Anti-Leishmania infantum IgG Antibody Avidity in Visceral Leishmaniasis

IgG avidity tests are used to discriminate acute from chronic infections. There are few reports on the IgG avidity profile of patients with visceral leishmaniasis (VL). This study investigated the anti-Leishmania IgG avidity in patients with classic VL (n = 10), patients showing clinical cure after treatment (n = 18), and asymptomatic subjects with at least one positive Leishmania test (n = 20). All subjects were from areas in Brazil where VL is endemic. Serum samples were collected from each subject on two different occasions. IgG avidity was evaluated by Western blotting. The proportion of high-avidity antibodies was higher in all samples from patients with classic VL. In contrast, low-avidity antibodies predominated in subjects with a history of VL, including 13 cases (72.2%) in the first assessment and 14 (77.8%) in the second. Fifteen (75%) of the asymptomatic subjects presented a predominance of low-avidity antibodies in the first assessment, and the frequency of high-avidity antibodies increased over time in seven subjects (35%) of this group. Antibodies against the 14- and/or 16-kDa antigen fraction were detected in the first assessment in all patients with classic VL, in 10 (55.5%) treated patients, and in 10 (50%) asymptomatic subjects. These were high-avidity antibodies in most cases. In the asymptomatic group, an increase in IgG avidity against the 14- and/or 16-kDa antigen fraction was observed in three cases (15%). The results indicate distinct responses in infected and asymptomatic subjects, probably associated with the length of time after infection. In this respect, IgG avidity tests represent a new approach to better characterize asymptomatic VL.

Caracterización geomagnética del sistema cónico de diques traquíticos de Tejeda (Gran Canaria)

[ES] En la cuenca de Tejeda (Gran Canaria) existe un sistema cónico de más de 500 diques de composición traquítica y fonolítica. La investigación se ha centrado en el estudio de las características geológicas y magnéticas de siete diques traquíticos (con texturas afaníticas y porfídicas) representativos del sistema cónico. El estudio de la "anisotropía de la susceptibilidad magnética" (ASM) en 84 cilindros de roca confirma que: 1) es una propiedad magnética medible en este tipo de materiales sálicos, 2) el flujo de magma traquítico no fue homogéneo en el conducto de cada dique, ni existe una tendencia cónica de los planos de flujo de magma en los diques estudiados hacia una cámara magmática profunda

La imagen de Gran Canaria como destino turístico

[ES] En la cuenca de Tejeda (Gran Canaria) existe un sistema cónico de más de 500 diques de composición traquítica y fonolítica. La investigación se ha centrado en el estudio de las características geológicas y magnéticas de siete diques traquíticos (con texturas afaníticas y porfídicas) representativos del sistema cónico. El estudio de la ?anisotropía de la susceptibilidad magnética? (ASM) en 84 cilindros de roca confirma que: 1) es una propiedad magnética medible en este tipo de materiales sálicos, 2) el flujo de magma traquítico no fue homogéneo en el conducto de cada dique, ni existe una tendencia cónica de los planos de flujo de magma en los diques estudiados hacia una cámara magmática profunda.

Photocatalytic activity of nanostructured anatase coatings obtained by cold gas spray

[EN] This article describes a photocatalytic nanostructured anatase coating deposited by cold gas spray (CGS) supported on titanium sub-oxide (TiO22x) coatings obtained by atmospheric plasma spray (APS) onto stainless steel cylinders. The photocatalytic coating was homogeneous and preserved the composition and nanostructure of the starting powder. The inner titanium sub-oxide coating favored the deposition of anatase particles in the solid state. Agglomerated nano-TiO2 particles fragmented when impacting onto the hard surface of the APS TiO22x bond coat. The rough surface provided by APS provided an ideal scenario for entrapping the nanostructured particles, which may be adhered onto the bond coat due to chemical bonding; a possible bonding mechanism is described. Photocatalytic experiments showed that CGS nano-TiO2 coating was active for photodegrading phenol and formic acid under aqueous conditions. The results were similar to the performance obtained by competitor technologies and materials such as dip-coating P25 photocatalysts. Disparity in the final performance of the photoactive materials may have been caused by differences in grain size and the crystalline composition of titanium dioxide.

Conceptual and normative issues of memory enhancement

Our growing understanding of human mind and cognition and the development of neurotechnology has triggered debate around cognitive enhancement in neuroethics. The dissertation examines the normative issues of memory enhancement, and focuses on two issues: (1) the distinction between memory treatment and enhancement; and (2) how the issue of authenticity concerns memory interventions, including memory treatments and enhancements. rnThe first part consists of a conceptual analysis of the concepts required for normative considerations. First, the representational nature and the function of memory are discussed. Memory is regarded as a special form of self-representation resulting from a constructive processes. Next, the concepts of selfhood, personhood, and identity are examined and a conceptual tool—the autobiographical self-model (ASM)—is introduced. An ASM is a collection of mental representations of the system’s relations with its past and potential future states. Third, the debate between objectivist and constructivist views of health are considered. I argue for a phenomenological account of health, which is based on the primacy of illness and negative utilitarianism.rnThe second part presents a synthesis of the relevant normative issues based on the conceptual tools developed. I argue that memory enhancement can be distinguished from memory treatment using a demarcation regarding the existence of memory-related suffering. That is, memory enhancements are, under standard circumstances and without any unwilling suffering or potential suffering resulting from the alteration of memory functions, interventions that aim to manipulate memory function based on the self-interests of the individual. I then consider the issue of authenticity, namely whether memory intervention or enhancement endangers “one’s true self”. By analyzing two conceptions of authenticity—authenticity as self-discovery and authenticity as self-creation, I propose that authenticity should be understood in terms of the satisfaction of the functional constraints of an ASM—synchronic coherence, diachronic coherence, and global veridicality. This framework provides clearer criteria for considering the relevant concerns and allows us to examine the moral values of authenticity. rn

Il progetto Webassembly: un bytecode a supporto del web

A fronte di un notevole incremento di funzionalità e strutture, nell'ambiente Web si sono intrapresi numerosi percorsi volti alla creazione di progetti che vanno a supportare il sovraccarico riversato sul lavoro che i linguaggi e i software sono tenuti a svolgere. Ad oggi il Javascript è uno dei linguaggi maggiormente utilizzati in ambito Web, e si rivela spesso essenziale al corretto sviluppo di applicazioni particolarmente evolute. Questo linguaggio, come è noto, sposta l’elaborazione del codice sul lato client, quindi sarà il Browser a supportare il carico di lavoro. Inoltre, è proprio quest’ultimo ad essere incaricato della gestione delle risorse computazionali locali, necessarie a tutte le operazioni di interpretazione del codice presente nelle pagine Web. Il crescente numero di connessioni da dispositivi mobili e la complessità dei siti Web, aumentano il rischio di avvicinarsi ad un punto critico relativo alla velocità e alle prestazioni dei Browser, in questa direzione sono stati realizzati progetti come asm.js piuttosto che Typescript in grado di velocizzare o incrementare le funzionalità e le prestazioni del linguaggio Javascript. Webassembly vuole integrare i vantaggi proposti da questi linguaggi tramite una meccanica di conversione dei file in formato binario, il quale essendo molto più leggero e veloce, consente una elaborazione molto più performante da parte dei Browser. Questo documento espone una panoramica sulle funzionalità e la progettazione di questo linguaggio, analizzando elementi lessicali e relativi vantaggi rispetto alle tecnologie diffuse fino ad ora. Il quadro generale di questa tesi ci prepara all’apertura di un nuovo scenario molto più ampio e diverso, sostenuto da un approccio al Web strutturalmente innovativo.

MODELING THE DYNAMICS OF AIRWAY CONSTRICTION: EFFECTS OF AGONIST TRANSPORT AND BINDING

Recent advances have revealed that during exogenous airway challenge, airway diameters can not be adequately predicted by their initial diameters. Furthermore, airway diameters can also vary greatly in time on scales shorter than a breath. In order to better understand these phenomena, we developed a multiscale model which allows us to simulate aerosol challenge in the airways during ventilation. The model incorporates agonist-receptor binding kinetics to govern the temporal response of airway smooth muscle (ASM) contraction on individual airway segments, which together with airway wall mechanics, determines local airway caliber. Global agonist transport and deposition is coupled with pressure-driven flow, linking local airway constrictions with global flow dynamics. During the course of challenge, airway constriction alters the flow pattern, redistributing agonist to less constricted regions. This results in a negative feedback which may be a protective property of the normal lung. As a consequence, repetitive challenge can cause spatial constriction patterns to evolve in time, resulting in a loss of predictability of airway diameters. Additionally, the model offers new insight into several phenomena including the intra- and inter-breath dynamics of airway constriction throughout the tree structure.

The airway epithelium: soldier in the fight against respiratory viruses

The airway epithelium acts as a frontline defense against respiratory viruses, not only as a physical barrier and through the mucociliary apparatus but also through its immunological functions. It initiates multiple innate and adaptive immune mechanisms which are crucial for efficient antiviral responses. The interaction between respiratory viruses and airway epithelial cells results in production of antiviral substances, including type I and III interferons, lactoferrin, β-defensins, and nitric oxide, and also in production of cytokines and chemokines, which recruit inflammatory cells and influence adaptive immunity. These defense mechanisms usually result in rapid virus clearance. However, respiratory viruses elaborate strategies to evade antiviral mechanisms and immune responses. They may disrupt epithelial integrity through cytotoxic effects, increasing paracellular permeability and damaging epithelial repair mechanisms. In addition, they can interfere with immune responses by blocking interferon pathways and by subverting protective inflammatory responses toward detrimental ones. Finally, by inducing overt mucus secretion and mucostasis and by paving the way for bacterial infections, they favor lung damage and further impair host antiviral mechanisms.

Two-Dimensional Manganese(II) Coordination Polymer Based on Phthalate and Pyrazine Bridges Exhibiting Antiferromagnetic Porperties

Benzodifuran-functionalised pyrene and anthracene fluorophores 1 and 2 were obtained in reasonable yields. Their single crystal structures, electrochemical, optical absorption, and fluorescence characteristics have been described. They show strong luminescence with high quantum yields of 0.53 for 1 and 0.48 for 2. Magnetic measurements for the 2D coordination polymer [Mn(Pht(Pyz(H2O)2]n (1), in which metal centres are linked together by pyrazine (Pyz) and 1,6-bridging o-phthalate ligand (Pht2-), revealed antiferromagnetic interactions between Mn(II) ions.

A Mitogen-activated protein kinase controls differentiation of bloodstream forms of Trypanosoma brucei

African trypanosomes undergo differentiation in order to adapt to the mammalian host and the tsetse fly vector. To characterize the role of a mitogen-activated protein (MAP) kinase homologue, TbMAPK5, in the differentiation of Trypanosoma brucei, we constructed a knockout in procyclic (insect) forms from a differentiation-competent (pleomorphic) stock. Two independent knockout clones proliferated normally in culture and were not essential for other life cycle stages in the fly. They were also able to infect immunosuppressed mice, but the peak parasitemia was 16-fold lower than that of the wild type. Differentiation of the proliferating long slender to the nonproliferating short stumpy bloodstream form is triggered by an autocrine factor, stumpy induction factor (SIF). The knockout differentiated prematurely in mice and in culture, suggestive of increased sensitivity to SIF. In contrast, a null mutant of a cell line refractory to SIF was able to proliferate normally. The differentiation phenotype was partially rescued by complementation with wild-type TbMAPK5 but exacerbated by introduction of a nonactivatable mutant form. Our results indicate a regulatory function for TbMAPK5 in the differentiation of bloodstream forms of T. brucei that might be exploitable as a target for chemotherapy against human sleeping sickness.

Trypanosoma congolense procyclins: unmasking cryptic major surface glycoproteins in procyclic forms

In the tsetse fly, the protozoan parasite Trypanosoma congolense is covered by a dense layer of glycosylphosphatidylinositol (GPI)-anchored molecules. These include a protease-resistant surface molecule (PRS), which is expressed by procyclic forms early in infection, and a glutamic acid- and alanine-rich protein (GARP), which appears at later stages. Since neither of these surface antigens is expressed at intermediate stages, we investigated whether a GPI-anchored protein of 50 to 58 kDa, previously detected in procyclic culture forms, might constitute the coat of these parasites. We therefore partially purified the protein from T. congolense Kilifi procyclic forms, obtained an N-terminal amino acid sequence, and identified its gene. Detailed analyses showed that the mature protein consists almost exclusively of 13 heptapeptide repeats (EPGENGT). The protein is densely N glycosylated, with up to 13 high-mannose oligosaccharides ranging from Man(5)GlcNAc(2) to Man(9)GlcNAc(2) linked to the peptide repeats. The lipid moiety of the glycosylphosphatidylinositol is composed of sn-1-stearoyl-2-lyso-glycerol-3-HPO(4)-1-(2-O-acyl)-d-myo-inositol. Heavily glycosylated proteins with similar repeats were subsequently identified in T. congolense Savannah procyclic forms. Collectively, this group of proteins was named T. congolense procyclins to reflect their relationship to the EP and GPEET procyclins of T. brucei. Using an antiserum raised against the EPGENGT repeat, we show that T. congolense procyclins are expressed continuously in the fly midgut and thus form the surface coat of cells that are negative for both PRS and GARP.

Binding specificities and potential roles of isoforms of eukaryotic initiation factor 4E in Leishmania

The 5' cap structure of trypanosomatid mRNAs, denoted cap 4, is a complex structure that contains unusual modifications on the first four nucleotides. We examined the four eukaryotic initiation factor 4E (eIF4E) homologues found in the Leishmania genome database. These proteins, denoted LeishIF4E-1 to LeishIF4E-4, are located in the cytoplasm. They show only a limited degree of sequence homology with known eIF4E isoforms and among themselves. However, computerized structure prediction suggests that the cap-binding pocket is conserved in each of the homologues, as confirmed by binding assays to m(7)GTP, cap 4, and its intermediates. LeishIF4E-1 and LeishIF4E-4 each bind m(7)GTP and cap 4 comparably well, and only these two proteins could interact with the mammalian eIF4E binding protein 4EBP1, though with different efficiencies. 4EBP1 is a translation repressor that competes with eIF4G for the same residues on eIF4E; thus, LeishIF4E-1 and LeishIF4E-4 are reasonable candidates for serving as translation factors. LeishIF4E-1 is more abundant in amastigotes and also contains a typical 3' untranslated region element that is found in amastigote-specific genes. LeishIF4E-2 bound mainly to cap 4 and comigrated with polysomal fractions on sucrose gradients. Since the consensus eIF4E is usually found in 48S complexes, LeishIF4E-2 could possibly be associated with the stabilization of trypanosomatid polysomes. LeishIF4E-3 bound mainly m(7)GTP, excluding its involvement in the translation of cap 4-protected mRNAs. It comigrates with 80S complexes which are resistant to micrococcal nuclease, but its function is yet unknown. None of the isoforms can functionally complement the Saccharomyces cerevisiae eIF4E, indicating that despite their structural conservation, they are considerably diverged.