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M C Moore

Publications and source records attributed to M C Moore.

At least 55 records · Page 3Linked to original sources

Comparison of the time courses of insulin and the portal signal on hepatic glucose and glycogen metabolism in the conscious dog.

To investigate the temporal response of the liver to insulin and portal glucose delivery, somatostatin was infused into four groups of 42-h-fasted, conscious dogs (n = 6/group), basal insulin and glucagon were replaced intraportally, and hyperglycemia was created via a peripheral glucose infusion for 90 min (period 1). This was followed by a 240-min experimental period (period 2) in which hyperglycemia was matched to period 1 and either no changes were made (CON), a fourfold rise in insulin was created (INS), a portion of the glucose (22.4 mumol.kg-1.min-1) was infused via the portal vein (Po), or a fourfold rise in insulin was created in combination with portal glucose infusion (INSPo). Arterial insulin levels were similar in all groups during period 1 (approximately 45 pM) and were 45 +/- 9, 154 +/- 20, 43 +/- 7, and 128 +/- 14 pM during period 2 in CON, INS, Po, and INSPo, respectively. The hepatic glucose load was similar between periods and among groups (approximately 278 mumol.kg-1.min-1). Net hepatic glucose output was similar among groups during period 1 (approximately 0.1 mumol.kg-1.min-1) and did not change significantly in CON during period 2. In INS net hepatic glucose uptake (NHGU; mumol.kg-1.min-1) was -3.8 +/- 3.3 at 15 min of period 2 and did not reach a maximum (-15.9 +/- 6.6) until 90 min. In contrast, NHGU reached a maximum of -13.0 +/- 3.7 in Po after only 15 min of period 2. In INSPo, NHGU reached a maximum (-23.6 +/- 3.5) at 60 min. Liver glycogen accumulation during period 2 was 21 +/- 10, 84 +/- 17, 65 +/- 16, and 134 +/- 17 mumol/gram in CON, INS, Po, and INSPo, respectively. The increment (period 1 to period 2) in the active form of liver glycogen synthase was 0.7 +/- 0.4, 6.5 +/- 1.2, 2.8 +/- 1.0, and 8.5 +/- 1.3% in CON, INS, Po, and INSPo, respectively. Thus, in contrast to insulin, the portal signal rapidly activates NHGU. In addition, the portal signal independent of a rise in insulin, can cause glycogen accumulation in the liver.

Animals↗

A critical period for the organization of alternative male phenotypes of tree lizards by exogenous testosterone?

Male tree lizards (Urosaurus ornatus) exhibit permanent adult differences in color and size that are functionally linked with behavioral differences: males with a central blue throat patch are territorial, more aggressive, and smaller than males lacking the patch, who are nomads or satellites foregoing territory defense. Gonadectomy or long-lasting hormone implants in hatchlings affect the development of these permanent adult differences, but similar manipulations in adults are ineffective. Analogous early hormone actions in vertebrate sexual differentiation typically must occur during a critical period. Whether there is a critical period for early hormone actions affecting development of male types in tree lizards is unclear. We followed a protocol identical to our previous experiments on hatchlings, but we manipulated testosterone (T) in later-aged juveniles to determine if they remained sensitive to such hormone manipulations. Testosterone implants given at 60 days posthatching (day 60) did not alter adult throat color, indicating that sensitivity of throat color to T declines by day 60. This contrasts to our earlier work where adult color was affected by T manipulations on day 30. However, size and throat color responded differently to exogenous T, as juveniles given T implants at day 60 grew less than control-implanted males.

Animals↗

Regulation of net hepatic glucose uptake: interaction of neural and pancreatic mechanisms.

Insulin and glucagon levels, the mass of glucose presented to the liver and the portal signal are important regulators of the liver's response to glucose delivery. The portal signal not only serves to direct glucose into the liver but also appears to stimulate its deposition in glycogen. Moreover, the portal signal impacts on tissues other than the liver: intraportal glucose delivery is associated with changes in glucose uptake by nonhepatic tissues and neurally-mediated enhancement of pancreatic insulin secretion. Our current understanding of the neural control of hepatic glucose metabolism includes a tonic block to the entry of glucose into the liver, probably mediated both by sympathetic neural activity and by a low insulin:glucagon ratio. An increase in the portal vein glucose level is detected by sensors in the portal region, which cause a decrease in the firing rate in the hepatic branch of the vagus nerve. The change in the afferent firing rate is processed in the hypothalamus and instigates a change in the efferent firing rate in the hepatic and pancreatic branches of the vagus (with corresponding increases in insulin secretion and net hepatic glucose uptake). The portal signal thus relieves the sympathetic inhibition of hepatic glucose uptake and enhances hepatic glucose uptake directly by stimulating the parasympathetic innervation to the liver and indirectly by enhancing insulin release.

Blood Glucose↗

Neural and pancreatic influences on net hepatic glucose uptake and glycogen synthesis.

The role of the liver nerves in the disposition of peripherally administered glucose was examined in seven hepatic innervated (HI) and nine hepatic denervated (HD) 42-h-fasted conscious dogs. After a 40-min basal period, there was a 4-h experimental period during which the hepatic glucose load was increased twofold via peripheral glucose infusion. Somatostatin was infused to suppress pancreatic endocrine secretion, and insulin and glucagon were infused intraportally to produce a fourfold increase in insulin and a gradual decrease (approximately 25%) in glucagon. The area under the curve of net hepatic glucose uptake (NHGU) during the glucose infusion period totaled 483 +/- 82 and 335 +/- 32 mg/kg in HD and HI, respectively (P < 0.05). The area under the curve of the hepatic fractional extraction of glucose was 27% greater in HD (P < 0.05). Net hepatic lactate output was similar in the two groups, and net hepatic glycogen synthesis was 3.8 +/- 0.8 vs. 2.7 +/- 0.5 mg.kg dog wt-1.min-1 in HD and HI, respectively (P = 0.13). The direct pathway of glycogen synthesis was responsible for 54-58% of net hepatic glycogen synthesis in both HI and HD (n = 6 for both). In summary 1) NHGU in response to peripheral glucose infusion was approximately 44% greater in HD than in HI, 2) net hepatic glycogen synthesis was enhanced by 41% in HD although the probability of this change was 0.13, and 3) the contribution of the direct pathway to glycogen synthesis was the same in HD and HI. These data are consistent with a role for the liver nerves in regulating the magnitude of NHGU in response to glucose administration. They also indicate that the absence of liver nerves may reduce glycogen turnover during glucose infusion.

Alanine↗

Influence of androgens on differentiation of secondary sex characters in tree lizards, Urosaurus ornatus.

Vertebrates species vary in the degree to which the sexes differ in their expression of secondary sex characters, which can be expressed in one sex but not the other, fully expressed in both sexes, or expressed to different degrees in the two sexes. Sex steroid hormones contribute to the development of sex differences, either through action early in life (organization), following sexual maturation (activation), or both. However, relatively little is known about the contributions of sex steroid hormones to species-level variation in sexual dimorphism. We began to address this by assessing in tree lizards, Urosaurus ornatus, the effects of testosterone (T) and dihydrotestosterone (DHT) on expression of the male-typical traits: femoral pore secretions, accessory sex tissues, patches of ventrolateral blue, intensity and hue of throat color, and body size. We administered long-lasting hormone implants of these androgens to intact or ovariectomized adult females, intact hatchling females, and intact hatchling males to determine the relative contribution of organizational and activational influences of androgens on sexual differentiation of these traits. Waxy femoral pore secretions and full intensity of the orange background color of the throat fan (dewlap) required only activation and both androgens were equally effective. Both androgens caused hypertrophy of accessory tissues associated with the hemipenes, but only in hatchling males. Full expression of ventrolateral blue patches required organization by DHT. Androgens had complex organizational actions on growth. In the doses used in the experiment, DHT inhibited body-length growth but not mass growth of hatchling males. Only T inhibited the growth (length and mass) of hatchling females. Because earlier work found that castration also reduced the growth of hatchling males, the organizational effects of androgen on growth might be dose-related. Results for hormonal control of dewlap type were complex. In this population dewlap color is solid orange in females, but polymorphic in males with 50% expressing solid orange (O) and 50% orange-blue (orange with a central blue patch, OB). These color morphs represent permanent male alternatives: OB males are territorial and more aggressive than O males who do not defend territories. Results of the hormone manipulations are most consistent with the interpretation that dewlap morph type requires both organization and activation by androgen. T appears to be more important in organizing morph differences, whereas DHT appears to be more important in activating expression of underlying morph differences. Females only expressed male-typical OB dewlaps when given DHT, and only about 50% did so.

Animals↗

Hormonal responses to aggression vary in different types of agonistic encounters in male tree lizards, Urosaurus ornatus.

Hormonal responses to male-male interactions have been detected in some studies of vertebrates but not others. One hypothesis that may partially explain these discrepancies is that differences in the duration of male-male interactions cause different hormonal responses. In social systems based on dominance-subordinance hierarchies interactions often last longer than if exclusive territories are maintained. Tests of the hypothesis that encounter duration explains discrepancies in hormonal responses would be facilitated by a species that shows elements of both types of social systems, such as species in which males practice alternative reproductive tactics. We compared plasma levels of corticosterone and testosterone in males of the territorial morph of the tree lizard (Urosaurus ornatus) subjected either to short (15 min) male-male encounters or to long (7 days) dominance interactions. In the long interactions, dominant males had lower levels of corticosterone than did subordinate males over the first day, but this difference subsequently disappeared. In sharp contrast, winners of short-term encounters had elevated plasma corticosterone levels which peaked the day after the encounter. Thus, males isolated after a short encounter experienced an increase in corticosterone that was apparently inhibited in males who continued interacting with other males. The delayed increase in corticosterone after a short encounter may facilitate metabolic recovery from the encounter, mobilize metabolic substrates useful in subsequent encounters, or may alter subsequent behavior. The response does not appear to be simply recovery from exercise because in a second experiment males exercised for 15 min did not show a similar delayed increase in corticosterone the following day. Testosterone levels were also monitored and did not change in any of these treatments. These results demonstrate that the duration and the outcome of male-male interactions may each independently influence hormone levels.

Adrenal Cortex Hormones↗

Early exposure to androgens affects adult expression of alternative male types in tree lizards.

Males of many species exhibit strongly dimorphic reproductive behavior and morphology associated with alternative reproductive tactics. Little is known about the physiological control of these individual differences. The relative plasticity hypothesis proposes that such within-sex differences arise from either organizational or activational actions of sex steroid hormones depending on whether adults can switch tactics or not. This hypothesis predicts that differences between individuals in a species where adults cannot switch between tactics (are "fixed") should be organized by early actions of hormones. Three experiments explored the possible organizational role of testosterone (T) on the development of male alternatives in the tree lizard (Urosaurus ornatus), which has two fixed male morphs. Orange (O) males have a mostly orange throat fan (dewlap), are nonterritorial nomads, and are larger than orange-blue (OB) males which have an orange dewlap with a central blue patch and are territorial. In the first experiment intact males on the day of hatching were (1) sham-operated and implanted with empty capsules, (2) castrated, or (3) testosterone-implanted. As adults, the castration group had more O males than the control and the T-implanted group had more OB males than the control. Adult body size in castrated and T-implanted groups parallelled naturally occurring morph differences, but both were smaller than controls. A second experiment with a lower dose yielded similar results for dewlap type and growth. In a third experiment, intact males were given an empty capsule or a T-implant at 30 days posthatching. Again, the frequency of OB males in the T-implanted group was significantly greater than that in the empty implant group, indicating that either the critical period extends past Day 30 or there is no well-defined critical period. Together, these results support the hypothesis that the organizational action of T or one of its metabolites contributes to the differentiation of these within-sex differences.

Age Factors↗

A study of anti-hepatitis C positive blood donors: the first year of screening.

In the U.K., blood donations have been routinely screened for anti-HCV since September 1991. In order to get the most epidemiological benefit from these extensive screening data, the histories obtained at counselling from donors confirmed to be anti-HCV positive, 'indeterminate' and falsely positive have been analysed in detail. In addition, the associations with potential risk factors have been investigated by comparing these groups of donors with a control group of 771 routine donors bled on one day during the study, at North London Blood Transfusion Centre. This paper documents the prevalence and demography of HCV infection in asymptomatic blood donors, to assess various possible sources of infection and the association between liver function test results and alcohol consumption in donors. One in 1400 previously untested donors was confirmed positive for anti-HCV. Age (the group 30-49 years being highest), tattooing and intravenous drug use in both sexes, ear-piercing in males and blood transfusion in females were all significantly associated with an increased risk of HCV infection. Intravenous drug use proved to be the factor most strongly associated with risk. Liver function tests (alanine aminotransferase) were elevated in a significant number of donors confirmed to be anti-HCV positive but no clear correlation between alanine aminotransferase level and either time since infection or alcohol consumption was found. Alcohol consumption was significantly higher in donors confirmed to be anti-HCV positive and was particularly marked in those admitting to previous intravenous drug use.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Disposition of a mixed meal by the conscious dog.

The disposition of a mixed meal administered intragastrically was examined in 13 24-h-fasted conscious dogs, using the arteriovenous (AV) difference technique (and isotopic methods in 6 dogs). Postprandial net gut output totaled (in g of glucose equivalents) 42 +/- 6 glucose, 3 +/- 0.3 lactate, 2 +/- 0.2 alanine, and 0.2 +/- 0.0 glycerol. The gut oxidized 2 +/- 1 g of glucose, and 0.2 +/- 0.1 g remained within the intestinal lumen. Of the administered glucose 68 +/- 6% were accounted for, and volatile fatty acid production by the gut (n = 1) accounted for at least an additional 4%. Of the labeled glucose in the meal 82 +/- 5% appeared in the systemic circulation, an apparent overestimate of absorption of glucose from the meal. Cumulative net hepatic uptakes (in g of glucose equivalents) were 4.1 +/- 3.1 glucose, 12.1 +/- 2.1 gluconeogenic amino acids, and 1.5 +/- 0.2 glycerol. Net hepatic glycogen synthesis and lactate and CO2 production accounted for 6.2 +/- 4.1, 9.3 +/- 2.8, and 1.6 +/- 0.8 g of glucose equivalents, respectively. In summary, the AV difference method could account for the gut disposition of about two-thirds of the meal glucose. Nonsplanchnic tissues disposed of threefold more glucose than the liver. Net hepatic uptake of glucose equivalents as gluconeogenic amino acids was threefold > glucose uptake, and net hepatic uptake of gluconeogenic amino acids was > net gut release of gluconeogenic amino acids. In conclusion, the net hepatic uptake of glucose and gluconeogenic substrates provided adequate carbon for net hepatic synthesis of glycogen and production of lactate and CO2. In a net sense, peripheral tissues must have been the source of some of the gluconeogenic carbon taken up by the liver after the meal.

Amino Acids↗

Hepatic denervation alters the transition from the fed to the food-deprived state in conscious dogs.

The hepatic nerves can modulate hepatic glycogenolysis and glycogenesis and thus might be expected to be involved in the response of the animal to the transition from the fed to the food-deprived state. Therefore the arterial concentrations and net hepatic balance of glucose and its metabolites, as well as the hepatic glycogen concentrations, were compared in hepatic-innervated and -denervated dogs 18, 24 and 42 h after their usual daily meal. Arterial concentrations of glucose, alanine, lactate and glycerol; net hepatic balances of glucose, alanine and glycerol; and glycogen concentrations were similar in hepatic-innervated and -denervated dogs at each time investigated. Net hepatic balances of lactate (with negative values indicating uptake) in hepatic-innervated and -denervated dogs, respectively, were: 18 h, 4.1 +/- 4.3 vs. -4.3 +/- 3.6 mumol.kg-1 x min-1; 24 h, 4.8 +/- 3.6 vs. -6.7 +/- 1.7 mumol.kg-1 x min-1 (P < 0.05); 42 h, -7.0 +/- 2.0 vs. -6.8 +/- 1.0 mumol.kg-1 x min-1. Based on changes in net hepatic lactate balance, the denervated liver responds more rapidly to food deprivation than the innervated liver, but the metabolic state of the liver appears similar by 42 h after a meal.

Alanine↗

Effect of hepatic nerves on disposition of an intraduodenal glucose load.

We examined the disposition of a continuous 4-h intraduodenal glucose infusion (8 mg.kg-1 x min-1, labeled with [1-13C]glucose and [3-3H]glucose) in nine conscious hepatic-denervated dogs. Cumulative net hepatic uptakes (in grams of glucose equivalents) were 13.7 +/- 2.5 glucose, 3.1 +/- 0.6 gluconeogenic amino acids, and 0.8 +/- 0.1 glycerol. Net hepatic glycogen synthesis totalled 11.0 +/- 0.9 g, 55-62% via the direct pathway. All values were similar to those in hepatic-innervated dogs. Glycogen synthase activity and rate of glycogen synthesis were positively correlated (r2 = 0.913, P < 0.05). Variability in net hepatic glycogen synthesis and the mass of glycogen synthesized via the indirect pathway was reduced in hepatic-denervated dogs (P < 0.05). In conclusion, the glycemic response and rate of net glycogen synthesis during an intraduodenal glucose infusion was no different in hepatic-denervated and -innervated dogs. Net hepatic glucose uptake was sufficient to account for all net hepatic glycogen synthesis and lactate production, consistent with an intrahepatic source of gluconeogenic precursors for glycogen synthesis via the indirect pathway. Hepatic nerves appear responsible for much of the variability in net hepatic glycogen synthesis and in the mass of glycogen synthesized via the indirect pathway in normal dogs.

Amino Acids↗

Regulation of net hepatic substrate balance by phenacylimidazolium ions in the conscious dog.

Phenacylimidazolium ions have the capacity to promote hepatic glycogen synthesis in vitro via activation of glycogen synthase and inactivation of phosphorylase. The purpose of the present study was to determine whether these compounds alter net hepatic substrate balance in vivo. Following a control period somatostatin was infused into 42h-fasted, conscious dogs and insulin (3X-basal) and glucagon (basal) were replaced intraportally. The glucose load to the liver was doubled with a peripheral glucose infusion and the phenacylimidazolium compound, 254236 (EX; n = 5) was infused intraportally at varying rates in four separate periods (0 (P1), 0.5 (P2), 1.0 (P3), 2.0 (P4) mumol kg-1 min-1). In a separate group of animals (C; n = 5) saline was infused intraportally during P1-P4 to match the volume rate of delivery that occurred in EX. In C net hepatic glucose uptake was 8.5 +/- 1.7 mumol kg-1 min-1 during P1 and did not change significantly throughout the study. In EX net hepatic glucose uptake increased (p < 0.05) from 9.0 +/- 2.5 during P1 to 16.2 +/- 3.1 mumol kg-1 min-1 during P4. Whereas net hepatic lactate output was evident throughout P1-P4 in C, the liver consistently switched to net lactate uptake during P3 (1.2 +/- 1.7 mumol kg-1 min-1) and P4 (2.2 +/- 1.0 mumol kg-1 min-1) in EX. Sympathoadrenal activation (increased catecholamines) was evident in EX during period 4. The increased hepatic retention of carbon (glucose and lactate) coincident with 254236 infusion in conscious dogs is less than that observed in vitro but is consistent with a role for phenacylimidazolium ions in promoting hepatic glycogen synthesis.

Animals↗

Seasonal changes of the adrenocortical response to stress in birds of the Sonoran Desert.

Many avian species of the North American Sonoran desert, e.g., the black-throated sparrow, Amphispiza bilineata, cactus wren, Campylorhynchus brunneicapillus, and curve-billed thrasher, Toxostoma curvirostre, can potentially breed from March/April to August. It is possible that, at least in summer, intense heat and aridity may have inhibitory effects on breeding by precipitating a stress response. Stress typically results in a rise in secretion of adrenocorticosteroid hormones that then inhibit reproduction by suppressing release of gonadal hormones. However, we found that plasma levels of corticosterone were not higher during summer, compared with winter, even in 1989 when summer temperatures were higher than normal. In June 1990, temperatures were also above normal and soared to the highest level recorded in Arizona (50 degrees C). Plasma levels of corticosterone during June were high in black-throated sparrows, but less so in two other species (Abert's towhee, Pipilo aberti, and Inca dove, Scardafella inca) found in more shady riparian and suburban habitat with constant access to water. The adrenocortical response to stress (as measured by the rate of corticosterone increase following capture) was reduced in the hottest summer months in black-throated sparrows, cactus wrens, and curve-billed thrashers, but less so in Abert's towhee an Inca dove. These data suggest that at least some birds breeding in the open desert with restricted access to water are able to suppress the classical adrenocortical response to stress. The response is then reactivated in winter after breeding has ceased. It is possible that this stress modulation may allow breeding to continue despite severe heat. Analysis of plasma from these species indicated that the apparent modulation of the adrenocortical response to stress was not an artifact of reduced affinity or capacity of corticosterone binding proteins.

Adrenal Cortex↗

Behavioral and hormonal correlates of alternative reproductive strategies in a polygynous lizard: tests of the relative plasticity and challenge hypotheses.

Species with alternative reproductive tacts are good models to investigate the poorly understood question of whether individual variation within sexes results from the same physiological mechanisms that control variation between sexes. We have shown previously that adult male tree lizards, Urosaurus ornatus, of different throat color morphs express different levels of aggression in the laboratory. Further field results support the suggestion that the two morphs practice alternative reproductive tactics because the two morphs express different levels of aggressive behavior under field conditions and exhibit dramatic and opposite responses to aggressive challenges. However, despite these behavioral differences, the two morphs do not differ in levels of testosterone or corticosterone either in undisturbed situations or following aggressive challenge. These results are consistent with the relative plasticity hypothesis which proposes that organizational, rather than activational, actions of steroid hormones will be more important in morph differentiation when morphs are fixed in adult life, as they are in tree lizards. These results also support the hypothesis that steroid hormonal levels are insensitive to social modulation in males of species such as U. ornatus without paternal care.

Aggression↗

Insulin is required for the liver to respond to intraportal glucose delivery in the conscious dog.

To determine whether insulin is essential for the augmented hepatic glucose uptake observed in the presence of intraportal glucose delivery, SRIF was used to induce acute insulin deficiency in 5 conscious dogs, and glucose was infused into the portal vein or a peripheral vein in two sequential, randomized periods. Insulin and C-peptide levels were below the limits of detection after SRIF infusion, and the load of glucose presented to the liver was approximately doubled and equivalent during the portal and peripheral periods. Net hepatic glucose output was 2.9 +/- 0.9 and 2.1 +/- 1.1 mumol.kg-1.min-1 during portal and peripheral glucose delivery, respectively. In an additional set of protocols, pancreatectomized dogs were used to investigate the effects of prolonged insulin deficiency (n = 5) and acute insulin replacement (n = 4) on the hepatic response to intraportal glucose delivery. In the prolonged insulin deficiency protocol, SRIF was used to lower glucagon and thereby reduce circulating glucose levels, and glucose was infused into the portal or peripheral circulations in two sequential, randomized periods. As with acute insulin deficiency, net hepatic glucose output was still evident and similar (3.6 +/- 1.1 and 4.2 +/- 1.3 mumol.kg-1.min-1) during portal and peripheral glucose delivery, respectively. When the pancreatectomized dogs were restudied using a similar protocol, but one in which insulin was replaced (4X-basal), and the glucose load to the liver was matched to that which occurred in the prolonged insulin deficiency protocol, net hepatic glucose uptake was 23.6 +/- 6.1 mumol.kg-1.min-1 during portal glucose delivery but only 10.3 +/- 3.5 mumol.kg-1.min-1 during peripheral glucose delivery. These results suggest that the induction of net hepatic glucose uptake and the augmented hepatic response to intraportal glucose delivery require the presence of insulin.

Alanine↗

Reciprocal changes in corticosterone and testosterone levels following acute and chronic handling stress in the tree lizard, Urosaurus ornatus.

To examine the reciprocal interactions among gonadal and adrenal steroid secretion, male tree lizards (Urosaurus ornatus) were subjected to two forms of stress. They were subjected either to the acute stress of being held in collecting bags for up to 4 hr or to the chronic stress of being maintained in individual cages in the laboratory for up to 3 weeks. In both cases, levels in stressed animals were compared to levels in free-living animals as controls. Under both conditions plasma levels of corticosterone increased and plasma levels of testosterone decreased compared to free-living controls. The response to the acute stress was much greater for both hormones than to the chronic stress, although in both cases testosterone levels changed less in response to stress than corticosterone levels. The corticosterone response to acute stress was extremely rapid with levels increasing over six-fold in the first 10 min. Plasma levels of corticosterone and testosterone were negatively correlated among individuals in the chronic stress experiment, but not in the acute stress experiment. This correlational evidence is consistent with the hypothesis of a direct effect of corticosterone levels on testosterone levels and suggests that these may only be expressed under some conditions.

Animals↗