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Y M Wang

Publications and source records attributed to Y M Wang.

At least 73 records · Page 4Linked to original sources
PubMed1999

Acute hepatitis C virus structural gene sequences as predictors of persistent viremia: hypervariable region 1 as a decoy.

We hypothesized that hepatitis C virus (HCV) persistence is related to the sequence variability of putative envelope genes. This hypothesis was tested by characterizing quasispecies in specimens collected every six months from a cohort of acutely HCV-infected subjects (mean duration of specimen collection, 72 months after seroconversion). We evaluated 5 individuals who spontaneously cleared viremia and 10 individuals with persistent viremia by cloning 33 1-kb amplicons that spanned E1 and the 5' half of E2, including hypervariable region 1 (HVR1). To assess the quasispecies complexity and to detect variants for sequencing, the first PCR-positive sample was examined by using a previously described method that combines heteroduplex analysis and analysis of single-stranded conformational polymorphisms. The ratio of nonsynonymous to synonymous substitutions (dN/dS) within each sample was evaluated as an indicator of relative selective pressure. Amino acid sequences were analyzed for signature patterns, glycosylation signals, and charge. Quasispecies complexity was higher and E1 dN/dS ratios (selective pressure) were lower in those with persistent viremia; the association with persistence was strengthened by the presence of a combination of both characteristics. In contrast, a trend toward higher HVR1 dN/dS ratios was detected among those with persistent viremia. We did not detect any such association for factors that may affect complexity such as serum HCV RNA concentration. HVR1 had a lower positive charge in subjects with persistent viremia, although no consistent motifs were detected. Our data suggest that HCV persistence is associated with a complex quasispecies and immune response to HVR1.

Acute Disease↗
PubMed1999

Gd(DTPA-BBA) as a contrast agent in magnetic resonance imaging in rats.

Gadolinium (III)-di(benzyl carbamoylmethyl) diethylenetrinitrilotriacetic acid [Gd(DTPA-BBA)] is a newly developed paramagnetic complex designed for use as a hepatobiliary-specific contrast agent. The purpose of this study was to examine the relaxivity, biodistribution, and magnetic resonance (MR) imaging characteristics of Gd(DTPA-BBA) in rats. Our results showed that the T1 relaxivity of Gd(DTPA-BBA) (3.89 dm3/mmol/s in aqueous solution) was similar to that of Gd(III) diethylenetriamine-pentaacetate [Gd(DTPA)]2- (4.08 dm3/mmol/s) and Gd(III) benzyloxypropionicte-traacetate [Gd(BOPTA)]2- (4.40 dm3/mmol/s). Biodistribution studies indicated that Gd(DTPA-BBA) exhibited hepatobiliary and urinary elimination. In MR imaging studies, Gd(DTPA-BBA) provided biphasic enhancement of normal liver parenchyma, which was characterized by an initial steep increase in enhancement followed by a plateau. The initial relative enhancement (RE%) of the liver, at 1 minute after administration of 0.2 mmol/kg Gd(DTPA-BBA) was 113 +/- 19. The plateau RE% of the liver (48 +/- 13) occurred within 10 minutes and persisted for at least 60 minutes after injection of the contrast agent. In addition, Gd(DTPA-BBA) provided better RE% of the liver than [Gd(DTPA)]2-. The contrast RE% of liver abscess capsules reached a plateau within 5 minutes after injection of 0.1 mmol/kg Gd(DTPA-BBA). Although the hepatic enhancement of Gd(DTPA-BBA) was inferior to that of [Gd(BOPTA)]2-, the results suggest that Gd(DTPA-BBA) has potential as an MR contrast agent for nonspecific and hepatobiliary uses.

Animals↗
PubMed1999

Purification and characterization of the venom phospholipases A2 from Asian monotypic crotalinae snakes.

Phospholipases A2 were purified from the venoms of Asian monotypic crotalinae snakes including Callosellasma, Hypnale, Deinagkistrodon, and Tropidolaemus by a combination of gel filtration and reversed-phase chromatographic methods. One to four isoforms of the enzyme were found in each of the venoms. The venom enzymes were subjected to N-terminal sequencing up to the 30th amino acids, and their molecular weights were analyzed by electrospray-ionization mass spectrometry. Homologous antiplatelet phospholipase with a conserved Glu 6 residue was found in each of the venoms. Basic phospholipases with Trp 6 (W6) but without detectable enzyme activities were also isolated from the venom of C. rhodostoma, H. hypnale, and T. wagleri. These W6 enzymes showed strong heparin-binding affinity and capable of inducing edema in rat paws. The fact that the venoms of Callosellasma and Hypnale contain similar types of phospholipases is in accord with recent reports that these two taxa formed a clade. Deinagkistrodon venom does not contain phospholipase variants other than the Glu-6 subtype as Trimeresurus, Agkistrodon, and Protobothrops venoms do. Interestingly, the Glu-6 enzyme from T. wagleri venom has a molecular weight of 15,319 Daltons, higher than those of most other venom phospholipases. Our results show that new types of the enzyme are more likely to be found in the venom of monotypic species; the amino acid sequence data or the subtypes of venom-phospholipases are potentially useful as markers or a character system for studying higher-order systematics of venomous snakes.

Amino Acid Sequence↗
PubMed1999

[Comparison of vasorelaxing actions of vasonatrin peptide, C-type natriuretic peptide and atrial natriuretic peptide].

The vasorelaxing effects of vasonatrin peptide (VNP), C-type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP) on isolated rat pulmonary artery, abdominal aorta and celiac vein were measured by in vitro perfusion. The results showed that VNP, CNP and ANP caused concentration-dependent relaxation in isolated rat pulmonary artery, abdominal aorta and celiac vein with endothelium or without endothelium. The maximal responses (Rmax) of VNP were (76 +/- 17)%, (51 +/- 14)% and (62 +/- 14)% in pulmonary artery, abdominal aorta and celiac vein with endothelium respectively, whereas those of CNP were (31 +/- 8)%, (22 +/- 7)% and (41 +/- 8)%, and ANP (38 +/- 10)%, (41 +/- 10)% and (11 +/- 4)%. The median effective concentration (EC50) of VNP were 16 +/- 11, 35 +/- 18 and 12 +/- 8 nmol/L in pulmonary artery, abdominal aorta and celiac vein with endothelium respectively, while those of CNP were 148 +/- 112, 299 +/- 84 and 14 +/- 12 nmol/L, and ANP 66 +/- 47, 16 +/- 15 and 909 +/- 445 nmol/L. VNP were more effective than CNP and ANP, and the differences were statistically significant (P < 0.05-0.01). The potency of these peptides for relaxing the blood vessels can be summarized as: VNP > ANP > or = CNP for pulmonary artery; VNP > ANP > CNP for abdominal aorta; VNP > CNP > ANP for celiac vein. There was no significant difference between vessels with intact endothelium and those denuded of endothelium (P > 0.05).

Animals↗
PubMed1999

Isolation of Japanese encephalitis virus from mosquitoes collected in Northern Taiwan between 1995 and 1996.

Mosquito collections were carried out from May to October in 1995 and 1996 at Yingko and Sanhsia of Taipei County and Chunan of Miaoli County. A grand total of 13,576 mosquitoes consisting of 13 species in 407 pools were processed and inoculated into Aedes albopictus clone C6/36 cell cultures. One hundred thirty seven pools of these showed the presence of viral antigens in the infected C6/36 cell lysates which were identified by the indirect fluorescent antibody test using a monoclonal antibody against Japanese encephalitis (JE) virus. The postive pools, were divided into 97, 20, 1, 8, 1, 1, 7, and 2 pools from Culex tritaeniorhynchus Giles, Aedes albopictus Skuse, Aedes vexans nocturnus (Theobald), Armigeres subalbatus (Coquillett), Culex annulus Theobald, Culex fuscanus Wiedemann, Culex quinquefasciatus Say, and Culex sitiens Wiedemann respectively. The dominant species collected at night was Culex tritaeniorhynchus, while Aedes albopictus was the dominant species collected in daytime. Besides the pigpens, avian habitats are also a dominate source of JE virus in this study.

Animals↗
PubMed1999

Leptospirosis: report of one case.

An 8-year-old male aborigine was referred to our hospital with a presumptive diagnosis of Kawasaki disease. The major symptom presented was a persistent fever for six days. Several other symptoms were drowsiness, headache, nausea, vomiting, abdominal pain, diarrhea, nuchal rigidity, lymphadenopathy, subconjunctival hemorrhage, and muscle aching of the calf. During hospitalization, cerebrospinal fluid studies showed pleocytosis. Abdominal sonograms revealed hepatosplenomegaly, moderate ascites and gallbladder wall thickening. These data were suggestive of leptospirosis. The microscopic agglutination test of leptospiral antibodies further confirmed the diagnosis. After treatment with intravenous aqueous penicillin and gentamicin, the clinical course improved significantly.

Child↗
PubMed1998

Effect of site directed mutagenesis on the activity of recombinant trimucrotoxin, a neurotoxic phospholipase from Trimeresurus mucrosquamatus venom.

Trimucrotoxin, the basic phospholipase A2 from Trimeresurus mucrosquamatus venom, is neurotoxic and myotoxic, and structurally similar to crotoxin B subunit. To investigate the amino acid residues responsible for its neurotoxicity, we have mutated its interface-recognition residues including a conserved Asn6 in all the Crotalinae neurotoxic phospholipases. The wild-type and the mutants were expressed in E. coli as fusion-proteins and activated in vitro by factor Xa cleavage after folding. The completion of folding and activation were checked with electrospray ionization mass spectrometry and circular dichroism measurement. Enzymatic activities and neurotoxicities toward the chick tissue of four trimucrotoxin mutants (N6A, N6E, N6R and 6E7T8L) were compared with those of the wild type which was as active as that was isolated from the venom. Mutants N6A and N6E retained more than half of the original enzymatic activity but their neurotoxicities reduced to 33% and 10% that of the wild type, respectively. Mutants N6R and 6E7T8L retained 20-25% of the enzyme activity toward the anionic micellar substrate but were inactive toward the zwitterionic micellar substrate, and their neurotoxicities were less than 3% of that of the wild type. These results demonstrate the importance of residues 6-8 in trimucrotoxin for its neuronal specificity and the specificity toward potential substrates.

Amino Acid Sequence↗
PubMed1998

Increased MPTP neurotoxicity in vesicular monoamine transporter 2 heterozygote knockout mice.

The neurotoxic action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been proposed to be attenuated by sequestration into intracellular vesicles by the vesicular monoamine transporter (VMAT2). The purpose of this study was to determine if mice with genetically reduced levels of VMAT2 (heterozygote knockout; VMAT2 +/-) were more vulnerable to MPTP. Striatal dopamine (DA) content, the levels of DA transporter (DAT) protein, and the expression of glial fibrillary acidic protein (GFAP) mRNA, a marker of gliosis, were assessed as markers of MPTP neurotoxicity. In all parameters measured VMAT2 +/- mice were more sensitive than their wild-type littermates (VMAT2 +/+). Administration of MPTP (7.5, 15, or 30 mg/kg, b.i.d.) resulted in dose-dependent reductions in striatal DA levels in both VMAT2 +/- and VMAT2 +/+ animals, but the neurotoxic potency of MPTP was approximately doubled in the VMAT2 +/- mice: 59 versus 23% DA loss 7 days after 7.5 mg/kg dose for VMAT2 +/- and VMAT2 +/+ mice, respectively. Dopaminergic nerve terminal integrity, as assessed by DAT protein expression, also revealed more drastic reductions in the VMAT2 +/- mice: 59 versus 35% loss at 7.5 mg/kg and 95 versus 58% loss at 15 mg/kg for VMAT2 +/- and VMAT2 +/+ mice, respectively. Expression of GFAP mRNA 2 days after MPTP was higher in the VMAT2 +/- mice than in the wild-type: 15.8- versus 7.8-fold increase at 7.5 mg/kg and 20.1- versus 9.6-fold at 15 mg/kg for VMAT2 +/- and VMAT2 +/+ mice, respectively. These observations clearly demonstrate that VMAT2 +/- mice are more susceptible to the neurotoxic effects of MPTP, suggesting that VMAT2-mediated sequestration of the neurotoxin into vesicles may play an important role in attenuating MPTP toxicity in vivo.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Assessment of hepatitis C virus sequence complexity by electrophoretic mobilities of both single-and double-stranded DNAs.

To assess genetic variation in hepatitis C virus (HCV) sequences accurately, we optimized a method for identifying distinct viral clones without determining the nucleotide sequence of each clone. Twelve serum samples were obtained from seven individuals soon after they acquired HCV during a prospective study, and a 452-bp fragment from the E2 region was amplified by reverse transcriptase PCR and cloned. Thirty-three cloned cDNAs representing each specimen were assessed by a method that combined heteroduplex analysis (HDA) and a single-stranded conformational polymorphism (SSCP) method to determine the number of clonotypes (electrophoretically indistinguishable cloned cDNAs) as a measure of genetic complexity (this combined method is referred to herein as the HDA+SSCP method). We calculated Shannon entropy, incorporating the number and distribution of clonotypes into a single quantifier of complexity. These measures were evaluated for their correlation with nucleotide sequence diversity. Blinded analysis revealed that the sensitivity (ability to detect variants) and specificity (avoidance of false detection) of the HDA+SSCP method were very high. The genetic distance (mean +/- standard deviation) between indistinguishable cloned cDNAs (intraclonotype diversity) was 0.6% +/- 0.9%, and 98.7% of cDNAs differed by <2%, while the mean distance between cloned cDNAs with different patterns was 4.0% +/- 3.2%. The sensitivity of the HDA+SSCP method compared favorably with either HDA or the SSCP method alone, which resulted in intraclonotype diversities of 1.6% +/- 1.8% and 3.5% +/- 3.4%, respectively. The number of clonotypes correlated strongly with genetic diversity (R2, 0.93), but this correlation fell off sharply when fewer clones were assessed. This HDA+SSCP method accurately reflected nucleotide sequence diversity among a large number of viral cDNA clones, which should enhance analyses to determine the effects of viral diversity on HCV-associated disease. If sequence diversity becomes recognized as an important parameter for staging or monitoring of HCV infection, this method should be practical enough for use in laboratories that perform nucleic acid testing.

Cloning, Molecular↗
PubMed1998

Treatment of Takayasu's aortitis with percutaneous transluminal angioplasty and wall stent--a case report.

The authors describe a young woman who developed severe toxemia during pregnancy, requiring emergency lower segment cesarian section at 27 weeks of gestation. Postpartum angiography showed a discrete stenotic lesion of the abdominal aorta proximal to the origin of the renal artery. Angioplasty was performed, followed by the insertion of a wall stent at the site of the stenosis. Her hypertension control improved dramatically after the stenting. This is, so far, the first reported case using a wall stent following angioplasty to relieve abdominal aortic stenosis due to Takayasu's arteritis.

Adult↗
PubMed1998

Phase I and pharmacokinetic study of paclitaxel in combination with biricodar, a novel agent that reverses multidrug resistance conferred by overexpression of both MDR1 and MRP.

PURPOSE: To evaluate the feasibility of administering biricodar (VX-710; Incel, Vertex Pharmaceuticals Inc, Cambridge, MA), an agent that modulates multidrug resistance (MDR) conferred by overexpression of both the multidrug resistance gene product (MDR1) P-glycoprotein and the MDR-associated protein (MRP) in vitro, in combination with paclitaxel. The study also sought to determine the maximum-tolerated dose (MTD) of paclitaxel that could be administered with biologically relevant concentrations of VX-710 and characterize the toxicologic and pharmacologic profiles of the VX-710/ paclitaxel regimen. PATIENTS AND METHODS: Patients with solid malignancies were initially treated with VX-710 as a 24-hour infusion at doses that ranged from 10 to 120 mg/m2 per hour. After a 2-day washout period, patients were re-treated with VX-710 on an identical dose schedule followed 8 hours later by paclitaxel as a 3-hour infusion at doses that ranged from 20 to 80 mg/m2. The pharmacokinetics of both VX-710 and paclitaxel were studied during treatment with VX-710 alone and VX-710 and paclitaxel. Thereafter, patients received VX-710 and paclitaxel every 3 weeks. RESULTS: VX-710 alone produced minimal toxicity. The toxicologic profile of the VX-710/paclitaxel regimen was similar to that reported with paclitaxel alone; neutropenia that was noncumulative was the principal dose-limiting toxicity (DLT). The MTD levels of VX-710/ paclitaxel were 120 mg/m2 per hour and 60 mg/m2, respectively, in heavily pretreated patients and 120/60 to 80 mg/m2 per hour in less heavily pretreated patients. At these dose levels, VX-710 steady-state plasma concentrations (Css) ranged from 2.68 to 4.89 microg/mL, which exceeded optimal VX-710 concentrations required for MDR reversal in vitro. The pharmacokinetics of VX-710 were dose independent and not influenced by paclitaxel. In contrast, VX-710 reduced paclitaxel clearance. At the two highest dose levels, which consisted of VX-710 120 mg/m2 per hour and paclitaxel 60 and 80 mg/m2, pertinent pharacokinetic determinants of paclitaxel effect were similar to those achieved with paclitaxel as a 3-hour infusion at doses of 135 and 175 mg/m2, respectively. CONCLUSION: VX-710 alone is associated with minimal toxicity. In combination with paclitaxel, biologically relevant VX-710 plasma concentrations are achieved and sustained for 24 hours, which simulates optimal pharmacologic conditions required for MDR reversal in vitro. The acceptable toxicity profile of the VX-710/ paclitaxel combination and the demonstration that optimal pharmacologic conditions for MDR reversal are achievable support a rationale for further trials of VX710/paclitaxel in patients with malignancies that are associated with de novo or acquired resistance to paclitaxel caused by overexpression of MDR1 and/or MRP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Fresh vs aged benzylpenicillin on non-IgE responses in mice.

AIM: To study whether or not the freshly prepared benzylpenicillin could induce different non-IgE antibody response from aged benzylpenicillin. METHODS: Antibody response was determined by enzyme-linked immunosorbent assay (ELISA). Antigen molecules recognized by antibodies and antigenic cross reactions were tested by hapten inhibition assay. RESULTS: Isotypes of specific non-IgE antibodies induced by freshly prepared benzylpenicillin were mainly IgM, and then IgG and IgA. Some parts of specific antibodies recognized benzylpenicillin molecule and major parts combined with degraded or transforming products. Isotypes of antibodies responsible for cross reaction were mainly IgG between benzylpenicillin and ampicillin and IgM between benzylpenicillin and piperacillin. CONCLUSION: Freshly prepared and aged benzylpenicillin induced different non-IgE antibody response.

Ampicillin↗
PubMed1998

Gene expression, immunolocalization, and secretion of human defensin-5 in human female reproductive tract.

This study describes the novel localization of the antimicrobial peptide human intestinal defensin-5 (HD-5) in female genital tract epithelia. Using a 3' rapid amplification of cDNA ends (RACE) protocol, HD-5 was cloned from a vaginal epithelial cell RNA preparation, and its identity was confirmed by sequencing. Tissue samples from multiple donors were subsequently screened for HD-5 expression by reverse transcription polymerase chain reaction. HD-5 message was invariantly expressed by normal vagina and ectocervix and inflamed fallopian tube, but variably expressed by normal endocervix, endometrium, and fallopian tube (60, 64, and 29% of specimens, respectively). Expression in endometrium was the highest during the early secretory phase of the menstrual cycle. Using immunohistochemistry and confocal microscopy, HD-5 peptide was localized in the upper half of the stratified squamous epithelium of the vagina and ectocervix, with the intensity of cellular staining increasing toward the lumen. In positive endocervix, endometrium, and fallopian tube specimens, HD-5 was located in apically oriented granules and on the apical surface of a proportion of columnar epithelial cells. Using Western blot analysis, secreted HD-5 was detected in cervicovaginal lavages, with the highest concentrations found during the secretory phase of the menstrual cycle. We hypothesize that HD-5 is an intrinsic component of the female urogenital innate immune defense system and that its expression may be modulated by hormonal and proinflammatory factors.

Adult↗
PubMed1998

Repeated alcohol administration differentially affects c-Fos and FosB protein immunoreactivity in DBA/2J mice.

To identify alcohol-responsive brain areas, we have immunohistochemically analyzed expression of c-Fos, FosB, and other Fos-related antigens in the brain of inbred DBA/2J mice after a single or repeated injection of alcohol (4 g/kg). We observed increased expression of c-Fos after alcohol administration in the central nucleus of amygdala, paraventricular nuclei of hypothalamus and thalamus, and several other brain areas. Although increased expression of c-Fos in the nucleus accumbens was also observed, this increase was not statistically significant. Repeated administration of alcohol had the tendency to reduce alcohol-induced c-Fos expression in these areas. Immunohistochemical analysis using an antibody recognizing most Fos-related antigens revealed increases of expression of these proteins in a partially overlapping set of brain regions. In contrast to c-Fos, FosB expression was found to be elevated significantly higher after repeated than after acute treatment with alcohol in several brain areas, including the shell of nucleus accumbens. In contrast to previous c-Fos studies, our studies confirm that alcohol administration indeed activates the reward circuits, including the basal ganglia, and suggest that FosB could serve as a more sensitive marker for this activation.

Alcoholic Intoxication↗
PubMed1997

Knockout of the vesicular monoamine transporter 2 gene results in neonatal death and supersensitivity to cocaine and amphetamine.

Vesicular monoamine transporters are known to transport monoamines from the cytoplasm into secretory vesicles. We have used homologous recombination to generate mutant mice lacking the vesicular monoamine transporter 2 (VMAT2), the predominant form expressed in the brain. Newborn homozygotes die within a few days after birth, manifesting severely impaired monoamine storage and vesicular release. In heterozygous adult mice, extracellular striatal dopamine levels, as well as K+- and amphetamine-evoked dopamine release, are diminished. The observed changes in presynaptic homeostasis are accompanied by a pronounced supersensitivity of the mice to the locomotor effects of the dopamine agonist apomorphine, the psychostimulants cocaine and amphetamine, and ethanol. Importantly, VMAT2 heterozygous mice do not develop further sensitization to repeated cocaine administration. These observations stress the importance of VMAT2 in the maintenance of presynaptic function and suggest that these mice may provide an animal model for delineating the mechanisms of vesicular release, monoamine function, and postsynaptic sensitization associated with drug abuse.

Amphetamine↗
PubMed1997

N-terminal arginylation of sciatic nerve and brain proteins following injury.

N-terminal protein arginylation has been demonstrated in vitro and in situ and has been reported to increase following injury to sciatic nerves of rats. The present study attempts to demonstrate these reactions in vivo by applying [3H]Arg to the cut end of sciatic nerves in anesthetized rats and assaying for N-terminal arginylation using Edman chemistry and acid precipitation of labeled proteins in the proximal nerve segment. No evidence was found for arginylation in an aqueous soluble fraction. However, N-terminal arginylation was detected in a urea soluble fraction at 2 hours after nerve crush. The data show that arginylation of rat sciatic nerve proteins occurs in vivo and suggest that the arginylated proteins formed an aqueous insoluble/urea soluble aggregate after arginylation. In other experiments, rat brains were injured and assayed for arginylation in vitro to test the hypothesis that injury causes an up-regulation of these reactions. Results showed an activation of the reaction at 2 hours post crush and indicate that increases in N-terminal arginylation are likely to be a general response to injury in nervous tissue.

Animals↗
PubMed1997

Susceptibility of three laboratory strains of Aedes albopictus (Diptera: Culicidae) to Japanese encephalitis virus from Taiwan.

The susceptibility of 3 laboratory strains of Aedes albopictus (Skuse) (Sanhsia [SH], Yungho [YH], Liyang [LY], and 1 strain of Culex tritaeniorhynchus Giles from northern and central Taiwan were compared for susceptibility to the MQ1-2 strain of Japanese encephalitis (JE) virus. The median infective dose (MID50) by intrathoracic inoculation was 0.23, 0.76, 1.60, and -0.03 log10 WMICLD50 (50% weanling mice intracranial lethal dose) with Ae. albopictus SH, YH, LY, and Cx. tritaeniorhynchus, respectively. After feeding on a sweetened blood-virus mixture, the oral MID50 was 2.03, 4.32, and 4.98 log10 WMICLD50 for SH, YH, and LY, respectively, and 1.02 log10 WMICLD50 for Cx. tritaeniorhynchus. The SH Ae. albopictus strain transmitted virus to normal mice after 14 d. with an average transmission rate of 45%. Based on these results, the SH strain was the most susceptible and important potential vector among 3 Ae. albopictus strains for the sympatric MQ1-2 strain of JE.

Aedes↗