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Biomedical subjects

J Diamond

Publications and source records attributed to J Diamond.

At least 19 recordsLinked to original sources
PubMed1995

NGF-dependent and NGF-independent recovery of sympathetic function after chemical sympathectomy with 6-hydroxydopamine.

To help clarify the distinction between the nerve growth factor (NGF)-dependent collateral sprouting of sympathetic nerves and their NGF-independent regeneration after crush, we used 6-hydroxydopamine (OHDA) to destroy the sympathetic terminals in adult rats; this leaves the axons damage-free. Would recovery occur by regeneration and/or collateral sprouting? A single 6-OHDA injection abolished the sympathetic pilomotor field revealed by electrical stimulation of a cutaneous nerve. Recovery began within 2 days, and by 20 days the field was reestablished. If the field was "isolated" by adjacent denervations at the time of 6-OHDA treatment, the recovering pilomotor field expanded extensively into the surrounding territory. In the presence of anti-NGF, however, the pilomotor field expansion ceased at about 60% of its former size; if anti-NGF treatment was discontinued, expansion recommended and extended into the surrounding skin. We suggest that the latter, NGF-dependent, growth phase corresponds to collateral sprouting, and the initial NGF-independent one to regeneration. After simple nerve crush, however, such regeneration can triple the normal sympathetic field size. This difference between crush- and 6-OHDA-induced regeneration might relate to the "cell body reaction" (CBR); the CBR is reduced with increasing distance of the lesion and is undetectable after a 6-OHDA lesion. Since the CBR and the vigor of regeneration are both increased by repeated axonal injury, we tested the effects of multiple 6-OHDA treatments; this significantly increased the initial NGF-independent expansion. We hypothesize that regeneration is regulated largely by mechanisms associated with the CBR, and that neurotrophin-dependent collateral sprouting occurs independently of these.

Animals↗
PubMed1995

BCR-ABL, ABL-BCR, BCR, and ABL genes are all expressed in individual granulocyte-macrophage colony-forming unit colonies derived from blood of patients with chronic myeloid leukemia.

It has been suggested that the BCR-ABL gene of chronic myeloid leukemia (CML) is not uniformly expressed in Philadelphia (Ph)-positive cells, and that BCR-ABL gene expression precludes transcription of the normal BCR or ABL genes. Therefore, we have analyzed granulocyte-macrophage colony-forming unit (CFU-GM) colonies derived from peripheral blood of 11 CML patients by cytogenetic and by reverse transcriptase-polymerase chain reaction (PCR) amplification of BCR-ABL, ABL-BCR, BCR, and ABL. All CFU-GM colonies with analyzable metaphases were found to contain a Ph chromosome. In 2 patients, the initial PCR screening failed to detect BCR-ABL transcripts in 2 of 11 and 1 of 7 Ph-positive colonies. However, when amplification for BCR-ABL was repeated in quintuplicate, all but 1 colony from a single patient showed one or more positive results. Amplifications of the four genes in each colony showed that BCR-ABL, ABL-BCR, and the normal BCR and ABL were simultaneously expressed in the majority of CFU-GM colonies. Replicate PCR tests for BCR and for ABL in colonies initially scored as negative also uncovered previously undetected positive amplifications. We conclude that BCR-ABL expression does not suppress transcription from the normal BCR and ABL genes, and that Ph-positive, BCR-ABL-negative colonies derived from peripheral blood CFU-GM are rare or nonexistent.

Base Sequence↗
PubMed1995

NGF deprivation of adult rat brain results in cholinergic hypofunction and selective impairments in spatial learning.

Cholinergic hypofunction has often been correlated with a variety of behavioural impairments. In the present study, adult Wistar rats were intraventricularly infused with antibodies to nerve growth factor (anti-NGF) to examine the effects on cholinergic neurons of the basal forebrain, and on behavioural performance. Immunocytochemical techniques indicated that chronically infused anti-NGF penetrates into the basal forebrain, cortex, striatum, corpus callosum and hippocampus, confirming previous findings after a single injection. Treatment with anti-NGF for 1 or 2 weeks resulted in a significant decrease of 27-33% in density of choline acetyltransferase immunostaining of the cholinergic cell bodies in the medial septum and vertical diagonal band, and a 26% reduction in choline acetyltransferase enzyme activity in the septal area. An array of spatial learning Morris water maze tasks was used to distinguish between acquisition skills and the flexible use of learned information in novel tests. Rats subjected to the spatial learning paradigm received anti-NGF infusion for 2 weeks prior to and for another 2 weeks during the behavioural testing. The anti-NGF-treated animals were found to be no different from those receiving control serum in the Morris water maze acquisition task, either in the latency to find the platform or in the time spent searching in the training quadrant when the platform was removed. However, in consecutive extinction trials, anti-NGF rats continued to search in the empty training quadrant, suggesting the occurrence of perseveration; control rats expanded their search over other areas of the pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The effect of epidermal growth factor on mucosal function after ileal resection.

Since epidermal growth factor (EGF) enhances gut mucosal regeneration, the present study was undertaken to evaluate the effect of EGF on brush-border membrane enzyme activity and glutamine uptake in the intestinal remnant following extensive small bowel resection. Twenty-four adult male New Zealand White rabbits were divided into three groups: Group 1 (n = 12) served as controls. Groups 2 and 3 (n = 6 each) underwent a 50-60% mid-jejunoileal resection with anastomosis of the remaining intestine, leaving 90 cm between the pylorus and the ileocecal valve. Group 3 rabbits had a subcutaneous osmotic pump implanted to deliver EGF for 7 days at 0.3 micrograms/kg/hr. Rabbits from Groups 2 and 3 were sacrificed 3 weeks postoperation. Mucosa from the proximal and distal segments of the remaining intestine was analyzed for wet/dry weight, maltase and aminooligopeptidase activity, and glutamine uptake. There was a twofold increase in mucosal dry weight/cm of intestine in rabbits without EGF at 3 weeks (Group 2) and a fourfold increase in those given EGF (Group 3). The maltase enzyme capacity (UEnzyme/rabbit) increased from 37 +/- 10 in controls (Group 1) to 167 +/- 30 without EGF and 207 +/- 30 with EGF. The aminooligopeptidase enzyme capacity (UEnzyme/rabbit) increased from 55 +/- 10 to 147 +/- 20 and 226 +/- 30 in Groups 1, 2, and 3, respectively. Glutamine uptake capacity (microM glutamine/min) also increased significantly, from 63 +/- 19 in Group 1 to 88 +/- 6 without EGF and 162 +/- 18 with EGF (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

In situ expression of platelet-derived growth factor (PDGF-beta) during chronic rejection is abolished by retransplantation.

We have shown that Fischer 344-->Lewis renal allografts (ALLO) develop chronic rejection which is not detected in Lewis-->Lewis isografts (ISO). The progression of chronic rejection in ALLO can be reversed by retransplantation (RE-TX) of kidneys from ALLO back into syngeneic Fischer 344 recipients. The purpose of this study was to assess the in situ expression of PDGF-beta, a cytokine associated with wound injury, in ISO, ALLO, and RE-TX. In situ PDGF-beta mRNA expression in kidney sections was assessed early (8 weeks) and late (16 weeks) during the development of chronic rejection. Kidneys from ALLO were transplanted back into syngeneic Fischer recipients at 12 weeks and evaluated for PDGF-beta expression 12 weeks later. Differences in glomerular staining were graded quantitatively on a minimum of 25 glomeruli per section with grade 0, no positive cells in the glomerulus; grade 1, 1 or 2 positive cells; grade 2, 3 or more positive cells in a segmental distribution; and grade 3, > 4 positive cells of moderate intensity in a diffuse distribution. According to this grading system, glomerular PDGF-beta mRNA expression in isografts (N = 6) at 8 and 16 weeks after transplantation was 0.09 +/- 0.03 and 0.2 +/- 0.04, respectively. In allografts (N = 6), PDGF-beta mRNA was significantly higher (P < .001) for the same time periods, 1.28 +/- 0.6 and 1.89 +/- 0.08, respectively. In situ expression of PDGF in retransplants (N = 6) at 24 weeks, 0.07 +/- 0.02, was significantly diminished (P < .001) at 24 weeks compared to allografts at 8 or 16 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Merkel cells are not the mechanosensory transducers in the touch dome of the rat.

The identity of the mechanosensory transducing elements in the vertebrate touch receptors that contain Merkel cell-neurite complexes is unknown. The Merkel cells, however, have long been the favoured candidates. We have now selectively eliminated the Merkel cells from rat touch domes by first loading them with quinacrine, and then irradiating the domes with near-UV light. Mechanical stimulation of these domes revealed a range of mechanosensory function, evaluated qualitatively, that varied from non-responsive to normal. Since irradiation eliminated the quinacrine fluorescence, the status of the Merkel cells was evaluated by EM. In both responsive and unresponsive domes fixed for EM immediately following irradiation, the Merkel cells and associated nerve endings appeared to be normal. After 2 or more days, even in domes that continued to be normally responsive, there was a striking reduction in the normal complement of about 90 Merkel cells, and most of the remaining Merkel cells appeared to be degenerating. However, numerous 'isolated' (Merkel cell-free) nerve endings remained in the basal epidermis. A few of these nerve endings showed signs of damage, but in the non-responsive domes abnormal nerve endings were routinely observed. The EM studies did not exclude the possibility that a few surviving innervated Merkel cells, or even one such, had escaped detection and were responsible for a persisting mechanosensitivity. To resolve this issue a mechanical stimulating technique with a spatial resolution of 55 microns was used to map the mechanosensory profile of a single responsive dome irradiated 2.75 days earlier. This dome was then serially sectioned for EM study. Only seven Merkel cells had survived which appeared to be both viable and innervated, but almost all of the tested sites were normally responsive. When the correlation was made, seven of these sites were located 55-100 microns away from the nearest surviving Merkel cell, four were 110-165 microns away, and three were more than 165 microns away. Even when allowance is made for errors in the positioning of the stimulus, the responses at the last seven sites cannot be attributed to the presence of underlying Merkel cells. We conclude that mechanosensory transduction within touch domes is not a function of the Merkel cells, but must reside in the associated nerve endings.

Animals↗
PubMed1995

Ontogenetic development of gut function, growth, and metabolism in a wild bird, the Red Jungle Fowl.

We measured the ontogeny of growth rate, food intake, metabolic rates, organ masses, and intestinal nutrient transporter and hydrolase activities in a wild bird for comparison with previous measurements of the same quantities in four domesticated or laboratory animals. Analysis of covariance with body mass as a covariate showed that body mass accounted for most of the age-related variation in all variables, but that age itself still had a significant effect on most variables. Among organs studied, the ceca exhibited the greatest mass increase with age. Energy intake and resting and basal metabolic rates increased with age, but digestive efficiency, cost of growth, and sustained metabolic scope were independent of age. Although intestinal brush-border glucose and proline uptakes and sucrase activity declined with age, the corresponding capacities increased with age because of compensating increases in intestinal mass. Intestinal passive permeability to glucose was undetectably low. Unlike the four domesticated animals studied to date, jungle fowl possess no intestinal reserve capacities (excesses of capacity over dietary nutrient intake). Cecal absorption may contribute significantly to glucose uptake capacity with increasing age.

Animal Nutritional Physiological Phenomena↗
PubMed1995

Adaptive responses to feeding in Burmese pythons: pay before pumping.

Burmese pythons normally consume large meals after long intervals. We measured gut contents, O2 consumption rates, small intestinal brush-border uptake rates of amino acids and glucose, organ masses and blood chemistry in pythons during the 30 days following ingestion of meals equivalent to 25% of their body mass. Within 1-3 days after ingestion, O2 consumption rates, intestinal nutrient uptake rates and uptake capacities peaked at 17, 6-26 and 11-24 times fasting levels, respectively. Small intestinal mass doubled, and other organs also increased in mass. Changes in blood chemistry included a 78% decline in PO2 and a large 'alkaline tide' associated with gastric acid section (i.e. a rise in blood pH and HCO3- concentrations and a fall in Cl- concentration). All of these values returned to fasting levels by the time of defecation at 8-14 days. The response of O2 consumption (referred to as specific dynamic action, SDA) is the largest, and the upregulation of intestinal nutrient transporters the second largest, response reported for any vertebrate upon feeding. The SDA is a large as the factorial rise in O2 consumption measured in mammalian sprinters and is sustained for much longer. The extra energy expended for digestion is equivalent to 32% of the meal's energy yield, with much of it being measured before the prey energy was absorbed.

Adaptation, Physiological↗
PubMed1995

Skeletal muscle mitogen-activated protein kinases and ribosomal S6 kinases. Suppression in chronic diabetic rats and reversal by vanadium.

The mitogen-activated protein (MAP) kinases and ribosomal S6 protein kinases in the skeletal muscle of insulin-resistant long-term (2 and 6 months' duration) diabetic rats were investigated to understand further the changes in insulin intracellular signaling pathways that accompany diabetes. The effects of insulin-mimetic vanadium compounds on the activity of these kinases were also examined. In the insulin-resistant 2-month diabetic rats, the basal activities of MAP kinases were relatively unchanged, while the basal activities of S6 kinases were significantly increased. Intravenous injection of insulin moderately activated both the 42-kDa MAP kinase (p42mapk) and a 44-kDa MAP kinase (p44erk1) in the 2-month control rats but not in the 2-month diabetic rats. Insulin treatment markedly stimulated the activity of a novel 31-kDa S6 kinase and the previously described 90-kDa ribosomal S6 kinase encoded by one of the rsk genes (p90rsk) in the 2-month control rats, while the effect was substantially reduced in the diabetic rats. In the 6-month diabetic rats, the basal phosphotransferase activities of both MAP kinases were depressed threefold or greater. This correlated with reductions in the amount of immunoreactive p42mapk and p44erk1 proteins in extracts from the diabetic rats. The basal activity of the 31-kDa S6 kinase activity was also reduced fourfold in the 6-month diabetic rats. Treatment of the 2-month diabetic rats with vanadyl sulfate resulted in euglycemia, prevented the increase in the basal activity of S6 kinase, and improved the activation of S6 kinase by insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Intraventricular administration of antibodies to nerve growth factor retards kindling and blocks mossy fiber sprouting in adult rats.

Repeated subconvulsive electrical stimulation of certain areas of the forebrain leads to kindling, a progressive and permanent amplification of evoked epileptiform activity, which is a model for human temporal lobe epilepsy. Recent studies have shown that kindling induces synthesis of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) but not neurotrophin-3 (NT-3) in the hippocampus and cortex. Kindling also elicits mossy fiber sprouting and functional synaptogenesis in the supragranular layer, the hilus, and the CA3 region of the hippocampus. Intraventricular administration of antibodies to NGF has been shown to effectively block septohippocampal sprouting in the adult rat, and has been reported to retard amygdaloid kindling. In the present study, we have investigated the possible role of NGF in both kindling and kindling-associated sprouting. We have confirmed a kindling-induced sprouting of the mossy fibers into the stratum oriens of the CA3 region of the hippocampus, utilizing a new semiquantitative method of analysis based on Timm staining. Previous studies found no overt signs of hippocampal damage with this kindling paradigm, indicating that the increased Timm staining likely reflects a purely activity-induced sprouting. Intraventricular infusion of affinity-purified anti-NGF IgGs (which cross-react with NT-3 but not BDNF) resulted in both significant retardation of kindling and inhibition of the kindling-induced mossy fiber sprouting. The findings suggest a role for NGF in both these phenomena.

Animals↗
PubMed1995

Balanced parental contribution to the ABL component of the BCR-ABL gene in chronic myeloid leukemia.

Genomic imprinting has recently been associated with the reciprocal t(9;22) chromosome translocation of chronic myeloid leukaemia (CML). This translocation gives rise to a 22q-, or Philadelphia (Ph), chromosome and a derivative 9q+. Based on heterochromatin polymorphisms, it was reported that the former is of maternal and the latter of paternal origin in every case of CML. This parental bias led to the hypothesis that the genes disrupted by the translocation, BCR and ABL, were themselves imprinted, and that in CML the BCR-ABL gene was formed by BCR sequences of maternal and ABL sequences of paternal origin. We have identified a BstNl restriction fragment length polymorphism in the ABL coding sequence which enabled us to investigate directly the expression and inheritance of the two ABL alleles in heterozygous CML patients. Amplification of the specific BCR-ABL and normal ABL mRNA messages by reverse transcriptase-polymerase chain reaction in these patients showed that the ABL moiety of the BCR-ABL gene has an even chance of being the paternal or the maternal copy. We conclude therefore that there is no parental bias in the origin of the translocated ABL gene and no evidence for genomic imprinting of ABL in CML.

Alleles↗
PubMed1993

Pertussis immunisation and serious acute neurological illnesses in children.

OBJECTIVE: To determine long term outcome in children who had a severe acute neurological illness in early childhood associated with pertussis immunisation. DESIGN: Follow up study of cases and matched controls. SETTING: Assessment of children at home and at school throughout Britain. SUBJECTS: Children recruited into the national childhood encephalopathy study in 1976-9 were followed up, with one of their two original matched controls, in 1986-9. MAIN OUTCOME MEASURES: Performance in educational attainment tests; behaviour problems reported by teachers and parents; continuing convulsions; evidence of other neurological or physical dysfunction. RESULTS: Over 80% of cases and controls were traced. Case children were significantly more likely than controls to have died or to have some form of educational, behavioural, neurological, or physical dysfunction a decade after their illness. The prevalence of one or more of these adverse outcomes in case children who had been immunised with diphtheria, tetanus, and pertussis vaccine within seven days before onset of their original illness was similar to that in case children who had not been immunised recently. The relative risk for recent diphtheria, tetanus, and pertussis immunisation in children who had died or had any dysfunction in comparison with controls was 5.5 (95% confidence interval 1.6 to 23.7). However, the number of cases associated with vaccine (12) was extremely small and statistically vulnerable, and other possible agents or predisposing factors could not be excluded. CONCLUSIONS: Diphtheria, tetanus, and pertussis vaccine may on rare occasions be associated with the development of severe acute neurological illnesses that can have serious sequelae. Some cases may occur by chance or have other causes. The role of pertussis vaccine as a prime or concomitant factor in the aetiology of these illnesses cannot be determined in any individual case. The balance of possible risk against known benefits from pertussis immunisation supports continued use of the vaccine.

Acute Disease↗
PubMed1992

Sympathetic nerves in adult rats regenerate normally and restore pilomotor function during an anti-NGF treatment that prevents their collateral sprouting.

We have used anti-nerve growth factor (anti-NGF) [corrected] administration to study the NGF dependency of the reinnervation of denervated skin by sympathetic nerves in the adult rat. Sympathetic pilomotor fields were revealed by electrical stimulation of selected dorsal cutaneous nerves; the affected skin rapidly assumed a "gooseflesh" appearance, sharply demarcated from surrounding unstimulated skin. Examined 2-5 days after section of neighboring nerves, the "isolated" pilomotor field of the spared nerve was found to be coextensive with an area of amine-fluorescent fibers that were associated with pilomotor muscles and blood vessels. After its isolation, a pilomotor field begins to expand into the surrounding deprived territory, reaching a maximum size at approximately 40 days. Fluorescence studies confirmed that new sympathetic fiber growth had occurred into the expanded regions of such fields. Daily injections of polyclonal anti-NGF serum completely prevented these pilomotor field expansions. Following termination of the anti-NGF treatment, expansion proceeded normally. Finally, if the onset of anti-NGF treatment was delayed until pilomotor field expansion had already commenced, further expansion was halted. Regeneration of sympathetic fibers was evoked by crushing a selected nerve. Recovery of pilomotor function in the totally denervated skin was first detected at about 20 days postcrush, and the field progressively enlarged over the next 40 days. Although the imposed NGF deprivation is known to cause a demonstrable shrinkage, and presumably atrophy, of sympathetic ganglia, the anti-NGF treatment appeared to impair neither the restoration of a pilomotor field after nerve crush, nor its continued expansion into skin regions well beyond that originally supplied by the nerve, i.e., into territory whose invasion by collateral sprouts would have been totally prevented by the treatment. During such NGF deprivation, fluorescent regenerating fibers were visualized in the nerve trunk. We conclude that even though the regenerating and collaterally sprouting sympathetic fibers probably utilise the same degenerating dermal pathways to reach and functionally reinnervate the same denervated targets, only the collateral sprouting of the uninjured axons is dependent upon endogenous NGF. These findings extend the results described earlier for nociceptive fibers, and suggest that the contrasting dependencies upon growth factors of sprouting and regeneration might apply throughout the adult nervous system.

Animals↗
PubMed1992

Antibody to NGF inhibits collateral sprouting of septohippocampal fibers following entorhinal cortex lesion in adult rats.

We have used an antiserum raised against mouse 2.5S NGF to examine the involvement of endogenous neurotrophins in the collateral sprouting of septohippocampal fibers in the adult rat brain. The antiserum was administered intraventricularly. Immunocytochemical techniques indicated that the injected antibodies penetrated into brain tissue that included the basal forebrain, cortex, striatum, corpus callosum, and hippocampus. Unilateral lesioning of the entorhinal cortex was done to evoke the sprouting of the cholinergic septohippocampal fibers. At 8 days postlesion, the sprouting was much advanced, as evidenced by an increase in density of the acetylcholinesterase (AChE) staining in the outer molecular layer (OML) of the dentate gyrus and by the associated increase in the absolute number of AChE-positive fibers in the OML. As well, there was a widening of the inner molecular layer (IML), interpreted as being due to sprouting of noncholinergic axons in that region. In rats injected daily with anti-NGF or anti-NGF Fab fragments, no increase in AChE density, or in the population of AChE-positive fibers, was observed in the OML. In contrast, the widening of the IML seemed to be unaffected by the anti-NGF treatment. No changes were observed in the AChE related parameters in the dentate gyrus of nonlesioned animals treated similarly for 8 days with anti-NGF; there was, however, a decrease of choline acetyltransferase (ChAT) immunostaining in the ChAT-positive cells of the basal forebrain. Our findings and the confirmation that our polyclonal anti-NGF also recognizes other members of the NGF neurotrophin family, specifically brain-derived neurotrophic factor and neurotrophin-3, indicate that at least one of these neurotrophins plays a key role in the collateral sprouting of the cholinergic septohippocampal fibers (but not that presumed to occur within the IML) following an entorhinal cortex lesion.

Acetylcholinesterase↗
PubMed1992

Translocation of protein kinase C in bovine tracheal smooth muscle strips: the effect of methacholine and isoprenaline.

Investigations into the mechanisms involved in the contraction of smooth muscle have suggested that the generation of diacylglycerol and the activation of protein kinase C (PKC) may be important in the generation or maintenance of smooth muscle tone. The present study examined the possible role of PKC in the contraction of bovine tracheal smooth muscle. Methacholine (10 microM) induced a rapid elevation in PKC activity associated with the membrane fraction. PKC levels were significantly elevated in the membrane fraction 30 s after agonist addition, reached a maximum at 1 min and then declined to and remained at a lower level which was still elevated above basal. A concomitant decrease in cytosolic PKC activity of smaller magnitude was observed during this period of stimulation. This methacholine-induced re-distribution of PKC from the cytosol to the membrane was concentration-dependent and was blocked by atropine. Pre-treatment of tissues for 2 min with 100 microM isoprenaline prevented both the re-distribution of PKC and the contraction produced by 1 microM methacholine. Addition of 1 microM isoprenaline to tissues pre-contracted with 1 microM methacholine reversed the re-distribution of PKC produced during contraction and completely relaxed the tissues. Thus, under these conditions, translocation of PKC from the cytosol to the membrane seems to be well correlated with contractions of bovine tracheal smooth muscle. Whether the PKC translocation is responsible for the observed changes in muscle tone or whether the enzyme translocation is a result of drug-induced changes in [Ca2+]i, remains to be determined.

Analysis of Variance↗
PubMed1992

The matches, achieved by natural selection, between biological capacities and their natural loads.

Natural selection tends to eliminate unutilized capacities because of their costs. Hence we ask how large are the reserve capacities by which biological capacities exceed natural loads, and how closely are related biological capacities matched to each other. Measured capacities (Vmax values) of small intestinal brush-border nutrient transporters are typically around twice their natural loads (dietary intakes of their substrates); the ratio is higher for a transporter of a hyperessential nutrient. Preliminary evidence suggests matching of capacities between different steps in carbohydrate metabolism, and between the intestine, liver, kidneys, and spleen. Symmorphosis - the postulated matching of capacities to each other and to loads - is a testable hypothesis of economic design, useful in detecting and explaining cases of apparently uneconomic design.

Animals↗