Evaluation of Borrelia burgdorferi BbHtrA Protease as a Vaccine Candidate for Lyme Borreliosis in Mice

Borrelia burgdorferi synthesizes an HtrA protease (BbHtrA) which is a surface-exposed, conserved protein within Lyme disease spirochetes with activity toward CheX and BmpD of Borrelia spp, as well as aggrecan, fibronectin and proteoglycans found in skin, joints and neural tissues of vertebrates. An antibody response against BbHtrA is observed in Lyme disease patients and in experimentally infected laboratory mice and rabbits. Given the surface location of BbHtrA on B. burgdorferi and its ability to elicit an antibody response in infected hosts, we explored recombinant BbHtrA as a potential vaccine candidate in a mouse model of tick-transmitted Lyme disease. We immunized mice with two forms of BbHtrA: the proteolytically active native form and BbHtrA ablated of activity by a serine to alanine mutation at amino acid 226 (BbHtrA^S226A). Although inoculation with either BbHtrA or BbHtrA^S226A produced high-titer antibody responses in C3H/HeJ mice, neither antigen was successful in protecting mice from B. burgdorferi challenge. These results indicate that the search for novel vaccine candidates against Lyme borreliosis remains a challenge.     

Do you do text?

Retrieving information from text has become an important areain bioinformatics, and not too surprisingly, this journal haspublished more than 30 papers on this topic since the firstarticle published by the journal in 1998. In addition, ISCB(International Society for Computational Biology) (www.iscb.org)has organized special sessions in the ISMB conferences (IntelligentSystems for Molecular Biology, see www.iscb.org/ismb2005) anda specialized interest group (www.pdg.cnb.uam.es/BioLink/) forthe last five years. In parallel, major computer science conferencesin related areas have begun     

Synthesis and biological evaluation of (-)-laulimalide analogues

Analogues of the marine natural product (-)-laulimalide were prepared by total synthesis and evaluated in vitro for anticancer activity.     

Butterfly selected lines explore the hormonal basis of interactions between life histories and morphology

Hormonal mechanisms underlie many life-history traits and their interactions. We studied the role of ecdysteroids with regard to wing pattern and development time of the polyphenic butterfly Bicyclus anynana. Ecdysteroid titers and sensitivity to ecdysone injection were assayed for two-trait selected lines (ventral eyespot size and development time concurrently). These two traits are genetically and phenotypically coupled, having a common endocrinal basis. Two-trait selection had been applied both antagonistically (opposite the correlation) and synergistically (in the same direction as the correlation). Although selected lines had diverged most in eyespot size, the widest differences in timing of ecdysteroid titers were observed between the development time selection regimes; fast selected lines had an earlier hormonal increase after pupation than slow selected lines (even when corrected for differential pupal times). This endocrine peak was also earlier for females than for males. Furthermore, sensitivity to ecdysone injection as measured by a subsequent decrease in pupal time was significantly lower for slow selected lines than for fast or unselected lines. We conclude that the observed response in eyespot size to artificial selection must have been achieved via alteration of, or selection on, other developmental mechanisms, because the dynamics of the alternative, hormonal, pathway were dictated by development time selection. The developmental system is flexible enough to allow evolution in directions opposing the correlation between wing pattern and developmental time, and responses to selection are not constrained by a shared hormonal system.     

Entamoeba histolytica trophozoites transfer lipophosphopeptidoglycans to enteric cell layers

Transfer of antigens frequently follows adhesion of protozoan parasites to host cells. We were interested in such transfer from the Entamoeba surface to enterocytes following adhesion of trophozoites. Therefore, cocultures of enterocytes in vitro and ex vivo with Entamoeba histolytica (strain HM-1:IMSS) or Entamoeba dispar (strain SAW760) trophozoites were processed for immunocytochemistry. The EH5 monoclonal antibody against amoebic proteophosphoglycans marked a dotted pattern on the apical side of enterocytes in in vitro cocultures with HM-1:IMSS and SAW760 trophozoites. Basolateral staining was present in cocultures following dysfunction of tight junctions, or when trophozoites made direct contact with the basolateral side of enterocytes in in vitro and ex vivo cocultures. Based on the molecular mass in Western blot, the transferred proteophosphoglycan was identified as a lipophosphopeptidoglycan. In conclusion, trophozoites transfer LPPG to the apical side of enterocytes following adhesion and prior to dysfunction of tight junctions.     

Factors influencing glycosylation of Trichoderma reesei cellulases. II: N-glycosylation of Cel7A core protein isolated from different strains

A systematic analysis of the N-glycosylation of the catalytic domain of cellobiohydrolase I (Cel7A or CBH I) isolated from several Trichoderma reesei strains grown in minimal media was performed. Using a combination of chromatographic, electrophoretic, and mass spectrometric methods, the presence of glucosylated and phosphorylated oligosaccharides on the three N-glycosylation sites of Cel7A core protein (from T. reesei strains Rut-C30 and RL-P37) confirms previous findings. With N-glycans isolated from other strains, no end-capping glucose could be detected. Phosphodiester linkages were however found in proteins from each strain and these probably occur on both the alpha1-3 and the alpha1-6 branch of the high-mannose oligosaccharide tree. Evidence is also presented for the occurrence of mannobiosyl units on the phosphodiester linkage. Therefore the predominant N-glycans on Cel7A can be represented as (ManP)(0-1)GlcMan(7-8)GlcNAc2 for the hyperproducing Rut-C30 and RL-P37 mutants and as (Man(1-2)P)(0-1-2)Man(5-6-7)GlcNAc2 for the wild-type strain and the other mutants. As shown by ESI-MS, random substitution of these structures on the N-glycosylation sites explains the heterogeneous glycoform population of the isolated core domains. PAG-IEF separates up to five isoforms, resulting from posttranslational modification of Cel7A with mannosyl phosphodiester residues at the three distinct sites. This study clearly shows that posttranslational phosphorylation of glycoproteins is not atypical for Trichoderma sp. and that, in the case of the Rut-C30 and RL-P37 strains, the presence of an end-capped glucose residue at the alpha1-3 branch apparently hinders a second mannophoshoryl transfer.     

Depressed ventilatory reflexes after capsaicin challenge in streptozotocin-treated rats

Diabetic sensory neuropathy is an affliction that decreases sensory perception in a number of organ systems. Although little is known of its pulmonary effects certain diabetic patients have reduced airway reactivity to cold air and elevated cough threshold to irritant inhalation, reflexes reported to be mediated by pulmonary C-fibers. Therefore we studied the effects the selective C-fiber activator capsaicin (0.01% aerosol, 30 s) on variables of ventilation using a whole-body plethysmograph in age-matched rats treated with streptozotocin (STZ) or its vehicle at 6 and 12 weeks after treatment. Body weight increased and plasma glucose and glycosylated hemoglobin were stable in vehicle-treated rats. In STZ-treated rats body weight decreased and plasma glucose and glycosylated hemoglobin increased. Capsaicin challenge decreased tidal volume, respiratory rate and therefore minute ventilation in non-treated and vehicle-treated rats. However capsaicin challenge increased tidal volume thereby altering minute ventilation in STZ-treated rats. Specific airway resistance increased in both groups after capsaicin challenge. Changes in ventilation in response to capsaicin challenge in STZ-treated rats may involve C-fiber sensory neuropathy.     

Evidence for Megalake Chad, north-central Africa, during the late Quaternary from satellite data

The existence of a very large Lake Chad during the late Quaternary, Megalake Chad, has long been questioned. A Megalake Chad would present strong evidence for climatic fluctuations of great magnitude during the Holocene in tropical Africa. In this paper we used satellite data from Landsat and Modis sensors to collect and analyse new information on landforms in a 2 000 000 km² region of the Lake Chad Basin. We detected 2300 km of remains marking the ancient shoreline of Megalake Chad. The satellite data also indicated many Saharan rivers and relict deltas leading to the long paleoshoreline. Large dunefield flattenings were observed and interpreted as the result of wave-cut erosion by the paleolake. Similarities were noticed between the landforms observed along the paleoshoreline of Megalake Chad and that of the former Aral Sea. This finding has significant consequences for reconstructing paleohydrology and paleoenvironments through the Lake Chad basin, and continental climate change.