Role of pituitary hormones in regulating renal vitamin D metabolism in man.

Studies in animals and tissue culture have shown the importance of prolactin and growth hormone in regulating renal 1 alpha-hydroxylase activity and plasma concentrations of 1,25-dihydroxycholecalciferol (1,25(OH)2D3). Evidence for a similar role for these hormones in man was sought by using a radioreceptor assay to measure plasma 1,25(OH)2D3 concentrations in 20 normal subjects, 12 patients receiving dialysis, 11 patients with primary hyperparathyroidism, 10 pregnant women, seven women with prolactinoma, and 14 patients with acromegaly. Circulating 1,25(OH)2D3 concentrations were appreciably raised in the patients with primary hyperparathyroidism and the pregnant women (P less than 0.001), slightly but significantly increased in the patients with prolactinoma (P less than 0.05), and greatly raised in those with acromegaly (P less than 0.001). These results suggest that prolactin and growth hormone are important regulators of renal vitamin D metabolism in the physiological conditions of pregnancy, lactation, and growth in man.     

Interaction between the tRNA-Binding and C-Terminal Domains of Yeast Gcn2 Regulates Kinase Activity In Vivo

The stress-activated protein kinase Gcn2 regulates protein synthesis by phosphorylation of translation initiation factor eIF2α. Gcn2 is activated in amino acid-deprived cells by binding of uncharged tRNA to the regulatory domain related to histidyl-tRNA synthetase, but the molecular mechanism of activation is unclear. We used a genetic approach to identify a key regulatory surface in Gcn2 that is proximal to the predicted active site of the HisRS domain and likely remodeled by tRNA binding. Mutations leading to amino acid substitutions on this surface were identified that activate Gcn2 at low levels of tRNA binding (Gcd^- phenotype), while other substitutions block kinase activation (Gcn^- phenotype), in some cases without altering tRNA binding by Gcn2 in vitro. Remarkably, the Gcn^- substitutions increase affinity of the HisRS domain for the C-terminal domain (CTD), previously implicated as a kinase autoinhibitory segment, in a manner dampened by HisRS domain Gcd^- substitutions and by amino acid starvation in vivo. Moreover, tRNA specifically antagonizes HisRS/CTD association in vitro. These findings support a model wherein HisRS-CTD interaction facilitates the autoinhibitory function of the CTD in nonstarvation conditions, with tRNA binding eliciting kinase activation by weakening HisRS-CTD association with attendant disruption of the autoinhibitory KD-CTD interaction.     

Patterns and sources of variation in Daphnia phosphorus content in nature

It has recently been shown that Daphnia can vary in the phosphorus (P)-content of their body tissues, but the relative importance of genetic versus environmental causes for this variation is unexplored. We measured variation in P-content (as % body mass) of Daphnia from eight lakes and conducted experiments to contrast three sources of variation: interspecific variation, clonal variation and phenotypic plasticity. Daphnia P-content decreased with increasing seston C:P ratio across lakes. This relationship reflected both inter- and intraspecific variation. Daphnia parvula and D. dubia exhibited high P-content and were found in shallow lakes with low C:P seston, whereas D. pulicaria had low P-content and was found in deep, stratified lakes having high C:P seston. Populations of D. dentifera spanned this lake gradient and exhibited P-content that was negatively related to seston C:P. Evidence for phenotypic plasticity came from experiments with D. pulicaria and D. dentifera collected from a lake with P-deficient seston and fed a P-sufficient diet in the laboratory. In addition, populations of D. dentifera differed in P-content even after 7 d of feeding on P-sufficient resources, suggesting within-species clonal variation. However, mesocosm experiments revealed broad and surprisingly continuous variation in the P-content of individual clones of D. pulex (range 1.54–1.05%) and D. mendotae (1.51–1.07%) over a gradient in dietary C:P. The broad range in P-content exhibited by individual clones, acclimated for generations, suggests that variation in Daphnia P-content from laboratory experiments needs to be interpreted with caution. These results also show that phenotypic variation in response to environment can be a larger source of variation in P-content than genetic differences within or among species.     

Interstitial bone stress distributions accompanying ingrowth of a screen-like prosthesis anchorage layer

Recent development of screen-like bonded weaves of titanium wire for orthopaedic implant anchorage affords a unique opportunity for analytic studies of porous ingrowth micromechanics. The regular geometry of individual wires and the periodicity of the mesh weave are exploited in a series of two-dimensional finite element models, mapping interstitial bone stress fields as a function of ingrowth depth and wire size, shape, and spacing.

When the depth of bone ingrowth was less than one wire diameter, peak bone stresses always occurred at the leading (i.e. deepest) edge of bone ingrowth, immediately adjacent to the wire. As ingrowth depth approached a full wire diameter, peak local bone stresses were 2–9 times the nominal applied host bone stress, with greater stresses occurring for lower screen weave densities. Within multiple screen layers, the top layer consistently experienced the peak stress and transmitted most of the applied load, regardless of the number of underlying screen layers surrounded by bone. Neither wire size variations nor partial wire flattening substantially affected general trends in stress predictions.     

Book reviews

Environmental Biology of Fishes -     

Synergism between diacylglycerols and calcium ionophore in the induction of human B cell proliferation mimics the inositol lipid polyphosphate breakdown signals induced by crosslinking surface immunoglobulin

Resting human tonsillar B cells were stimulated to divide by heat killed Staphylococcus aureus Cowan strain 1 which was shown to induce hydrolysis of phosphatidylinositol 4, 5-bisphosphate known to give rise to diacylglycerol and an increase in cytosolic free calcium. Addition of the diacylglycerols, 1-oleoyl-2 acetyl glycerol or sn-1, 2-dioctanoylglycerol, together with the calcium ionophore ionomycin to B cell cultures induced marked cell proliferation whereas these agents were ineffective when used alone. Both diacylglycerols were shown to compete with [3H] phorbol 12,13 dibutyrate in binding to protein kinase C. These data support the hypothesis that synergism between cytosolic calcium and endogenous diacylglycerol, which activates protein kinase C, is involved in signal transduction in the proliferation of human B cells.