Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries

Hypertension is a well‐established risk factor for adverse cardiovascular events, and older age is a risk factor for the development of hypertension. Genomewide association studies have linked ATP2B1, the gene for the plasma membrane calcium ATPase 1 (PMCA1), to blood pressure (BP) and hypertension. Here, we present the effects of reduction in the expression of PMCA1 on BP and small artery structure and function when combined with advancing age. Heterozygous PMCA1 null mice (PMCA1^Ht) were generated and conscious BP was measured at 6 to 18 months of age. Passive and active properties of isolated small mesenteric arteries were examined by pressure myography. PMCA1^Ht mice exhibited normal BP at 6 and 9 months of age but developed significantly elevated BP when compared to age‐matched wild‐type controls at ≥12 months of age. Decreased lumen diameter, increased wall thickness and increased wall:lumen ratio were observed in small mesenteric arteries from animals 9 months of age and older, indicative of eutrophic remodelling. Increases in mesenteric artery intrinsic tone and global intracellular calcium were evident in animals at both 6 and 18 months of age. Thus, decreased expression of PMCA1 is associated with increased BP when combined with advancing age. Changes in arterial structure precede the elevation of BP. Pathways involving PMCA1 may be a novel target for BP regulation in the elderly.     

A model for the control of testosterone secretion

We produce here a model to explain the control of testosterone secretion. In this model the hypothalamic secretion of the hormone LHRH (luteinizing hormone releasing hormone) is controlled by a combination of local testosterone concentration and of the local concentration of the pituitary hormone LH (luteinizing hormone). Since LHRH stimulates the release of LH, and LH in turn stimulates the release of testosterone, the three hormones constitute a three-component "feedback" network. We show how this model is able to account for the pulsatility of the release of these three hormones. Furthermore, the model is consistent with results obtained from a wide range of experimental manipulations of the system. For example, it accounts for the changes observed in hormone release patterns after castration. In particular, it follows that no "neural clock", or "neural pulse-generator", is required to force the system into pulsatile behaviour.     

Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain

We introduced two mutations into the carboxy-terminal regulatory region of chicken pp60c-src. One, F527, replaces tyrosine 527 with phenylalanine. The other, Am517, produces a truncated pp60c-src protein lacking the 17 carboxy-terminal amino acids. Both mutant proteins were phosphorylated at tyrosine 416 in vivo. The specific activity of the Am517 mutant protein kinase was similar to that of wild-type pp60c-src whereas that of the F527 mutant was 5- to 10-fold higher. Both mutant c-src genes induced focus formation on NIH 3T3 cells, but the foci appeared at lower frequency, and were smaller than foci induced by polyoma middle tumor antigen (mT). The wild-type or F527 pp60c-src formed a complex with mT, whereas the Am517 pp60c-src did not. The results suggest that one, inability to phosphorylate tyrosine 527 increases pp60c-src protein kinase activity and transforming ability; two, transformation by mT involves other events besides lack of phosphorylation at tyrosine 527 of pp60c-src; three, activation of the pp60c-src protein kinase may not be required for transformation by the Am517 mutant; and four, the carboxyl terminus of pp60c-src appears to be required for association with mT.     

The effects of three different demineralization agents on osteopontin localization in adult rat bone using immunohistochemistry

Immunohistochemical localization of osteopontin, a phosphorylated acidic glycoprotein, was compared in adult rat femur fixed in 4% paraformaldehyde at 4° C for 48 h and demineralized at 4° C in ethylenediaminetetraacetic acid (EDTA), modified Jenkin's solution, or 15% formic acid, until radiographs indicated demineralization was complete. Formic acid was also evaluated at room temperature. EDTA solution (15 days) resulted in intense staining of osteocytes, periosteal osteoclasts and osteoblastic cells in osteonal bone. Osteoblasts were negative in the periosteum. No megakaryocyte staining was present; however, occasional neutrophils in the bone marrow were non-specifically stained. Demineralization in modified Jenkin's solution (16 days) showed osteopontin localization in bone matrix, hypertrophic and articular chondrocytes, and osteocytes. In cortical bone, almost all cement lines demarcating osteons showed very dense labeling. In the bone marrow, occasional megakaryocytes were immunopositive and neutrophils were non-specifically stained. Jenkin's produced non-specific staining of skeletal muscle and connective tissue. Formic acid demineralization (14 days, 4° C) resulted in osteopontin expression in osteoblasts, osteocytes, osteoclast precursors, bone matrix, osteoid, cement lines, and chondrocytes; osteoclasts, although present in very low numbers, were also positive. More labeled osteoblasts could be identified compared to Jenkin's demineralization. Also more intense non-specific staining of the bone marrow neutrophils was obtained than with Jenkin's. Harsh, rapid demineralization with formic acid (4 days, room temperature) produced a loss in antigenicity demonstrated by a reduction in staining intensity not experienced with the 4° C protocol; however, osteopontin was still localized in bone matrix and hypertrophic zone chondrocytes. These results indicate that demineralization is compatible with retention of immunoreactive osteopontin in adult rat bone. Both EDTA and formic acid demineralization produce excellent immunostaining and are preferred over the modified Jenkin's solution to minimize background levels of non-specific staining.     

Preference for medium dense grass tussocks byHippodamia convergens [Col.: Coccinellidae]

The preference in the choice of hibernacula of the convergent lady beetle,Hippodamia convergens Guérin-Meneville, was investigated with regard to morphological aspects of 2 introduced range grasses,Panicum coloratum (L.), andEragrostis curvula (Schrad.) Beetles strongly preferred tussocks with a ratio in the range of 1.0–3.0 stems per cm² for lovegrass. Preference for klein grass tussocks ranging from 110–130 stems/clump was found. No preference was shown for a particular tussock circumference. It was demonstrated that tussocks could successfully be designated as suitable for beetle aggregation.     

Inhibition by superoxide dismutase of methemoglobin formation from oxyhemoglobin.

The formation of methemoglobin from oxyhemoglobin in a solution containing photoreduced riboflavin and oxygen was inhibited by superoxide dismutase. The rate of the reaction was pH-dependent in the range of 6.8 to 7.8, increasing as the pH was reduced. Inhibition by superoxide dismutase was enhanced as the EDTA concentration increased and was dependent on enzymatic activity. Under conditions in which superoxide dismutase inhibition was incomplete, catalase inhibited the reaction but mannitol had no effect. The data support the mediation of methemoglobin formation by superoxide. The hypothesis is offered that superoxide anion reduced the heme-bound oxygen in oxygemoglobin by one electron, permitting the subsequent dissociation of ferrihemoglobin and peroxide. The ability of superoxide dismutase to inhibit the formation of methemoglobin may represent one of its functions in the mature erythrocyte.     

Landmark maps for honeybees

Experiments by Fabre (1915), Thorpe (1950), Chmurzynski (1964), and most recently Gould (1986) suggest that insects have maps of their terrain which enable them to find their way directly to a goal when they are displaced several hundred metres from it. This paper discusses what might constitute an insect's map in terms of a two-part computational model. The first part describes how an insect reaches a goal when the insect is sufficiently close that it can see some of the landmarks which are visible from the goal. The second part considers the problem of navigating when there is no similarity between the view from the release-site and the view from the goal.We start from a model designed to explain how a bee might return to a goal using a two-dimensional snapshot of the landscape seen from the goal (Collett and Cartwright 1983). To guide its return, the model bee continuously compares its snapshot with its current retinal image and moves so as to reduce the discrepancy between the two. Bees can only be guided in the right direction by the difference between current retinal image and snapshot when there is some resemblance between the two. In a realistically cluttered world, snapshot and retinal image become very dis-similar only a short distance from the goal.To increase the distance from which a model bee can return, the bee takes two snapshots at the goal. The first snapshot excludes landmarks near to the goal and the second snapshot includes them. With close landmarks filtered from both snapshot and retinal image, the match between the two deteriorates gradually as the bee moves away from the goal. A model bee using a filtered snapshot and image finds its way back to the neighbourhood of the goal from a relatively long distance (Fig. 2). The bee then switches to the second snapshot and is guided to the precise spot by its memory of the close landmarks.For longer range guidance, the model bee is equipped with an album of snapshots, each taken at a different location within the terrain. Linked to each snapshot is a vector encoding the distance and direction from the place where the snapshot was taken to the hive. When the bee is displaced to a new position, it selects the snapshot which best matches its current image and follows the associated home-vector back to the hive (Fig. 3). Such a hive-centred map can also be used to devise novel routes to places other than the hive. For instance, a bee can reach a foraging site from anywhere in its terrain by adding the home-vector recalled at the starting position to a vector specifying the distance and direction of the foraging site from the hive. The sum of these two vectors defines a direct trajectory to the foraging site.     

Intrathecal morphine as sole analgesic during labour.

In 12 consecutive unselected patients admitted to a consultant maternity unit one single injection of subarachnoid morphine sulphate 1.5 mg abolished pain during the first stage of labour. Pain in the second stage was abolished in four patients and lessened in three. During the early puerperium, pain at the site of the episitotomy was much reduced. Side effects included itching of the face, nausea and vomiting, and frontal headache, but these were mild and simply treated. They were even less severe in the last four patients, in whom barbotage was not used in administering the morphine. The high rate of forceps delivery and caesarean section (three cases of each) was not thought to be associated with the use of intrathecal morphine. These findings show that intrathecal morphine can abolish the pain of labour, whether spontaneous or induced, while preserving the mother''s full awareness of labour and her co-operation in the second and third stages of labour. Further, controlled, trials are warranted.