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Critical role for a stage-specific actin in male exflagellation of the malaria parasite

Male gametogenesis occurs directly after uptake of malaria parasites by the mosquito vector and leads to the release of eight nucleated flagellar gametes. Here, we report that one of the two parasite actin isoforms, named actin II, is essential for this process. Disruption of actin II in Plasmodium berghei resulted in viable asexual blood stages, but male gametogenesis was specifically inhibited.

Comparative structural analysis of lipid binding START domains

BACKGROUND: Steroidogenic acute regulatory (StAR) protein related lipid transfer (START) domains are small globular modules that form a cavity where lipids and lipid hormones bind. These domains can transport ligands to facilitate lipid exchange between biological membranes, and they have been postulated to modulate the activity of other domains of the protein in response to ligand binding. More t

Actin regulation in the malaria parasite

Many intracellular pathogens hijack host cell actin or its regulators for cell-to-cell spreading. In marked contrast, apicomplexan parasites, obligate intracellular, single cell eukaryotes that are phylogenetically older than the last common ancestor of animals and plants, employ their own actin cytoskeleton for active motility through tissues and invasion of host cells. A hallmark of actin-based

Comparative structural analysis of human DEAD-box RNA helicases

DEAD-box RNA helicases play various, often critical, roles in all processes where RNAs are involved. Members of this family of proteins are linked to human disease, including cancer and viral infections. DEAD-box proteins contain two conserved domains that both contribute to RNA and ATP binding. Despite recent advances the molecular details of how these enzymes convert chemical energy into RNA rem

Arp1, an actin-related protein, in Plasmodium berghei

Actin-related proteins (Arps) constitute a family of eukaryotic cytoskeletal proteins involved in such diverse events as cell motility, cytokinesis, vesicle transport, and chromatin remodelling. Previously, in a study of Plasmodium berghei gene expression in ookinetes and oocysts, we detected stage-specific increased expression of a gene encoding an Arp. Here we further characterize this gene and

Structural basis for the interaction between tankyrase-2 and a potent Wnt-signaling inhibitor

We report two crystal structures of the PARP domain of human tankyrase-2 (TNKS2). Tankyrases are involved in fundamental cellular processes such as telomere homeostasis and Wnt signaling. The complex of TNKS2 with the potent inhibitor XAV939 provides insights into the molecular basis of the strong interaction and suggests routes for further development of tankyrase inhibitors.

Crystal structure of human RNA helicase A (DHX9) : structural basis for unselective nucleotide base binding in a DEAD-box variant protein

RNA helicases of the DExD/H-box superfamily are critically involved in all RNA-related processes. No crystal structures of human DExH-box domains had been determined previously, and their structures were difficult to predict owing to the low level of homology among DExH-motif-containing proteins from diverse species. Here we present the crystal structures of the conserved domain 1 of the DEIH-moti

Crystallization and preliminary structural characterization of the two actin-depolymerization factors of the malaria parasite

The malaria parasite Plasmodium depends on its actin-based motor system for motility and host-cell invasion. Actin-depolymerization factors are important regulatory proteins that affect the rate of actin turnover. Plasmodium has two actin-depolymerization factors which seem to have different functions and display low sequence homology to the higher eukaryotic family members. Plasmodium actin-depol

Toward a unified nomenclature for mammalian ADP-ribosyltransferases

ADP-ribosylation is a post-translational modification of proteins catalyzed by ADP-ribosyltransferases. It comprises the transfer of the ADP-ribose moiety from NAD+ to specific amino acid residues on substrate proteins or to ADP-ribose itself. Currently, 22 human genes encoding proteins that possess an ADP-ribosyltransferase catalytic domain are known. Recent structural and enzymological evidence

Intestinal transmission of macromolecules in newborn dairy calves of different ages at first feeding.

Four groups of eight newborn calves were used to study the intestinal transmission of colostral immunoglobulin from the intestinal lumen to the blood circulation. The first feed was given one, eight, 16 or 24 hours after birth. Thereafter, three feeds were given with eight hour intervals. All feeds were from the same pool of colostrum and the amount fed each time corresponded to 3 per cent of the

Degradation of [Mercaptopropionic acid1, D‐arginine8] ‐ vasopressin (dDAVP) in Pancreatic Juice and Intestinal Mucosa Homogenate

Abstract: The degradation of the vasopressin analogue dDAVP was studied by reversed phase high‐performance liquid chromatography (HPLC) after incubations in pancreatic juice and intestinal mucosa homogenates. dDAVP remained stable in pancreatic juice for a period of 60 min. while the parent hormone arginine vasopressin (AVP) was completely degraded within 5 min. In intestinal mucosa homogenates dD

Increased intestinal marker absorption due to regional permeability changes and decreased intestinal transit during sepsis in the rat

Wang Q, Pantzar N. Jeppsson B, Weström BR, Karlsson BW. Increased intestinal marker absorption due to regional permeability changes and decreased intestinal transit during sepsis in the rat. Scand J Gastroenterol 1994;29:1001-1008. Background: The intestinal barrier properties are impaired during inflammation and sepsis, but the mechanisms behind this are unknown and were therefore investigated du

Bidirectional small intestinal permeability changes to different-sized molecules after HCl-induced injury in the rat

A rat model was developed to assess bidirectional passage of macromolecules and low-molecular-weight markers across the intestinal barrier in intact and injured mucosa. Isolated in situ loops of distal small intestine were luminally perfused for 30 min with saline as control or HCl (pH 2.0) to induce an acute injury. The lumen-to-blood passage was followed during perfusion with bovine serum albumi

Development of exocrine pancreas function in chronically cannulated pigs during 1-13 weeks of postnatal life

The development of exocrine pancreas function was studied in Swedish Landrace pigs surgically fitted with a chronic pancreatic duct catheter and a duodenal re-entrant cannula. The juice secretion and output of total protein and trypsin activity were followed before (basal secretion) and after feeding (postprandial secretion) during the first 1-13 weeks of life. The results showed that throughout t

Levels of serum protease inhibitors during fetal and postnatal development of the pig

Using electroimmunoassay the levels of the individual protease inhibitors, α2-macroglobulin f, α2-macroglobulin s, inter-α-trypsin inhibitor, α1-protease inhibitor and α2-antitrypsin were studied in the serum and the amniotic fluid during the fetal and postnatal development of the pig. High concentrations, far above the adult ones, of α2-antitrypsin and especially α1-protease inhibitor, were obser

Protease inhibitors and their relation to protease activity in human milk

Protease inhibitors and protease (caseinolytic, elastinolytic and esterolytic) activity were analysed in 190 milk samples from 94 mothers from day 1 to day 160 after delivery The main protease inhibitors in human milk are α1-antichymotrypsin and α1-antitrypsin. As measured by electroimmunoassay, the level of α1-antichy-motrypsin in day 1 colostrum was higher than that in normal serum. Trace amount

Intestinal transmission of macromolecules (BSA and FITC-labelled dextrans) in the neonatal pig : Influence of age of piglet and molecular weight of markers

The intestinal transmission of two macromolecular markers, of similar molecular weight but different susceptibility to proteolytic digestion, was investigated in the neonatal pig. Piglets of varying age (0 h-7 days old) were given a mixture of bovine scrum albumin (BSA) and fluorescein-isothiocyanalc labelled dextran 70,000 (FiTC-D 70) by stomach tube, and the scrum concentrations were determined