Biomedical subjects

Z Liu

Publications and source records attributed to Z Liu.

At least 541 records · Page 30Linked to original sources

PubMed1999

Effects of organic modifiers on retention mechanism and selectivity in micellar electrokinetic capillary chromatography studied by linear solvation energy relationships.

The effects of six organic modifiers (urea, methanol, dioxane, tetrahydrofuran, acetonitrile and 2-propanol) on the retention mechanism and separation selectivity of the bulk buffer in micellar electrokinetic capillary chromatography (MECC) with sodium dodecyl sulfate (SDS) micelles as pseudo-stationary phase have been investigated through linear solvation energy relationships (LSERs). It is found that the retention value in MECC systems with or without organic modifier is primarily dependent on the solvophobic interaction and the hydrogen bonding interaction with the solute as proton acceptor, while the dipolar interaction and the hydrogen bonding interaction with the solute as proton donor play minor roles. The effects of the organic modifiers on the solvophobic, dipolar and hydrogen bonding interactions are evaluated in terms of the relationship between regression coefficient of the LSER equations and the modifier concentration. The variations of the solvophobic interaction and the dipolar interaction with change of the modifier concentration can be approximately explained using the solubility parameter and the dipolarity/polarizability parameter of the organic modifier, respectively. However, the relationships between the hydrogen bond acidity and basicity of the bulk buffer and the organic modifiers are rather complicated. Those results may be caused from the displacement of organic modifiers to the water adsorbed on the micellar surface as well as changes in the acidity and basicity of the bulk buffer with the addition of organic modifiers. In addition, it is found that the phase ratio is influenced significantly by the use of organic modifier.

Benzene Derivatives↗

PubMed1999

Opposite translational control of GLUT1 and GLUT4 glucose transporter mRNAs in response to insulin. Role of mammalian target of rapamycin, protein kinase b, and phosphatidylinositol 3-kinase in GLUT1 mRNA translation.

Prolonged exposure of 3T3-L1 adipocytes to insulin increases GLUT1 protein content while diminishing GLUT4. These changes arise in part from changes in mRNA transcription. Here we examined whether there are also specific effects of insulin on GLUT1 and GLUT4 mRNA translation. Insulin enhanced association of GLUT1 mRNA with polyribosomes and decreased association with monosomes, suggesting increased translation. Conversely, insulin arrested the majority of GLUT4 transcripts in monosomes. Insulin inactivates the translational suppressor eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) through the mammalian target of rapamycin (mTOR). Hence, we examined the effect of rapamycin on GLUT1 mRNA translation and protein expression. Rapamycin abrogated the insulin-mediated increase in GLUT1 protein synthesis through partial inhibition of GLUT1 mRNA translation and partial inhibition of the rise in GLUT1 mRNA. 4E-BP1 inhibited GLUT1 mRNA translation in vitro. Because phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB), in concert with mTOR, inactivate 4E-BP1, we explored their role in GLUT1 protein expression. Cotransfection of cytomegalovirus promoter-driven, hemagglutinin epitope-tagged GLUT1 with dominant inhibitory mutants of PI3K or PKB inhibited the insulin-elicited increase in hemagglutinin-tagged GLUT1 protein. These results unravel the opposite effects of insulin on GLUT1 and GLUT4 mRNA translation. Increased GLUT1 mRNA translation appears to occur via the PI3K/PKB/mTOR/4E-BP1 cascade.

3T3 Cells↗

PubMed1999

Hyperexpression of CD40 ligand (CD154) in inflammatory bowel disease and its contribution to pathogenic cytokine production.

CD40 ligand (CD40L or CD154), a type II membrane protein with homology to TNF, is transiently expressed on activated T cells and known to be important for B cell Ig production and for activation and differentiation of monocytes and dendritic cells. Both Crohn's disease and ulcerative colitis are characterized by local production of cytokines such as TNF and by an influx of activated lymphocytes into inflamed mucosa. Herein, we investigated whether CD40L signaling participates in immune responses in these diseases. Our results demonstrated that CD40L was expressed on freshly isolated lamina propria T cells from these patients and was functional to induce IL-12 and TNF production by normal monocytes, especially after IFN-gamma priming. The inclusion of a blocking mAb to CD40L or CD40 in such cocultures significantly decreased monocyte IL-12 and TNF production. Moreover, lamina propria and peripheral blood T cells from these patients, after in vitro activation with anti-CD3, showed increased and prolonged expression of CD40L as compared with controls. Immunohistochemical analyses indicated that the number of CD40+ and CD40L+ cells was significantly increased in inflamed mucosa, being B cells/macrophages and CD4+ T cells, respectively. These findings suggest that CD40L up-regulation is involved in pathogenic cytokine production in inflammatory bowel disease and that blockade of CD40-CD40L interactions may have therapeutic effects for these patients.

Adult↗

PubMed1999

Signalling between mitochondria and the nucleus regulates the expression of a new D-lactate dehydrogenase activity in yeast.

We have adapted a LacZ promoter trap screen developed by Burns et al. (1994) to search for genes whose expression is dependent on Rtg2p, a protein with an N-terminal hsp70/actin/sugar kinase ATP binding domain. Rtg2p acts upstream of the basic helix-loop-helix/leucine zipper transcription factors, Rtg1p and Rtg3p. All three proteins are known to be required for the expression of the CIT2 gene, which encodes a peroxisomal isoform of citrate synthase whose expression is also dependent on the functional state of mitochondria. Using this screen, we have identified a previously uncharacterized gene, YEL071w, predicted to encode a protein of 496 amino acids that shares 80% homology and 60% sequence identity with actin interacting protein 2, encoded by the AIP2 gene; both proteins also share sequence similarity to aD-lactate dehydrogenase encoded by the DLD1 gene. Expression of YEL071w is dependent on the functional state of mitochondria and on all three of the Rtg proteins, whereas AIP2 expression is independent of the Rtg proteins and the functional state of mitochondria. Like CIT2, the 5' flanking region of YEL071w contains two R box binding sites for the Rtg1p/Rtg3p heterodimeric transcription complex. Both R boxes are necessary for full YEL071w expression. We show that YEL071w and AIP2 encode proteins withD-lactate dehydrogenase activity, the former located in the cytoplasm and the latter in the mitochondrial matrix. Our data thus provide gene assignments for two previously unrecognized D-lactate dehydrogenase activities in yeast.

Amino Acid Sequence↗

PubMed1999

Capillary electrochromatography with a silica column with a dynamically modified cationic surfactant.

A novel mode of capillary electrochromatography (CEC), called dynamically modified silica-capillary electrochromatography, is described in this paper. The column packed with bare silica was dynamically modified with long chain quaternary ammonium salt, cetyltrimethylammonium bromide (CTAB), which was added into the mobile phase. CTAB ions were adsorbed onto the surface of bare silica, and the resulted hydrophobic layer on the silica gel was used as the stationary phase. Using the dynamically modified silica column, neutral solutes were separated by CEC. The highest number of theoretical plates obtained was about 71,500/m and the relative standard deviations for t0 and capacity factor of toluene were 4.7% and 4.9% for 20 consecutive runs, respectively. The separation mechanism of neutral solutes and the influence of mobile phase composition on the separation was investigated. The separation of nitrogen-containing solutes was carried out with this mode and the peak tailing of basic solute was effectively eliminated because the adsorption of basic solute on silica was blocked by the preferred adsorption of CTAB.

Cations↗

PubMed1999

Steroid receptor coactivator-1 (SRC-1) enhances ligand-dependent and receptor-dependent cell-free transcription of chromatin.

Progesterone receptor (PR) functions as a transcription factor that modulates the transcription of target genes in response to progesterone and other signals. The transcriptional activity of PR requires the involvement of coactivators such as steroid receptor coactivator-1 (SRC-1). To dissect the role of SRC-1 in PR transactivation, we established an in vitro transcription system with chromatin templates, in which PR induced transcription in a ligand-dependent and PRE-dependent manner. In the presence of ligand, purified PR bound to chromatin templates, resulting in chromatin remodeling. With this system, the ability of purified SRC-1 to act as a coactivator of PR was examined. SRC-1 potentiated transcription by ligand-activated PR, whereas it had no effect on transcription in the absence of ligands. As SRC-1 possesses intrinsic histone acetyltransferase activity, we tested the role of acetylation in PR-mediated transcription by using a histone deacetylase inhibitor, trichostatin A (TSA). We found that addition of TSA strongly enhanced PR-dependent transcription on chromatin but not on naked DNA template, and the effects of SRC-1 and TSA on PR transactivation were partially redundant. In addition, SRC-1 was able to potentiate PR transactivation with nonchromatin templates. Thus, our results substantiate a two-step mechanism whereby recruitment of coactivator SRC-1 by the ligand-activated PR in vivo leads to (i) chromatin remodeling through histone acetylation and (ii) recruitment/stabilization of the preinitiation complex.

Animals↗

PubMed1999

Synergetic Effect of Cationic Polymer Microparticles and Anionic Polymer on Fine Clay Flocculation.

Although much research has been done into flocculation systems involving anionic microparticles, few systematic investigations employing cationic polymer microparticles (CPM) have been reported. In the present work, emulsifier-free polymerization was conducted via copolymerization of styrene with three types of cationic monomer. This technique allowed cationic polymer microparticles with well-defined structures to be prepared. Dynamic flocculation experiments showed that the effectiveness of CPM alone as a flocculant for fine clay particles is affected by CPM charge density and by particle size, in the range 0.2 to 0.4 µm. A strong synergetic effect between CPM and anionic polyacrylamide with high molecular weight and low charge density was observed. This significantly reduced the dosage of polymeric flocculant required for effective flocculation. The best flocculation occurred at a value of the anionic polymer:CPM ratio of 1:8 (wt), with anionic polymer dosage approximately 0.06 wt% on clay. Electrostatic interaction between CPM and anionic polymer appears to be an important driving force for flocculation. Copyright 1999 Academic Press.

Journal Article↗

PubMed1999

Experimental studies on affinity chromatography in an electric field.

A multicompartment electrolyzer, which has been used for preparative electrophoresis [Z. Liu, Z. Huang, J.-Y. Cong, et al., Sep. Sci. Technol. 31 (1996) 427], is applied for carrying out affinity chromatography in an alternating electric field. The effect of electric field strength on the adsorption and desorption characteristics is experimentally examined with human serum albumin and Blue Sepharose Fast Flow as a model system. It is shown that the existence of an electric field leads to a significant change in the adsorption capacity of the blue dye, which may be used for establishing a preferential adsorption to achieve a high resolution. The adsorption speed increases slightly with respect to the increase of electric field strength, while adsorption capacity in the presence of an electric field is independent of the electric field strength. Different elution behavior is observed as function of adsorption condition and a high recovery of the adsorbed protein is obtained when the adsorption is carried out in the presence of an electric field.

Buffers↗

PubMed1999

Growth-factor-dependent migration of human lung-cancer cells.

Human lung tumors express different types of growth-factor receptors and corresponding ligands that might modulate several biological functions such as proliferation, differentiation, adhesion, and chemotaxis. In the present study, we have investigated the expression of different growth-factor receptors and their ligands in 5 established human lung-cancer cell lines. Using RT-PCR, we found that IGF-II/mannose-6-phosphate (M6P), c-met, EGF and c-kit receptors are expressed in 5/5 human lung-cancer cell lines. In order to investigate the biological function of these receptors, we performed Boyden-chamber assays using various growth factors as chemo-attractants. Human non-small-cell-lung-cancer cells (non-SCLC) migrated to recombinant human (rh)IGF I and IGF II at concentrations ranging from 1 to 1000 ng/ml, to HGF at 10 to 100 ng/ml, to EGF at 1 to 100 ng/ml and SCF at 1 to 50 ng/ml. In addition, we performed Boyden-chamber assays using U-1810-, U-1752- and Wart-derived serum-free conditioned medium as chemo-attractants. Serum-free conditioned medium stimulated migration of producer cells in a dose-dependent manner. The autocrine motility stimulating effect of U-1810-derived serum-free conditioned medium could be inhibited by 50% in the presence of neutralizing ahIGF-II antibodies in the assay, suggesting a possible autocrine motility loop in vitro.

Cell Movement↗

PubMed1999

Molecular mechanism for cooperation between Sp1 and steroidogenic factor-1 (SF-1) to regulate bovine CYP11A gene expression.

Bovine cholesterol side-chain cleavage cytochrome P450 (P450scc; product of the CYP11A gene) gene expression is regulated by gonadotropins via cAMP in the ovary, and by ACTH via cAMP in adrenal cortical cells. Previously, we characterized response elements located at -57/-32 and at -111/-101 bp in the 5'-flanking region of the bovine CYP11A gene required for cAMP-stimulated transcription in both mouse Y-1 adrenal tumor cells and bovine ovarian cells in primary culture, which bind SF-1 (or Ad4-BP) and Sp1, respectively. The role of these transcription factors in CYP11A transcription was further confirmed by deletion and mutation analyses. In addition, results obtained employing a double mutation of the Sp1- and SF-1-binding sites and a mammalian two-hybrid system indicate that Sp1 and SF-1 function cooperatively in the transactivation of the bovine CYP11A promoter in both bovine luteal cells and Y-1 cells. Here we report that SF-1 and Sp1 are able to associate with one another in vitro and in vivo. The NH2-terminal region of SF-1, especially the DNA-binding domain, is the binding site for Sp1. In addition, as CBP is a common coactivator required for the transcriptional activity of numerous transcription factors including nuclear receptors, we investigated whether CBP functions as a cofactor for the regulation of bovine CYP11A promoter activity. We show here that CBP enhanced the PKA-induced CYP11A promoter activity, while a double mutation of both Sp1 and SF-1 sites within the CYP11A promoter region abolished CBP-induced activity. Furthermore, CBP stimulated Sp1-dependent transactivation, and a CBP/Sp1 complex in vivo was demonstrated by a co-immunoprecipitation assay. Also, CBP potentiated the transcriptional activity of GAL4-SF-1 in the presence of PKA. Thus, the cooperation between SF-1 and Sp1, required for the regulation of bovine CYP11A gene expression, is mediated by a direct protein-protein interaction and/or the common coactivator CBP.

Adrenal Gland Neoplasms↗

PubMed1999

Malignant astrocytoma cell attachment and migration to various matrix proteins is differentially sensitive to phosphoinositide 3-OH kinase inhibitors.

Phosphoinositide 3-OH kinase (PI3-K) has been shown to play an important role in the signaling pathway necessary for cytoskeletal reorganization in non-astrocytic cells. We investigated the role of PI3-K in U-251 MG human malignant astrocytoma cell adhesion and migration. Attachment of U-251 MG cells to vitronectin, fibronectin, laminin, and collagen was inhibited in a concentration-dependent manner by two specific inhibitors of PI3-K (Wortmannin and LY294002). Attachment to vitronectin, fibronectin, and laminin was more sensitive to inhibition of PI3-K (45% inhibition at 10 nM Wortmannin) than attachment to collagen (25% inhibition at 100 nM Wortmannin). Similarly, migration toward these substrates showed differential sensitivity to inhibition. Attachment of the cells to these matrix proteins resulted in an increase in PI3-K activity, as compared to that of cells in suspension, with attachment to vitronectin resulting in the greatest increase in PI3-K activity. p125 focal adhesion kinase (p125FAK) was found to co-immunoprecipitate with PI3-K from the NP40-soluble cell fraction of a 1% NP40 detergent lysate of cells in the early stages of adhesion to vitronectin and fibronectin, but not during adhesion to collagen. The expression of p125FAK protein and level of phosphorylation were similar on adherence to all three substrates. These data indicate that the sensitivity of U-251MG cell attachment and migration to PI3-K inhibitors is substrate-dependent, and that complex formation of PI3-K and p125FAK correlates with this sensitivity to PI3-K inhibitors. Our data suggest a role for PI3-K and p125FAK complex formation in PI3-K activation.

Astrocytoma↗

PubMed1999

[Effects of aluminum on the number of neurons granulovacuolar degeneration in rats].

Effect of aluminum on neurobehavior and the number of neurons in different domains of brain as well as granulovacuolar degeneration (GVD) in hippocampus were observed in Sprague-Dawley rats by intraperitoneal injection with aluminum chloride for 60d. The injection of aluminum at the dosage of 4.0 or 10.0 mg/kg could decrease active avoidance response and spontaneous motor activity in the shuttle-box test and the open field test significantly. Sections from cerebrum, cerebellum and hippocampus were detected with microscope after HE staining. Aluminum(10.0 mg/kg) could result in the decrease of neurons in cerebrum, Pukinje cells in cerebellum and pyramidal neurons in hippocampus. GVD of nerve cells in hippocampus were observed in each group, while the dosages of Al injected was 4.0 and 10.0 mg/kg, the number of GVD cells increased significantly. The incidence of GVD per 300 nerve cells was significantly related to the dosage of aluminum.

Aluminum↗

PubMed1999

Transcribed dinucleotide microsatellites and their associated genes from channel catfish Ictalurus punctatus.

The presence of trinucleotide microsatellites within genes is a well-known cause for a number of genetic diseases. However, the precise distribution of dinucleotide microsatellites within genes is less well documented. Here we report 15 unique cDNAs containing dinucleotide repeats from the channel catfish Ictalurus punctatus. Gene identities of nine of the 15 cDNAs were determined, of which three encode structural genes, and six encode regulatory proteins. Five cDNAs harbored dinucleotide repeats in the 5' untranslated region (5'-NTR), nine in the 3'-NTR, and one in the coding region. The presence of these transcribed dinucleotide repeats and their potential expansion in size within coding regions could lead to disruption of the original protein and/or formation of new genes by frame shift. The low number of dinucleotide repeats within coding regions suggests that they were strongly selected against. All the transcribed microsatellite loci examined were polymorphic making them useful for gene mapping in catfish.

Animals↗

PubMed1999

Predictors of sputum culture conversion among patients with tuberculosis in the era of tuberculosis resurgence.

BACKGROUND: Sputum culture conversion among patients with tuberculosis (TB) is the most important indicator for the effectiveness of treatment and the infectivity of the disease. We sought to investigate predictors for documented sputum culture conversion among TB cases reported in the surveillance system. METHODS: This study included 780 patients with pulmonary TB who were initially sputum culture positive in New Jersey in 1994-1995. These patients were followed up for at least 1 week and up to 1 year. Kaplan-Meier curves and Cox proportional hazards models were performed to analyze the data. RESULTS: Overall, 469 (60.1%) of the 780 patients had documented sputum culture conversion. The elderly (36%) and non-Hispanic whites (41.3%) were the least likely to have documented sputum conversion. Patients who were initially given 4 or more drugs were 36% more likely to have documented sputum conversion than those who were initially given fewer than 4 drugs, after adjusting for other factors. Patients who were under the care of chest clinics and the model TB center were about 3 times more likely to have documented sputum conversion than those under care of private physicians. Sex, recurrent TB, foreign-born status, homelessness, injecting drug use, human immunodeficiency virus infection and drug-resistant TB were not significantly associated with the documentation of sputum culture conversion. CONCLUSIONS: A substantial proportion of sputum culture-positive TB patients have no documented sputum culture conversion. The type of care provider was the predominant determinant for the documentation of sputum culture conversion.

Adult↗

PubMed1999

Ketogenic diet reduces spontaneous seizures and mossy fiber sprouting in the kainic acid model.

The high fat, low carbohydrate, low protein ketogenic diet (KD) has been used to control refractory epilepsy in children since 1920, although its mechanism of action is unknown. Previous animal studies have shown that the KD can increase acute seizure threshold, but the effect of the KD on the process of epileptogenesis has not been studied. We tested the effect of an experimental KD on epileptogenesis in adult rats using the kainic acid (KA) model. P54 rats underwent KA-induced status epilepticus, followed by assignment to a control diet or a KD consisting of (by weight), 14% protein, 70% fat and no carbohydrate. KD-fed animals tolerated the diet and maintained ketosis. KD-fed rats had significantly fewer and briefer spontaneous recurrent seizures and less supragranular mossy fiber sprouting, although the degree of hippocampal pyramidal cell damage was similar in both groups. These results provide the first evidence that the KD retards epileptogenesis in an experimental model.

Animals↗

PubMed1999

Viral myocarditis: identification of five differentially expressed genes in coxsackievirus B3-infected mouse heart.

Differences in host susceptibility to viral myocarditis caused by a given strain of coxsackievirus B3 (CVB3) are known to be largely related to host genetic factors. Little is known, however, about the key genes that encode determinants (mediators) of myocarditis development or the nature of injury. To identify these genes and further understand the molecular mechanisms of the disease process, we have used a murine model and the differential display technique to fingerprint mRNAs from CVB3-infected mouse hearts. Total RNA was extracted from hearts of 4- and 10-week-old A/J(H-2(a)) mice at day 4 after CVB3 infection, and mRNAs were detected by reverse transcriptase-polymerase chain reaction and subsequently analyzed on polyacrylamide DNA sequencing gels. The differentially displayed bands were confirmed by Northern hybridization using the bands as cDNA probes. Twenty-eight upregulated or downregulated bands were selected from the sequencing gels; among these, 2 upregulated and 3 downregulated cDNA fragments were confirmed by Northern hybridization. DNA sequence analysis and GenBank searching have determined that 4 of the 5 candidate genes are homologous to genes encoding Mus musculus inducible GTPase, mouse mitochondrial hydrophobic peptide (a subunit of NADH dehydrogenase), mouse beta-globin, and Homo sapiens cAMP-regulated response element binding protein (CREB) binding protein (CBP), respectively. The remaining candidate gene matches an unpublished cDNA clone, M musculus Nip21 mRNA (GenBank accession number, AF035207), which is homologous to human Nip2, a Bcl-2 binding protein. Our data suggest preliminarily that both structural and nonstructural genes are involved in myocarditis development. For the structural gene, beta-globin, we further confirmed its downregulation at the protein level by measuring the mean cell volume of red blood cells and found it was marginally reduced in the CVB3-infected group (P<0.06), with no change in hemoglobin concentration. Cardiac myoglobin concentration was also measured and found to be decreased (P<0.005), with a parallel decrease in total soluble protein in the CVB3-infected mouse myocardium (P<0.01). We also noted that the ratio of myoglobin to total protein was not significantly changed; this may be due to the downregulation of additional genes in the host heart, a number being observed on the differential display gels. The significant downregulation of beta-globin major gene expression in the heart may be relevant to impaired cardiac function in both the early and late postinfection period. The other identified nonstructural genes are known to be involved in regulation of gene expression, signal transduction pathways, and apoptotic cell death. The altered expression of structural and nonstructural genes may play important roles in the mediation of myocarditis development and perhaps other pathological processes in the heart.

Animals↗

PubMed1999

Consequences of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor blockade during status epilepticus in the developing brain.

To investigate if AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor activation contributes to acute manifestations and long term consequences of status epilepticus (SE), we administered the AMPA receptor antagonist NBQX to P35 rats undergoing kainic acid (KA)-induced SE. NBQX (30 mg/kg/dose) given intraperitoneally (i.p.) at 30, 60 and 90 min after i.p. KA injection (12 mg/kg) reduced severity of SE. When tested as adults, rats that had received KA and NBQX were similar to controls with no long term impairment in visuospatial memory (assessed by the water maze test), or histologic damage in the CA1 or CA3 hippocampal subfields. However, both P35 groups, those receiving KA alone and those receiving KA and NBQX, had similar rates of spontaneous recurrent seizures (SRS). In P15 rats, NBQX resulted in increased acute mortality from KA associated SE. These results indicate that the effects of NBQX on KA-induced SE are age dependent, and that non-NMDA receptor activation contributes to the acute manifestations and to the long term sequelae seen after KA-induced SE in the prepubescent rat brain.

Animals↗

PubMed1999

[Rapid detection of an HPFH deletion by PCR amplification with three primers bridging the breakpoint].

OBJECTIVE: To establish a rapid and reliable PCR method for detecting a deletional hereditary persistence of fetal hemoglobin (HPFH) found in Chinese. METHODS: Based on some novel DNA sequences across the 3'breakpoint of a HPFH deletion observed in our laboratory, we designed a PCR amplification with three primers bridging the breakpoint. In this system, oligonucleotide primers have been chosen which allow specific identification of both normal and deletional chromosomes under identical condition in either the same or parallel PCR reactions. RESULTS: The expected two specific amplification bands were produced; one was 565bp in length and stood for the normal alleles,the other,37bp in length represented the mutant alleles of beta-globin gene cluster. This duplex system could directly genotype DNA samples bearing this type of HPFH deletion. CONCLUSION: This rapid and inexpensive method could be used as a routine method in the molecular screening of carriers and for the prenatal diagnosis of this disease.

Base Sequence↗