Bilateral fractures of femoral neck in patients with moderate renal failure receiving fluoride for spinal osteoporosis.

Two patients with moderate renal failure sustained spontaneous bilateral hip fractures during treatment with fluoride, calcium, and vitamin D for osteoporosis. They had been taking sodium fluoride (40-60 mg/day) for 11 and 21 months, respectively. Histological examination of a specimen of the bone showed severe fluorosis in the first case, and quantitative analysis of bone showed osteomalacia and skeletal fluorosis in the other case. These abnormalities were considered to be the consequence of excessive retention of fluoride due to renal insufficiency. As bilateral femoral neck fractures are very rare these data suggest a causal link between fractures and fluoride in patients with renal failure. Thus fluoride should be given at a lower dosage, if at all, to patients with even mild renal failure.     

Intact chloroplast electron flow. Effects of ribose 5-phosphate

Additions of ribose 5-phosphate to intact spinach chloroplasts were used to probe the effects of ADP regeneration on pH-gradient formation and electron-transfer reactions. In weakly illuminated chloroplasts, the ATP/ADP ratio dropped by 64% and the transthylakoid pH gradient decreased by a minimum of 0.2 units in response to ribose 5-phosphate. Nitrite reduction increased 2-fold while, under conditions of cyclic electron flow, the half-time for cytochrome f reduction decreased by a factor of two from 4.1 to 1.9 ms. The results suggest that metabolic ATP consumption, during the conversion of ribulose 5-phosphate to ribulose 1,5-bisphosphate, enhances electron transfer between plastohydroquinone and cytochrome f through decreases in the transthylakoid pH gradient caused by phosphorylation of ADP.     

The Social Structure of Inachus phalangium,a Spider Crab Associated with the Sea Anemone

The behaviour of the spider crab Inachus phalangium (Fabricius, 1775), which lives in association with the sea anemone Anemonia sulcata (Pennant), was studied in the field. The crab was found in the littoral zone of the Mediterranean Sea near Banyuls sur Mer, France, in the whole depth range studied (0.5–25 m). The crabs had a long-lasting association with individual Anemonia sulcata, occasionally with Aiptasia mutabilis. Most crabs were found in association with the same anemone for several days, some crabs were found in association with the same anemone for longer than one month. In the areas studied, on average 65 Inachus phalangium were found on 100 anemones. Crabs released in the vicinity of anemones moved towards them and entered them. Inachus phalangium could walk between the tentacles of Anemonia sulcata and Aiptasia mutabilis without eliciting feeding reactions of the anemone. The crabs left the anemones for moulting. After moulting masking material was removed from the exuvia and used again. The animals returned into an anemone while still soft. Material used for masking, usually algae, could be picked off the body and eaten. Masking material may be a food reservoir in addition to providing camouflage. Anemones were left only during night-time. The crabs left their anemone to moult, to feed in the vicinity, fleeing from larger conspecifics, and to migrate to a different anemone. Outside the anemone's protection Inachus was eaten by several species of fish. Individuals appeared to avoid each other. 57% of all animals were found alone on an anemone. Large males and females were more frequently found alone than were small males and females. Fights were observed between members of the same and of the opposite sex. During fights, legs and claws could be torn off. Adult males migrated more often between anemones and moved over larger distances when migrating than did adult females. Adult males probably migrated in search of sexually mature females. Such a roving strategy is evolutionarily stable only when the higher costs (in terms of energy expenditure and mortality) are compensated for by a higher number of offspring than produced in the alternative, pair-bonding strategy.     

Enhanced thermodynamic stabilities of yeast iso-1-cytochromes c with amino acid replacements at positions 52 and 102.

We have determined the structures and thermodynamic stabilities of the wild type Asn-52 and unusually thermostable mutant Ile-52 yeast iso-1-cytochromes c (Das, G., Hickey, D. R. McLendon, D., McLendon, G., and Sherman, F. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 496-499). Although both structures were similar, Water-166, buried within the wild type protein, is excluded from the Ile-52 mutant, which substantially reorganizes the local hydrogen bonding. Wild type Cys-102 was replaced with alanine or serine to eliminate dimerization in vitro. The Cys-102 (wild type), Ala-102, and Ser-102 proteins were equally stable, whereas the chemically modified Cys-102-SCH3 was less stable. The order of stability observed with replacements at positions 52 and 102 was as follows: Ile-52 Ala-102 greater than Ala-52 Ala-102 greater than Asn-52 Ala-102 ("normal") greater than Gly-52 Ala-102. No significant stabilization was attributed to potential energy interactions expressed as helix-forming propensities of replacements at position 52. A high correlation between differences in free energy changes and transfer free energies suggests hydrophobic interactions are the main factor for enhancing stability in the Ile-52 mutant. Additional possible contributions to the thermostability of the Ile-52 variant are energetic effects due to packing and hydrogen bonding changes surrounding position 52.     

Enhanced Rate of Expression and Biosynthesis of Neuropeptide Y After Kainic Acid-Induced Seizures

Recent studies have shown marked increases in brain content of neuropeptide Y (NPY) after seizures induced by intraperitoneal injection of kainic acid and after pentylenetetrazole kindling in the rat. We have now investigated possible changes in the rate of biosynthesis of NPY after kainic acid treatment, by using pulse-labeling of the peptide and by determining prepro-NPY mRNA concentrations. For pulse labeling experiments, [3H]tyrosine was injected into the frontal cortex, and the incorporation of the amino acid into NPY was determined after purifying the peptide by gel filtration chromatography, antibody affinity chromatography, and reversed-phase HPLC. At 2 and 30 days after kainic acid treatment, the rate of tyrosine incorporation was enhanced by approximately 380% in the cortex. In addition, concentrations of pre-pro-NPY mRNA were determined in four different brain areas by hybridization of Northern blots with a complementary 32P-labeled RNA probe 2, 10, 30, and 60 days after kainic acid treatment. Marked increases were observed in the frontal cortex (by up to 350% of controls), in the dorsal hippocampus (by 750%), and in the amygdala/pyriform cortex (by 280%) at all intervals investigated. In the striatum only a small, transient increase was observed. The data demonstrate increased expression of prepro-NPY mRNA and an enhanced rate of in vivo synthesis of NPY as a result of seizures induced by the neurotoxin kainic acid.     

Structural transition of alpha 1-antitrypsin by a peptide sequentially similar to beta-strand s4A

Crystal structure studies have shown that cleaved and intact serpins differ essentially in the topology of beta-sheet A. This is five-stranded in the intact molecules and six-stranded after cleavage by insertion of strand s4A whose C-terminus has become free [L?bermann, H., Tokuoka, R., Deisenhofer, J. & Huber, R. (1984) J. Mol. Biol. 177, 531-556; Wright, T. H., Qian, H. X. & Huber, R. (1990) J. Mol. Biol. 213, 513-528]. The structural transition is accompanied by changes in spectral properties and an increase in thermal stability. We show here that an N alpha-acetyl-tetradecapeptide with the amino acid sequence of strand s4A, residues 345-358 of human alpha 1-antitrypsin, associates with intact alpha 1-antitrypsin and forms a stoichiometric complex with properties very similar to cleaved alpha 1-antitrypsin. Complex generation has the characteristics of a folding process.     

Biosynthesis and structure of membrane and secretory immunoglobulins

Summary Almost all of the body's extracellular immunoglobulin (Ig) is derived from Ig-secreting plasma cells of lymphoid tissues. The secreted material is a heterogeneous mixture of different classes and specificities. Lymphoid tissues also contain a large number of essentially non-secretory cells — B lymphocytes — which bear Ig firmly associated with their plasma membranes. Ig molecules thus exist in two functionally different forms, as membrane-bound antigen receptors on the surface of B lymphocytes on the one hand, and as humoral secreted Ig antibodies on the other. On B cells, membrane-bound heavy chains have an apparent mol. wt. slightly larger than that of secreted heavy chains from plasma cells. Membrane-bound but not secreted heavy chains bind detergents, thus suggesting the presence of a hydrophobic region in membrane-bound heavy chains, which is absent in secreted heavy chains. Most investigations have dealt with immunoglobulin M. The two types of IgM heavy chains differ at their carboxy termini. Recent investigations at the nucleic acid level demonstrate that membrane-associated µ chains contain a 41-residue hydrophobic tail adjacent to the last constant domain, whereas secretory µ chains contain a 20-residue hydrophilic tail. At the present time, evidence is accumulating that all membrane-bound Ig heavy chain classes may contain similar hydrophobic structures necessary for anchorage of the molecules into the lipid bilayer.     

Origines du peuplement mammalien en Afrique du Nord durant le miocène terminal

The late Miocene North African mammalianassemblage is considered here from three viewpoints: survivals, extinctions, and immigrations. The Eurasiatic affinities of the large mammals slightly prevail over the Ethiopian affinities. Amongst the North African large mammals, 4 to 8 taxa are Eurasiatic immigrants, while 4 to 6 are of Subsaharian origin. Contrarily, the micromammalian fauna is highly endemic, with only one species, a murid (Paraethomys miocaenicus), considered here as being related to an Asiatic form (Karnimata darwini). Our study of Eurasian and African Miocene faunas reveals that during the late Astaracian-early Turolian interval, the Saharo-Arabic belt permitted very little latitudinal faunal exchanges. However, during the middle and late Turolian such faunal exchanges became frequent. The micromammal record unequivocally indicates that a brief period of faunal exchange occurred between Africa and western Europe at the end of the Miocene, corresponding with the Messinian Salinity Crisis. The increased intercontinental faunal exchange between Africa and Eurasia during the late Miocene coincides with, and counterbalances the extinction of more than 10 taxa at the Mio/Pliocene boundary.