Unlocking ground-based imagery for habitat mapping.

Fine-grained environmental data across large extents are needed to resolve the processes that impact species communities from local to global scales. Ground-based images (GBIs) have the potential to capture habitat complexity at biologically relevant spatial and temporal resolutions. Moving beyond existing applications of GBIs for species identification and monitoring ecological change from repeat photography, we describe promising approaches to habitat mapping, leveraging multimodal data and computer vision. We illustrate empirically how GBIs can be applied to predict distributions of species at fine scales along Street View routes, or to automatically classify and quantify habitat features. Further, we outline future research avenues using GBIs that can bring a leap forward in analyses for ecology and conservation with this underused resource.

Thermoregulation: effects of environmental temperature on turnover of hypothalamic norepinephrine.

The hypothesis that norepinephrine is a transmitter in the temperature regulating center of the hypothalamus is based on observations of changes in the rectal temperatures of animals after injections of norepinephrine into the hypothalamus. By introducing tritiated norepinephrine as a label into the endogenous norepinephrine stores in the brain and then measuring the disappearance of tritiated norepinephrine from discrete areas, one can monitor the activity of norepinephrine-containing neurons in those areas. In the rat exposed to heat, the turnover of endogenous norepinephrine appears to be increased selectively in the hypothalamus, whereas exposure to cold has no effect.

Cholera toxin induces pineal enzymes in culture.

Addition of choleragen to rat pineal organ cultures caused a long-lasting stimulation of adenylate cyclase activity, and this was followed by increases in seroton N-acetyltransferase and cyclic adenosine monophosphate phosphodiesterase activities. These effects of choleragen were not blocked by the beta-adrenoceptor antagonist propranolol, but the increases in cyclic adenosine monophosphate phosphodiesterase and serotonin N-acetyltransferase activities could be prevented by the protein synthesis inhibitor cycloheximide. The results indicate that cholera toxin can mimic the induction of pineal enzymes that normally follows beta-adrenoceptor activation and suggest that increased cyclic adenosine monophosphate is a necessary and sufficient signal for such changes in enzyme activity.

Selective extraction of small and large molecules from the cerebrospinal fluid by Purkinje neurons.

Cerebellar Purkinje neurons accumulated propidium iodide, granular blue, and horseradish peroxidase conjugated to wheat germ agglutinin but not unconjugated horseradish peroxidase, bisbenzimide, or Evans blue when these compounds were infused into the lateral cerebral ventricles of awake, unrestrained rats. Accumulation of propidium iodide by Purkinje neurons of the vermis was associated with a reproducible behavioral abnormality characterized by truncal tremor, ataxia, and nystagmus. Both the accumulation of propidium iodide in Purkinje cells and the behavioral abnormality were prevented by prior intracerebroventricular administration of ouabain or colchicine, drugs that block neuronal transport processes. The ability of cerebellar Purkinje neurons to extract small and large molecules from the cerebrospinal fluid has important implications for their physiology and pathology.

Substance P analog, DiMe-C7: evidence for stability in rat brain and prolonged central actions.

A metabolically protected analog of substance P, [pGlu5-MePhe8-MeGly9]SP(5-11) (DiMe-C7), was approximately equipotent with substance P in causing increased locomotor activity after microinfusion into the ventral tegmental area of rat brain, but the effects of DiMe-C7 on behavior were considerably prolonged. There was little metabolic degradation of tritiated DiMe-C7 for up to 1 hour after infusion, whereas tritiated substance P was completely degraded within 10 minutes.

Catchment properties and the photosynthetic trait composition of freshwater plant communities.

Unlike in land plants, photosynthesis in many aquatic plants relies on bicarbonate in addition to carbon dioxide (CO2) to compensate for the low diffusivity and potential depletion of CO2 in water. Concentrations of bicarbonate and CO2 vary greatly with catchment geology. In this study, we investigate whether there is a link between these concentrations and the frequency of freshwater plants possessing the bicarbonate use trait. We show, globally, that the frequency of plant species with this trait increases with bicarbonate concentration. Regionally, however, the frequency of bicarbonate use is reduced at sites where the CO2 concentration is substantially above the air equilibrium, consistent with this trait being an adaptation to carbon limitation. Future anthropogenic changes of bicarbonate and CO2 concentrations may alter the species compositions of freshwater plant communities.

Age and histopathologic heterogeneity in Alzheimer's disease. Evidence for subtypes.

In support of heterogeneity in Alzheimer's disease (AD), the existence of clinical and biologic subtypes has been claimed. We have investigated this claim by a statistical analysis of the relationships between the number of neurons in nucleus locus ceruleus (nLC), cortical levels of neurotransmitters, number of cortical plaques and tangles, and age. We separated AD patients into two groups: AD-1, with a less severe loss of nLC neurons; and AD-2, with a greater loss. The AD-2 cases were associated with less choline acetyltransferase activity, smaller concentrations of somatostatin and norepinephrine, and more plaques and tangles in the cerebral cortex. Although the mean age at death was less and the duration of dementia was greater in AD-2 patients than in AD-1 patients, the differences in these age-related variables were not significant. Further evidence of heterogeneity came from discriminant function analyses based on nLC neuronal counts and age at death. These findings, suggesting two subtypes of AD, suggest heterogeneity.

Increased brain dopamine and dopamine receptors in schizophrenia.

In postmortem samples of caudate nucleus and nucleus accumbens from 48 schizophrenic patients, there were significant increases in both the maximum number of binding sites (Bmax) and the apparent dissociation constant (KD) for tritiated spiperone. The increase in apparent KD probably reflects the presence of residual neuroleptic drugs, but changes in Bmax for tritiated spiperone reflect genuine changes in receptor numbers. The increases in receptors were seen only in patients in whom neuroleptic medication had been maintained until the time of death, indicating that they may be entirely iatrogenic. Dopamine measurements for a larger series of schizophrenic and control cases (n greater than 60) show significantly increased concentrations in both the nucleus accumbens and caudate nucleus. The changes in dopamine were not obviously related to neuroleptic medication and, unlike the receptor changes, were most severe in younger patients.

Differences between early and late-onset Alzheimer's disease.

Alzheimer's disease of early onset versus that of late onset represent different syndromes, with distinct neuropathologies. Patients with early onset disease exhibit a more severe and more widespread loss of neurons from cortical and sub-cortical regions and the neurochemical changes involve not only the cholinergic system, but also neurons containing GABA, somatostatin and norepinephrine.

The interaction between MK-801 and receptors for N-methyl-D-aspartate: functional consequences.

Electrophysiological studies using a cortical slice preparation revealed that MK-801 is a potent, non-competitive, antagonist of N-methyl-D-aspartate (NMDA)-induced depolarisations. Also, MK-801 was a highly selective antagonist, exhibiting a high degree of use-dependency. It completely blocked responses to NMDA and quinolinic acid but had no effect on responses produced by kainic acid or quisqualic acid. Using [3H]MK-801, high affinity binding sites for MK-801 were detected in membranes of the rat brain. The pharmacological specificity and regional distribution of binding sites for MK-801 were consistent with an action of the compound at the level of the NMDA receptor-associated ion channel. Administered parenterally, MK-801 had a remarkable neuroprotective role. It caused essentially complete protection against loss of neurones produced by injection of neurotoxic doses of NMDA or quinolinic acid into the striatum or hippocampus. Furthermore, MK-801 was highly effective in preventing loss of hippocampal neurones following bilateral occlusion of the common carotid arteries in the gerbil.

Tritiated peptides. 12. Synthesis and biological activity of [4-3H-Phe8]substance P.

Substance P has been prepared 3H labeled at Phe8 by catalytic deiodination of a protected precursor. Synthesis of the precursor was by solid-phase methodology on polydimethylacrylamide resin and by condensation in solution of fragments covering sequences 1-4, 5-7, and 8-11. Free peptide made by each route analyzed satisfactorily and had the same chromatographic characteristics as unlabeled substance P. It was indistinguishable from the latter by radioimmunoassay when N and C terminally directed antisera were used and in the ability to cause contractions of isolated guinea pig ileum. Specific radioactivity was 23 Ci/mmol.

Novel quinuclidine-based ligands for the muscarinic cholinergic receptor.

Recent clinical studies on Alzheimer's patients have implied that only agents displaying high efficacy at the cortical muscarinic receptor have yielded encouraging results. This paper describes the design, synthesis, and biochemical characterization of novel quinuclidine-based muscarinic agonists which can readily penetrate into the central nervous system and which are capable of displaying high efficacy at cortical sites. With use of a biochemical assay capable of measuring receptor affinity and predicting cortical efficacy, it has been discovered that an oxadiazole ring and related heterocycles can function as bioisosteric replacements for the ester moiety found in several known muscarinic ligands. Within this series there exist compounds which span the efficacy range from high-efficacy agonist through partial agonists to antagonists with affinity comparable or superior to that of classical quaternary ammonium ligands. Consistent with recent molecular biology studies, structure-activity trends are interpreted in terms of separate binding sites for agonists and antagonists with H-bonding interactions characterizing agonist behavior and lipophilic binding characterizing antagonist behavior. Thus the aminooxadiazole moiety has structural features which are optimized for an agonist profile.

Effects of phenoxybenzamine on the uptake and metabolism of noradrenaline in the rat heart and vas deferens.

1. In the isolated rat heart perfused with various concentrations of (+/-)-(3)H-noradrenaline ((3)H-NA) the addition of phenoxybenzamine, cocaine or desipramine to the perfusion medium resulted in an inhibition of (3)H-NA uptake which appeared on kinetic analysis to be of a competitive nature.2. Phenoxybenzamine also blocked the formation of labelled metabolites of (3)H-NA in the heart at all perfusion concentrations of (3)H-NA; this effect appeared to be unrelated to the inhibition of the neuronal uptake of NA produced by phenoxybenzamine, since no blockade of (3)H-NA metabolism was produced by cocaine in similar experiments.3. In slices of rat vas deferens incubated with various concentrations of (3)H-NA, cocaine and desipramine and phenoxybenzamine were also shown to act as competitive inhibitors of NA uptake. Cocaine and phenoxybenzamine were less potent inhibitors of uptake in the vas deferens than they were in the heart; desipramine was equally potent in both tissues.4. When vas deferens slices were incubated in a medium containing phenoxybenzamine for 30 min before the addition of (3)H-NA, the resulting inhibition of (3)H-NA uptake was increased and changed to a non-competitive type of interaction.5. In hearts or vasa deferentia taken from animals pretreated in vivo with phenoxybenzamine (20 mg/kg), a significant inhibition of (3)H-NA uptake was found when the tissues were exposed to low concentrations of (3)H-NA but not when higher concentrations of (3)H-NA were used.

The role of uptake2 in the extraneuronal metabolism of catecholamines in the isolated rat heart.

1. (+/-)-(3)H-NA and labelled metabolites of NA were estimated in rat hearts after perfusion with various concentrations of NA in the range 0.01-50.0 mug/ml. Labelled metabolites of NA accounted for only a small proportion of the total uptake of radioactivity at low perfusion concentrations, but accounted for 50% of the total uptake at 1 mug NA/ml., thereafter declining to progressively smaller proportions at higher perfusion concentrations.2. If the formation of labelled metabolites of (3)H-NA was blocked by a combination of monoamine oxidase and catechol-O-methyl transferase inhibitors, the accumulation of unchanged (3)H-NA was doubled when hearts were perfused with 1 mug NA/ml.3. In hearts perfused with 0.5 mug NA/ml., an accumulation of unchanged (3)H-NA was demonstrated in the presence of a combination of metabolic inhibitors and metaraminol. This appeared to be due to Uptake(2), since the accumulation of NA under these conditions could be prevented by a low concentration of normetanephrine.4. Phenoxybenzamine prevented extraneuronal uptake (Uptake(2)) and metabolism of (3)H-NA with an estimated ID50 of 2.5 muM. The inhibition of Uptake(2) by phenoxybenzamine (2.0 muM) was diminished at very high NA concentrations, suggesting that the drug may act competitively with NA.5. It was concluded that Uptake(2) operates at all catecholamine concentrations in the rat heart, but that in the lower range (less than 2.5 mug/ml. for NA and less than 0.75 mug/ml. for adrenaline) any catecholamine taken up by this process is rapidly metabolized. Thus the accumulation of unchanged amine is seen only at high perfusion concentrations.6. The relevance of these results to an understanding of the possible physiological and pharmacological importance of Uptake(2) is discussed.

Inhibition of catecholamine Uptake-2 by steroids in the isolated rat heart.

Various steroids (17-beta-oestradiol, corticosterone, deoxycorticosterone, progesterone, testosterone and androsterone) produced a dose-dependent inhibition of the uptake of (3)H-noradrenaline by the Uptake(2) mechanism in the isolated perfused heart. It is suggested that these results may explain the potentiating effects of such steroids on the responses of vascular smooth muscle to catecholamines.

Differences in the uptake, storage and metabolism of (+)- and (-)-noradrenaline.

1. The rate of uptake of (+)- and (-)-noradrenaline was measured in isolated perfused hearts of reserpine treated rats, mice and guinea-pigs by fluorimetric analysis of the removal of catecholamine from the perfusion medium. In rat and mouse heart (-)-noradrenaline was taken up significantly more rapidly than (+)-noradrenaline, but no stereochemical specificity was found for noradrenaline uptake in guinea-pig hearts.2. Using radioactively labelled (+)-(14)C-noradrenaline and (-)-(3)H-noradrenaline, the kinetic constants for uptake into noradrenaline-containing and dopamine-containing synaptosomes from rat brain were determined. The uptake by noradrenaline terminals in the hypothalamus had a higher affinity for (-)-noradrenaline than for the (+)-isomer, but no differences in affinity were found for uptake into dopamine terminals.3. When equal amounts of labelled (+)- and (-)-noradrenaline were injected in vivo in double isotope experiments, the (+)-isomer disappeared more rapidly than the (-)-isomer from rat heart and spleen, but no significant differences were found between the rates of disappearance of the two isomers from rat brain or in the whole mouse.4. Analysis of the radioactive metabolites of the two isomers of noradrenaline after administration of mixed doses of the labelled substances showed that a significantly higher proportion of (+)-noradrenaline was metabolized to normetanephrine than of (-)-noradrenaline, in the whole mouse, rat heart and rat brain.

Relative affinities of drugs acting at cholinoceptors in displacing agonist and antagonist radioligands: the NMS/Oxo-M ratio as an index of efficacy at cortical muscarinic receptors.

1. Radioligand binding assays using [3H]-N-methylscopolamine (NMS) and [3H]-oxotremorine M (Oxo-M) have been devised to predict the efficacy of test compounds at muscarinic receptors in rat cerebral cortex. 2. Muscarinic antagonists, including non-selective and both M1- and M2-selective compounds, displayed similar affinity for both binding assays. 3. Full agonists such as carbachol and muscarine possessed a ratio of potencies against the antagonist versus the agonist ligand (NMS/Oxo-M ratio) of greater than 4000. 4. Compounds which have been shown previously to display partial agonist activity in functional assays e.g. pilocarpine and RS86 had intermediate NMS/Oxo-M ratios of 100-150. A second group of compounds which included oxotremorine had somewhat higher ratios (500-1400). 5. The ratio of affinity constants for the two assays predicted the ability of agonists to stimulate cortical phosphatidyl-inositol turnover. 6. These results suggest that the NMS/Oxo-M ratio may be a useful prediction of efficacy for novel compounds acting at cortical muscarinic receptors.

[3H]-Quinuclidinyl benzilate binding to muscarinic receptors in rat brain: comparison of results from intact brain slices and homogenates.

1. The binding of [3H]-( +/- )-quinuclidinyl benzilate ([3H]-( +/- )-QNB) to muscarinic sites in rat brain slice and homogenate preparations was compared. 2. Evidence is presented in support of the view that only the (-)-enantiomer of QNB binds with high affinity to muscarinic sites. 3. The Kd value for [3H]-(-)-QNB binding in slices was eight times higher than that measured in homogenates. 4. Similarly, the potencies of various muscarinic ligands as inhibitors of [3H]-(-)-QNB binding were consistently lower in slices than in homogenates. 5. It is proposed that the results may reflect differences in the binding properties of muscarinic receptors in intact tissue slice and homogenate preparations.

Time course of the effects of 6-hydroxydopamine on catecholamine-containing neurones in rat hypothalamus and striatum.

1. The effects of intraventricular injection of 6-hydroxydopamine (6-OHDA) on tyrosine hydroxylase activity, uptake of (3)H-noradrenaline and endogenous catecholamine concentration in rat hypothalamus and striatum were investigated at various times after the injection of 6-OHDA.2. In the hypothalamus after the injection of 250 mug of 6-OHDA there was a rapid decrease in tyrosine hydroxylase activity, (3)H-noradrenaline uptake and noradrenaline content, which was essentially complete within 2 hours.3. In the striatum after this dose of 6-OHDA there was a much slower reduction in tyrosine hydroxylase activity and (3)H-noradrenaline uptake during the first 48 h after drug injection. For the first 24 h the dopamine concentration in this brain area was increased significantly above control values, but had fallen below control values by 48 hours.4. After the injection of a smaller dose of 6-OHDA (25 mug) the only detectable change in the striatum was a rapid increase in the dopamine concentration. In the hypothalamus this dose induced a rapid depletion of noradrenaline, not accompanied initially by any significant reduction in tyrosine hydroxylase activity.5. These results are consistent with the hypothesis that 6-OHDA causes a rapid degeneration of catecholamine-containing nerve terminals in the central nervous system (CNS). These degenerative changes, indicated by the loss of tyrosine hydroxylase and noradrenaline uptake sites, did not appear to be preceded by an initial displacement of endogenous catecholamines by 6-OHDA, except possibly at early times after the administration of small doses of the drug.

Inhibition of catecholamine uptake in the isolated rat heart by haloalkylamines related to phenoxybenzamine.

1. Twenty-one haloalkylamine derivatives were tested as inhibitors of both the neuronal uptake of (3)H-noradrenaline (NA) by the Uptake(1) mechanism and the extraneuronal uptake of (3)H-NA by the Uptake(2) mechanism in the isolated rat heart.2. At a concentration of 50 muM most of the compounds tested caused a significant inhibition of both uptake processes, although there were wide differences in the relative effects on Uptake(1) and Uptake(2). Some tentative structure activity relationships for uptake inhibition were formulated from these results.3. Phenoxybenzamine was confirmed to be a potent inhibitor of both the Uptake(2) and Uptake(1) mechanisms, with IC50 values for these two systems of 2.8 muM and 0.9 muM respectively.4. The substances N-(9-fluorenyl)-N-methyl-beta-chloroethylamine (SKF 550), N-(3,4-dimethoxyphenylisopropyl)-N-benzyl-beta-chloroethylamin (SKF 625A) and N-(4-methoxyphenoxyisopropyl)-N-benzyl-beta-chloroethylamine (SKF 784A) were significantly more potent than phenoxybenzamine as Uptake(2) inhibitors, and were all less potent than phenoxybenzamine as Uptake(1) inhibitors. The compound SKF 550 is the most potent and selective inhibitor of Uptake(2) so far described. It has an IC50 for Uptake(2) of 0.08 muM, and an IC50 for Uptake(1) of approximately 40.0 muM.5. Comparison of the present results with the known activities of these blocking agents suggests that no correlation exists between adrenoceptor blocking activity and ability of the substances to act as inhibitors of Uptake(2) or Uptake(1).