Search PubMed⌕ Search

Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 487 records · Page 27Linked to original sources
PubMed1999

Interleukin-18 protects mice against acute herpes simplex virus type 1 infection.

We examined the effects of interleukin-18 (IL-18) in a mouse model of acute intraperitoneal infection with herpes simplex virus type 1 (HSV-1). Four days of treatment with IL-18 (from 2 days before infection to 1 day after infection) improved the survival rate of BALB/c, BALB/c nude, and BALB/c SCID mice, suggesting innate immunity. One day after infection, HSV-1 titers were higher in the peritoneal washing fluid of control BALB/c mice than in that of IL-18-treated mice. A genetic deficiency of gamma interferon (IFN-gamma), however, diminished the survival rate and the inhibition of HSV-1 growth at the injection site in the mice. Anti-asialo GM1 treatment had no influence on the protective effect of IL-18 in infected mice. IL-18 augmented IFN-gamma release in vitro by peritoneal cells from uninfected mice, while no appreciable IFN-gamma production was found in uninfected mice administered IL-18. Although IFN-gamma has the ability to induce nitric oxide (NO) production by various types of cells, administration of the NO synthase inhibitor NG-monomethyl-L-arginine resulted in superficial loss of the improved survival, but there was no influence on the inhibition of HSV-1 replication at the injection site in IL-18-treated mice. Based on these results, we propose that IFN-gamma produced before HSV-1 infection plays a key role as one of the IL-18-promoted protection mechanisms and that neither NK cells nor NO plays this role.

Acute Disease↗
PubMed1999

Extracellular signal-regulated kinases 1 and 2 activation in endothelial cells exposed to cyclic strain.

The aim of this study was to determine whether extracellular signal-regulated kinases 1/2 (ERK1/ERK2) are activated and might play a role in enhanced proliferation and morphological change induced by strain. Bovine aortic endothelial cells (BAEC) were subjected to an average of 6 or 10% strain at a rate of 60 cycles/min for up to 4 h. Cyclic strain caused strain- and time-dependent phosphorylation and activation of ERK1/ERK2. Peak phosphorylation and activation of ERK1/ERK2 induced by 10% strain were at 10 min. A specific ERK1/ERK2 kinase inhibitor, PD-98059, inhibited phosphorylation and activation of ERK1/ERK2 but did not inhibit the increased cell proliferation and cell alignment induced by strain. Treatment of BAEC with 2,5-di-tert-butyl-1, 4-benzohydroquinone, to deplete inositol trisphosphate-sensitive calcium storage, and gadolinium chloride, a Ca2+ channel blocker, did not inhibit the activation of ERK1/ERK2. Strain-induced ERK1/ERK2 activation was partly inhibited by the protein kinase C inhibitor calphostin C and completely inhibited by the tyrosine kinase inhibitor genistein. These data suggest that 1) ERK1/ERK2 are not critically involved in the strain-induced cell proliferation and orientation, 2) strain-dependent activation of ERK1/ERK2 is independent of intracellular and extracellular calcium mobilization, and 3) protein kinase C activation and tyrosine kinase regulate strain-induced activation of ERK1/ERK2.

Animals↗
PubMed1999

Effect of granulocyte/colony-stimulating factor on the onset of the adult respiratory distress syndrome.

To evaluate the effect of granulocyte/colony-stimulating factor (G-CSF) on the onset of the adult respiratory distress syndrome (ARDS), we investigated whether the incidence of ARDS due to pulmonary infection differed between the G-CSF group which received chemotherapy with G-CSF and historical controls without G-CSF. We evaluated 132 patients with hematological malignancy in complete remission without any main organ dysfunction who had been treated between April 1983 and December 1997. We compared the incidence of ARDS due to pulmonary infection between those who received G-CSF and those who did not. There was no remarkable difference in the number of patients, gender, age, or distribution of primary diseases between the two groups. The intensity of chemotherapy was not considered to significantly differ between the two groups, though the chemotherapy regimens administered differed slightly. In the G-CSF group, the duration of neutropenia was significantly shorter and the frequency of documented infection was significantly decreased. We could not find any relationship between ARDS due to pulmonary infection and any anticancer agent or antibiotics. There was no relationship between the kind of G-CSF and the incidence of ARDS due to pulmonary infection (per chemotherapy session; p > 0.10, per case; p > 0.30, chi2 test). The incidence of ARDS due to pulmonary infection per chemotherapy session was 4.21%, and showed a higher tendency in the G-CSF group (p < 0.100, chi2 test). The incidence of ARDS due to pulmonary infection per case was 25.4% and was significantly higher in the G-CSF group (p < 0.025, chi2 test). The incidence of ARDS due to pulmonary infection was higher in the G-CSF group than in the controls, suggesting that G-CSF promotes the development of ARDS due to pulmonary infection.

Adolescent↗
PubMed1999

Effect of magnesium deficiency on autonomic circulatory regulation in conscious rats.

A close relationship between magnesium and cardiovascular function has been reported; however, the effect of magnesium deficiency on autonomic cardiovascular regulation has not been clarified. We investigated the effect of magnesium deficiency on the autonomic regulation of oscillations of the R-R interval, arterial blood pressure (BP), and renal sympathetic nerve activity (RSNA) by using the maximum entropy method in conscious rats. Its effect on baroreflex control of RSNA and heart rate were also investigated with a logistic function curve. Mean BP in magnesium-deficient rats was higher than that in control rats (mean+/-SE, 114.0+/-4.3 versus 101.6+/-3.4 mm Hg; P<0.05), and urinary excretion of catecholamine was increased by 2.4-fold. The fraction of low-frequency oscillation of RSNA was reduced (31.7+/-0.9% versus 36.2+/-1.5%, P<0.05) and the correlation between low-frequency oscillations of BP and RSNA was weakened in magnesium-deficient rats. There was no difference in high-frequency oscillation of the R-R interval, which is related to vagal tone, whereas sympathetic tone became dominant (square root of low-frequency/high-frequency ratio of R-R interval, 1.00+/-0.05 versus 0.67+/-0.05, P<0.0001) in magnesium-deficient rats. The maximal gain in the BP-RSNA relation tended to be reduced in magnesium-deficient rats (-7.7+/-1.1% versus -12.2+/-1.9%/mm Hg, P=0. 07); however, that in the BP-heart rate relation was increased (-8. 1+/-0.7 versus -4.5+/-0.5 bpm/mm Hg, P<0.01). These results suggest that magnesium deficiency induces sympathetic excitation, which results in hypertension but attenuates the baroreflex-related response of sympathetic nerves, whereas magnesium deficiency enhances the sensitivity of the sinus node to autonomic regulation.

Animals↗
PubMed1999

Amygdalar volume and emotional memory in Alzheimer's disease.

OBJECTIVE: Everyday experience suggests that highly emotional events are often the most memorable. Experimental work in animals and humans has demonstrated that the amygdaloid complex plays a crucial role in emotional memory, i.e., memory of events arousing strong emotions. The aim of this study was to elucidate the relationship between medial temporal damage and impaired memory of real-life emotional events in patients with Alzheimer's disease. METHOD: In 36 patients with probable Alzheimer's disease who experienced the 1995 earthquake in Kobe, Japan, memories of events surrounding the earthquake were examined as an index of emotional memory with the use of a semistructured interview, and amygdalar and hippocampal volumes were quantified by magnetic resonance imaging. The effects of the atrophy of these structures on recall performance were determined by multiple regression analysis. RESULTS: Irrespective of generalized brain atrophy and cognitive impairments, emotional memory was correlated more with normalized amygdalar volume (right and left averaged) than with normalized hippocampal volume. General knowledge of the earthquake was correlated with neither amygdalar nor hippocampal volume. CONCLUSIONS: The results indicate that impairment of emotional event memory in patients with Alzheimer's disease is related to intensity of amygdalar damage and provide evidence of the amygdala's involvement in emotional memory in humans.

Aged↗
PubMed1999

The 20-kilodalton (kDa) human growth hormone (hGH) differs from the 22-kDa hGH in the effect on the human prolactin receptor.

Previously we have demonstrated that 20-kDa human GH (20K-hGH) is a full agonist for hGH receptor (hGHR) even though its complex formation with hGHR and hGH-binding protein differs from that of 22-kDa human GH (22K-hGH). In this study, we focused on the effect of 20K-hGH on human PRL receptor (hPRLR). To elucidate the effects of 20K-hGH on hPRLR and compare them with those of 22K-hGH, we prepared two cells stably expressing full-length hPRLR, Ba/F3-hPRLR and CHO-hPRLR. In the proliferation of Ba/F3-hPRLR cells, which can grow in a dose-response to lactogenic hormones, both 20K- and 22K-hGH exhibited bell-shaped curves in the absence of exogenous zinc ion (Zn2+); however, the curve of 20K-hGH was shifted to a 10-fold higher concentration than that of 22K-hGH in view of EC50 value (the EC50 of 20K- and 22K-hGH were 15 nM and 1.5 nM, respectively). Addition of Zn2+ up to 25 microM increased the activities of both 20K- and 22K-hGH; however, the enhancement by Zn2+ was greater in 20K-hGH than in 22K-hGH, thereby the activities of both hGH isoforms reached the same level at 25 microM Zn2+. Nevertheless, in the presence of 0.25-1 microM free Zn2+, which is equal in human serum, the activity of 20K-hGH was still lower than that of 22K-hGH. The modest effect of 20K-hGH on activating hPRLR in the absence of Zn2+ was confirmed in the rat serine protease inhibitor 2.1 (Spi2.1) gene promoter activation and JAK2/Stat5 tyrosine phosphorylation in CHO-hPRLR. In addition, in human breast cancer cell T-47D, 20K-hGH was proved to stimulate Stat5 tyrosine phosphorylation to much lower degree than 22K-hGH via not hGHR but hPRLR. Taken together, our data suggest that 20K-hGH may be a weaker agonist for hPRLR than 22K-hGH in the human body; therefore 20K-hGH may alleviate the hPRLR-mediated side-effects such as breast cancer when administered to human body.

Animals↗
PubMed1999

A formal total synthesis of (-)-cephalotaxine.

A formal total synthesis of (-)-cephalotaxine (1) has been achieved. The key step is an intramolecular aldol condensation of the diketone 9, which in turn was obtained in three steps from the azabicyclic compound 6 derived from D-proline according to Seebach's procedure. Treatment of 9 with a catalytic amount of sodium 2-methyl-2-butanolate in benzene at room temperature gave the alpha, beta-unsaturated ketone 8 in 43% yield. Catalytic hydrogenation of 8 followed by reduction of the ketone 22 with sodium borohydride and acetylation of the resulting alcohol 23 gave the acetoxy derivative 24, which, after deprotection, was acylated with (methylthio)acetic acid to give the amide 26. Compound 26 was converted into optically active ketolactam 4 following the synthetic operations developed for the synthesis of the racemic compound.

Acetylation↗
PubMed1999

Characterization of a palytoxin-induced non-selective cation channel in mouse megakaryocytes.

We used the whole-cell clamp and fura-2 techniques to study the membrane current and intracellular Ca2+ concentration ([Ca2+]i) changes of mouse megakaryocytes in response to palytoxin (PTX), a highly potent marine toxin. At a holding potential of -60 mV, PTX induced a sustained inward current in a dose-dependent manner. The reversal potentials measured in the presence of various extracellular major cations indicated that the PTX-induced channel had a non-selective permeability to alkali metal ions. Although elimination of intracellular Ca2+ had no effect on the PTX-induced current, removal of external Ca2+ inhibited the current activation. During the sustained phase of the PTX-induced current, treatment with ADP activated an additional current. Pretreatment with ouabain, an inhibitor of Na+-K+-ATPase, suppressed the PTX-induced current. During the stable phase of the PTX-induced current, challenge with NiCl2 (5 mM) or 2,4-dichlorobenzamil (DCB, 25 microM), a non-selective cation channel blocker, partially reversed the current. Simultaneous measurement of the membrane current and [Ca2+]i showed that PTX induced the current response without increasing the [Ca2+]i. Taken together, these results indicate that PTX induces a non-selective cation channel in mouse megakaryocytes. This channel is distinct from the ADP-operated channel and is sensitive to ouabain, NiCl2 and DCB.

Acrylamides↗
PubMed1999

Evaluation of a PC-based teleconferencing system for reading chest radiographs.

Chest radiographs from 50 patients, including 25 with lung cancer, were digitized at a resolution of 100 dots/inch (40 dots/cm) and saved in JPEG format at a low compression ratio. The average size of the stored images was 55 kByte (range 6-86 kByte). Four respiratory specialists observed these images on the cathode ray tube (CRT) display of a PC-based teleconferencing system with a resolution of 800 x 600 pixels. One month later they observed the original chest radiographs. A receiver operating characteristic (ROC) analysis was performed on their diagnoses, based on a five-point confidence scale about the presence of lung cancer. The observer-specific Az values for the teleconferencing system ranged from 0.801 to 0.944, and the corresponding Az values for the conventional radiographs from 0.926 to 0.957. No significant differences were found between the teleconferencing images and the original images, which suggests that a PC-based teleconferencing system could be useful in the diagnosis of lung cancer on chest radiographs.

Evaluation Studies as Topic↗
PubMed1999

Serum amyloid A, cytokines, and corticosterone responses in germfree and conventional mice after lipopolysaccharide injection.

To determine why germfree mice are less susceptible to lipopolysaccharide (LPS) than conventional mice, we studied serum levels of serum amyloid A (SAA), tumor necrosis factor (TNF), interleukin 1 (IL-1), IL-6, and corticosterone in mice after treatment with LPS. A single injection of LPS caused an elevation of SAA, an acute-phase protein in the mouse, in both conventional and germfree IQI mice, and the response was significantly less in germfree mice. LPS-induced elevations of serum TNF, IL-1, and IL-6 levels were also significantly less in germfree mice, while serum corticosterone levels were greater in germfree mice than in conventional mice. These results suggest that the lower susceptibility to LPS and a smaller response of SAA elevation by LPS in germfree mice may result from less elevation in serum of these cytokines in these mice, which are known to mediate the acute phase response of SAA. High levels of serum corticosterone in germfree mice may be partly responsible for the lower responsiveness of these inflammatory cytokines to LPS in these mice.

Animals↗
PubMed1999

Molecular analysis of the Corynebacterium glutamicum transketolase gene.

Transketolase is important in production of the aromatic amino acids in Corynebacterium glutamicum. The complete nucleotide sequence of the C. glutamicum transketolase gene has been identified. The DNA-derived protein sequence is highly similar to the transketolase of Mycobacterium tuberculosis, taxonomically related to C. glutamicum. The alignment of the N-terminus regions between both transketolases showed TTG to be the most probable start codon. Potential ribosomal binding and promoter regions were situated upstream from the TTG. The deduced amino acid sequence consists of 700 residues with a calculated molecular mass of 75 kDa, and contains all amino acid residues involved in cofactor and substrate binding in the well-characterized yeast transketolase sequence.

Amino Acid Sequence↗
PubMed1999

Detection of an autoantibody from Pug dogs with necrotizing encephalitis (Pug dog encephalitis).

An autoantibody against canine brain tissue was detected in the cerebrospinal fluid (CSF) and serum of two Pug dogs (Nos. 1 and 2) by indirect immunofluorescence assay (IFA). Dog No. 1, a 2-year-old male, exhibited severe depression, ataxia, and generalized seizures and died 2 months after the onset of symptoms. Dog No. 2, a 9-month-old male, exhibited severe generalized seizures and died 17 months after the onset of symptoms. Histopathologic examination revealed a moderate to severe multifocal accumulation of lymphocytes, plasma cells, and a few neutrophils in both the gray and white matter of the cerebrum in dog No. 1. In dog No. 2, the cellular infiltrates were mild, but there was a severe, diffuse, and multifocal necrosis in the cerebral cortex with prominent astrocytosis. With the aid of IFA using fluorescein isothiocyanate-labeled antidog IgG goat serum and a confocal imaging system, specific reactions for glial cells were detected in the CSF of these Pug dogs but not in six canine control CSF samples. Double-labeling IFA using CSF from these Pug dogs and a rabbit antiserum against glial fibrillary acidic protein (GFAP) revealed that the autoantibody recognized GFAP-positive astrocytes and their cytoplasmic projections. By immunoblot analysis, the autoantibody from CSF of these Pug dogs recognized two common positive bands at 58 and 54 kd, which corresponded to the molecular mass of human GFAP. The role of this autoantibody for astrocytes is not yet clear. However, if the presence of the autoantibody is a specific feature of Pug dog encephalitis, it will be a useful clinical diagnostic marker and a key to the pathogenesis of this unique canine neurologic disease.

Animals↗
PubMed1999

Insulin resistance contributes to carotid arterial wall thickness in patients with non-insulin-dependent-diabetes mellitus.

The aim of this study was to clarify whether insulin resistance contributes to atherosclerosis in patients with non-insulin-dependent diabetes mellitus (NIDDM). Fifty-three NIDDM patients (36 males and 17 females, 53+/-10 years old (mean+/-SD)) were studied. As an index of atherosclerosis, we measured the average thickness (IMT) as well as basal thickness excluding the maximum thickness and the height of the maximum thickness of the carotid artery wall. Euglycemic hyperinsulinemic glucose clamp was conducted for 90 min to evaluate average glucose infusion rate (GIR) as an index of insulin sensitivity in the peripheral tissues. For another 180 min after intake of oral glucose load with 0.3 g/kg, the euglycemic hyperinsulinemic clamp was continued to measure ratio of splanchnic glucose uptake (SGU) as an index of insulin sensitivity of the liver. The patients were separated into three activity groups according to the grade of their leisure-time physical activity. GIR (r = -0.32, p < 0.05) but not SGU (r=0.139) showed a significant inverse relationship with IMT. Multivariant regression analysis indicated that age and total cholesterol remain as independent risk factors for basal thickness and GIR as only independent risk factor for the height of the maximum thickness. Paralleling the degrees of habitual exercise (low, moderate, and high active group), GIR was higher (6.19+/-1.02, 6.38+/-1.38, 7.44+/-1.80, respectively) and IMT was lower (1.34+/-0.33 mm, 1.20+/-0.31 mm, and 1.12+/-0.29 mm, respectively) in male NIDDM as well as in female NIDDM. These data suggest that insulin resistance in the peripheral tissues but not the splanchnic tissues may independently contribute to carotid arterial wall thickness and especially to plaque lesion, and that habitual exercise might reduce insulin resistance leading to attenuation of atherosclerosis.

Aged↗
PubMed1999

17beta-estradiol induces protein thiol/disulfide oxidoreductases and protects cultured bovine aortic endothelial cells from oxidative stress.

OBJECTIVE: To examine whether or not estrogens induced the expression of protein thiol/disulfide oxidoreductases such as protein disulfide isomerase (PDI), thioredoxin (Trx), Trx reductase, and glutaredoxin (Grx) in vascular endothelial cells. METHODS: The regenerative effects of the protein thiol/disulfide oxidoreductases, PDI, Trx and Grx, on oxidatively damaged proteins were assayed using H2O2-inactivated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a reporter enzyme. The induction of protein thiol/disulfide oxidoreductases and the accumulation of protein adducts generated by lipid peroxidation were examined by Western blotting in estrogen-treated bovine aortic endothelial cells (BAECs). RESULTS: Reduced PDI, Trx and Grx regenerated the H2O2-inactivated GAPDH in vitro. The levels of these protein disulfide oxidoreductases in BAECs were increased by pretreatment with 0.01-10 micromol/l 17beta-estradiol, the largest increase (about fourfold of the control) being found for PDI. Other sex hormones such as progesterone and testosterone did not affect the contents of these oxidoreductases in BAECs. 4-Hydroxy-2-nonenal (HNE)-protein adducts, which are generated by lipid peroxidation, were accumulated in BAECs exposed to paraquat, whereas the pretreatment of BAECs with 17beta-estradiol suppressed their accumulation. CONCLUSIONS: The estrogen-mediated induction of the protein thiol/disulfide oxidoreductases such as PDI, Trx, Trx reductase and Grx suggested a possible involvement of these oxidoreductases in the antioxidant protection of estrogen observed in the vascular system.

Animals↗
PubMed1999

Analysis of binding properties between 20 kDa human growth hormone (hGH) and hGH receptor (hGHR): the binding affinity for hGHR extracellular domain and mode of receptor dimerization.

It has recently been shown that 20 kDa human growth hormone (hGH) forms the 1:2 hGH:hGH receptor (hGHR) complex and expresses full agonistic activity, although it hardly forms the 1:1 GH:GHR complex as compared with 22 kDa hGH. To clarify this mechanism, we analyzed the mode of receptor dimerization of 20 kDa hGH using the intact form and mutants. Complex formation analysis between hGHR extracellular domain (hGHBP) and either site1 mutant (K157A) or site2 mutant (G105R) by gel-filtration showed that the site1 mutant apparently formed no 1:1 complex and that the site2 mutant formed only the 1:1 complex. Cell proliferation analysis revealed that the activity curve (vs ligand concentration) of 20 kDa hGH showed a bell-shaped pattern. This indicates that the receptor dimerization of 20 kDa hGH proceeds in a sequential manner. Based on this sequential binding we have produced a mathematical model for receptor dimerization as a function of [hGH], [hGHBP], K(d) values for the first hGHBP binding (K(d1)) and the second hGHBP binding (K(d2)). The result of 20 kDa hGH binding to (S201C) hGHBP immobilized on biosensor tip showed that the K(d1) value was 1. 6x10(-8) M. Adopting this value as a constant in the function described above, we have obtained calculative hGHR dimerization curves vs hGH concentration. Since the K(d2) value could not be experimentally determined, the curves were simulatively obtained with varied K(d2) values. The simulated curve pattern coincided with the experimental result of the cell proliferation in Ba/F3-hGHR when the value 2.5x10(-10) M was adopted as K(d2). In conclusion, although the affinity of 20 kDa hGH for the first hGHR binding is reduced to one-tenth, that for the second binding is increased ten-fold in comparison with those of 22 kDa hGH, indicating that 20 kDa hGH can be an effective hGH isoform in the presence of hGHBP.

Alternative Splicing↗
PubMed1999

Changes in c-Fos expression induced by noxious stimulation in the trigeminal spinal nucleus caudalis and C1 spinal neurons of rats after hyperbaric exposure.

The present study aims to test the hypothesis that hyperbaric exposure inhibits nociceptive processing in the trigeminal spinal nucleus caudalis and C1 spinal neurons. We investigated the c-Fos-like immunoreactivity of the brainstem and upper cervical spinal cord (C1 region) following an injection of mustard oil (15 microliters of 20%) into the nasal mucosa of pentobarbital anesthetized rats after exposure to hyperbaric (2-atmospheres, 1 h) and normobaric pressures. After the hyperbaric exposure, the mean number of Fos-immunoreactive neurons in the ipsilateral laminae I-II and III-IV of the trigeminal spinal nucleus caudalis were significantly lower than those in the normobaric condition. Similarly, the mean number of c-Fos positive neurons in the superficial layer (I-II) of the ipsilateral C1 segment were significantly reduced as compared with that in the normobaric condition. When treated with the vehicle alone, no significant difference was detected in the numbers of c-Fos positive neurons in the trigeminal spinal nucleus caudalis and C1 regions between hyperbaric and normobaric conditions. These results suggest that hyperbaric exposure may attenuate nociceptive signals from the area innervated by the trigeminal nerves at the level of both the trigeminal spinal nucleus caudalis and C1 dorsal horn.

Animals↗
PubMed1999

Foods contributing to absolute intake and variance in intake of fat, fatty acids and cholesterol in middle-aged Japanese.

On the basis of 351 one-day weighed diet records, we selected foods/recipes contributing to nutrients of interest for a data-based food frequency questionnaire by contribution analysis and multiple regression analysis. Total fat was largely of animal and vegetable origin, irrespective of analytic methods. Saturated fatty acid was mostly from animal and vegetable sources according to contribution analysis, and that of animal origin was the main contributor by multiple regression analysis. Mono-unsaturated fatty acid was substantially supplied by animal and vegetable products by either analytic method. Poly-unsaturated fatty acid, n-6 poly-unsaturated fatty acid and linoleic acid were found to be of vegetable origin and chicken egg according to contribution analysis; while vegetable oil and mayonnaise were the major contributors to variance in intake. Arachidonic acid was, however, mostly provided by animal sources including chicken egg and fish, irrespective of analytic methods. N-3 poly-unsaturated fatty acids and alpha-linolenic acid were of vegetable and marine origin. Eicosapentaenoic and docosahexaenoic acids were particularly from marine products, irrespective of analytic methods, except for chicken egg in docosahexaenoic acid by contribution analysis. Cholesterol was of animal and marine origin by either analytic method. Thus, foods contributing to absolute intake and variance in intake of fat, fatty acids and cholesterol differed considerably.

Animals↗