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Biomedical subjects

A Crisanti

Publications and source records attributed to A Crisanti.

At least 19 recordsLinked to original sources
PubMed2004

Spherical 2 + p spin-glass model: an exactly solvable model for glass to spin-glass transition.

We present the full phase diagram of the spherical 2 + p spin-glass model with p > or = 4. The main outcome is the presence of a phase with both properties of full replica symmetry breaking phases of discrete models, e.g., the Sherrington-Kirkpatrick model, and those of one replica symmetry breaking. This phase has a finite complexity which leads to different dynamic and static properties. The phase diagram is rich enough to allow the study of different kinds of glass to spin glass and spin glass to spin glass phase transitions.

Journal Article↗
PubMed2004

Spin-glass complexity.

We study the quenched complexity in spin-glass mean-field models satisfying the Becchi-Rouet-Stora-Tyutin supersymmetry. The outcome of such study, consistent with recent numerical results, allows, in principle, to conjecture the absence of any supersymmetric contribution to the complexity in the Sherrington-Kirkpatrick model. The same analysis can be applied to any model with a full replica symmetry breaking phase, e.g., the Ising p-spin model below the Gardner temperature. The existence of different solutions, breaking the supersymmetry, is also discussed.

Journal Article↗
PubMed2004

Serodiagnosis of infectious diseases with antigen microarrays.

AIMS: To generate protein microarrays by printing microbial antigens on slides to enable the simultaneous determination in human sera of antibodies directed against Toxoplasma gondii, rubella virus, cytomegalovirus and herpes simplex virus (HSV) types 1 and 2. METHODS AND RESULTS: Antigens were printed on activated glass slides using high-speed robotics. The slides were incubated with serum samples and subsequently with fluorescently labelled secondary antibodies. Human IgG and IgM bound to the printed antigens were detected using confocal scanning microscopy and quantified with internal calibration curves. The microarray assay could detect as little as 0.5 pg of both IgG and IgM bound onto the glass surface. Precision profiles ranged from 1.7 to 18.5% for all the antigens. Microarrays and commercial ELISAs were utilized to detect serum antibodies against the ToRCH antigens in a panel of characterized human sera. Overall >80% concordance was obtained between microarray and ELISA kits in the classification of sera. CONCLUSIONS: These results indicate that the microarray is a suitable assay format for the serodiagnosis of infectious diseases. SIGNIFICANCE AND IMPACT OF STUDY: Antigen microarrays can be optimized for clinical use, their performance is equivalent to ELISA but they offer significant advantages in throughput, convenience and cost.

Animals↗
PubMed2003

Chaos in temperature in the Sherrington-Kirkpatrick model.

We prove the existence of chaos in temperature in the Sherrington-Kirkpatrick model. The effect is exceedingly small, namely, of the ninth order in perturbation theory. The equations describing two systems at different temperatures constrained to have a fixed overlap are studied analytically and numerically, yielding information about the behavior of the overlap distribution function PT1(,T2)(q) in finite-size systems.

Journal Article↗
PubMed2003

Clinical efficacy and cost-effectiveness evidence of spa therapy in osteoarthritis. The results of "Naiade" Italian Project.

AIM: The "Naiade" Project was carried out in execution of the Decree of December 1994 by the Italian Ministry of Health, with the objective of defining the therapeutic role of spa therapy in the various sectors of medicine. In this study the authors refer to the results obtained in osteoarthritis (OA). METHODS: The OA study included the observation of patients for 2 consecutive years, with the compilation of a series of clinical and socio-economic data. The initial sample was of 11437 patients suffering from primary and secondary OA, and in the 2(nd) year the total number of assessable patients was 6111 (53.4%). All patients underwent 1 annual cycle of balneotherapy and mud packs therapy for 2 consecutive years. The thermal treatments were carried out in 98 Italian spas with sulphurous water, sodium chloride-bromide-iodide water, sulphate water, and bicarbonate water. Analysis of the data collected confirmed the clinical efficacy of spa treatments for OA, particularly for localisations in the cervical and lumbar spine. The benefits of these treatments and the persistence of the therapeutic effects over time were clearly demonstrated by the collection of some socio-economic indicators relative to the year before each cycle of thermal therapy. RESULTS: In fact, the analysis of these indicators showed a significant reduction in recourse to additional treatments (hospital admissions, physical and pharmacological therapies) and absence from work. CONCLUSION: The obtained data was particularly interesting for the number of samples examined, the follow-up over a period of 2 years, and the collection of clinical and, especially, socio-economic parameters. The results of the Naiade Project confirmed the value of spa therapies in the treatment of OA.

Balneology↗
PubMed2003

[Epidemiology of malaria in a village of Sudanese savannah in Mali (Bancoumana). Anti-TRAP and anti-CS humoral immunity response].

Vaccine development research is an important component of malaria control strategies. Thrombospondin related anonymous protein (TRAP) and the circumsporozoite (CS) protein are two antigens of sporozoite surface. Immune response to these two antigens may contribute to the development of anti-sporozoite vaccine. Recent studies suggest that antibodies anti-TRAP may partially block sporozoites penetration in hepatocyte, and thereby reducing malaria morbidity. We carried out a study to assess the seroprevalence of anti-TRAP and anti-CS antibodies and to identify a possible role of these antibodies on malaria morbidity in children 1-9 years old living in a rural hyperendemic village. We performed 5 cross sectional surveys and a longitudinal follow up in 1993 and 1994. During each cross sectional study, children were examined for fever and splenomegaly; all febrile children received thick film examination, and serologic analysis was performed in one third of these, randomly selected. The results show that the seroprevalence of anti-TRAP and anti-CS varied with age and season (p < 0.05). Association between the prevalence of anti-TRAP and splenomegaly was observed during two cross sectional surveys (June and October 1993). The presence of anti-TRAP antibody was associated with Plasmodium falciparum infection at the beginning of the transmission season (June 1993 and July 1994). A negative association between the level of anti-TRAP title and parasitemia was observed (March and October 1994). These findings suggest no clear evidence of the protective role of anti-TRAP antibodies in uncomplicated malaria, possibly due to the limited persistence of these antibodies under natural situations.

Antibodies, Protozoan↗
PubMed2002

First-order phase transition and phase coexistence in a spin-glass model.

We study the mean-field static solution of the Blume-Emery-Griffiths-Capel model with quenched disorder, an Ising-spin lattice gas with random magnetic interaction. The thermodynamics is worked out in the full replica symmetry breaking scheme. The model exhibits a high temperature/low density paramagnetic phase. As temperature decreases or density increases, a phase transition to a full replica symmetry breaking spin-glass phase occurs. The nature of the transition can be either of the second order or, at temperature below a given critical value, of the first order in the Ehrenfest sense, with a discontinuous jump of the order parameter, a latent heat, and coexistence of phases.

Journal Article↗
PubMed2002

Analysis of the infinity-replica symmetry breaking solution of the Sherrington-Kirkpatrick model.

In this work we analyze the Parisi infinity-replica symmetry breaking solution of the Sherrington-Kirkpatrick model without external field using high order perturbative expansions. The predictions are compared with those obtained from the numerical solution of the infinity-replica symmetry breaking equations, which are solved using a pseudospectral code that allows for very accurate results. With these methods we are able to get more insight into the analytical properties of the solutions. We are also able to determine numerically the end point x(max) of the plateau of q(x) and find that lim(T-->0)x(max)(T)>0.5.

Journal Article↗
PubMed2001

A prime-boost immunisation regimen using DNA followed by recombinant modified vaccinia virus Ankara induces strong cellular immune responses against the Plasmodium falciparum TRAP antigen in chimpanzees.

Two chimpanzees were vaccinated intramuscularly against malaria using plasmid DNA expressing the pre-erythrocytic antigens thrombospondin related adhesion protein (PfTRAP) and liver stage specific antigen-1 (PfLSA-1) of Plasmodium falciparum together with GM-CSF protein. A recombinant modified vaccinia virus Ankara (MVA) expressing PfTRAP was injected intramuscularly 6 weeks later to boost the immune response. This sequence of antigen delivery induced a specific and long-lasting T cell and antibody response to PfTRAP as detected by ELISPOT assay and ELISA. Antibody responses were detected after four DNA injections, and were boosted by injection of recombinant MVA expressing PfTRAP. Interferon-gamma secreting antigen-specific T cells were detected in both animals, but only after boosting with recombinant MVA. By screening a panel of PfTRAP-derived peptides, an epitope was identified that was recognized by cytotoxic T lymphocytes in one of the chimpanzees studied. T cells specific for this epitope were present in PBMCs and liver-infiltrating lymphocytes at a frequency of between 1 in 200 and 1 in 500. The high immunogenicity of this prime-boost regimen in chimpanzees supports further assessment of this delivery strategy for the induction of protection against P. falciparum malaria in humans.

Animals↗
PubMed2001

Nuclear factors bind to a conserved DNA element that modulates transcription of Anopheles gambiae trypsin genes.

The Anopheles gambiae trypsin family consists of seven genes that are transcribed in the gut of female mosquitoes in a temporal coordinated and mutually exclusive manner, suggesting the involvement of a complex transcription regulatory mechanism. We identified a highly conserved 12-nucleotide motif present in all A. gambiae and Anopheles stephensi trypsin promoters. We investigated the role of this putative trypsin regulatory element (PTRE) in controlling the transcription of the trypsin genes. Gel shift experiments demonstrated that nuclear proteins of A. gambiae cell lines formed two distinct complexes with probes encompassing the PTRE sequence. Mapping of the binding sites revealed that one of the complex has the specificity of a GATA transcription factor. Promoter constructs containing mutations in the PTRE sequence that selectively abolished the binding of either one or both complexes exerted opposite effects on the transcriptional activity of trypsin promoters in A. gambiae and Aedes aegypti cell lines. In addition, the expression of a novel GATA gene was highly enriched in A. gambiae guts. Taken together our data prove that factors binding to the PTRE region are key regulatory elements possibly involved in the blood meal-induced repression and activation of transcription in early and late trypsin genes.

Amino Acid Sequence↗
PubMed2001

Cloning and phylogenetic analysis of the ribosomal internal transcribed spacer-1 (ITS1) of Cryptosporidium wrairi and its relationship to C. parvum genotypes.

We have cloned and sequenced the ribosomal internal transcribed spacer-1 (ITS1) of Cryptosporidium wrairi. Phylogenetic analysis of this region provided further support to the validity of C. wrairi as a distinct species and also to the concept that many of the genotypes recently identified within C. parvum are in fact separate species. Analysis placed the "cattle" and "mouse" genotypes of C. parvum as each other's closest relatives and C. wrairi as a sister group to these two genotypes, followed by the "human" genotype.

Animals↗
PubMed2000

Stable germline transformation of the malaria mosquito Anopheles stephensi.

Anopheline mosquito species are obligatory vectors for human malaria, an infectious disease that affects hundreds of millions of people living in tropical and subtropical countries. The lack of a suitable gene transfer technology for these mosquitoes has hampered the molecular genetic analysis of their physiology, including the molecular interactions between the vector and the malaria parasite. Here we show that a transposon, based on the Minos element and bearing exogenous DNA, can integrate efficiently and stably into the germ line of the human malaria vector Anopheles stephensi, through a transposase-mediated process.

Animals↗
PubMed2000

Cryptosporidium parvum: the many secrets of a small genome.

The coccidium Cryptosporidium parvum is an obligate intracellular parasite of the phylum Apicomplexa. It infects the gastrointestinal tract of humans and livestock, and represents the third major cause of diarrhoeal disease worldwide. Scarcely considered for decades due to its apparently non-pathogenic nature, C. parvum has been studied very actively over the last 15 years, after its medical relevance as a dangerous opportunistic parasite and widespread water contaminant was fully recognised. Despite the lack of an efficient in vitro culture system and appropriate animal models, significant advances have been made in this relatively short period of time towards understanding C. parvum biology, immunology, genetics and epidemiology. Until recently, very little was known about the genome of C. parvum, with even basic issues, such as the number and size of chromosomes, being the object of a certain controversy. With the advent of pulsed field gradient electrophoresis and the introduction of molecular biology techniques, the overall structure and fine organisation of the genome of C. parvum have started to be disclosed. Organised into eight chromosomes distributed in a very narrow range of molecular masses, the genome of C. parvum is one of the smallest so far described among unicellular eukaryotic organisms. Although fewer than 30 C. parvum genes have been cloned so far, information about the overall structure of the parasite genome has increased exponentially over the last 2 years. From the first karyotypic analyses to the recent development of physical maps for individual chromosomes, this review will try to describe the state-of-the-art of our knowledge on the nuclear genome of C. parvum and will discuss the available experimental evidence concerning the presence of extra-chromosomal elements.

Animals↗
PubMed2000

Toward Anopheles transformation: Minos element activity in anopheline cells and embryos.

The ability of the Minos transposable element to function as a transformation vector in anopheline mosquitoes was assessed. Two recently established Anopheles gambiae cell lines were stably transformed by using marked Minos transposons in the presence of a helper plasmid expressing transposase. The markers were either the green fluorescent protein or the hygromycin B phosphotransferase gene driven by the Drosophila Hsp70 promoter. Cloning and sequencing of the integration sites demonstrated that insertions in the cell genome occurred through the action of Minos transposase. Furthermore, an interplasmid transposition assay established that Minos transposase is active in the cytoplasmic environment of Anopheles stephensi embryos: interplasmid transposition events isolated from injected preblastoderm embryos were identified as Minos transposase-mediated integrations, and no events were recorded in the absence of an active transposase. These results demonstrate that Minos vectors are suitable candidates for germ-line transformation of anopheline mosquitoes.

Animals↗
PubMed2000

Two conserved amino acid motifs mediate protein targeting to the micronemes of the apicomplexan parasite Toxoplasma gondii.

The micronemal protein 2 (MIC2) of Toxoplasma gondii shares sequence and structural similarities with a series of adhesive molecules of different apicomplexan parasites. These molecules accumulate, through a yet unknown mechanism, in secretory vesicles (micronemes), which together with tubular and membrane structures form the locomotion and invasion machinery of apicomplexan parasites. Our findings indicated that two conserved motifs placed within the cytoplasmic domain of MIC2 are both necessary and sufficient for targeting proteins to T. gondii micronemes. The first motif is based around the amino acid sequence SYHYY. Database analysis revealed that a similar sequence is present in the cytoplasmic tail of all transmembrane micronemal proteins identified so far in different apicomplexan species. The second signal consists of a stretch of acidic residues, EIEYE. The creation of an artificial tail containing only the two motifs SYHYY and EIEYE in a preserved spacing configuration is sufficient to target the surface protein SAG1 to the micronemes of T. gondii. These findings shed new light on the molecular mechanisms that control the formation of the microneme content and the functional relationship that links these organelles with the endoplasmic reticulum of the parasite.

Amino Acid Motifs↗
PubMed2000

The initiation translation factor eIF-4A of Cryptosporidium parvum is encoded by two distinct mRNA forms and shows DNA sequence polymorphism distinguishing genotype 1 and 2 isolates.

The eukaryotic translation initiation factor eIF-4A is an ATP-dependent RNA helicase involved in ribosome attachment to the 5' end of mRNAs. Employing as a probe a Cryptosporidium parvum genomic amplicon encoding a partial polypeptide related to eIF-4A, we screened a C. parvum sporozoite cDNA library to clone the full length of the gene. Two complete cDNAs were characterized, Cp.F6 and Cp.F10, which consisted of 1,900 and 1,418 bp, respectively. The overlapping portions of the sequences shared 100% identity and encoded a polypeptide of 405 amino acids whose identity to known eIF-4A molecules ranged between 77 and 39%. The 2 cDNAs differed in the length of their respective 3' untranslated regions, of 577 bp in Cp.F6 and 72 bp in Cp.F10, in both of which a putative polyadenylation signal was identified. The structure of the cloned cDNAs, along with genomic Southern blot data indicating that eIF-4A is encoded by a single copy gene, strongly suggested that Cp.F6 and Cp.F10 reflect a differential 3' end processing of mRNA precursors, not observed so far in C. parvum. Northern blot analysis confirmed that the sporozoites express 2 eIF-4A mRNAs and showed that the lower molecular weight transcript is 10- to 20-fold more abundant. We also investigated the polymorphism of the eIF-4A gene and defined a novel polymerase chain reaction-restriction fragment length polymorphism marker discriminating between C. parvum isolates of genotypes 1 and 2.

Amino Acid Sequence↗
PubMed1999

CTRP is essential for mosquito infection by malaria ookinetes.

The malaria parasite suffers severe population losses as it passes through its mosquito vector. Contributing factors are the essential but highly constrained developmental transitions that the parasite undergoes in the mosquito midgut, combined with the invasion of the midgut epithelium by the malaria ookinete (recently described as a principal elicitor of the innate immune response in the Plasmodium-infected insect). Little is known about the molecular organization of these midgut-stage parasites and their critical interactions with the blood meal and the mosquito vector. Elucidation of these molecules and interactions will open up new avenues for chemotherapeutic and immunological attack of parasite development. Here, using the rodent malaria parasite Plasmodium berghei, we identify and characterize the first microneme protein of the ookinete: circumsporozoite- and TRAP-related protein (CTRP). We show that transgenic parasites in which the CTRP gene is disrupted form ookinetes that have reduced motility, fail to invade the midgut epithelium, do not trigger the mosquito immune response, and do not develop further into oocysts. Thus, CTRP is the first molecule shown to be essential for ookinete infectivity and, consequently, mosquito transmission of malaria.

Animals↗