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Y Wu

Publications and source records attributed to Y Wu.

At least 1,009 records · Page 56Linked to original sources
PubMed1994

Cooperative membrane insertion of magainin correlated with its cytolytic activity.

Using oriented circular dichroism, we have found that magainin adopts an alpha-helical conformation with two distinct orientations when interacting with a lipid bilayer. At low concentrations, magainin is absorbed parallel to the membrane surface. However, at high concentrations, magainin is inserted into the membrane. This transition occurs at roughly the same critical concentration required for cytolytic activity, implying that the membrane insertion is responsible for magainin's cell-lysing activity.

Anti-Infective Agents↗
PubMed1994

Tumorigenic activity of the 4,5- and 9,10-dihydrodiols of benzo[j]fluoranthene and their syn- and anti-diol epoxides in newborn mice.

Benzo[j]fluoranthene (B[j]F), trans-4,5-dihydro-4,5-dihydroxy-B[j]F, and trans-9,10-dihydro-9,10-dihydroxy-B[j]F were evaluated for tumorigenic activity in newborn CD1 mice. These dihydrodiols were assayed at doses of 1.10 and 0.275 mumol/mouse. B[j]F and the syn- and anti-diol epoxides derived from these dihydrodiols were evaluated at doses of 1.10, 0.275, and 0.110 mumol/mouse (80 mice/group). trans-4,5-Dihydro-4,5-dihydroxy-B[j]F was more potent than trans-9,10-dihydro-9,10-dihydroxy-B-[j]F in inducing pulmonary tumors in both female and male mice. Administration of 1.10 mumol of trans-4,5-dihydro-4,5-dihydroxy-B[j]F resulted in a 90-92% incidence of pulmonary tumors with an average of 3.6 and 4.2 tumors/mouse among female and male mice, respectively. A similar tumorigenic activity was observed for B[j]F in lung. trans-9,10-Dihydro-9,10-dihydroxy-B[j]F was significantly less tumorigenic (P < 0.05), producing a 44 and 64% incidence of pulmonary tumors at a dose of 1.10 mumol with an average of 0.8 and 1.0 tumor/mouse in female and male mice, respectively. A statistically significant (P < 0.001) incidence of hepatic tumors was also produced among male mice administered either B[j]F, trans-4,5-dihydro-4,5-dihydroxy-B[j]F, or trans-9,10-dihydro-9,10-dihydroxy-B[j]F at a dose of 1.10 mumol/mouse. In comparing the tumorigenicity of the diasteromeric diol epoxides derived from both trans-4,5-dihydro-4,5-dihydroxy-B[j]F and trans-9,10-dihydro-9,10-dihydroxy-B[j]F, the anti-diasteromers exhibited greater tumorigenic activity. The most tumorigenic diol epoxide was anti-4,5-dihydroxy-6,6a-epoxy-4,5,6,6a-tetrahydro-B[j]F. At a dose of 0.275 mumol, this diol epoxide induced a 96 and 100% incidence of pulmonary tumors in female and male mice, with an average of 8.6 and 5.0 tumors/mouse, respectively. anti-9,10-Dihydroxy-11,12-epoxy-9,10,11,12-tetrahydro-B[j]F at this dose produced a 56 and 95% incidence of pulmonary tumors in female and male mice with an average of 1.0 and 2.8 tumors/mouse, respectively. syn-4,5-Dihydroxy-6,6a-epoxy-4,5,6,6a-tetrahydro-B[j]F and syn-9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydro-B[j]F at a dose of 0.275 mumol did not induce a significant incidence (P > 0.05) of pulmonary tumors in female or male mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Coupled replication-translation of amplifiable messenger RNA. A cell-free protein synthesis system that mimics viral infection.

Amplifiable messenger RNAs (Wu, Y., Zhang, D. Y., and Kramer, F. R. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 11769-11773) were used as templates in coupled replication-translation reactions. These amplifiable mRNAs contained a preselected messenger sequence embedded within the sequence of MDV-1 RNA, which is a small, naturally occurring template for Q beta replicase. When these recombinant mRNAs were incubated in vitro in reactions that contained both an Escherichia coli cell-free translation system and Q beta replicase, the encoded protein was synthesized more efficiently than in corresponding reactions that did not contain Q beta replicase. Moreover, when coupled replication-translation reactions were carried out in a continuous-flow format (Spirin, A. S., Baranov, V. I., Ryabova, L. A., Ovodov, S. Yu., and Alakhov, Yu. B. (1988) Science 242, 1162-1164), the synthesis of biologically active protein continued for a prolonged period. The results suggest that the mechanism of replication and translation in coupled reactions is similar to the mechanism by which Q beta phage genomic RNA is simultaneously replicated and translated in Q beta-infected E. coli: protein synthesis occurs on nascent RNA strands; many more sense strands are synthesized than antisense strands; and the integrity of the messenger sequence is preserved because a relatively small number of antisense strands serve as master templates for the synthesis of new messenger strands.

Cell-Free System↗
PubMed1994

Analysis of the specificity of anti-PM-Scl autoantibodies.

OBJECTIVE: To compare the specificity of anti-PM-Scl autoantibodies in serum samples from 43 patients with myositis, scleroderma, or both. METHODS: Anti-PM-Scl immunoprecipitates from HeLa cell extract were used as antigen for immunoblot analyses to determine the antigenic components. A series of complementary DNA fragments was expressed in Escherichia coli for immunoblot examination of the reaction with the 100-kd protein. RESULTS: The immunoblot against immunoprecipitates was sensitive and specific for detecting reactions with components of the PM-Scl antigen: 42 of 43 sera (97.7%) reacted with the 100-kd, 27 of 43 (62.8%) with the 70-kd, and 5 of 43 (11.6%) with the 37-kd protein (not previously recognized as antigenic). Forty-one sera reacted with N-terminal protein S1 (amino acids 11-437), 39 with central protein S2 (amino acids 439-749), and 24 with C-terminal protein S3 (amino acids 750-882). Of 42 sera tested, 28 (66.7%) reacted most strongly with S1, and 6 (14.3%) reacted most strongly with S2. Absorption studies implied additional, conformational epitopes not present on the bacterially expressed antigen. CONCLUSION: There was an overall similarity in reactivity to the PM-Scl antigen, but there were differences in the reactivity to the 70-kd and 37-kd proteins, as well as in the relative strength of the reactivity to the S2 protein.

Antibodies, Anti-Idiotypic↗
PubMed1994

Crystal structure and NMR conformation of a cyclic pseudotetrapeptide containing urethane backbone linkages.

Urethane bonds, derived from the hydroxyl group of the tyrosine side chain, have been investigated as a new type of amide bond mimetic in the design of pseudopeptides. The structure of a representative cyclic pseudotetrapeptide that consists of an -Ala-Tyr(urethane)Ala-Tyr(urethane) sequence fused into a rigid ring has been studied in the solid state by x-ray crystallography and in solution by two-dimensional nmr techniques. The cyclic pseudotetrapeptide has an oblong shape. The backbone urethane bonds assume a trans-trans conformation. The carbonyl groups in the ring have an alternating pattern of down, up, down, up with respect to the average ring plane. Solution nmr studies give observed nuclear Overhauser effects and coupling constants largely in agreement with the crystal structure. However, in solution the observed structure is likely to be conformationally averaged, and in the averaged structure, the urethane bond is perpendicular to the plane of the aromatic ring of the tyrosine, while in the crystal it is close to this plane. These differences may be explained by intermolecular hydrogen-bonding interactions. Four aspects of the conformation of the cyclic pseudotetrapeptide were investigated in detail: the tyrosine residue with the attached side-chain urethane bond (the tyrosine-urethane unit), the conformation of the two urethane backbone linkages, the conformation of the two conventional peptide bonds within this unusual ring structure, and the tight turns within the cyclic pseudotetrapeptide. The conformation of the tight turns present in the cyclic pseudotetrapeptide is very similar to that of a beta-bend of type II. Intermolecular hydrogen bonding, joining adjacent layers of the cyclic pseudotetrapeptide in the solid state, resemble a parallel beta-pleated sheet. The presence of these structural motifs in the cyclic pseudotetrapeptide indicates that the tyrosine urethane unit may find applications in peptide and protein engineering.

Amino Acid Sequence↗
PubMed1994

A 17S multiprotein form of murine cell DNA polymerase mediates polyomavirus DNA replication in vitro.

We have identified and purified a multiprotein form of DNA polymerase from the murine mammary carcinoma cell line (FM3A) using a series of centrifugation, polyethylene glycol precipitation, and ion-exchange chromatography steps. Proteins and enzymatic activities associated with this mouse cell multiprotein form of DNA polymerase include the DNA polymerases alpha and delta, DNA primase, proliferating cell nuclear antigen (PCNA), DNA ligase I, DNA helicase, and DNA topoisomerases I and II. The sedimentation coefficient of the multiprotein form of DNA polymerase is 17S, as determined by sucrose density gradient analysis. The integrity of the murine cell multiprotein form of DNA polymerase is maintained after treatment with detergents, salt, RNase, DNase, and after chromatography on DE52-cellulose, suggesting that the association of the proteins with one another is independent of nonspecific interaction with other cellular macromolecular components. Most importantly, we have demonstrated that this complex of proteins is fully competent to replicate polyomavirus DNA in vitro. This result implies that all of the cellular activities required for large T-antigen dependent in vitro polyomavirus DNA synthesis are present within the isolated 17S multiprotein form of the mouse cell DNA replication activities. A model is proposed to represent the mammalian Multiprotein DNA Replication Complex (MRC) based on the fractionation and chromatographic profiles of the individual proteins found to co-purify with the complex.

Animals↗
PubMed1994

Relationships between biomarkers of exposure and neurological effects in a group of workers exposed to acrylamide.

A study was performed among 41 workers heavily exposed to a mixture of acrylamide and acrylonitrile in the city of Xinxiang, Henan province, People's Republic of China. The workers underwent a complete medical and neurological examination and provided blood and urine for the determination of several biomarkers of exposure. Among the exposed workers, signs and symptoms indicating peripheral neuropathy were found with statistically significant increased frequencies compared to a group of controls from the same city. Based on neuropathic signs and symptoms and quantifiable indicators of peripheral nervous dysfunction, such as vibration thresholds and electroneuromyography measurements, a neurotoxicity index (NIn) specific for acrylamide-induced peripheral neuropathy was designed. The NIn, which adequately predicted the clinical diagnosis of peripheral neuropathy, was significantly correlated with the levels of mercapturic acids in 24-hr urine, hemoglobin adducts of acrylamide, accumulated in vivo doses of acrylamide, employment time, and vibration sensitivity. The NIn was correlated also with hemoglobin adducts of acrylonitrile, which was explained primarily by a correlation between acrylamide and acrylonitrile exposure in this workshop. However, it was not significantly correlated with momentary measures of exposure such as concentrations of acrylamide in the air or in the plasma of exposed workers. This study is the first in which adduct monitoring has been applied to the same group of individuals in which adverse health effects have been observed. The results seem to indicate that hemoglobin adducts are useful as predictors of acrylamide-induced peripheral neuropathy and that measurements of vibration thresholds are useful for identifying early neurotoxic effects in workplaces with hazardous exposures to acrylamide.

Acetylcysteine↗
PubMed1994

Dietary cholesterol, fat, and lung cancer incidence among older women: the Iowa Women's Health Study (United States).

To test the hypothesis that a high intake of dietary cholesterol and fat is associated with elevated risks of lung cancer, we analyzed data from a population-based, prospective, cohort study conducted among 41,837 postmenopausal Iowa (United States) women who completed, in 1986, a comprehensive mailed questionnaire including information on usual intake of 127 food items. All cohort members were followed for cancer incidence through the statewide cancer registry. By 1991, after six years of follow-up, 272 incident lung-cancer cases were identified. After controlling for total energy intake and other confounding factors, dietary cholesterol, total fat, and animal fat were unrelated to lung cancer risk. Intake in the upper three quartiles of plant-derived fat, however, was related to a 30 to 40 percent lower incidence of lung cancer, comparative with those in the lowest quartile, with more pronounced reduction in risk observed among smokers (relative risk = 0.6, 95 percent confidence interval = 0.4-0.9). This prospective cohort study suggests that high intake of fat of plant origin may be associated with reduced risk of lung cancer, while dietary cholesterol and animal fat intake is unrelated to the etiology of this malignancy in postmenopausal women.

Animal Population Groups↗
PubMed1994

Subunit- and brain region-specific reduction of GABAA receptor subunit mRNAs during chronic treatment of rats with diazepam.

The mRNA levels for several GABAA receptor subunits were measured by Northern blot analysis. Rats were treated for 3 wk by continuous release of diazepam (DZP) from subcutaneous reservoirs, and then sacrificed immediately or 48 h after removing the reservoirs. Poly(A)+ RNAs, isolated from cerebral cortex, cerebellum, and hippocampus, were hybridized with oligonucleotide probes for GABAA receptor subunits and a cDNA probe for beta-actin. Subunit mRNAs were expressed relative to the corresponding beta-actin mRNA. DZP treatment decreased the alpha 1 subunit mRNA level 40% in hippocampus, but it was not changed in cortex or cerebellum. The alpha 5 subunit mRNA level was decreased in cerebral cortex (28%) and hippocampus (15%). The gamma 2 subunit mRNA level was decreased (40%) only in cortex. DZP treatment did not affect alpha 2, alpha 3, alpha 4, beta 2, or beta 3 subunit mRNA levels. Decreases in mRNA levels had reversed within 48 h after stopping chronic treatment. Acute DZP did not change alpha 1, alpha 5, or gamma 2 subunit mRNA levels. The decreases in GABAA receptor subunit mRNA levels were specific to subunit and brain region. These results, coupled with those after chronic flurazepam treatment, also indicated that the effects on GABAA receptor subunit mRNA levels are specific to the benzodiazepine (BZ) used for chronic treatment.

Animals↗
PubMed1994

Opioid antagonist modulation of DNA synthesis in mouse tongue epithelium is circadian dependent.

In addition to neuromodulation, endogenous opioids also serve as growth factors. To investigate the possible involvement of opioid peptides in the renewal of epithelium, mice were given systemic injections of the opioid antagonist, naltrexone (NTX) (10 mg/kg). Disruption of opioid-receptor interaction by NTX resulted in an elevation (43-150% from control levels) of the number of basal epithelial cells undergoing DNA synthesis in the tip, dorsal, and ventral surfaces of the tongue. This stimulatory effect lasted up to 8 h following drug exposure, and was recorded at 1700 h but not 0700 h. These results are the first indication that endogenous opioids function in cellular renewal processes, and do so in a circadian rhythm-dependent manner.

Animals↗
PubMed1994

Comparison of anticonvulsant tolerance, crosstolerance, and benzodiazepine receptor binding following chronic treatment with diazepam or midazolam.

In a previous study, rats treated chronically with flurazepam were tolerant to the anticonvulsant action of some benzodiazepines (BZs), but not others (34). To determine if this differential crosstolerance was unique to flurazepam, rats were treated chronically with diazepam or midazolam, and tested for tolerance to the anticonvulsant actions of diazepam, midazolam, clonazepam, and clobazam. Regional benzodiazepine receptor binding in brain was also studied. In contrast to previous findings with flurazepam, 1 week treatment with diazepam or with midazolam did not cause tolerance. Rats treated with diazepam for 3 weeks were tolerant to diazepam, clonazepam, clobazam, and midazolam. In contrast, rats treated 3 weeks with midazolam were tolerant to diazepam and midazolam, but not clobazam or clonazepam. Neither diazepam nor midazolam treatment for 3 weeks altered BZ binding in cerebral cortex, cerebellum, or hippocampus. The effects of chronic BZ treatment depended not only on the BZ given chronically, but also on the BZ used to evaluate these effects, suggesting drug-specific interactions of different BZs with their receptors.

Animals↗
PubMed1994

Closed state of gramicidin channel detected by X-ray in-plane scattering.

An analogue of gramicidin A (gA) was synthesized with the formyl group replaced by a BOC group. The analogue (BOC-gA) exhibited single channel conduction, but the channel is 5-order-of-magnitude destabilized relative to the gA channel. Hydrated mixtures of gramicidin and dilauroyl phosphatidylcholine in the molar ratio of 1:10 were prepared into uniformly aligned multiple bilayers, and X-ray scattering with the momentum transfer in the plane of the membrane was measured. Analysis with the help of computer simulations showed that 70% of BOC-gA are monomers. Thus for the first time it was shown that gramicidin monomers are stable inside the monolayers of a lipid membrane. Furthermore, the monomers have the same beta helical conformation as the dimeric channel. The result suggests the possibility that when a gramicidin channel is closed, it dissociates into two monomers floating in opposite monolayers.

Computer Simulation↗
PubMed1994

Surface shape change during fusion of erythrocyte membranes is sensitive to membrane skeleton agents.

We previously reported that the induction of membrane fusion between pairs of erythrocyte ghosts is accompanied by the formation of a multipore fusion zone that undergoes an area expansion with condition-dependent characteristics. These characteristics allowed us to hypothesize substantial, if not major, involvement of the spectrin-based membrane skeleton in controlling this expansion. It was also found that the fusion zone, which first appears in phase optics as a flat diaphragm, has a lifetime that is also highly condition-dependent. We report here that 2,3-diphosphoglycerate, wheat germ agglutinin, diamide, and N-ethylmaleimide, all known to have binding sites primarily on skeleton components (including spectrin), have condition-dependent effects on specific components of the fusion zone diameter versus time expansion curve and the flat diaphragm lifetime. We also report a pH/ionic strength condition that causes a dramatic stabilization of flat diaphragms in a manner consistent with the known pH/ionic strength dependence of the spectrin calorimetric transition, thus further supporting the hypothesis of spectrin involvement. Our data suggest that the influence of the membrane skeleton on cell fusion is to restrain the rounding up that takes place after membrane fusion and that it may have variable, rather than fixed, mechanical properties. Data show that WGA, a known ligand for sialic acid, and DPG, a known metabolite, influences the flat diaphragm stability and late period expansion rates, raising the possibility that some of these mechanical properties are biologically regulated.

2,3-Diphosphoglycerate↗
PubMed1994

Distinct mechanical relaxation components in pairs of erythrocyte ghosts undergoing fusion.

It was previously reported (Chernomordik and Sowers, 1991) that erythrocyte ghosts which were exposed to a 42 degrees C, 10-min heat treatment would, upon electrofusion, produce over 15-20 s a fusion product with an "open lumen" (i.e., the fusion product became converted to one large sphere), while electrofusion of ghost membranes not so exposed would lead to chains of polyghosts. In phase optics the chains of polyghosts showed a "flat diaphragm" at virtually every ghost-ghost junction (i.e., the ghosts do not appear to be fused even though fluorescent-labeled lipid analogs can laterally diffuse from a labeled ghost to an adjacent unlabeled ghost). In the present study we found that the diameter increase in open lumen- and flat diaphragm-producing fusion processes both had a rapid but short early phase (0-5 s after fusion) which was exponential or nearly so and a slow but long late phase (5-120 s after fusion) which was essentially linear. Heat treatments at 39 or 42 degrees C caused a minor acceleration in only the late phase, while temperatures of 45 or 50 degrees C caused an immediate and dramatic acceleration in the rate of diameter increase (spheres in 1-2 s). Ghost membranes in the presence of glycerol at 20% (v/v) did not form open lumens when exposed to the 42 degrees C (but not the > or = 45 degrees C) heat treatment. This suggested that the heat treatment was denaturing a critical protein. Both of these observations are consistent with the involvement of the spectrin network since it is the only protein in the erythrocyte membrane which is known (Brandts et al., 1977) to have a calorimetric transition over the same temperature range used in our heat treatments. The diameter versus time curves were sensitive to: (i) the residual effects of the fusogenic electric pulse only up to about 1 s after the pulse, (ii) the strength of the dielectrophoretic field after the pulse, but not before the pulse,(iii) the ambient temperature during the measurement.

Animals↗
PubMed1994

Endotoxic damage to the stria vascularis: the pathogenesis of sensorineural hearing loss secondary to otitis media?

This study presents animal experiments on endotoxin (lipopolysaccharides: LPS) damage to the inner ear with special reference to the stria vascularis. The experimental group animals (albino guinea pigs) were injected with LPS into the perilymphatic space. Pyrogen-free saline (PFS) was injected into the control group. Strial structural evaluation and hearing tests were carried out before and one, three and five days after treatment. In PFS-treated (control) ears, no significant change was found either in hearing or structure. However, thresholds of N1/P1 were elevated and latencies prolonged in LPS-treated ears. They had severe strial damage mainly to the cellular organelles. The mitochondria became swollen with a disordered, broken, degenerated or absent crest. Secondary lysosomes and autophagosomes increased in number with the presence of medulative inclusions. Na(+)-K(+)-ATPase reactant was obviously diminished. It is concluded that LPS-induced strial ototoxicity produces ion imbalance, causing changes in endolymph composition and energy failure in the organ of Corti and is also responsible for the pathogenesis of inner ear sequelae secondary to otitis media.

Animals↗
PubMed1994

Biochemical effects of manufactured gas plant residue following ingestion by B6C3F1 mice.

The toxic potential of manufactured gas plant residue (MGP) given in the diet to male and female B6C3F1 mice was evaluated. In addition, the bioavailability of chemical components of MGP were also investigated by monitoring polycyclic aromatic hydrocarbon (PAH) metabolites in urine and DNA adduct formation in forestomach and lung tissue. Basal gel diets containing 0.05, 0.25, 0.50% MGP or 0.005% benzo[a]pyrene (BaP) were fed to animals for 94 and 185 d. Mice readily consumed adulterated diets without any evidence of acute toxicity. The total amount of MGP and BaP consumed by mice ranged from 118 to 2604 mg and from 12 to 29 mg, respectively. Male mice fed a control or BaP diet and female mice fed a 0.05% MGP diet had the highest body weight gains. Male and female mice fed a 0.50% MGP diet had the lowest body weight gains. The bioavailability of chemical components of MGP was evaluated by monitoring the urinary excretion of PAH metabolites by male mice fed a 0.25% MGP diet. 1-Hydroxypyrene was determined by high-performance liquid chromatography analysis to be the major fluorescent metabolite excreted by mice throughout the 185 d of diet administration. At necropsy, no chemical-related gross lesions were detected. In addition, no treatment-related microscopic lesions were evident in tissues obtained from animals fed a 0.50% MGP- or BaP-adulterated diet. The 32P-postlabeling assay was used to evaluate MGP- and BaP-induced DNA adduct formation in lung and forestomach tissue. The level of DNA adducts formed from the chemical components of MGP paralleled the amount of material ingested by animals. Lung DNA adduct levels were considerably higher than forestomach levels when mice ingested a 0.25% or 0.50% MGP diet. These studies demonstrate that the continuous ingestion of MGP or BaP for 185 d does not result in acute toxicity or chemical-related lesions at doses up to 0.50% MGP or 0.005% BaP.

Administration, Oral↗
PubMed1994

Dietary calcium reduces blood pressure, parathyroid hormone, and platelet cytosolic calcium responses in spontaneously hypertensive rats.

Dietary calcium effects on blood pressure, parathyroid hormone (PTH), and platelet cytosolic calcium concentrations were investigated. The dietary calcium (low, 0.2%; medium, 0.5%; and high, 2.0% wt/wt) was supplemented in spontaneously hypertensive rats from 6 through 22 weeks of age. Mean systolic blood pressure was decreased by age 12 weeks with calcium supplementation (low, 227 +/- 6 mm Hg; medium, 211 +/- 6 mm Hg; and high, 182 +/- 7 mm Hg; P < .001). By the 10th week of age, the low calcium group had significantly (P < .05) more elevated (44 +/- 2.3 pg/ml) plasma PTH compared with the high calcium-supplemented group (15 +/- 4.5 pg/mL). Regression analysis showed a significant (P < .001) positive correlation (r = 0.3) between systolic blood pressure and PTH. The platelet cytosolic calcium concentration was determined using the fura-2 method. The basal calcium was 134 +/- 5.5 nmol/L for the low calcium group and thrombin increased to 228 +/- 8 nmol/L (P < .0001; +70% change). The normal calcium group had 202 +/- 8 nmol/L; thrombin increased to 239 +/- 10 nmol/L (P < .0026; +19% change). The high calcium group had basal levels 145 +/- 7 nmol/L, with thrombin stimulating to 212 +/- 8 nmol/L (P < .0001; +46% change). Although thrombin increased platelet cytosolic calcium concentration in all groups, normal and high dietary calcium groups had smaller percentage increases (51% and 24% lesser, respectively) compared with the low dietary calcium group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗