Heme binding and polymerization by Plasmodium falciparum histidine rich protein II: influence of pH on activity and conformation.

The histidine rich protein II (HRPII) from Plasmodium falciparum has been implicated as a heme polymerase which detoxifies free heme by its polymerization to inactive hemozoin. Histidine-iron center coordination is the dominant mechanism of interaction between the amino acid and heme. The protein also contains aspartate allowing for ionic/coordination interactions between the carboxylate side chain and the heme metal center. The pH profile of heme binding and polymerization shows the possibility of these two types of binding sites being differentiated by pH. Circular dichroism studies of the protein show that pH and heme binding cause a change in conformation above pH 6 implying the involvement of His-His+ transitions. Heme binding at pHs above 6 perturbs HRPII conformation, causing an increase in helicity.     

Mucosal layers and related nerve fibres in non-chagasic and chagasic human colon—a quantitative immunohistochemical study

Chagasic megacolon is accompanied by extensive myenteric and, simultaneously, moderate submucosal neuron loss. Here, we examined changes of the innervation pattern of the lamina propria (LP) and muscularis mucosae (MM). Two alternating sets of cryosections were taken from seven non-chagasic colonic and seven chagasic megacolonic specimens (the latter included both the dilated megacolonic and the non-dilated transitional oral and anal zones) and were immunohistochemically triple-stained for smooth-muscle actin (SMA), synaptophysin (SYN) and glial acid protein S100 and, alternatively, for SMA, vasoactive intestinal peptide (VIP) and somatostatin (SOM). Subsequent image analysis and statistical evaluation of nervous tissue profile areas revealed that, in LP, the most extreme differences (i.e. increase in thickness or decrease in nerve, glia and muscle tissue profile area, respectively) compared with control values occurred in the dilated megacolonic zone itself. In contrast, the most extreme differences in the MM were in the anal-to-megacolonic zone (except the profile area of muscle tissue, which was lowest in the megacolonic zone). This parallels our previous results in the external muscle coat. A partial and selective survival of VIP-immunoreactive in contrast to SOM-immunoreactive nerve fibres was observed in both mucosal layers investigated. Thus, VIPergic nerve elements might be crucial for the maintenance of the mucosal barrier. The differential changes of neural tissue parameters in LP and MM might reflect a multifactorial rather than a pure neurogenic development of megacolon in chronic Chagas’ disease.     

Resolution of genetic and uterine environmental effects in a family study of new dermatoglyphic measure: sole pattern ridge counts

The heritability of sole pattern ridge counts was examined in two family studies of endogamous castes from peninsular India. The phenotypes included ridge counts for each of the eight configurational areas separately, all areas combined, and only distal areas combined. Differences in heritability estimates were found between populations as well as among the individual configurational areas. Although some ridge counts do not show familial resemblance, others appear to be moderately heritable. Estimates of h2 range from 0.36 to 0.63 in one family series and from 0.22 to 0.51 in the other. In addition, significant uterine environmental effects were detected in one family series but not in the other.     

Fatty acyl-coenzyme A is required for budding of transport vesicles from Golgi cisternae

We describe a new role for fatty acylation. Conditions were established under which vesicular transport from the cis to the medial Golgi compartment in vitro depends strongly upon the addition of a fatty acyl-coenzyme A, e.g., palmitoyl-CoA. Using an inhibitor of long-chain acyl-CoA synthetase, we demonstrate that the fatty acid has to be activated by CoA to stimulate transport. A nonhydrolyzable analog of palmitoyl-CoA competitively inhibits transport. Electron microscopy and biochemical studies show that fatty acyl-CoA is required for budding of (non-clathrin-) coated transport vesicles from Golgi cisternae and that budding is inhibited by the nonhydrolyzable analog.     

Fine structure of muscles in the tickHyalomma (Hyalomma) dromedarii (Ixodoidea: Ixodidae)

Skeletal and visceral muscles are distinguished in the unfed nymphHyalomma (Hyalomma) dromedarii according to position, structure and function. The skeletal muscles include the capitulum, dorsoventral and leg oblique muscles. Their muscle fibres have the striated pattern of successive sarcomeres whose thick myosin filaments are surrounded by orbitals of up to 12 thin actin filaments. The cell membrane invaginates into tubular system (T) extending deeply into the sarcoplasm and closely associated to cisternae of sarcoplasmic reticulum (SR). The T and SR forming two-membered dyads are considered to be the main route of calcium ions whose movements are synchronized with the motor impulse to control contraction and relaxation in most muscles. Two types of skeletal muscle fibres are recognized, and are suggested as representing different physiological phases.In the visceral-muscle fibres investing tick internal organs, the actin and myosin filaments are slightly interrupted, and the T and SR are well demonstrated. Both skeletal and visceral muscles are invaginated by tracheoles and innervated by nerve-axons containing synaptic vesicles.     

Noncovalent modulation by ATP of the acyl transfer from acyl-glyceraldehyde-3-phosphate dehydrogenase to phosphate

The effect of ATP on the formation, spectral properties, and reactions of [beta-(2-furyl)acryloyl]glyceraldehyde-3-phosphate dehydrogenase (FA-GPDH) has been investigated. The chromophoric FA-GPDH has the advantage of providing spectrophotometric signals of the interaction of acyl enzyme with nucleotides and dinucleotides. The results are consistent with the exclusive existence of two acyl-enzyme conformations previously inferred from the interaction of the acyl enzyme with NAD+ and NADH. ATP interaction stabilizes a conformation different from that stabilized by NAD+. The inhibitory effects of ATP on these reactions are consistent with the reported inhibitory effect of ATP on the steady-state reaction with the true substrate. The physiological significance of these results to the regulation of glycolysis, via the ligand-dependent fate of 3-phosphoglycerol-GPDH, is discussed.