitivity of high-power interferometers, e.g., gravitational wave interferometers, and may enable high-sensitivity, quantum-enhanced interferometry at wavelengths for which efficient detectors are not available.

7.
Opt Lett ; 42(19): 4024-4027, 2017 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-28957188

RESUMEN

We demonstrate a new phase-matching geometry for four-wave mixing processes in hot Rb85 vapor, in which all four fields propagate in different directions but two of them are degenerate in frequency. When used as a parametric amplifier with an injected seed, two types of quantum mechanically correlated twin-beam states, either frequency degenerate or nondegenerate, can be generated. The quantum noise reduction in the intensity difference is almost 7 dB for the nondegenerate type and nearly 5 dB for the degenerate type. The spatial nondegeneracy of the four waves allows a variety of configurations of parametric processes, leading to flexible control for both phase insensitive and sensitive parametric amplification. The spatially nondegenerate but frequency degenerate four-wave mixing process will find wide applications in quantum metrology, quantum communication, and quantum information of continuous variables.

8.
Opt Lett ; 42(9): 1752-1755, 2017 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-28454152

RESUMEN

In studying quantum correlation and quantum memory of continuous variables of light fields and atoms, a crucial step is the retrieval of the quantum fields by converting an atomic spin wave to light, and retrieval efficiency is a crucial parameter. In this Letter, we implement a double-pass Raman scheme in Rb87 by incorporating coherent feedback. We find that the transfer efficiency from an atomic spin wave, which is generated from a Raman process in a high gain regime, to light fields is enhanced by the double-pass scheme as compared to the commonly used single-pass scheme. An atomic spin wave as high as 88% is read out, limited only by decoherence of the atomic spin waves. Our analysis shows that the enhancement effect is because a double-pass scheme introduced the coherent feedback mechanism which selects the spatial mode of an atomic spin wave via the correlated optical field and enhances the coupling efficiency between the atom and light. The correlations between the write-in and readout signals generated in such a two-pass Raman process are also better than the single-pass case. We believe such a two-pass scheme with feedback mechanism should be useful for studying continuous variables in quantum systems.

9.
Opt Express ; 24(16): 17766-78, 2016 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-27505745

RESUMEN

Collective atomic excitation can be realized by the Raman scattering. Such a photon-atom interface can form an SU(1,1)-typed atom-light hybrid interferometer, where the atomic Raman amplification processes take the place of the beam splitting elements in a traditional Mach-Zehnder interferometer. We numerically calculate the phase sensitivities and the signal-to-noise ratios (SNRs) of this interferometer with the method of homodyne detection and intensity detection, and give their differences of the optimal phase points to realize the best phase sensitivities and the maximal SNRs from these two detection methods. The difference of the effects of loss of light field and atomic decoherence on measure precision is analyzed.

10.
Opt Express ; 23(8): 10009-17, 2015 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-25969042

RESUMEN

We demonstrate experimentally controlled storage and retrieval of the optical phase information in a higher-order interference scheme based on Raman process in (87)Rb atomic vapor cells. An interference pattern is observed in intensity correlation measurement between the write Stokes field and the delayed read Stokes field as the phase of the Raman write field is scanned. This result implies that the phase information of the Raman write field can be written into the atomic spin wave via Raman process in a high gain regime and subsequently read out via a spin-wave enhanced Raman process, thus achieving optical storage of phase information. This technique should find applications in optical phase image storage, holography and information processing.

11.
Neural Plast ; 2015: 927817, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26078886

RESUMEN

Cordycepin has been widely used in oriental countries to maintain health and improve physical performance. Compound nerve action potential (CNAP), which is critical in signal conduction in the peripheral nervous system, is necessary to regulate physical performance, including motor system physiological and pathological processes. Therefore, regulatory effects of cordycepin on CNAP conduction should be elucidated. In this study, the conduction ability of CNAP in isolated frog sciatic nerves was investigated. Results revealed that cordycepin significantly decreased CNAP amplitude and conductive velocity in a reversible and concentration-dependent manner. At 50 mg/L cordycepin, CNAP amplitude and conductive velocity decreased by 62.18 ± 8.06% and 57.34% ± 6.14% compared with the control amplitude and conductive velocity, respectively. However, the depressive action of cordycepin on amplitude and conductive velocity was not observed in Ca(2+)-free medium or in the presence of Ca(2+) channel blockers (CdCl2/LaCl3). Pretreatment with L-type Ca(2+) channel antagonist (nifedipine/deltiazem) also blocked cordycepin-induced responses; by contrast, T-type and P-type Ca(2+) channel antagonists (Ni(2+)) failed to block such responses. Therefore, cordycepin decreased the conduction ability of CNAP in isolated frog sciatic nerves via L-type Ca(2+) channel-dependent mechanism.


Asunto(s)
Potenciales de Acción/efectos de los fármacos , Desoxiadenosinas/farmacología , Conducción Nerviosa/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Nervio Ciático/fisiología , Animales , Anuros , Señalización del Calcio/efectos de los fármacos , Técnicas In Vitro
12.
Opt Express ; 21(9): 10490-5, 2013 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-23669906

RESUMEN

We experimentally demonstrate efficient Raman conversion to respective Stokes and anti-Stokes fields in both pulsed and continuous modes with a Rb-87 atomic vapor cell. The conversion efficiency is about 40-50% for the Stokes field and 20-30% for the anti-Stokes field, respectively. This efficient conversion process is realized with coherent feedback of both the Raman pump and the frequency-converted fields (Stokes or anti-Stokes). The experimental setup is simple and can be applied easily to produce light sources with larger frequency shifts using other Raman media with long coherence time. They may have potential applications in nonlinear optics, Raman spectroscopy and precision measurement.


Asunto(s)
Rayos Láser , Espectrometría Raman/instrumentación , Diseño Asistido por Computadora , Diseño de Equipo , Análisis de Falla de Equipo
13.
Phys Rev Lett ; 105(13): 133603, 2010 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-21230776

RESUMEN

Coherent conversion between a Raman pump field and its Stokes field is observed in a Raman process with a strong atomic spin wave initially prepared by another Raman process operated in the stimulated emission regime. The oscillatory behavior resembles the Rabi oscillation in atomic population in a two-level atomic system driven by a strong light field. The Rabi-like oscillation frequency is found to be related to the strength of the prebuilt atomic spin wave. High conversion efficiency of 40% from the Raman pump field to the Stokes field is recorded and it is independent of the input Raman pump field. This process can act as a photon frequency multiplexer and may find wide applications in quantum information science.

14.
Nat Commun ; 10(1): 148, 2019 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-30635582

RESUMEN

Quantum memories are essential for quantum information processing. Techniques have been developed for quantum memory based on atomic ensembles. The atomic memories through optical resonance usually suffer from the narrow-band limitation. The far off-resonant Raman process is a promising candidate for atomic memories due to broad bandwidths and high speeds. However, to date, the low memory efficiency remains an unsolved bottleneck. Here, we demonstrate a high-performance atomic Raman memory in 87Rb vapour with the development of an optimal control technique. A memory efficiency of above 82.0% for 6 ns~20 ns optical pulses is achieved. In particular, an unconditional fidelity of up to 98.0%, significantly exceeding the no-cloning limit, is obtained with the tomography reconstruction for a single-photon level coherent input. Our work marks an important advance of atomic memory towards practical applications in quantum information processing.

15.
Neurosci Lett ; 412(2): 108-13, 2007 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-17174470

RESUMEN

Bis(7)-tacrine [bis(7)-tetrahydroaminacrine] acts as an AChE inhibitor and also exerts modulatory effects on many ligand-gated ion channels and voltage-gated Ca(2+) and K(+) channels. It has been reported previously that tacrine and some other AChE inhibitors suppressed I(K(A)) in central and peripheral neurons. The present study aimed to explore whether bis(7)-tacrine could modulate the function of native delayed rectifier potassium channels in DRG neurons and K(V)1.2 encoded potassium channels expressed in oocytes. We found that both delayed rectifier potassium currents (I(K(DR))) in rat DRG neurons and the currents recorded from oocytes expressing K(V)1.2 (I(K(K(V)1.2))) were suppressed by bis(7)-tacrine, the potency of which was two orders greater than that of tacrine. The IC(50) values for bis(7)-tacrine and tacrine inhibition of I(K(KD)) in DRG neurons were 0.72+/-0.05 and 58.3+/-3.7 microM, respectively; while the two agents inhibited I(K(K(V)1.2)) in oocytes with an IC(50) of 0.24+/-0.06 and 102.1+/-21.5 microM, respectively. The possible mechanism for bis(7)-tacrine inhibition of I(K(A)) and I(K(K(V)1.2)) was identified as the suppression of their activation, inactivation.


Asunto(s)
Canales de Potasio de Tipo Rectificador Tardío/metabolismo , Canal de Potasio Kv.1.2/metabolismo , Neuronas Aferentes/metabolismo , Bloqueadores de los Canales de Potasio/farmacología , Tacrina/análogos & derivados , Animales , Células Cultivadas , Inhibidores de la Colinesterasa/farmacología , Canales de Potasio de Tipo Rectificador Tardío/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Ganglios Espinales/citología , Técnicas de Transferencia de Gen , Activación del Canal Iónico/efectos de los fármacos , Activación del Canal Iónico/fisiología , Canal de Potasio Kv.1.2/efectos de los fármacos , Canal de Potasio Kv.1.2/genética , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Inhibición Neural/efectos de los fármacos , Inhibición Neural/fisiología , Neuronas Aferentes/efectos de los fármacos , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Técnicas de Placa-Clamp , Ratas , Ratas Sprague-Dawley , Tacrina/farmacología , Xenopus
16.
Eur J Pharmacol ; 796: 1-6, 2017 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-27988284

RESUMEN

Cordycepin has important neuroprotective effects in hypoxic or ischemic insult. However, the direct electrophysiological evidence of cordycepin's neuroprotection from hypoxic or ischemic insult remains unknown. Hence, in this study, the electrophysiological mechanism by which cordycepin protects against ischemic and hypoxic damages has been studied using an energy-deprivation injury model through whole-cell patch clamp techniques. Results revealed that cordycepin (80µM) significantly delayed hypoxia-induced membrane depolarization, including cordycepin reduced slope, and extended the duration of slow depolarization, prolonged the ability to generate spontaneous action potential (AP) firing, delayed the onset of rapid depolarization, and maintained the more hyperpolarized membrane potential after rapid depolarization. Additionally, cordycepin also delayed the hypoxia-induced decrease in the evoked AP amplitude. Furthermore, cordycepin can rescue the neuronal electrophysiological function after the 5min hypoxia pretreatment insult as seen the recovery on the evoked spike amplitude, membrane potential, and evoked AP latency during reoxygenation of hippocampal slices with cordycepin. Collectively, the results in this study provide direct evidence demonstrating the important neuroprotective effects of cordycepin against the hypoxic insult via improvement of the neuronal electrophysiological function, and the mechanism underlying the anti hypoxia-induced membrane depolarization is strongly recommended.


Asunto(s)
Región CA1 Hipocampal/citología , Desoxiadenosinas/farmacología , Potenciales de la Membrana/efectos de los fármacos , Células Piramidales/citología , Células Piramidales/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Animales , Hipoxia de la Célula/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Potenciales Evocados/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
17.
Sheng Li Xue Bao ; 58(5): 494-9, 2006 Oct 25.
Artículo en Zh | MEDLINE | ID: mdl-17041736

RESUMEN

To investigate the role of ion channels in the coupling responses of neutrophils to extracellular stimulus, it is necessary to study the membrane ion channel activities using patch-clamp technique. However, little has been known about the ion channel activities in neutrophils due to the difficulties in forming giga-seal with pipettes because of small diameter of neutrophils and the easily developed polarization. Some studies indicated that favorable results could be achieved through pretreatment at low temperature before electrophysiological recordings. But it remains unclear whether the pretreatment affects the membrane current and why the seal rate increases after low temperature pretreatment. The purpose of this study was to investigate the effects of 4 degrees C pretreatment on the membrane current and cell polarity in human neutrophils. In the experiments, human neutrophils were isolated from fresh peripheral blood of healthy volunteers and divided into two groups (room temperature group and 4 degrees C pretreatment group). Voltage-dependent K(+) (Kv) currents were recorded in whole-cell voltage-clamp mode and large-conductance Ca(2+)-activated K(+) (BK(Ca)) currents were recorded using inside-out patches. The results showed that 4 degrees C pretreatment significantly inhibited cell polarity (P<0.05), and it took more time for neutrophils to form a polarity-cycle [(534+/-32) s, n=20] compared with those at room temperature [(257+/-24) s, n=20]. Meanwhile, seal rate significantly increased in 4 degrees C pretreatment group (64%) compared with that in the room temperature group (27.5%). The seal rate and cell polarity rate during 0 approximately 1 min after 4 degrees C pretreatment were significantly different from those at room temperature, while no significant difference was found during 9 approximately 10 min between the two groups. Our results suggest that 4 degrees C pretreatment can inhibit cell polarity and increase seal rate, but has no effects on membrane currents. It is also suggested that 0 approximately 1 min after 4 degrees C pretreatment is a more suitable time for electrophysiological recording in neutrophils.


Asunto(s)
Neutrófilos/fisiología , Polaridad Celular , Frío , Humanos , Canales de Potasio de Gran Conductancia Activados por el Calcio/fisiología , Potenciales de la Membrana , Canales de Potasio con Entrada de Voltaje/fisiología
18.
PLoS One ; 9(6): e98894, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24896240

RESUMEN

Gastric cancer (GC) is one of the leading causes of cancer death in the world. The role of histone deacetylase 4 (HDAC4) in specific cell and tissue types has been identified. However, its biological roles in the development of gastric cancer remain largely unexplored. Quantitative real time PCR (qRT-PCR) and western blot were used to analyze the expression of HDAC4 in the clinical samples. siRNA and overexpression of HDAC4 and siRNA p21 were used to study functional effects in a proliferation, a colony formation, a adenosine 5'-triphosphate (ATP) assay and reactive oxygen species(ROS) generation, cell cycle, cell apoptosis rates, and autophagy assays. HDAC4 was up-regulated in gastric cancer tissues and several gastric cancer cell lines. The proliferation, colony formation ability and ATP level were enhanced in HDAC4 overexpression SGC-7901 cells, but inhibited in HDAC4 knockdown SGC-7901 cells. HDAC4 knockdown led to G0/G1 phase cell arrest and caused apoptosis and ROS increase. Moreover, HDAC4 was found to inhibit p21 expression in gastric cancer SGC-7901 cells. p21 knockdown dramatically attenuated cell proliferation inhibition, cell cycle arrest, cell apoptosis promotion and autophagy up-regulation in HDAC4-siRNA SGC-7901 cells. We demonstrated that HDAC4 promotes gastric cancer cell progression mediated through the repression of p21. Our results provide an experimental basis for understanding the pro-tumor mechanism of HDAC4 as treatment for gastric cancer.


Asunto(s)
Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Regulación Neoplásica de la Expresión Génica , Histona Desacetilasas/metabolismo , Proteínas Represoras/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Adenosina Trifosfato/metabolismo , Anciano , Apoptosis/genética , Estudios de Casos y Controles , Puntos de Control del Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular , Histona Desacetilasas/genética , Humanos , Persona de Mediana Edad , Especies Reactivas de Oxígeno/metabolismo , Proteínas Represoras/genética , Neoplasias Gástricas/patología , Ensayo de Tumor de Célula Madre
19.
Neuropharmacology ; 72: 148-56, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23643746

RESUMEN

The medial prefrontal cortex (mPFC) has been implicated in modulating anxiety. However, it is unknown whether excitatory or inhibitory neurotransmission in the infralimbic (IL) subregion of the mPFC underlies the pathology of anxiety-related behavior. To address this issue, we infused the GABAA receptor (GABAAR) antagonist bicuculline to temporarily activate the IL cortex. IL cortex activation decreased the time spent in the center area in the open field test, decreased exploration of the open-arms in the elevated plus maze test, and increased the latency to bite food in the novelty-suppressed feeding test. These findings substantiate the GABAergic system's role in anxiety-related behaviors. IL cortex inactivation with the AMPA receptor (AMPAR) antagonist CNQX produced opposite, anxiolytic effects. However, infusion of the NMDA receptor (NMDAR) antagonist AP5 into the IL cortex had no significant effect. Additionally, we did not observe motor activity deficits or appetite deficits following inhibition of GABAergic or glutamatergic neurotransmission. Interestingly, we found parallel and corresponding electrophysiological changes in anxious mice; compared to mice with relatively low anxiety, the relatively high anxiety mice exhibited smaller evoked inhibitory postsynaptic currents (eIPSCs) and larger AMPA-mediated evoked excitatory postsynaptic currents (eEPSCs) in pyramidal neurons in the IL cortex. The changes of eIPSCs and eEPSCs were due to presynaptic mechanisms. Our results suggest that imbalances of neurotransmission in the IL cortex may cause a net increase in excitatory inputs onto pyramidal neurons, which may underlie the pathogenic mechanism of anxiety disorders.


Asunto(s)
Ansiedad/patología , Potenciales Postsinápticos Excitadores/fisiología , Corteza Prefrontal/fisiopatología , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , 6-Ciano 7-nitroquinoxalina 2,3-diona/uso terapéutico , Animales , Animales Recién Nacidos , Ansiedad/inducido químicamente , Ansiedad/tratamiento farmacológico , Bicuculina/toxicidad , Modelos Animales de Enfermedad , Antagonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/uso terapéutico , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Conducta Exploratoria/efectos de los fármacos , Antagonistas de Receptores de GABA-A/toxicidad , Técnicas In Vitro , Potenciales Postsinápticos Inhibidores/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Técnicas de Placa-Clamp , Corteza Prefrontal/efectos de los fármacos
20.
PLoS One ; 3(10): e3414, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18923708

RESUMEN

BACKGROUND: Kuntiz-type toxins (KTTs) have been found in the venom of animals such as snake, cone snail and sea anemone. The main ancestral function of Kunitz-type proteins was the inhibition of a diverse array of serine proteases, while toxic activities (such as ion-channel blocking) were developed under a variety of Darwinian selection pressures. How new functions were grafted onto an old protein scaffold and what effect Darwinian selection pressures had on KTT evolution remains a puzzle. PRINCIPAL FINDINGS: Here we report the presence of a new superfamily of ktts in spiders (TARANTULAS: Ornithoctonus huwena and Ornithoctonus hainana), which share low sequence similarity to known KTTs and is clustered in a distinct clade in the phylogenetic tree of KTT evolution. The representative molecule of spider KTTs, HWTX-XI, purified from the venom of O. huwena, is a bi-functional protein which is a very potent trypsin inhibitor (about 30-fold more strong than BPTI) as well as a weak Kv1.1 potassium channel blocker. Structural analysis of HWTX-XI in 3-D by NMR together with comparative function analysis of 18 expressed mutants of this toxin revealed two separate sites, corresponding to these two activities, located on the two ends of the cone-shape molecule of HWTX-XI. Comparison of non-synonymous/synonymous mutation ratios (omega) for each site in spider and snake KTTs, as well as PBTI like body Kunitz proteins revealed high Darwinian selection pressure on the binding sites for Kv channels and serine proteases in snake, while only on the proteases in spider and none detected in body proteins, suggesting different rates and patterns of evolution among them. The results also revealed a series of key events in the history of spider KTT evolution, including the formation of a novel KTT family (named sub-Kuntiz-type toxins) derived from the ancestral native KTTs with the loss of the second disulfide bridge accompanied by several dramatic sequence modifications. CONCLUSIONS/SIGNIFICANCE: These finding illustrate that the two activity sites of Kunitz-type toxins are functionally and evolutionally independent and provide new insights into effects of Darwinian selection pressures on KTT evolution, and mechanisms by which new functions can be grafted onto old protein scaffolds.


Asunto(s)
Venenos de Araña/farmacología , Animales , Sitios de Unión , Evolución Molecular , Canal de Potasio Kv.1.1/antagonistas & inhibidores , Conformación Proteica , Selección Genética , Venenos de Araña/química , Venenos de Araña/genética , Arañas , Inhibidores de Tripsina
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