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PubMed1998

The role of IL-4 in adult acquired and congenital toxoplasmosis.

The course of Toxoplasma gondii infection was studied in IL-4-deficient mice from three genetic backgrounds and their wild-type counterparts following peroral inoculation of tissue cysts. Survival rates were significantly reduced in disease-susceptible C57 BL/6 mice and F1 (C57BL/6 x 129Sv) mice deficient in IL-4 compared with wild-type controls. In contrast, this difference was not observed in T. gondii-resistant BALB/c mice. However, brain tissue cyst burdens in IL-4-deficient mice were either equivalent to (C57BL/6 and BALB/c mice) or significantly less (B6/129 mice) than similarly infected wild-type mice. Thus strain-specific differences in the course of T. gondii were demonstrated in the absence of IL-4. The course of T. gondii infection was also compared between B6/129 IL-4-deficient mice and their wild-type counterparts following peroral challenge with 20 tissue cysts on day 12 of pregnancy. Age-matched non-pregnant IL-4-/- and IL-4+/+ mice were also infected to assess the role of IL-4 on T. gondii infection during pregnancy. Disease phenotypes, as measured by mortality, were reversed if infections were initiated during pregnancy compared with non-pregnant infection. Thus significant mortality occurred immediately post partum in IL-4+/+ mothers, while all IL-4-/- mothers survived. Cyst burdens 28 days p.i. were significantly lower in IL-4-/- mothers than IL-4+/+ mothers and both IL-4-/- and IL-4+/+ non-pregnant mice. Congenital disease transmission as measured by foetal death or vertical disease transmission was independent of the presence or absence of IL-4. These studies demonstrate a role for IL-4 in pregnancy-induced immunosuppression and the associated increased susceptibility to T. gondii infection.

Animals↗
PubMed2004

Stage-specific expression genes of the Spirometra erinaceieuropaei plerocercoid screened by mRNA differential display technique.

BACKGROUND: The stage-specific expression of genes is one of the most characteristics of parasites. It has been found that a lot of genes of Spriometra erinaceieuropaei are specifically expressed in pleroceroid in large amount, but not expressed when the plerocercoid development into adult worm. The study is to screen other stage-specific ecpression genes of plerocercoid of Spirtmetra erinceieuropaei. METHODS: RNA was separately extracted by acid guanidinium thiocyanate-phenol-chloroform from plerocercoids and adult worms of Spirometra erinaceieuropaei, DNA contaminated in the RNA was digested by RNase-free DNase. After the RNA was reverse transcripted to cDNA using T12MA, T12MC, T12MG and T12MT anchor-primers, PCR was done using the same T12MN and one random primer with alpha 35S-dATP in the system. The PCR products were fractionated on an 8% denatured polyacrylamide gel. Differential bands of the plerocercoid found in the gel were cut out, amplified by PCR and sequenced. Northern hybridization was used to identify the stage-specific expression genes. RESULTS: Eleven differential bands were selected from the gel and classified into 3 kinds of gene fragments by hybridization, after they were amplified by PCR. Fragments 1 (238 bp) and 2 (383 bp), were confirmed by Northern hybridization, as being expressed in the plerocercoid. However, fragment 3 (433 bp), was expressed in both the plerocercoid and the adult worm. Data from the 3 gene fragments underwent homological analysis in GenBank. The sequence which was homologous with fragments 1 and 2 was not found, but fragment 3 had high homology with many kinds of 28S rRNA. CONCLUSIONS: The gene expressions of plerocercoids are different from adult worms because they live in different hosts. Two types of different gene fragments from the plerocercoid were found by mRNA differential display technique.

Animals↗
PubMed2005

Amino acids as placeholders: base-composition pressures on protein length in malaria parasites and prokaryotes.

BACKGROUND: The composition and sequence of amino acids in a protein may serve the underlying needs of the nucleic acids that encode the protein (the genome phenotype). In extreme form, amino acids become mere placeholders inserted between functional segments or domains, and--apart from increasing protein length--playing no role in the specific function or structure of a protein (the conventional phenotype). METHODS: We studied the genomes of two malarial parasites and 521 prokaryotes (144 complete) that differ widely in GC% and optimum growth temperature, comparing the base compositions of the protein coding regions and corresponding lengths (kilobases). RESULTS: Malarial parasites show distinctive responses to base-compositional pressures that increase as protein lengths increase. A low-GC% species (Plasmodium falciparum) is likely to have more placeholder amino acids than an intermediate-GC% species (P. vivax), so that homologous proteins are longer. In prokaryotes, GC% is generally greater and AG% is generally less in open reading frames (ORFs) encoding long proteins. The increased GC% in long ORFs increases as species' GC% increases, and decreases as species' AG% increases. In low- and intermediate-GC% prokaryotic species, increases in ORF GC% as encoded proteins increase in length are largely accounted for by the base compositions of first and second (amino acid-determining) codon positions. In high-GC% prokaryotic species, first and third (non-amino acid-determining) codon positions play this role. CONCLUSION: In low- and intermediate-GC% prokaryotes, placeholder amino acids are likely to be well defined, corresponding to codons enriched in G and/or C at first and second positions. In high-GC% prokaryotes, placeholder amino acids are likely to be less well defined. Increases in ORF GC% as encoded proteins increase in length are greater in mesophiles than in thermophiles, which are constrained from increasing protein lengths in response to base-composition pressures.

Amino Acid Sequence↗
PubMed2006

Members of the Hyposoter didymator Ichnovirus repeat element gene family are differentially expressed in Spodoptera frugiperda.

BACKGROUND: The abundance and the conservation of the repeated element (rep) genes in Ichnoviruses genomes suggest that this gene family plays an important role in viral cycles. In the Ichnovirus associated with the wasp Hyposoter didymator, named HdIV, 10 rep genes were identified to date. In this work, we report a relative quantitative transcription study of these HdIV rep genes in several tissues of the lepidopteran host Spodoptera frugiperda as well as in the H. didymator wasps. RESULTS: The data obtained in this work indicate that, in the early phases of infection (24 hours), HdIV rep genes each display different levels of transcripts in parasitized 2nd instar or HdIV-injected last instar S. frugiperda larvae. Only one, rep1, is significantly transcribed in female wasps. Transcript levels of the HdIV rep genes were found as not correlated to their copy number in HdIV genome. Our results also show that HdIV rep genes display different tissue specificity, and that they are primarily transcribed in S. frugiperda fat body and cuticular epithelium. CONCLUSION: This work is the first quantitative analysis of transcription of the ichnovirus rep gene family, and the first investigation on a correlation between transcript levels and gene copy numbers in Ichnoviruses. Our data indicate that, despite similar gene copy numbers, not all the members of this gene family are significantly transcribed 24 hours after infection in lepidopteran larvae. Additionally, our data show that, as opposed to other described HdIV genes, rep genes are little transcribed in hemocytes, thus suggesting that they are not directly associated with the disruption of the immune response but rather involved in other physiological alterations of the infected lepidopteran larva.

Amino Acid Sequence↗
PubMed2004

Signal sequence analysis of expressed sequence tags from the nematode Nippostrongylus brasiliensis and the evolution of secreted proteins in parasites.

BACKGROUND: Parasitism is a highly successful mode of life and one that requires suites of gene adaptations to permit survival within a potentially hostile host. Among such adaptations is the secretion of proteins capable of modifying or manipulating the host environment. Nippostrongylus brasiliensis is a well-studied model nematode parasite of rodents, which secretes products known to modulate host immunity. RESULTS: Taking a genomic approach to characterize potential secreted products, we analyzed expressed sequence tag (EST) sequences for putative amino-terminal secretory signals. We sequenced ESTs from a cDNA library constructed by oligo-capping to select full-length cDNAs, as well as from conventional cDNA libraries. SignalP analysis was applied to predicted open reading frames, to identify potential signal peptides and anchors. Among 1,234 ESTs, 197 (~16%) contain predicted 5' signal sequences, with 176 classified as conventional signal peptides and 21 as signal anchors. ESTs cluster into 742 distinct genes, of which 135 (18%) bear predicted signal-sequence coding regions. Comparisons of clusters with homologs from Caenorhabditis elegans and more distantly related organisms reveal that the majority (65% at P < e-10) of signal peptide-bearing sequences from N. brasiliensis show no similarity to previously reported genes, and less than 10% align to conserved genes recorded outside the phylum Nematoda. Of all novel sequences identified, 32% contained predicted signal peptides, whereas this was the case for only 3.4% of conserved genes with sequence homologies beyond the Nematoda. CONCLUSIONS: These results indicate that secreted proteins may be undergoing accelerated evolution, either because of relaxed functional constraints, or in response to stronger selective pressure from host immunity.

Animals↗
PubMed2006

Discovery of quantitative trait loci for resistance to parasitic nematode infection in sheep: I. Analysis of outcross pedigrees.

BACKGROUND: Currently most pastoral farmers rely on anthelmintic drenches to control gastrointestinal parasitic nematodes in sheep. Resistance to anthelmintics is rapidly increasing in nematode populations such that on some farms none of the drench families are now completely effective. It is well established that host resistance to nematode infection is a moderately heritable trait. This study was undertaken to identify regions of the genome, quantitative trait loci (QTL) that contain genes affecting resistance to parasitic nematodes. RESULTS: Rams obtained from crossing nematode parasite resistant and susceptible selection lines were used to derive five large half-sib families comprising between 348 and 101 offspring per sire. Total offspring comprised 940 lambs. Extensive measurements for a range of parasite burden and immune function traits in all offspring allowed each lamb in each pedigree to be ranked for relative resistance to nematode parasites. Initially the 22 most resistant and 22 most susceptible progeny from each pedigree were used in a genome scan that used 203 microsatellite markers spread across all sheep autosomes. This study identified 9 chromosomes with regions showing sufficient linkage to warrant the genotyping of all offspring. After genotyping all offspring with markers covering Chromosomes 1, 3, 4, 5, 8, 12, 13, 22 and 23, the telomeric end of chromosome 8 was identified as having a significant QTL for parasite resistance as measured by the number of Trichostrongylus spp. adults in the abomasum and small intestine at the end of the second parasite challenge. Two further QTL for associated immune function traits of total serum IgE and T. colubiformis specific serum IgG, at the end of the second parasite challenge, were identified on chromosome 23. CONCLUSION: Despite parasite resistance being a moderately heritable trait, this large study was able to identify only a single significant QTL associated with it. The QTL concerned adult parasite burdens at the end of the second parasite challenge when the lambs were approximately 6 months old. Our failure to discover more QTL suggests that most of the genes controlling this trait are of relatively small effect. The large number of suggestive QTL discovered (more than one per family per trait than would be expected by chance) also supports this conclusion.

Animals↗
PubMed2004

Current epidemiology of atopic dermatitis in south-eastern Nigeria.

BACKGROUND: Atopic dermatitis (AD) is a common pruritic, eczematous skin disorder that runs a chronic and relapsing course. In Nigeria, it is currently on the increase, particularly amongst infants, and has created cost burdens for families. It occurs in association with a personal or family history of asthma, allergic rhinitis and conjunctivitis. Major and minor criteria exist as guidelines for arriving at a diagnosis of AD, and surveys from Western countries have shown that these features, in particular the minor features, vary with ethnicity and genetic background and can be used to aid diagnosis. African dermatologists have also voiced concern that the much used Hanifin criteria for diagnosis of AD may need some adaptation for use in Africa. OBJECTIVE: To document the features and disease outcomes of AD seen amongst dermatology hospital patients in Enugu, south-eastern Nigeria, with a view to reflecting current features amongst Nigerian Blacks. METHODS: A prospective study of AD patients seen over a 2-year period at a tertiary referral dermatology clinic (University of Nigeria Teaching Hospital, Enugu, Nigeria) was carried out. A total of 1019 patients aged between 4 weeks and 57 years were included in the study. RESULTS: The prevalence of AD was 8.5%, which is much higher than the prevalence of AD reported in various parts of Nigeria 15 years ago. AD occurred before the age of 10 years in 523 (51.3%) patients, whilst 250 (24.5%) had onset after 21 years. The earliest age of onset in infants was in the first 6 weeks of life, and this was found in 129 patients (12.7%). Education and occupation of household heads were the most significant (P < 0.001) factors associated with seeking proper health care for the child's AD. Four hundred and forty-one (43.3%) patients presented with subacute atopic eczema and 326 (32%) patients with severe impeteginized eczema. Four hundred and twenty-five patients (41.7%) had at least one first-degree family member with AD (16.7%), allergic rhinitis (10.3%), asthma (14.6%) and allergic conjunctivitis (2.1%), while 55 (13.3%) of controls had a positive family history (P < 0.01) of allergy. A personal history of AD only, without concomitant respiratory allergies, was seen in 486 (47.7%) patients. The face was affected in 431 (42.3%) patients. Inverse distribution of a flexural rash was observed over the extensor aspect of the joints: the elbow in 502 patients (49.3%), the wrist joint in 183 patients (17.9%) and the knee joints in 354 patients (34.7). The commonly observed minor features included xerosis in 719 patients (71%), papular lichenoid lesions in 547 patients (54.1%), infraorbital folds in 498 patients (49.2%), palmar hyper linearity in 524 patients (51.8%) and raised peripheral blood eosinophils in 519 patients (51%), particularly for those with severe AD. Fissured heels, forehead lichenification, orbital darkening, nail pitting, sand paper-like skin lesions on the elbows/knees/lateral malleolli, knuckle dermatitis of the hands, palmar erythema and pitted keratolysis occurred more uncommonly as minor features. Infective complications were very common and included bacterial infections (folliculitis, impetiginized dermatitis and pyodermas) in 425 (41.7%) patients, fungal infections in 377 (37%) patients, parasitic infections (scabies) in 90 (8.8%) patients and viral infection (herpes simplex and molluscum contagiosum) in 29 (2.9%) patients. Thirteen of these atopics were also HIV positive. Aggravating factors most commonly reported included heat intolerance, excessive sweating, humidity, grass intolerance, thick woollen clothing and drug reactions. Only three patients had food intolerance. Three hundred and ten patients (30.4%) recalled their AD being worse in the hot humid periods and 383 (37.6%) could not recall any periods of relief or remission. CONCLUSIONS: The prevalence of AD amongst south-eastern Nigerian Blacks is on the increase, as in other areas, although it is still lower here than in other parts of the world. Many conventional minor features were found, but some occurred less frequently than in other countries, which may be attributed to ethnicity. Further studies will be required to confirm the ethnic differences in these features of AD amongst Nigerians and other Africans, to clarify the features of AD that are peculiar to Africans.

Adolescent↗
PubMed1992

Astrocyte activation correlates with cytokine production in central nervous system of Trypanosoma brucei brucei-infected mice.

BACKGROUND: During the late-stage disease associated with human African trypanosomiasis, caused by infection with either Trypanosoma gambiense or T. rhodesiense, parasites invade the central nervous system (CNS), eventually leading to development of CNS pathology. This can be exacerbated by subcurative chemotherapy. The mechanisms through which the inflammatory processes within the CNS are controlled remain unclear. EXPERIMENTAL DESIGN: Mice infected with T. b. brucei were treated with a trypanocidal drug regimen on day 28 postinfection that cleared parasites from all sites except the brain. Brains of mice killed at different times during infection and after chemotherapy were analyzed, using immunocytochemistry for astrocyte activation and polymerase chain reaction assisted amplification of RNA to detect cytokine transcripts. RESULTS: Drug-treated animals developed a posttreatment meningoencephalitis similar to that which can occur in humans with late-stage African trypanosomiasis. Between days 14 and 21 postinfection, before chemotherapy and the subsequent development of inflammatory lesions in the brain, astrocytes became activated. The production of several cytokines correlated with this astrocyte activation. Low levels of interleukin-1 alpha transcripts were detected in uninfected controls, but levels increased with astrocyte activation in the infected animals. Transcripts for the macrophage inflammatory protein-1 and tumor necrosis factor-alpha were first detected on day 21 postinfection, with higher levels in mice after development of the posttreatment meningoencephalitis, whereas granulocyte macrophage-colony stimulating factor was detected only in animals that developed posttreatment reaction. Interleukin-6 and interferon-gamma were also first detected on day 21 postinfection, correlating with astrocyte activation but subsequently declined with time in both treated and untreated mice. CONCLUSIONS: These results indicate that cytokines are being produced within the CNS before any inflammation and that astrocytes may be the source of some of these cytokines. Thus astrocyte activation may be key in the control and development of the CNS inflammatory processes that occur in African sleeping sickness.

Animals↗
PubMedDate not supplied

A 63 kDa VSP9B10A-like protein expressed in a C-8 Giardia duodenalis Mexican clone.

BACKGROUND: It is well documented that Giardia duodenalis undergoes surface antigenic variation both in vivo and in vitro. Proteins involved have been characterized and referred to as VSP (variable surface protein). METHODS: Two cloned cDNA inserts of 0.45 and 1.95 kb were obtained from G. duodenalis expression library and sequenced. Comparison sequence analyses were made against Genbank. PCR analysis was performed on G. duodenalis isolates to identify isolates bearing genes encoding such a peptide. Specific antiserum was prepared against 450-bp encoded peptide and tested by Western blot, immunofluorescence, and inhibition of adhesion of G. duodenalis to target cells. RESULTS: We cloned and characterized a G. duodenalis 450-bp DNA fragment; its DNA sequence analysis revealed that this fragment displayed 99% identity with vsp9B10A gene. Predicted amino acid sequence for this fragment also had significant (99%) identity to VSP9B10A. A second 1.95-kb insert, which encompassed the 450-bp cDNA fragment, was also isolated; its DNA and amino acid sequence displayed 99.5% identity with vsp9B10A gene and 99.2% with the corresponding inferred protein, respectively. This inferred protein contained 24 Cys-X-X-Cys motifs and long ORF of 642 aminoacids. PCR analysis showed that DNA sequence encoding a fragment of this gene was present in P1, CIEA:0487:2-C-8 clone and in INP:180800-B2 G. duodenalis human isolates, while it was absent in sheep isolate of G. duodenalis INP:150593-J10. CONCLUSIONS: Immunofluorescence analysis using antibodies raised against the peptide encoded by 450-bp fragment showed that expression of this epitope varies on trophozoite surface of the C-8 Mexican clone and is involved in parasite adhesion to target epithelial cells.

Amino Acid Sequence↗
PubMed2005

Comparative analysis of the kinomes of three pathogenic trypanosomatids: Leishmania major, Trypanosoma brucei and Trypanosoma cruzi.

BACKGROUND: The trypanosomatids Leishmania major, Trypanosoma brucei and Trypanosoma cruzi cause some of the most debilitating diseases of humankind: cutaneous leishmaniasis, African sleeping sickness, and Chagas disease. These protozoa possess complex life cycles that involve development in mammalian and insect hosts, and a tightly coordinated cell cycle ensures propagation of the highly polarized cells. However, the ways in which the parasites respond to their environment and coordinate intracellular processes are poorly understood. As a part of an effort to understand parasite signaling functions, we report the results of a genome-wide analysis of protein kinases (PKs) of these three trypanosomatids. RESULTS: Bioinformatic searches of the trypanosomatid genomes for eukaryotic PKs (ePKs) and atypical PKs (aPKs) revealed a total of 176 PKs in T. brucei, 190 in T. cruzi and 199 in L. major, most of which are orthologous across the three species. This is approximately 30% of the number in the human host and double that of the malaria parasite, Plasmodium falciparum. The representation of various groups of ePKs differs significantly as compared to humans: trypanosomatids lack receptor-linked tyrosine and tyrosine kinase-like kinases, although they do possess dual-specificity kinases. A relative expansion of the CMGC, STE and NEK groups has occurred. A large number of unique ePKs show no strong affinity to any known group. The trypanosomatids possess few ePKs with predicted transmembrane domains, suggesting that receptor ePKs are rare. Accessory Pfam domains, which are frequently present in human ePKs, are uncommon in trypanosomatid ePKs. CONCLUSION: Trypanosomatids possess a large set of PKs, comprising approximately 2% of each genome, suggesting a key role for phosphorylation in parasite biology. Whilst it was possible to place most of the trypanosomatid ePKs into the seven established groups using bioinformatic analyses, it has not been possible to ascribe function based solely on sequence similarity. Hence the connection of stimuli to protein phosphorylation networks remains enigmatic. The presence of numerous PKs with significant sequence similarity to known drug targets, as well as a large number of unusual kinases that might represent novel targets, strongly argue for functional analysis of these molecules.

Animals↗
PubMed1999

High-resolution structure of the conger eel galectin, congerin I, in lactose-liganded and ligand-free forms: emergence of a new structure class by accelerated evolution.

BACKGROUND: Congerin I is a member of the galectin (animal beta-galactoside-binding lectin) family and is found in the skin mucus of conger eel. The galectin family proteins perform a variety of biological activities. Because of its histological localization and activity against marine bacteria and starfish embryos, congerin I is thought to take part in the eels' biological defense system against parasites. RESULTS: The crystal structure of congerin I has been determined in both lactose-liganded and ligand-free forms to 1. 5 A and 1.6 A resolution, respectively. The protein is a homodimer of 15 kDa subunits. Congerin I has a beta-sheet topology that is markedly different from those of known relatives. One of the beta-strands is exchanged between two identical subunits. This strand swap might increase the dimer stability. Of the known galectin complexes, congerin I forms the most extensive interaction with lactose molecules. Most of these interactions are substituted by similar interactions with water molecules, including a pi-electron hydrogen bond, in the ligand-free form. This observation indicates an increased affinity of congerin I for the ligand. CONCLUSIONS: The genes for congerin I and an isoform, congerin II, are known to have evolved under positive selection pressure. The strand swap and the modification in the carbohydrate-binding site might enhance the cross-linking activity, and should be the most apparent consequence of positive selection. The protein has been adapted to functioning in skin mucus that is in direct contact with surrounding environments by an enhancement in cross-linking activity. The structure of congerin I demonstrates the emergence of a new structure class by accelerated evolution under selection pressure.

Amino Acid Sequence↗
PubMedDate not supplied

Transfection and physical properties of various saccharide, poly(ethylene glycol), and antibody-derivatized polyethylenimines (PEI).

BACKGROUND: The ideal non-viral vector should be cell-type directed and form complexes with DNA that are physically stable, small and electrically neutral. METHODS: We have synthesized several PEI derivatives that coat the PEI/DNA complexes with water-soluble residues able to stabilize the particles, to mask their surface charge and eventually to direct them to a particular tissue. The morphologies and sizes of the complexes were observed by TEM and DLS techniques, and their apparent surface charge was quantitated by zeta potential measurements; in vitro transfection efficacies were determined in serum-containing cell culture medium. RESULTS: When compared to DNA complexes formed with the unmodified PEI, extensive grafting with maltose (15-25% of the amine functions) led to beneficial electrostatic shielding of the particle surface, but was unable to prevent aggregation in physiological salt concentration. More extended hydrophilic residues were therefore explored as a mean of physical repulsion between the particles. Low grafting (2.7%) with a linear dextran non-asaccharide led to small and stable toroids having no apparent surface charge, yet still reaching effective transfection levels. Electron microscopy of complexes with a higher extent of grafting showed worm-like structures unsuited for cell entry. Conjugation of PEI with as little as 0.5% of a terminally galactose-derivatized polyethyleneglycol (PEG)-3400 also gave neutral complexes of another worm-like structure that failed to transfect receptor-expressing hepatocytes. CONCLUSION: These results show that conjugation of large and flexible hydrophilic residues to PEI, while protecting the complexes from parasitic interactions also interfere with DNA condensation. PEG conjugation after PEI/DNA complex formation may avoid this problem, provided intracomplex reorganization is slow. Finally an anti-GD2 antibody (mAb) grafted with PEI was synthesized. The corresponding protein-coated DNA complexes were compact and small (50-60 nm), yet did not enhance transfection of GD2 ganglioside-expressing cells.

Animals↗
PubMed2005

A2 gene of Old World cutaneous Leishmania is a single highly conserved functional gene.

BACKGROUND: Leishmaniases are among the most proteiform parasitic infections in humans ranging from unapparent to cutaneous, mucocutaneous or visceral diseases. The various clinical issues depend on complex and still poorly understood mechanisms where both host and parasite factors are interacting. Among the candidate factors of parasite virulence are the A2 genes, a family of multiple genes that are developmentally expressed in species of the Leishmania donovani group responsible for visceral diseases (VL). By contrast, in L. major determining cutaneous infections (CL) we showed that A2 genes are present in a truncated form only. Furthermore, the A2 genomic sequences of L. major were considered subsequently to represent non-expressed pseudogenes 1. Consequently, it was suggested that the structural and functional properties of A2 genes could play a role in the differential tropism of CL and VL leishmanias. On this basis, it was of importance to determine whether the observed structural/functional particularities of the L. major A2 genes were shared by other CL Leishmania, therefore representing a proper characteristic of CL A2 genes as opposed to those of VL isolates. METHODS: In the present study we amplified by PCR and sequenced the A2 genes from genomic DNA and from clonal libraries of the four Old World CL species comparatively to a clonal population of L. infantum VL parasites. Using RT-PCR we also amplified and sequenced A2 mRNA transcripts from L. major. RESULTS: A unique A2 sequence was identified in Old World cutaneous Leishmania by sequencing. The shared sequence was highly conserved among the various CL strains and species analysed, showing a single polymorphism C/G at position 58. The CL A2 gene was found to be functionally transcribed at both parasite stages. CONCLUSION: The present study shows that cutaneous strains of leishmania share a conserved functional A2 gene. As opposed to the multiple A2 genes described in VL isolates, the CL A2 gene is unique, lacking most of the nucleotide repeats that constitute the variable region at the 5'end of the VL A2 sequences. As the variable region of the VL A2 gene has been shown to correspond to a portion of the protein which is highly immunogenic, the present results support the hypothesis of a possible role of the A2 gene in the differential tropism of CL and VL leishmania parasites.

Animals↗
PubMed2005

Avoid, attack or do both? Behavioral and physiological adaptations in natural enemies faced with novel hosts.

BACKGROUND: Confronted with well-defended, novel hosts, should an enemy invest in avoidance of these hosts (behavioral adaptation), neutralization of the defensive innovation (physiological adaptation) or both? Although simultaneous investment in both adaptations may first appear to be redundant, several empirical studies have suggested a reinforcement of physiological resistance to host defenses with additional avoidance behaviors. To explain this paradox, we develop a mathematical model describing the joint evolution of behavioral and physiological adaptations on the part of natural enemies to their host defenses. Our specific goals are (i) to derive the conditions that may favor the simultaneous investment in avoidance and physiological resistance and (ii) to study the factors that govern the relative investment in each adaptation mode. RESULTS: Our results show that (i) a simultaneous investment may be optimal if the fitness costs of the adaptive traits are accelerating and the probability of encountering defended hosts is low. When (i) holds, we find that (ii) the more that defended hosts are rare and/or spatially aggregated, the more behavioral adaptation is favored. CONCLUSION: Despite their interference, physiological resistance to host defensive innovations and avoidance of these same defenses are two strategies in which it may be optimal for an enemy to invest in simultaneously. The relative allocation to each strategy greatly depends on host spatial structure. We discuss the implications of our findings for the management of invasive plant species and the management of pest resistance to new crop protectants or varieties.

Adaptation, Biological↗
PubMed2005

The transcriptome of Toxoplasma gondii.

BACKGROUND: Toxoplasma gondii gives rise to toxoplasmosis, among the most prevalent parasitic diseases of animals and man. Transformation of the tachzyoite stage into the latent bradyzoite-cyst form underlies chronic disease and leads to a lifetime risk of recrudescence in individuals whose immune system becomes compromised. Given the importance of tissue cyst formation, there has been intensive focus on the development of methods to study bradyzoite differentiation, although the molecular basis for the developmental switch is still largely unknown. RESULTS: We have used serial analysis of gene expression (SAGE) to define the Toxoplasma gondii transcriptome of the intermediate-host life cycle that leads to the formation of the bradyzoite/tissue cyst. A broad view of gene expression is provided by >4-fold coverage from nine distinct libraries (approximately 300,000 SAGE tags) representing key developmental transitions in primary parasite populations and in laboratory strains representing the three canonical genotypes. SAGE tags, and their corresponding mRNAs, were analyzed with respect to abundance, uniqueness, and antisense/sense polarity and chromosome distribution and developmental specificity. CONCLUSION: This study demonstrates that phenotypic transitions during parasite development were marked by unique stage-specific mRNAs that accounted for 18% of the total SAGE tags and varied from 1-5% of the tags in each developmental stage. We have also found that Toxoplasma mRNA pools have a unique parasite-specific composition with 1 in 5 transcripts encoding Apicomplexa-specific genes functioning in parasite invasion and transmission. Developmentally co-regulated genes were dispersed across all Toxoplasma chromosomes, as were tags representing each abundance class, and a variety of biochemical pathways indicating that trans-acting mechanisms likely control gene expression in this parasite. We observed distinct similarities in the specificity and expression levels of mRNAs in primary populations (Day-6 post-sporozoite infection) that occur prior to the onset of bradyzoite development that were uniquely shared with the virulent Type I-RH laboratory strain suggesting that development of RH may be arrested. By contrast, strains from Type II-Me49B7 and Type III-VEGmsj contain SAGE tags corresponding to bradyzoite genes, which suggests that priming of developmental expression likely plays a role in the greater capacity of these strains to complete bradyzoite development.

Animals↗
PubMed2006

Seasonal childhood anaemia in West Africa is associated with the haptoglobin 2-2 genotype.

BACKGROUND: Anaemia is a major cause of morbidity and mortality for children in Africa. The plasma protein haptoglobin (Hp) binds avidly to free haemoglobin released following malaria-induced haemolysis. Haptoglobin polymorphisms result in proteins with altered haemoglobin-binding capacity and different antioxidant, iron-recycling, and immune functions. Previous studies examined the importance of haptoglobin polymorphism in malaria and iron homeostasis, but it is unknown whether haptoglobin genotype might be a risk factor for anaemia in children in a malaria-endemic area. METHODS AND FINDINGS: A cohort of 780 rural Gambian children aged 2-6 y was surveyed at the start and end of the malaria season. Samples were taken to assess haemoglobin (Hb) concentration, iron status (ferritin, zinc protoporphyrin, transferrin saturation, and soluble transferrin receptor concentration), haptoglobin concentration, alpha-1-antichymotrypsin (a measure of inflammation), and malaria parasites on blood film. We extracted DNA and genotyped for haptoglobin, sickle cell, and glucose-6-phosphate (G6PD) deficiency. Mean Hb levels fell over the malaria season. Children with the haptoglobin 2-2 genotype (17%) had a greater mean drop in Hb level over the malaria season (an 8.9 g/l drop; confidence interval [CI] 5.7, 12.1) compared to other children (a 5.1 g/l drop; CI 3.8, 6.4). In multivariate regression analysis, controlling for baseline Hb level, age group, village, malaria parasites on blood film, iron status, haptoglobin concentration, and G6PD deficiency, haptoglobin genotype predicted Hb level at the end of the malaria season (p = 0.0009, coefficient = -4.2). Iron status was not influenced by haptoglobin genotype. CONCLUSIONS: The finding that haptoglobin 2-2 genotype is a risk factor for anaemia in children in a malaria-endemic area may reflect the reduced ability of the Hp2-2 polymer to scavenge free haemoglobin-iron following malaria-induced haemolysis. The magnitude of the effect of haptoglobin genotype (4 g/l Hb difference, p = 0.0009) was comparable to that of G6PD deficiency or HbAS (3 g/l difference, p = 0.03; and 2 g/l difference, p = 0.68, respectively).

Anemia↗
PubMed2006

Assortative mating and differential male mating success in an ash hybrid zone population.

BACKGROUND: The structure and evolution of hybrid zones depend mainly on the relative importance of dispersal and local adaptation, and on the strength of assortative mating. Here, we study the influence of dispersal, temporal isolation, variability in phenotypic traits and parasite attacks on the male mating success of two parental species and hybrids by real-time pollen flow analysis. We focus on a hybrid zone population between the two closely related ash species Fraxinus excelsior L. (common ash) and F. angustifolia Vahl (narrow-leaved ash), which is composed of individuals of the two species and several hybrid types. This population is structured by flowering time: the F. excelsior individuals flower later than the F. angustifolia individuals, and the hybrid types flower in-between. Hybrids are scattered throughout the population, suggesting favorable conditions for their local adaptation. We estimate jointly the best-fitting dispersal kernel, the differences in male fecundity due to variation in phenotypic traits and level of parasite attack, and the strength of assortative mating due to differences in flowering phenology. In addition, we assess the effect of accounting for genotyping error on these estimations. RESULTS: We detected a very high pollen immigration rate and a fat-tailed dispersal kernel, counter-balanced by slight phenological assortative mating and short-distance pollen dispersal. Early intermediate flowering hybrids, which had the highest male mating success, showed optimal sex allocation and increased selfing rates. We detected asymmetry of gene flow, with early flowering trees participating more as pollen donors than late flowering trees. CONCLUSION: This study provides striking evidence that long-distance gene flow alone is not sufficient to counter-act the effects of assortative mating and selfing. Phenological assortative mating and short-distance dispersal can create temporal and spatial structuring that appears to maintain this hybrid population. The asymmetry of gene flow, with higher fertility and increased selfing, can potentially confer a selective advantage to early flowering hybrids in the zone. In the event of climate change, hybridization may provide a means for F. angustifolia to further extend its range at the expense of F. excelsior.

Evolution, Molecular↗
PubMed2002

Transforming growth factor-beta1 mediates coexpression of the integrin subunit alphaE and the chymase mouse mast cell protease-1 during the early differentiation of bone marrow-derived mucosal mast cell homologues.

BACKGROUND: Mucosal mast cells (MMC) play a central role in gut hypersensitivities and inflammation. They are morphologically, biochemically and functionally distinct from their connective tissue counterparts. Massive hyperplasia of MMC occurs 7-10 days after intestinal infection with nematodes but it has never been possible to replicate this phenomenon in vitro. OBJECTIVE: (1) To determine whether mouse bone marrow-derived mast cells (mBMMC) grown in the presence of transforming growth factor (TGF)-beta1 could develop over the same time frame (7-10 days) as MMC in parasitized mice. (2) To compare the early expression of surface receptors (integrins alphaE and beta7, c-kit and FcepsilonR) with that of the MMC-specific granule chymase mouse mast cell protease-1 (mMCP-1). METHODS: Mouse bone marrow cells were cultured in the presence of IL-9, IL-3 and Stem Cell Factor (SCF) with or without TGF-beta1. mBMMC were quantified after toluidine blue or Leishmans' staining. Expression of MMC-specific mouse mast cell proteases was analysed by ELISA, immunohistochemistry and RT-PCR. Surface antigen expression was characterized by flow cytometry and confocal microscopy. RESULTS: TGF-beta1 promotes the development of abundant MMC-like mBMMC from bone marrow progenitor cells with kinetics, which closely parallel that seen in vivo. mRNA transcripts encoding mMCP-1 and -2 are readily detectable by day 4 ex vivo in cultures grown in the presence of TGF-beta1. Between 30 and 40% and 75-90% of the cells in these cultures on days 4 and 7, respectively, have typical mast cell morphology, are c-kit+, FcepsilonR+, integrin alphaEbeta7+, and express and secrete abundant mMCP-1. The integrin alphaE subunit is coexpressed with mMCP-1. CONCLUSION: The kinetics of mMCP-1+/alphaE+ mBMMC development, regulated by TGF-beta1, are consistent with that seen in vivo in the parasitized intestine. The normally down-regulatory functions of TGF-beta1 in haematopoiesis are superseded in this culture system by its ability to promote the early expression of alphaE and mMCP-1.

Animals↗