Complexin Research Articles

ASSESSMENT AND ROLE OF ARTERY-VEIN COMPLEX IN MYOPIC CHOROIDAL NEOVASCULARIZATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

To analyze the presence of an artery-vein complex (AVC) underneath myopic choroidal neovascularization (mCNV) and to determine its relationship with neovascular activity. Retrospective analysis of 681 eyes from 362 patients with high myopia defined by an axial length of >26 mm using optical coherence tomography (OCT) and OCT angiography imaging. Patients with clinical diagnosis of mCNV and good quality OCT angiography images were then selected. An AVC was defined by the identification of both perforating scleral vessels and dilated choroidal veins under or in contact with the mCNV in the same case. Swept source OCT (SS-OCT) and SS-OCT angiography images (TRITON; Topcon Corporation, Tokyo, Japan) were reviewed to detect AVC in the mCNV area. Fifty eyes of 49 highly myopic patients with mCNV were analyzed. Eyes with AVC were statistically older (69.95 ± 13.53 vs. 60.83 ± 10.47 years old; P < 0.01), needed less intravitreal injections/year along the follow-up period (0.80 ± 0.62 vs. 1.92 ± 0.17; P < 0.01), and showed less relapses/year (0.58 ± 0.75 vs. 0.46 ± 0.42; P < 0.05) when compared with eyes without AVC. Moreover, eyes with AVC were less likely to relapse during the first year from mCNV activation (n = 5/14 vs. n = 14/16; P < 0.01; P < 0.01). No significant differences were found regarding either axial length (30.55 ± 2.31 vs. 29.65 ± 2.24, P > 0.05) or best-corrected visual acuity (0.4 ± 0.5 vs. 0.4 ± 0.5 Logarithm of the Minimum Angle of Resolution (logMAR), P > 0.05) between groups. AVC complex has an influence over myopic choroidal neovascularization activity resulting in less aggressive neovascular lesions than those with perforating scleral vessels only.

NURSES’ ATTITUDE TOWARDS PATIENT’S RIGHTS AT ERADA MENTAL HEALTH COMPLEX IN JEDDAH CITY, SAUDI ARABIA

Background: Patients have a fundamental right to healthcare that is respectful, responsive, safe and effective. Healthcare professionals, especially nurses, have a duty to treat the patient respectfully, listen to concerns, answer questions clearly and honestly, and inform and educate the patient about the illness. Therefore, nurses are required to be knowledgeable and positively oriented towards patients’ rights. Objective: The purpose of the study is to investigate the attitudes of psychiatric nurses at Eradah mental health complex in Jeddah city towards patients’ rights. Material and Method: A descriptive cross-sectional research design was adopted in this study. The study used the convenient sampling method to recruit a sample of 171 psychiatric nurses. To collect data, the study used the questionnaire that consisted of two parts: the socio-demographic part and the attitudes towards patient’s rights part (28 statements). Result: The results of the study showed that psychiatric nurses at Eradah mental health complex had positive attitudes towards patients’ rights (4.06±0.76). The results showed that the highest positive attitudes were related to those patients should receive healthcare services in safe environment, having the right to choose the healthcare providing institution or change it if needed, and the right to benefit from any provided healthcare services that comply with their medical condition. In addition, it was found that there were no significant statistical differences in the psychiatric nurses’ attitudes towards patients’ rights referred to nurses’ age, gender, or years of experience. Conclusion: The study concluded that psychiatric nurses at Eradah mental health complex in Jeddah city had positive attitudes towards patients’ rights and these attitudes are not significantly associated with nurses’ gender, age, and years of experience

Intrinsic linking and knotting are arbitrarily complex in directed graphs

Fleming and Foisy (2018) recently proved the existence of a digraph whose every embedding contains a $4$-component link, and left open the possibility that a directed graph with an intrinsic $n$-component link might exist. We show that, indeed, this is th

Docetaxel gold complex nanoflowers: A chemo-biological evaluation for their use as nanotherapeutics

Docetaxel (DTX) is an anticancer treatment widely used in the clinic for the treatment of various human malignancies, including Non-Small-Cell Lung Cancer (NSCLC). Its low water solubility and systemic toxicity, however, negatively impact the clinical application of such drug. In order to improve DTX solubility in biological fluids and decrease its adverse effects in patients, the scientific community is currently focusing on developing drug delivery systems where DTX is the payload. In this context, the present study aims at presenting a step forward in the development of platforms based on gold complexes for multifunctional approaches (theragnostic tools) and stimuli-responsive therapies. Tetrachloroauric acid (HAuCl4) were complexed with the antitumor drug and dicarboxylic acid-terminated polyethylene-glycol (PEG) to form the nanometric complex named DTX-Au-PEG. Following reduction with sodium borohydride (NaBH4), the DTX-Au-PEG complex formed hybrid-metal nanoparticles (DTX IN PEG-AuNPs), where DTX was protected in the gold core embedded within the polymer chains. To achieve therapeutic targeting, DTX-Au-PEG complex and DTX IN PEG-AuNPs were chemical combined with the human anti-EGFR polyclonal antibody, which recognizes the hERG1 channel aberrantly expressed on the membrane of human lung cancer cells. The active targeting was demonstrated by various analytical techniques (Raman and UV–vis spectroscopies); whereas, in vitro experiments on tissue-mimetic, three-dimensional (3D) tumoroids grown at the Air-Liquid Interface (ALI) demonstrated that DTX encapsulation within a gold core strongly influenced the drug efficacy, with a significant increase of the DTX therapeutic index when AuNPs were specifically targeted against EGFR. Collectively, our study demonstrated that a drug delivery system based on Au (III)-DTX complexes constitutes an encouraging chemical approach to build Au (III) complexes into real chemotherapeutic drugs for cancer treatment.

The topology of the external activity complex of a matroid

We prove that the external activity complex Act&lt;(M) of a matroid is shellable. In fact, we show that every linear extension of Las Vergnas's external/internal order &lt;ext/int on M provides a shelling of Act&lt;(M). We also show that every linear extension of Las Vergnas's internal order &lt;int on M provides a shelling of the independence complex IN(M). As a corollary, Act&lt;(M) and M have the same h-vector. We prove that, after removing its cone points, the external activity complex is contractible if M contains U3,1 as a minor, and a sphere otherwise.

The C2C-MCT Domain of Munc13 is Essential for Priming Synaptic Vesicles

Munc13 and Complexin (CPX) play pivotal roles in both spontaneous and calcium triggered synaptic vesicle (SV) fusion. Using a high-throughput behavioral assay on chemically mutagenized C. elegans lacking CPX, we identified an early-stop mutation at the beginning of the C2C domain near the C-terminal end of the Munc13 ortholog, UNC-13. Munc13 C2C is implicated in tethering SVs to the plasma membrane. However, its mechanism of tethering vesicles is not well understood. Also, to our knowledge, the C2C domain of Munc13 has not been isolated and characterized in any system to date. Here, we report that one or two alpha helices of MUN domain preceding C2C and the predicted alpha helices of the last 60 residues (MCT) are crucial for C2C folding and stability. The precise deletion of C2C or MCT impairs synaptic transmission, decreases SV priming, and disrupts nervous system function in C. elegans. To understand the role of C2C domain in tethering and priming SVs, we characterized the membrane binding properties of Munc13 C2C-MCT using various approaches including co-sedimentation, co-flotation and tryptophan fluorescence. We found that the C2C-MCT domain binds membranes in a calcium- and charge-independent manner. Using behavioral assays in worms, a single point mutation in a predicted loop of C2C domain impaired nervous system function but did not affect lipid binding. In contrast, disrupting a hydrophobic patch in MCT abrogated lipid binding but did not affect nervous system function. Finally, artificially tethering the UNC-13 MUN domain to SVs rescued the unc-13 null mutant while plasma membrane tethered UNC-13 failed to restore function. On basis of these results, we conclude that SV localization of C2C-MCT is critical for efficient priming by Munc13, relies on protein-protein interactions, and acts upstream of the clamping function of CPX.

The metalanguage of a lexicographic definition in the descriptive dictionary (based on the dictionaries of the Serbian language)

In this paper we present the continuous hierarchical ordering of the first part of the definition of lexemes from the thematic group ?buildings? by analyzing the vertical organization of superordination of concepts in the lexicographical definition. We demonstrate that the vertical sequence mounts from a higher level of conceptual categorization, ?localizer,? in the form of complex and simple primitives (PLACE &gt; SPACE [WHERE], SPACE &gt; EXPANSE [SOMETHING THAT IS (BOUNDLESSLY) SPREADING IN EVERY DIRECTION]) and descends toward a lower hyperonimic level of ?buildings?. The suggested model links meanings systematically, on a micro-level of meaning within the polysemic structure, and on a macrolevel of meanings of lexemes belonging to a thematic group/class, which is significant for the descriptive lexicography and for the modeling of semantic description in the electronic dictionary of the contemporary Serbian language. Such description could facilitate the cross-referencing of lexemes and advanced search, which is essential both for linguists and dictionary users.

Correction: Re-visiting the trans insertion model for complexin clamping.

Correction: Re-visiting the trans insertion model for complexin clamping.

REGIONAL SECURITY COMPLEX IN ASEAN: Neutrality and Centrality at Brink in the South China Sea Issue

The South China Sea conflict has been a highly sensitive issue for the last 5 years in ASEAN. China and the US have been using the South China Sea as the New Cold War Arena of power and military hegemonic competition in the South East Asia region. This has been a major challenge for ASEAN as the only regional organization in the South East Asia region that has direct in the area must take major role in managing and resolving the dispute peacefully even though ASEAN has no defense pact like NATO. This paper argues that ASEAN, at this moment, must maintain its role as a mediator and independent-negotiator in the region but at the same time apply its principle of gradually adapting with the new international system. This article also suggests that in the future, ASEAN can take a major role in the governance of the South China Sea and the South East Asia region.

Synaptic Activity Regulates the Abundance and Binding of Complexin

Nervous system function relies on precise chemical communication between neurons at specialized junctions known as synapses. Complexin (CPX) is one of a small number of cytoplasmic proteins that are indispensable in controlling neurotransmitter release through SNARE and synaptic vesicle interactions. However, the mechanisms that recruit and stabilize CPX are poorly understood. The mobility of CPX tagged with photoactivatable green fluorescent protein (pGFP) was quantified in vivo using Caenorhabditis elegans. Although pGFP escaped the synapse within seconds, CPX-pGFP displayed both fast and slow decay components, requiring minutes for complete exchange of the synaptic pool. The longer synaptic residence time of CPX arose from both synaptic vesicle and SNARE interactions, and surprisingly, CPX mobility depended on synaptic activity. Moreover, mouse CPX-GFP reversibly dispersed out of hippocampal presynaptic terminals during stimulation, and blockade of vesicle fusion prevented CPX dispersion. Hence, synaptic CPX can rapidly redistribute and this exchange is influenced by neuronal activity, potentially contributing to use-dependent plasticity.

Complexin-Mediated Inhibition of Vesicle Fusion: Conserved Functions from Worm to Mouse

Synapses continually replenish their synaptic vesicle (SV) pools while suppressing spontaneous fusion events, thus maintaining a high dynamic range in response to physiological stimuli. The presynaptic protein complexin (CPX) inhibits fusion through interactions between its highly conserved central helix and the SNARE complex. Two poorly conserved domains (the accessory helix and the C-terminal domain) on either side of the central helix (CH) are also required for inhibition of spontaneous fusion. We found that the C-terminal domain (CTD) binds lipids through a novel protein motif, permitting complexin to inhibit spontaneous exocytosis in vivo by targeting complexin to highly curved membranes such as SVs. Membrane curvature enhanced CPX binding and induced conformational changes in a critical amphipathic region of the CTD. The accessory helix (AH) of CPX contributes to the inhibition of exocytosis but the molecular mechanism for this function remains unknown. Several models have been proposed for the role of AH based on the concept that AH competes with VAMP for a binding site on the SNARE complex. Using a series of AH mutations and chimeras with mouse AH together with NMR and CD spectroscopy, electrophysiology, and behavioral assays, we identified key features of the AH and CH required for inhibition of SV fusion by CPX. We propose that the AH stabilizes the CH through nucleation and propagation of helical secondary structure, thereby facilitating binding of the CH to the SNARE complex.

Uskok Starego Julianowa w sowiogórskim kompleksie gnejsowym i sytuacja geologiczna w miejscu jego występowania (Pogórze Wałbrzyskie, Sudety Środkowe, południowa Polska)

STARY JULIANOW FAULT IN SOWIE GORY GNEISS COMPLEX AND GEOLOGICAL SITUATION IN THE PLACE OF ITS OCCURRENCE (WAŁBRZYCH FOOTHILLS, CENTRAL SUDETES, SOUTHERN POLAND) Abstract. The paper describes localization and architecture of a uranium-bearing fault, called the Stary Julianow Fault (uStJ). The fault studied occurs in a north-western fragment of the sudetic part of the Gory Sowie Gneiss Massif (MGS ), in the area of the Walbrzych Foothills, between Stary Julianow and Dziecmorowice. It is one of faults that make up the northern part of a broad dislocation zone extending from Stary Julianow to Zagorze Ślaskie, in which the occurrence of hydrothermal mineralization, called mineralization from Dziecmorowice, was described. Information about the Stary Julianow Fault obtained during its exploration by underground workings to the depth of 345 m and the extension of 900 m, which were made in the years 1949–1952 in connection with uranium ore mining. The Stary Julianow Fault belongs to “older” faults with direction NW –SE and it is oriented crosswise to macrofold which occurs in Julianow region. The architecture of a fault zone of the Stary Julianow Fault consists of two parts: a fault core and a damage zone. The fault core is represented by narrow zone, composed of the fault rocks with the occurrence of uranium-bearing calcite lenses. The damage zone is brittle deformation with instances of carbonate mineralization and hydrothermal alteration of gneisses. It is particularly wide developed in the east side of the Stary Julianow Fault. The architecture and position of the Stary Julianow Fault in the tectonic structure of the region suggests its formation during the Variscan evolution of the Gory Sowie Gneiss Massif.

The accessory helix of complexin functions by stabilizing central helix secondary structure.

The presynaptic protein complexin (CPX) is a critical regulator of synaptic vesicle fusion, but the mechanisms underlying its regulatory effects are not well understood. Its highly conserved central helix (CH) directly binds the ternary SNARE complex and is required for all known CPX functions. The adjacent accessory helix (AH) is not conserved despite also playing an important role in CPX function, and numerous models for its mechanism have been proposed. We examined the impact of AH mutations and chimeras on CPX function in vivo and in vitro using C. elegans. The mouse AH fully restored function when substituted into worm CPX suggesting its mechanism is evolutionarily conserved. CPX inhibitory function was impaired when helix propagation into the CH was disrupted whereas replacing the AH with a non-native helical sequence restored CPX function. We propose that the AH operates by stabilizing CH secondary structure rather than through protein or lipid interactions.

Complexity of Complexin

Complexity of Complexin

Molecular mechanisms of COMPLEXIN fusion clamp function in synaptic exocytosis revealed in a new Drosophila mutant

The COMPLEXIN (CPX) proteins play a critical role in synaptic vesicle fusion and neurotransmitter release. Previous studies demonstrated that CPX functions in both activation of evoked neurotransmitter release and inhibition/clamping of spontaneous synaptic vesicle fusion. Here we report a new cpx mutant in Drosophila melanogaster, cpx(1257), revealing spatially defined and separable pools of CPX which make distinct contributions to the activation and clamping functions. In cpx(1257), lack of only the last C-terminal amino acid of CPX is predicted to disrupt prenylation and membrane targeting of CPX. Immunocytochemical analysis established localization of wild-type CPX to active zone (AZ) regions containing neurotransmitter release sites as well as broader presynaptic membrane compartments including synaptic vesicles. Parallel biochemical studies confirmed CPX membrane association and demonstrated robust binding interactions of CPX with all three SNAREs. This is in contrast to the cpx(1257) mutant, in which AZ localization of CPX persists but general membrane localization and, surprisingly, the bulk of CPX-SNARE protein interactions are abolished. Furthermore, electrophysiological analysis of neuromuscular synapses revealed interesting differences between cpx(1257) and a cpx null mutant. The cpx null exhibited a marked decrease in the EPSC amplitude, slowed EPSC rise and decay times and an increased mEPSC frequency with respect to wild-type. In contrast, cpx(1257) exhibited a wild-type EPSC with an increased mEPSC frequency and thus a selective failure to clamp spontaneous release. These results indicate that spatially distinct and separable interactions of CPX with presynaptic membranes and SNARE proteins mediate separable activation and clamping functions of CPX in neurotransmitter release.

Calcium Triggered Membrane Penetration of Synaptotagmin may Provide the Driving Force to Reverse the Complexin Clamp

Synaptic proteins, Complexin and Synaptotagmin act in sync to achieve the speed and the accuracy of the synaptic transmission. Complexin (CPX) arrests the SNARE assembly in the late stages promoting the docking of the synaptic vesicles at the active zone and along with Synaptotagmin, the calcium sensor, synchronizes the fusion of these vesicles with the influx of calcium ions following the nerve impulse. Recently, we obtained the first X-ray crystal structure representing the clamped state of SNAREpin at the docked vesicles, which shows that Complexin arrests fusion by blocking the complete assembly of the v-SNAREs in the adjacent SNARE complex. This trans- interaction generates an unusual zigzag array of half-zippered (pre-fusion) SNARE complexes between the two bilayers. Here we present experiments using a novel Nanodisc-based system that mimics a vesicle-bilayer junction that suggests a simple model for the reversal of the CPX clamp by Synaptotagmin and calcium. In this model, Synaptotagmin binds the stalled CPX-SNARE complex via its interactions with the t-SNAREs and upon binding Calcium, the membrane loops inserts rapidly into the bilayers, while Synaptotagmin stays bound in place on the SNAREpins. This is expected to perturb the attached SNAREpin out of the planarity of the zigzag array and thus, trigger the rapid disassembly of the stalled zigzag structure allowing the SNAREs to complete zippering and open a fusion pore.

Complexin Controls Spontaneous and Evoked Neurotransmitter Release by Regulating the Timing and Properties of Synaptotagmin Activity

Neurotransmitter release following synaptic vesicle (SV) fusion is the fundamental mechanism for neuronal communication. Synaptic exocytosis is a specialized form of intercellular communication that shares a common SNARE-mediated fusion mechanism with other membrane trafficking pathways. The regulation of synaptic vesicle fusion kinetics and short-term plasticity is critical for rapid encoding and transmission of signals across synapses. Several families of SNARE-binding proteins have evolved to regulate synaptic exocytosis, including Synaptotagmin (SYT) and Complexin (CPX). Here, we demonstrate that Drosophila CPX controls evoked fusion occurring via the synchronous and asynchronous pathways. cpx(-/-) mutants show increased asynchronous release, while CPX overexpression largely eliminates the asynchronous component of fusion. We also find that SYT and CPX coregulate the kinetics and Ca(2+) co-operativity of neurotransmitter release. CPX functions as a positive regulator of release in part by coupling the Ca(2+) sensor SYT to the fusion machinery and synchronizing its activity to speed fusion. In contrast, syt(-/-); cpx(-/-) double mutants completely abolish the enhanced spontaneous release observe in cpx(-/-) mutants alone, indicating CPX acts as a fusion clamp to block premature exocytosis in part by preventing inappropriate activation of the SNARE machinery by SYT. CPX levels also control the size of synaptic vesicle pools, including the immediate releasable pool and the ready releasable pool-key elements of short-term plasticity that define the ability of synapses to sustain responses during burst firing. These observations indicate CPX regulates both spontaneous and evoked fusion by modulating the timing and properties of SYT activation during the synaptic vesicle cycle.

Complexin activates and clamps SNAREpins by a common mechanism involving an intermediate energetic state

The core mechanism of intracellular vesicle fusion consists of SNAREpin zippering between vesicular and target membranes. Recent studies indicate that the same SNARE-binding protein, complexin (CPX), can act either as a facilitator or as an inhibitor of membrane fusion, constituting a controversial dilemma. Here we take energetic measurements with the surface force apparatus that reveal that CPX acts sequentially on assembling SNAREpins, first facilitating zippering by nearly doubling the distance at which v- and t-SNAREs can engage and then clamping them into a half-zippered fusion-incompetent state. Specifically, we find that the central helix of CPX allows SNAREs to form this intermediate energetic state at 9-15 nm but not when the bilayers are closer than 9 nm. Stabilizing the activated-clamped state at separations of less than 9 nm requires the accessory helix of CPX, which prevents membrane-proximal assembly of SNAREpins.

1456 CENTRAL ROLE FOR PELP1-ANDROGEN RECEPTOR COMPLEX IN PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 20111456 CENTRAL ROLE FOR PELP1-ANDROGEN RECEPTOR COMPLEX IN PROSTATE CANCER Lin Yang, Preethi Ravindranath, and Ganesh Raj Lin YangLin Yang Dallas, TX More articles by this author , Preethi RavindranathPreethi Ravindranath Dallas, TX More articles by this author , and Ganesh RajGanesh Raj Dallas, TX More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1369AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previously, we have shown that Estrogen Receptor beta (ER)β, PELP1 and Androgen Receptor (AR) can form a heterotrmeric protein complex in Prostate Cancer cells (PCa) in tissue culture. We had also shown that this protein complex plays a central role in the non-androgenic activation of AR in PCa. In this study, we examined whether ERβ, PELP1 and AR also formed a complex in vivo in both PCa cell lines, xenografts and human PCa tumors. METHODS Extracts from a large variety of PCa cell lines were prepared and evaluated by immunohistochemistry (IHC) and by co-immunoprecipitations (CO-IPs) for the presence of the heterotrimeric complex following treatment with estradiol (E2) or dihydrotestosterone (DHT). Then, following subcutaneously injection of Androgen-independent C4-2 Pca cells into 12 male nude mice and establishment of tumors, six mice were subject to surgical castration. Tumor samples from these mice were then harvested and extracts prepared to examine the formation of the trimeric complex before and after castration by IHC and CO-IP. In addition, fifty-eight samples from androgen dependent (ADPCa) and androgen independent human PCa (AIPCa) were screened for ERβ, PELP1 and AR expression by IHC and complex formation by CO-IP. RESULTS The complex between ERβ, PELP1 and AR was consistently detected in all PCa cell lines with AR. Treatment with DHT or E2 increased the detectability of the complex. In those PCa cell lines without AR, introduction of AR by transient or stable transfection restored the trimeric complex. The heterotrimeric complex between ERβ, PELP1 and AR was consistently detected PCa tumor samples from xenograft mice. Castration did not appear to significantly affect the detection of this trimeric complex in xenograft mice. In the human PCa tissue, PELP1 expression was increased significantly in AIPCa, while AR and ERβ expression was slightly decreased. Interestingly, while the complex between AR and PELP1 was detectable in both ADPCa and AIPCa samples, the level of the complex was significantly upregulated in AIPCa samples. CONCLUSIONS These data suggest that ERβ, PELP1 and AR form a heterotrimeric protein complex in PCa cells in vivo. This complex is present in all PCa cells with an intact AR. The complex appears to be upregulated up on androgenic and non-androgenic activation and in AIPCa Coupled with previous observations about the functional importance of this complex, these data appear to validate our approach to design agents targeting the formation of this complex. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e584 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lin Yang Dallas, TX More articles by this author Preethi Ravindranath Dallas, TX More articles by this author Ganesh Raj Dallas, TX More articles by this author Expand All Advertisement Advertisement Loading ...

Complexin and Synaptotagmin Genetically Interact in vivo Controlling the Rates of Spontaneous and Nerve-Evoked Vesicle Fusion

Presynaptic vesicle fusion is a highly regulated process that requires Synaptotagmin (SYT) and Complexin (CPX) proteins. Current data suggest that SNARE binding by the two proteins may be co-regulating the last step of release. However, their precise roles in synaptic function are still under debate. Here, we present a thorough analysis of synaptic transmission of null-mutants and over-expression transgenic animals for CPX and SYT at the Drosophila NMJ. Genetic interaction and kinetics analysis reveals that CPX and SYT expression modulate the rates of spontaneous and synchronous/asynchronous release. Additionally, SYT and CPX levels alter vesicle delivery during tetanic stimulation. Our finding indicate that different levels of SYT and CPX have computational consequences at nerve terminal that modulate basal noise, output gain, speed of transmission and the short-term plasticity.