Biomedical subjects

W Zhao

Publications and source records attributed to W Zhao.

At least 19 recordsLinked to original sources

PubMed2001

Posttranscriptional regulation of gene expression in learning by the neuronal ELAV-like mRNA-stabilizing proteins.

The view that memory is encoded by variations in the strength of synapses implies that long-term biochemical changes take place within subcellular microdomains of neurons. These changes are thought ultimately to be an effect of transcriptional regulation of specific genes. Localized changes, however, cannot be fully explained by a purely transcriptional control of gene expression. The neuron-specific ELAV-like HuB, HuC, and HuD RNA-binding proteins act posttranscriptionally by binding to adenine- and uridine-rich elements (AREs) in the 3' untranslated region of a set of target mRNAs, and by increasing mRNA cytoplasmic stability and/or rate of translation. Here we show that neuronal ELAV-like genes undergo a sustained up-regulation in hippocampal pyramidal cells only of mice and rats that have learned a spatial discrimination paradigm. This learning-specific increase of ELAV-like proteins was localized within cytoplasmic compartments of the somata and proximal dendrites and was associated with the cytoskeleton. This increase was also accompanied by enhanced expression of the GAP-43 gene, known to be regulated mainly posttranscriptionally and whose mRNA is demonstrated here to be an in vivo ELAV-like target. Antisense-mediated knockdown of HuC impaired spatial learning performance in mice and induced a concomitant down-regulation of GAP-43 expression. Neuronal ELAV-like proteins could exert learning-induced posttranscriptional control of an array of target genes uniquely suited to subserve substrates of memory storage.

Animals↗

PubMed2001

Transient changes of brain-derived neurotrophic factor (BDNF) mRNA expression in hippocampus during moderate ischemia induced by chronic bilateral common carotid artery occlusions in the rat.

Chronic bilateral common carotid artery occlusion (BCCAO) induces moderate ischemia (oligemia) in the rat forebrain in the absence of overt neuronal damage. In situ hybridization for brain-derived neurotrophic factor (BDNF) mRNA was used to search for a molecular response to moderate ischemia. BDNF mRNA was significantly increased in the hippocampal granule cells at 6 h of occlusion (ANOVA, Tukey test P<0.05). At 1, 7 and 14 days BDNF mRNA levels returned to control levels. The frequency of BDNF gene expression at 6 h was 83%, which was significantly higher than the 7% incidence of histological injury in the hippocampus (Fisher's exact test, P<0.002). Cerebral blood flow was reduced to 75% of control levels in the hippocampus after 1 week of BCCAO when measured with the autoradiographic method. Measurements of tissue flow with a microprobe for laser Doppler flow excluded decreases into the ischemic range during the period when elevated gene expression was observed. Prolonged moderate ischemia (oligemia) is a sufficient stimulus for BDNF gene expression in the hippocampus. These molecular studies provide direct evidence for an involvement of the hippocampus in the BCCAO model.

Animals↗

PubMed2001

v-Ha-RaS oncogene upregulates the 92-kDa type IV collagenase (MMP-9) gene by increasing cellular superoxide production and activating NF-kappaB.

Matrix metalloproteinase 9 (MMP-9) degrades basement membrane type IV collagen and is expressed during cellular migration and invasion. Here we show that v-Ha-Ras overexpression in rat kidney epithelial cells (REC) caused upregulation of MMP-9 gene expression in part by increasing cellular oxidant levels. v-Ha-Ras mediated the production of superoxide in Ras-transfected cells, which was associated with upregulated MMP-9 gene expression. Conversely, v-Ha-Ras expression decreased steady-state levels of mRNAs from tissue inhibitor of metalloproteinase 1 (TIMP-1), an inhibitor of MMP-9; plasminogen activator inhibitor 1 (PAI-1), which indirectly activates MMP-9 by increasing plasmin levels; and collagen IV, a substrate of MMP-9 and a major component of basement membrane. Gel mobility shift assays demonstrated that Ras overexpression enhanced NF-kappaB, but not AP-1 DNA binding to motifs in the MMP-9 gene promoter. The Ras-induced increase in NF-kappaB DNA binding could be inhibited by treatment with the antioxidants N-acetyl-L-cysteine and glutathione monoester, suggesting that intracellular oxidant levels can mediate MMP-9 transcription. Our findings identify an important role for Ras in the regulation of MMP-9 expression, and suggest that increased superoxide production can upregulate MMP-9 expression and thus contribute to malignant conversion.

Animals↗

PubMed2001

Simultaneous measurement of cerebral blood flow and mRNA signals: pixel-based inter-modality correlational analysis.

The analysis of pixel-based relationships between local cerebral blood flow (LCBF) and mRNA expression can reveal important insights into brain function. Traditionally, LCBF and in situ hybridization studies for genes of interest have been analyzed in separate series. To overcome this limitation and to increase the power of statistical analysis, this study focused on developing a double-label method to measure local cerebral blood flow (LCBF) and gene expressions simultaneously by means of a dual-autoradiography procedure. A 14C-iodoantipyrine autoradiographic LCBF study was first performed. Serial brain sections (12 in this study) were obtained at multiple coronal levels and were processed in the conventional manner to yield quantitative LCBF images. Two replicate sections at each bregma level were then used for in situ hybridization. To eliminate the 14C-iodoantipyrine from these sections, a chloroform-washout procedure was first performed. The sections were then processed for in situ hybridization autoradiography for the probes of interest. This method was tested in Wistar rats subjected to 12 min of global forebrain ischemia by two-vessel occlusion plus hypotension, followed by 2 or 6 h of reperfusion (n=4-6 per group). LCBF and in situ hybridization images for heat shock protein 70 (HSP70) were generated for each rat, aligned by disparity analysis, and analyzed on a pixel-by-pixel basis. This method yielded detailed inter-modality correlation between LCBF and HSP70 mRNA expressions. The advantages of this method include reducing the number of experimental animals by one-half; and providing accurate pixel-based correlations between different modalities in the same animals, thus enabling paired statistical analyses. This method can be extended to permit correlation of LCBF with the expression of multiple genes of interest.

Algorithms↗

PubMed2001

Redox modulation of the pro-fibrogenic mediator plasminogen activator inhibitor-1 following ionizing radiation.

Fibrosis is a common form of normal tissue damage after exposure to a wide variety of insults believed to involve oxidative stress. Plasminogen activator inhibitor-1 (PAI-1) is thought to play a major role in the development of progressive fibrosis via the inhibition of extracellular matrix degradation. Because radiation causes oxidative injury, which has been shown to trigger fibrogenic responses, the present study was designed to test the hypothesis that PAI-1 expression is redox-regulated after irradiation. Irradiating rat kidney tubule epithelial cells (NRK52E) with 1-20 Gy gamma-rays led to dose-dependent increases in steady-state levels of PAI-1 mRNA and immunoreactive protein within 24 and 48 h, respectively. Enhancement of intracellular soluble thiol pools after incubation with N-acetylcysteine (2.5 mM), from 3.27 +/- 0.27 nM/mg protein to 5.34 +/- 0.52 nM/mg protein in cells incubated with N-acetylcysteine 30 min before and assessed 4 h after irradiation, abolished the radiation-induced up-regulation of PAI-1. In addition, overexpression of catalase inhibited radiation-induced increases in PAI-1 expression, suggesting a mechanistic role for hydrogen peroxide (H2O2) in regulating PAI-1 expression after oxidative insult. In support of this notion, incubating NRK52E cells with H2O2 (100 microM) also led to a nearly 3-fold increase in PAI-1 gene expression. These results demonstrate that PAI-1 is redox-regulated after exposure to ionizing radiation or H2O2 and suggest that H2O2 scavenging might represent a fundamental mechanism for modulating fibrogenic disease via inhibition of the induction of profibrogenic mediators after acute or chronic oxidative stress.

Acetylcysteine↗

PubMed2001

Inhibition of murine prostate tumor growth and activation of immunoregulatory cells with recombinant canarypox viruses.

BACKGROUND: Immunization with modified tumor cells carrying recombinant immunomodulatory genes is being explored as cancer immunotherapy. In this study, we examine whether canarypox ALVAC viruses carrying immunostimulatory cytokine genes (granulocyte-macrophage colony-stimulating factor, interleukin 2, interleukin 12, and tumor necrosis factor-alpha) can induce antitumor immunity (to rechallenge) in the RM-1 model of a highly aggressive, weakly immunogenic murine prostate cancer. METHODS: For antitumor activity studies, RM-1 murine prostate cancer cells were infected with the parental ALVAC virus or one or two recombinant ALVAC-cytokine viruses and then injected into male C57BL/6 mice. For rechallenge studies, other mice were first given an injection subcutaneously with irradiated (nonproliferating) recombinant ALVAC-infected RM-1 cells and then (10 days later) with untreated RM-1 cells. For the determination of which immune cells were required for antitumor activity, mice were immunodepleted of CD4, CD8, or natural killer (NK) NK1.1 cells with the corresponding monoclonal antibodies and were then given an injection of ALVAC-cytokine-infected RM-1 cells. For all experiments, tumor outgrowth and animal survival were monitored. RESULTS: After subcutaneous injection into mice, RM-1 cells infected with one (except ALVAC-interleukin 2) or two ALVAC-cytokine recombinants had statistically significantly greater antitumor activity than RM-1 cells infected with parental ALVAC (P<.001 for all; two-sided test). The antitumor activity of RM-1 cells infected with any two ALVAC-cytokine recombinants was greater than, but not statistically significantly different from, that of RM-1 cells infected with any one ALVAC-cytokine recombinant. NK1.1 cells were necessary for antitumor activity, but tumor-specific CD4(+) regulatory T cells were also induced that inhibited CD8(+) RM-1-specific cytotoxic T cells, resulting in the lack of immunity to a rechallenge by RM-1 cells. DISCUSSION: Canarypox viruses can transfer immunostimulatory cytokine genes into RM-1 prostate cancer cells. When such cells were injected into mice, the cytokines induced an antitumor response against this highly aggressive, weakly immunogenic tumor. This response, however, did not protect the mouse against a rechallenge with RM-1 cells because suppressor CD4(+) T cells were induced that inhibited tumor-specific CD8(+) cytotoxic T cells.

Animals↗

PubMed2001

The effect of bone morphogenetic protein-7 (BMP-7) on functional recovery, local cerebral glucose utilization and blood flow after transient focal cerebral ischemia in rats.

Bone morphogenetic protein-7 (BMP-7) has been shown to enhance dendritic growth and improve functional recovery after experimental stroke. In this study, we examined the effect of BMP-7 on functional recovery, local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu) following transient middle cerebral artery occlusion. Sprague--Dawley rats (n=29) were anesthetized with halothane/nitrous oxide and received 2-h middle cerebral artery occlusion (MCAo) by poly-L-lysine-coated intraluminal suture. Rectal and cranial temperatures were regulated at 37.0--37.5 degrees C. BMP-7 or vehicle (volume, 25 microl) was administered intracisternally in a blinded fashion at 24 h after MCAo. Neurological status was evaluated during occlusion (60 min) and daily for 2 days after MCAo. In matched animal groups, LCMRglu was measured autoradiographically with [(14)C]2-deoxyglucose (2-DG) and LCBF with [(14)C]iodoantipyrine 48 h after MCAo. Four animals groups were studied: LCMRglu series (BMP-7, n=7; vehicle, n=8); LCBF series (BMP-7, n=6; vehicle, n=8). Average three-dimensional image data sets were constructed for each group and were compared by pixel-based statistical methods. Rectal and cranial temperatures, mean blood pressure, plasma glucose and blood gases were similar among groups. BMP-7 significantly improved the total neurological score compared to vehicle at 48 h after MCAo (7.3+/-0.4 vs. 9.0+/-0.2, respectively; P<0.0003). Compared to vehicle-rats, BMP-7 enhanced glucose utilization in the basal ganglia ipsilateral to stroke and improved LCBF in ipsilateral subthalamus, but decreased LCBF and LCMRglu in contralateral cortical regions.

Animals↗

PubMed2001

NK cells are essential for effective BCG immunotherapy.

Adjuvant intravesical bacillus Calmette-Guérin (BCG) therapy is a well-established and successful adjuvant immunotherapy in the treatment of superficial bladder cancer. Although the function of natural killer (NK) cells in other immunotherapeutic regimens (e.g., lymphokine-activated killer [LAK] cell or interleukin-2 [IL-2] therapy) has been established, the contribution of NK cells to effective BCG immunotherapy is not clear. We used a human in vitro system to analyze the role of NK cells in BCG-induced cellular cytotoxicity. After stimulation of mononuclear cells with BCG for 7 days, these BCG-activated killer (BAK) cells displayed substantial cytotoxicity against bladder tumor cells. Magnetic depletion experiments and fluorescence activated cell sorting revealed that NK cells were the major effector cell population. To address NK cell function in vivo, we studied a syngeneic orthotopic murine bladder cancer model and compared BCG immunotherapy in C57BL/6 wild-type mice, NK-deficient beige mice and mice treated with anti-NK1.1 monoclonal antibody. Four weekly instillations of viable BCG significantly prolonged survival in wild-type mice compared with control mice treated with solvent alone. In contrast, BCG therapy was completely ineffective in NK-deficient beige mice and in mice treated with anti-NK1.1 monoclonal antibody. These findings suggest a key role for NK cells during BCG immunotherapy.

Animals↗

PubMed2001

Cloning and expression pattern of the human NDRG3 gene.

We report the cloning and expression pattern of a novel N-myc downstream-regulated gene 3 (NDRG3), located on human chromosome 20q11.21-11.23. The NDRG3 cDNA is 2588 base pair in length, encoding a 363 amino acid polypeptide highly related to mouse Ndr3 protein. Northern blot reveals that NDRG3 is highly expressed in testis, prostate and ovary. By in situ hybridization, the NDRG3 mRNA was localized to the outer layers of seminiferous epithelium, indicating that it may play a role in spermatogenesis.

Amino Acid Sequence↗

PubMed2001

Ruminant brain ribonucleases: expression and evolution.

Molecular evolutionary analyses of mammalian ribonucleases have shown that gene duplication events giving rise to three paralogous genes occurred in ruminant ancestors. One of these genes encodes a ribonuclease identified in bovine brain. A peculiar feature of this enzyme and orthologous sequences in other ruminants are C-terminal extensions consisting of 17-27 amino acid residues. Evidence was obtained by Western blot analysis for the presence of brain-type ribonucleases in brain tissue not only of ox, but also of sheep, roe deer and chevrotain (Tragulus javanicus), a member of the earliest diverged taxon of the ruminants. The C-terminal extension of brain-type ribonuclease from giraffe deviates much in sequence from orthologues in other ruminants, due to a change of reading frame. However, the gene encodes a functional enzyme, which could be expressed in heterologous systems. The messenger RNA of bovine brain ribonuclease is not only expressed at a high level in brain tissue but also in lactating mammary gland. The enzyme was isolated and identified from this latter tissue, but was not present in bovine milk, although pancreatic ribonucleases A and B could be isolated from both sources. This suggests different ways of secretion of the two enzyme types, possibly related to structural differences. The sequence of the brain-type RNase from chevrotain suggests that the C-terminal extensions of ruminant brain-type ribonucleases originate from deletions in the ancestral DNA (including a region with stop codons), followed by insertion of a 5-8-fold repeated hexanucleotide sequence, coding for a proline-rich polypeptide.

Amino Acid Sequence↗

PubMed2001

Effects of all-trans-retinoic acid and arsenic trioxide on the hemostatic disturbance associated with acute promyelocytic leukemia.

To study the in vivo effect of all-trans-retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) on the expression of tissue factor (TF) and the other hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from acute promyelocytic leukemia (APL) patients. The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription-polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA), TF antigen of APL cell lysate, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As(2)O(3) therapy. The plasma level of P-selectin, TF, thrombin-antithrombin complex (TAT), soluble fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), plasmin-antiplasmin complex, tissue plasminogen activator (t-PA) activity, urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and D-dimer (D-D) significantly increased. Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG) activity, alpha(2)-plasminogen inhibitor activity (alpha(2)-PI), and plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The protein C activity (PC:A) and protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As(2)O(3) therapy downregulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, significantly inhibited coagulation activation, corrected secondary hyperfibrinolysis and the other hemostatic abnormalities, and thus greatly improved the bleeding symptom in early stage of the treatment.

Adolescent↗

PubMed2001

Molecular cloning, mapping and characterization of the human neurocalcin delta gene (NCALD).

We identified a new human gene that encodes a cognate of the bovine neurocalcin delta from a human fetal brain cDNA library; hence we named it human neurocalcin delta (NCALD) gene. The deduced polypeptide product of the cDNA is 22 kDa in size, and its amino acid sequence is 100% and 99% identical to that of the bovine and chicken neurocalcin, respectively. Northern blots showed that the NCALD gene is more abundantly expressed in brain, testis, ovary and small intestine. Tissue in situ hybridization confirmed the existence of the NCALD mRNA in the adult human testis. Radiation hybrid panel mapping localized the gene to chromosome 8 between molecular markers D8S270 and D8S257.

Adult↗

PubMed2001

U7C beamline and XAFS station of national synchrotron radiation laboratory.

The XAFS station on beamline U7C of National Synchrotron Radiation Laboratory (NSRL) was completely constructed in December 1998. The source for XAFS station is from a 3-pole superconducting wiggler with magnetic field of 6 T inserted in the straight section of the storage ring. Using a Si(111) double crystal monochromator with a fixed slit, the X-ray intensity at the sample position is about 3x10(9) photons/second at the energy of 8980 eV of Cu K-edge. The Keithley 65 17 electrometers are used to record the electron charges that are produced in the ionization chambers. A high ratio of signal to noise has been obtained for the XAFS spectra of Cu, Ni and Fe foils. Furthermore, the XAFS spectrum of Cu foil in NSRL is in good agreement with that obtained in BSRF and KEK.

Journal Article↗

PubMed2001

The hamster as a model of human visceral leishmaniasis: progressive disease and impaired generation of nitric oxide in the face of a prominent Th1-like cytokine response.

Active human visceral leishmaniasis (VL) is characterized by a progressive increase in visceral parasite burden, cachexia, massive splenomegaly, and hypergammaglobulinemia. In contrast, mice infected with Leishmania donovani, the most commonly studied model of VL, do not develop overt, progressive disease. Furthermore, mice control Leishmania infection through the generation of NO, an effector mechanism that does not have a clear role in human macrophage antimicrobial function. Remarkably, infection of the Syrian hamster (Mesocricetus auratus) with L. donovani reproduced the clinicopathological features of human VL, and investigation into the mechanisms of disease in the hamster revealed striking differences from the murine model. Uncontrolled parasite replication in the hamster liver, spleen, and bone marrow occurred despite a strong Th1-like cytokine (IL-2, IFN-gamma, and TNF/lymphotoxin) response in these organs, suggesting impairment of macrophage effector function. Indeed, throughout the course of infection, inducible NO synthase (iNOS, NOS2) mRNA or enzyme activity in liver or spleen tissue was not detected. In contrast, NOS2 mRNA and enzyme activity was readily detected in the spleens of infected mice. The impaired hamster NOS2 expression could not be explained by an absence of the NOS2 gene, overproduction of IL-4, defective TNF/lymphotoxin production (a potent second signal for NOS2 induction), or early dominant production of the deactivating cytokines IL-10 and TGF-beta. Thus, although a Th1-like cytokine response was prominent, the major antileishmanial effector mechanism that is responsible for control of infection in mice was absent throughout the course of progressive VL in the hamster.

Animals↗

PubMed2001

Cloning and characterization of a novel human leptin receptor overlapping transcript-like 1 gene (LEPROTL1).

A new full-length cDNA encoding a novel protein was isolated from our human fetal brain cDNA library. The cDNA consists of 2701 bp and has a putative open reading frame encoding 131 amino acids which possesses a JAK binding site (Pro(46)-Ile-Pro(48) which is preceded by a cluster of hydrophobic residues) and is highly homologous to the leptin receptor gene-related protein (OB-RGRP). Northern blot analysis showed that this new gene is widely expressed in human tissues and radiation hybrid mapping placed the gene to human chromosome 8p21.1-8p21.2.

Amino Acid Sequence↗

PubMed2001

Development of PMMA-precoating metal prostheses via injection molding: residual stresses.

Injection molding polymethylmethacrylate (PMMA) was developed as a potential metal prosthesis precoating method for surgical implantation. However, residual stresses generated in the injection-molded PMMA affect the mechanical performance of the coating polymer. This study used plane polariscope testing to demonstrate the residual stress distribution in the injection-molded polymer. Slitting and strain gages were combined with finite element analysis to give a quantitative measure of the residual stresses. The residual stress testing indicated that the highest circumferential residual stress in the injection-molded PMMA was approximately 5 MPa in tension. Two methods, water soaking and slitting, were developed for reducing residual stresses. A series of four surgical implantation simulation processes were designed. The two methods for reducing residual stress were used in the simulations.

Animals↗

PubMed2001

Delta-aminolevulinate dehydratase polymorphism and blood lead levels in Chinese children.

This study investigated the relationship between the delta-aminolevulinate dehydratase (ALAD) isozymes and the blood lead levels of Chinese children. The purpose of this study was to determine the precise ALAD genotyping in Chinese children and identify the contribution of the ALAD genotype to the body lead burden. Blood samples were obtained from 109 boys and 120 girls. These children were 6-10 years old and from a single primary school. Both the school and their homes were within a community in which a large smelter was located. An environmental questionnaire was obtained for each subject, and blood lead levels and ALAD isozyme phenotype were analyzed in a double-blinded fashion. The blood lead levels of 229 children ranged from 4.5 to 26.4 microg/dl; the mean was 10.3 microg/dl and the standard deviation was 3.3 microg/dl. The gene distribution of the ALAD isozyme phenotypes in these environmentally exposed children was ALAD 1-1 (92%), ALAD 1-2, (8%), and ALAD 2-2 (0%). The mean blood level of the environmentally exposed children, who were homozygous for the ALAD1 allele, was 9.7 microg/dl; the mean for those who were heterozygous for the ALAD2 allele was 11.7 microg/dl. Using the t test, the means of the groups were different at the level of t=2.2058, P<0.05. Step-wise regression and multiple analyses of covariance were employed to control the confounders to measuring the independent contribution of the ALAD genotype on blood lead levels. After controlling the confounders, the contribution of the ALAD genotype to the blood lead level was greater and still statistically significant (F=7.3201, P<0.01). These results indicate that individuals carrying the ALAD2 allele are more likely to have sustained increases in blood lead levels when exposed to a lead-contaminated environment.

Alleles↗

PubMed2001

Concentration-dependent effects of protein phosphatase (PP) inhibitors implicate PP1 and PP2A in different stages of memory formation.

Numerous studies have demonstrated roles for protein phosphorylation and for specific kinases in memory formation; however, a role for specific protein phosphatases has not been established. Previous studies using pharmacobehavioral methods to implicate protein phosphatase activity in memory formation have been unable to discriminate between protein phosphatases 1 (PP1) and 2A (PP2A), as available cell-permeable agents generally inhibit both enzyme classes. To address this difficulty the present study exploited differences in the potency of the selective phosphatase inhibitor, okadaic acid, toward PP1 and PP2A. Within the context of a temporally precise animal model of memory, developed using the day-old chick (Gallus domesticus), acute administration of various concentrations of okadaic acid was found to disrupt two temporally distinct stages of memory formation. When administered bilaterally into an area of the chick brain implicated in memory formation, concentrations of okadaic acid known to selectively inhibit PP2A in vitro disrupted memory from 50 min posttraining. Higher concentrations, reported to inhibit both PP2A and PP1 in vitro, produced significant retention deficits from 20 min posttraining. Identical temporally specific effects were also obtained by varying the concentration and time of administration of calyculin A, a phosphatase inhibitor with equal potency toward both enzyme classes. Hence, different phosphatase enzymes may contribute to different stages of the enzymatic cascade believed to underlie memory formation.

Animals↗