Synthesis and biological activity of novel C-terminal-extended and biotinylated growth hormone-releasing factor (GRF) analogs.

A series of novel hGRF(1-29)-NH2 analogs were synthesized and biotinylated. The immunological and biological activities of these analogs were then characterized. To distance the biotin moiety from the putative bioactive core, a C-terminal spacer arm consisting of -Gly-Gly-Cys-NH2 (-GGC) was added to hGRF(1-29)-NH2 (hGRF29) and analogs, with subsequent biotinylation performed at the cysteine residue. Neither addition of the C-terminal spacer arm nor biotinylation affected affinity of these analogs for GRF antibody. Relative to hGRF(1-44)-NH2 (hGRF44: potency = 1.0), the biotinylated analogs were equipotent in vitro to their nonbiotinylated, parent compounds: [desNH2Tyr1,D-Ala2,Ala15]hGRF29-GGC-(tpBiocyt in)-NH2 (4.7) = [Ala15]hGRF29-GGC-(tpBiocytin)-NH2 (3.9) greater than hGRF29-GGC-(tpBiocytin)-NH2 (0.8). Based upon cumulative GH release data in vivo (0-60 min postinjection), [desNH2Tyr1,D-Ala2,Ala15]hGRF29-GGC-(tpBiocyt in)-NH2, [Ala15]hGRF29-GGC-(tpBiocytin)-NH2, and hGRF29-GGC-(tpBiocytin)-NH2 displayed 8.6, 5.5, and 0.8 times, respectively, the potency of hGRF44. These in vivo potency values were not significantly different from the corresponding parent compounds (i.e., with or without the C-terminal spacer arm). In summary, biotinylated hGRF analogs have been developed that retain full immunoreactivity and potent bioactivity (in vitro and in vivo), thus permitting their use in GRF receptor isolation, ELISA, and histochemical procedures.     

Differences in learning by foraging juvenile pumpkinseed and bluegill sunfish in a structured habitat

Synopsis We investigated the ability of two congeneric species of sunfish to learn to forage on a novel prey item in feeding arenas containing structured habitats. Eight bluegill sunfish and eight pumpkinseed sunfish were given the opportunity to forage on whiteworms daily for 10 days. Each day, several behavioural measures were recorded for each fish. Both species of sunfish learned to feed over the 10-day period but the bluegill sunfish learned to feed more quickly than the pumpkinseed sunfish. Pumpkinseeds, however, attained a higher level of foraging efficiency. The differences in learning and foraging efficiency were related to body morphology.     

The problem of movelength and turn definition in analysis of orientation data.

This study examines the analysis of arthropod orientation data. Three problems are discussed: (1) dealing with time as it applies to spatial data, (2) determining the appropriate movelength to be used in collecting and in analyzing data, and (3) defining a turn, to discriminate between "gait noise" and course changes. The main objective is to determine the solution to defining the most appropriate movelength for comparisons between variables and between species. The technique described here for selecting the appropriate movelength that has relevance to both the locomotory rate of the animal and its body length, reduces variation resulting from lateral translational movements, prevents the use of movelengths that lead to artifactual or unrealistic turning values per move, and permits comparisons of species and individuals under various stimulus conditions.     

Cardiovascular actions of adenosines, but not adenosine receptors, differ in rat and guinea pig

This study compared the structure-activity relationships of 16 analogues at the A1 and A2 adenosine receptors (A1AR, A2AR) of rat and guinea pig. Radioligand binding studies revealed no marked differences in the affinities of each analogue at the A1AR of brain cortex or the A2AR of brain striatum. Bioassay employing Langendorff heart preparations showed that the guinea pig is more sensitive than the rat to A1AR-mediated slowing of conduction through the atrioventricular node and, in some instances, to A2AR-mediated coronary vasodilation. That difference could reflect factors such as receptor density or efficacy of coupling to effector systems.     

Glucocorticoid-induced osteoporosis: a cross-sectional study.

We studied 70 patients (48 women and 22 men) with either rheumatic disease (n = 25) or lung disease (n = 45) who had been treated with glucocorticoids for at least 6 months (mean cumulative dose, 24.2 +/- 27.1 g of prednisone; mean current dose, 11.0 +/- 8.6 mg/d, mean duration of therapy, 8.1 years. We measured bone mineral density (BMD) of the hip (femoral neck) and spine (L2-L4) using dual-photon absorptiometry and BMD of the distal one third radius using single-photon absorptiometry. Compared with age-matched controls, the study population had decreased BMD of the spine (87.0%), hip (87.2%), and radius (90.6%). Current dose, cumulative dose, and duration of therapy were not correlated with BMD in the spine or hip in the total study population. The most significant correlations with low bone mass at the hip and spine were short height and low weight. There was a high incidence of hypercalciuria (30%) as compared with an age- and sex-matched control group (6.4%). Glucocorticoids are known to decrease vertebral and radial bone density. We conclude that glucocorticoids also decrease hip bone density as measured at the femoral neck. The high incidence of hypercalciuria may have implications for therapy of glucocorticoid-induced osteoporosis.     

Influence of mefluidide on growth,development, and cell wall digestibility of sorghum

Application of mefluidide (N-[2,4-dimethyl-5-([(trifluoromethyl)sulfonyl]amino) phenyl]acetamide) inhibits plant development in perennial grasses. This study examined the effect of mefluidide on the morphological development and digestibility of sorghum. In the greenhouse, 5.9 × 10^–5 g active ingredient (a.i.) plant^–1 applied at the seedling, eight-leaf and boot stages reduced mean plant height 70%, 59%, and 2%, respectively. Heights were also reduced 14%, 15% and 35% by 5.9 × 10^–8, 5.9 × 10^–7 and 5.9 × 10^–6 gram a.i. plant^–1 applied at the eight-leaf stage. Field application of 0.26 or 0.52 kg ha^–1 mefluidide at either the eight-leaf or flagleaf stage reduced mean plant height of all cultivars. Basal tiller numbers increased 319% 28 d, and dry matter production was reduced 65% 42 d following mefluidide application at the eight-leaf stage. Treated stems were 34% higher and treated leaves were 7% higher in cellulase dry matter digestibility than control plants following mefluidide application at the eight-leaf stage. These results indicate that mefluidide application to vegetative stages in sorghum may enhance the forage value of the plants while it inhibits normal plant growth.     

Spatial organization and monogamy in the mara Dolichotis patagonum

Maras, Dolichotis patagonum , were observed and radio-tracked in Argentina. They travelled as monogamous pairs that bred either alone at solitary burrows or communally at settlements where up to 29 pairs shared warrens.
Members of a mara settlement grazed within 2.5 km of the communal warrens, using intensively about 1 ha per day, within drifting daily ranges of 11 ha, seasonal ranges of 98 ha and annual ranges of 193 ha.
Their home ranges drifted continuously. Consequently, the long-term movements of neighbouring pairs overlapped substantially, but at any given moment they were territorially spaced.
Monogamous, drifting territoriality is explained by the patchy dispersion of food, the need to minimize interference competition, and a cycle of grazing and fallowing in the use of food plants.
Two hypotheses explaining the adaptive significance of settlements are evaluated: one relates to resource availability (through the indirect effect of ground water and sheep dung on vegetation); and the other relates to predation (through the protective influence of human dwellings). The size of sheep flocks grazing at outstations during January provide a measure of the resource richness of patches where maras graze, and the richness of these patches in the dry season appear to limit the number of maras breeding at each settlement during the following wet season.
Maras face extremes of resource dispersion between the wet and dry seasons: in the former, sparsely dispersed grazing and interference competition favour spacing out and territoriality; in the latter, clumping of resources facilitates pairs congregating in herds around outstations and dry lagoons. Superimposed upon the ecological factors favouring spacing out during the wet season are the sociological factors that cause the maras to den communally. The resulting compromise is a social system unique among mammals.     

Eicosanoids in breast cancer patients before and after mastectomy.

In 19 patients with a malignant breast tumor, tumor tissue and blood were taken to determine the eicosanoid profile and platelet aggregation. Values were compared with those of patients with benign tumors (n = 4), or undergoing a mammary reduction (n = 7). Postoperatively, blood was taken as well in order to compare pre- and postoperative values. Eicosanoids were measured in peripheral blood monocytes and mammary tissue by means of HPLC; furthermore, TXA2, 6-keto-PGF1 alpha, and PGE2 were determined by RIA. Differences in pre- and postoperative values of cancer patients were seen in plasma RIA values: PGE2 and 6-k-PGF1 alpha were significantly higher preoperatively when compared with postoperatively, however, such differences were seen in the control groups as well. Compared to benign tumor or mammary reduction test material the eicosanoid profile of tissue obtained from malignant mammary tumors showed important differences. Except for PGF2 alpha, HHT and 15-HETE no detectable quantities of eicosanoids were found in the non-tumor material, whereas in the malignant tumor material substantial quantities of a number of eicosanoid metabolites were present. Statistically significant correlations could be established between patient/histopathology data and the results of the platelet aggregation assays, e.g. between menopausal status and ADP aggregation; oestrogen receptor (+/-) and collagen and arachidonic acid aggregation, inflammatory cell infiltration score and arachidonic acid aggregation and fibrosis score and ADP aggregation. The results show that eicosanoid synthesis in material from mammary cancer patients is different from that in benign mammary tissue. The implications, in particular, in relation to future prognosis of the patient, remain obscure.