83 research outputs found
Biostratigraphical characteristics of the Turonian-?Maastrichtian p.p. (Upper Cretaceous) deposits in the Simbruini-Ernici Mts. (central Apennines, Italy)
No full textThe biostratigraphical characteristics of three sequences outcropping in the Simbruini-Ernici Mts. are discussed in order to reconstruct the lithobiofacies evolution of the Central-Western Latium-Abruzzi carbonate platform during the Turonian-? Maastrichtian p.p.. For each section the macro- and microbiofacies are discussed, with the former characterized by the presence of rudists (Hippuritoida). The occurrence in the neighborhood of some fossiliferous beds of particular biostratigraphical value, us to make correlations with other areas. -Author
Phosphoinositide signaling and regulation in Trypanosoma brucei: Specialized functions in a protozoan pathogen.
No full textActive suppression of the class II transactivator-encoding AIR-1 locus is responsible for the lack of major histocompatibility complex class II gene expression observed during differentiation from B cells to plasma cells.
No full textCited by the Following Articles in PubMed:
Han Chen, Carolyn A. Gilbert, John A. Hudson, Sophia C. Bolick, Kenneth L. Wright, and Janet F. Piskurich. Positive Regulatory Domain I-Binding Factor 1 mediates repression of the MHC Class II Transactivator (CIITA) type IV promoter. Mol Immunol. Author manuscript; available in PMC 2007 September 20. Published in final edited form as: Mol Immunol. 2007 February; 44(6): 1461–1470. Published online 2006 June 12. doi: 016/j.molimm.2006.04.026.
Jonathan A. Harton and Jenny P.-Y. Ting. Class II Transactivator: Mastering the Art of Major Histocompatibility Complex Expression.
Mol Cell Biol. 2000 September; 20(17): 6185–6194
Inefficient complement system clearance of Trypanosoma cruzi metacyclic trypomastigotes enables resistant strains to invade eukaryotic cells.
No full textThe complement system is the main arm of the vertebrate innate immune system against pathogen infection. For the protozoan Trypanosoma cruzi, the causative agent of Chagas disease, subverting the complement system and invading the host cells is crucial to succeed in infection. However, little attention has focused on whether the complement system can effectively control T. cruzi infection. To address this question, we decided to analyse: 1) which complement pathways are activated by T. cruzi using strains isolated from different hosts, 2) the capacity of these strains to resist the complement-mediated killing at nearly physiological conditions, and 3) whether the complement system could limit or control T. cruzi invasion of eukaryotic cells. The complement activating molecules C1q, C3, mannan-binding lectin and ficolins bound to all strains analysed; however, C3b and C4b deposition assays revealed that T. cruzi activates mainly the lectin and alternative complement pathways in non-immune human serum. Strikingly, we detected that metacyclic trypomastigotes of some T. cruzi strains were highly susceptible to complement-mediated killing in non-immune serum, while other strains were resistant. Furthermore, the rate of parasite invasion in eukaryotic cells was decreased by non-immune serum. Altogether, these results establish that the complement system recognizes T. cruzi metacyclic trypomastigotes, resulting in killing of susceptible strains. The complement system, therefore, acts as a physiological barrier which resistant strains have to evade for successful host infection
Regulatory roles of PIP and IP enzymes in <i>T</i>. <i>brucei</i>.
No full textRegulatory roles of PIP and IP enzymes in T. brucei.</p
Identifying ground-robot impedance to improve terrain adaptability in running robots
No full text© The Author(s). To date, running robots are still outperformed by animals, but their dynamic behaviour can be described by the same model. This coincidence means that biomechanical studies can reveal much about the adaptability and energy efficiency of walking mechanisms. In particular, animals adjust their leg stiffness to negotiate terrains with different stiffnesses to keep the total leg-ground stiffness constant. In this work, we aim to provide one method to identify ground-robot impedance so that control can be applied to emulate the aforementioned animal behaviour. Experimental results of the method are presented, showing well-differentiated estimations on four different types of terrain. Additionally, an analysis of the convergence time is presented and compared with the contact time of humans while running, indicating that the method is suitable for use at high speeds.This work was partially funded by the Spanish National Plan for Research, Development and Innovation through grant DPI2013-40504-R. Mr. Juan Carlos Arevalo and Mr. Manuel Cestari would like to thank the Spanish National Research Council and the Spanish Ministry of Economy and Competitiveness for funding their PhD research.Peer Reviewe
Transcriptional Regulation of Telomeric Expression Sites and Antigenic Variation in Trypanosomes
No full textTrypanosoma cruzi e o sistema complemento : ativação da via das lectinas e papel da microvesículas derivadas das células do hospedeiro na resistência à lise
No full textTrypanosoma cruzi, o agente etiológico da doença de Chagas, precisa evadir o sistema imune inato do hospedeiro
vertebrado durante a infecção. O sistema complemento é o principal mecanismo de defesa do sistema imune inato.
Ele é composto de várias proteínas, ativadas em cascata, que culmina com a formação do complexo de ataque a
membrana e lise do patógeno. O sistema complemento pode ser ativado através da via clássica, das lectinas e
alternativa. T. cruzi tripomastigota metacíclicos, o estágio infectivo liberado durante a picada do inseto vetor, precisa
sobreviver ao ataque do sistema complemento e infectar as células hospedeiras para continuar o seu ciclo de vida e
provocar a doença. O principal objetivo dessa tese foi investigar como os tripomastigotas metacíclicos de T. cruzi
evadem o sistema complemento durante a infecção. Inicialmente, nós identificamos pela primeira vez que T. cruzi
ativa a via das lectinas. As proteínas do soro MBL (Mannan binding lectin), L-ficolina e H-ficolina ligam a
carboidratos na superfície dos tripomastigotas metacíclicos. Essas moléculas se associam a MASP2 (MBL-associated
serine protease 2), que cliva os componentes C2 e C4 para formar a C3 convertase (C4b2a) e ativar a cascata do
complemento. Nós também detectamos que várias cepas de T. cruzi no estágio tripomastigota metacíclico são
sensíveis à lise mediada pelo complemento com soro humano não imune, enquanto outras cepas são resistentes. O
sistema complemento foi capaz de limitar a invasão celular das cepas sensíveis, indicando que o complemento atua
como uma barreira fisiológica durante a infecção por T. cruzi. Por outro lado, nós propomos dois novos mecanismos
de evasão da lise mediada pelo complemento por T. cruzi tripomastigotas metacíclicos. Identificamos e
caracterizamos um receptor de C2 do complemento expresso no estágio tripomastigota metacíclico : CRIT
(Complement C2 receptor inhibitor trispanning) liga ao C2 e inibe a sua clivagem pela enzima MASP2, e
consequentemente, inibe a formação da C3 convertase e a lise do parasita. Por outro lado, identificamos que
tripomastigotas metacíclicos induzem monócitos e linfócitos a liberarem PMVs (Plasma membrane-derived vesicles).
As PMVs estabilizam a C3 convertase (evitando a sua dissociação da superfície de T. cruzi) e inibem a sua atividade
catalítica, portanto, elas contribuem para a inibição da lise pelo complemento. As PMVs também carream TGF-_ da
célula de origem. As PMVs contendo TGF-_ ligam ao T. cruzi e induzem um aumento da invasão celular. T. cruzi
também induz um aumento da liberação de PMVs em camundongo, assim como a parasitemia de T. cruzi em
camundongos aumenta na presença das PMVs, indicando que as PMVs é um fator do hospedeiro induzido por T.
cruzi que contribui para a evasão imune. Nós concluimos que a evasão do sistem complemento por T. cruzi é um
mecanismo multifatorial que depende tanto de receptores da superfície do parasita quanto de fatores do hospedeiro
modulados durante a infecção.Trypanosoma cruzi, the causative agent of Chagas disease, has to evade the innate immune system during
infection of vertebrate hosts. The complement system is the main arm of the innate immune system. It is
composed of several proteins activated in a cascade that culminates with formation of the membrane attack
complex and pathogen lysis. The complement system can be activated by the classical, lectin and alternative
pathways. Insect-derived metacyclic trypomastigotes, T. cruzi infective stages to mammalian hosts, have to
subvert the complement system and infect cells to continue their life cycle and cause disease. The main goal of
this thesis was to understand how T. cruzi metacyclic trypomastigotes evade the complement system to succeed
in infecting the host. First, we identify for the first time that T. cruzi metacyclic trypomastigotes activate the
complement lectin pathway. The human serum proteins mannan-binding lectin (MBL), L-ficolins and Hficolins
bind to N-linked carbohydrates on the surface of metacyclic trypomastigotes. These molecules associate
with MBL-associated serine protease 2 (MASP2), which cleaves C2 and C4 to generate C3 convertase and
activate the complement cascade. Furthermore, we found that metacyclic trypomastigotes of several T. cruzi
strains are susceptible to complement lysis by human serum, while metacyclic trypomastigotes of other strains
are resistant. The complement system limited eukaryotic cell invasion of the sensitive strains, indicating that the
complement system acts as a physiological barrier during T. cruzi infection. In addition to demonstrating this
role for the complement system, we present evidence for two novel mechanisms of complement evasion by
metacyclic trypomastigotes. First, we identify and characterize a complement C2 receptor expressed in
metacyclic trypomastigotes. CRIT (complement C2 receptor inhibitor trispanning) binds to C2 and inhibits its
cleavage by MASP2, thereby inhibiting C3 convertase formation and parasite lysis. Furthermore, metacyclic
trypomastigotes induce monocytes and lymphocytes to release plasma membrane-derived vesicles (PMVs).
PMVs bind to the complement C3 convertase and inhibit its catalytic activity, thereby protecting the parasites
from the complement lysis. We also detected that PMVs carry TGF- from the cell of origin. TGF- -bearing
PMVs bind to T. cruzi and promote increased cell invasion. T. cruzi induces an increase in PMV release from
mice, and T. cruzi parasitemia in mice is also high in the presence of PMVs, indicating that PMVs are a host
factor induced by T. cruzi which contributes to immune evasion. We conclude that evasion of the complement
system by T. cruzi is a multifaceted mechanism, encompassing modulation of both parasite surface receptors
and host factors during infection
PIP and IP synthesis and regulation in <i>T</i>. <i>brucei</i>.
No full text(A) Structure of PIP2 indicated by the inositol ring (black hexagon), phosphates (red circles), and DAG with fatty acid chain. PLC cleaves PIP2 and produces diacylglycerol and IP3. Black arrows indicate phosphate and inositol. The yellow arrow indicates the site of PLC cleavage, which occurs between DAG and phosphate sn1. The green arrow indicates the directionality of the PLC reaction. (B) The number of genes involved in PIP and IP synthesis, signaling (includes PLC and IP3 receptors), and PIP and IP kinases and phosphatases in eukaryotes and prokaryotes. The size of the black circles indicates the number of genes in each category. (C) Synthesis of PIPs and IPs based on T. brucei predicted and characterized enzymes. Enzymes, whose regulatory functions are discussed here, are indicated in blue. PIP-Pase indicates enzymes that dephosphorylate PIPs at positions 3, 4, or 5 of the inositol ring. It includes PIP5Pase, whose catalytic activity is detailed below in D. Metabolite short names are used for simplicity. (D) Regulation of VSG silencing by PIP5Pase. PIP5Pase dephosphorylates the 5-phosphate (green circle) of PIP3 and prevents this metabolite binding to RAP1, which preserves RAP1 function (and likely other proteins) in ES chromatin organization. Catalytic inactivation of PIP5Pase results in PIP3 binding to RAP1, which affects ES chromatin organization and results in transcription of VSG genes. 1, diacylglycerol kinase; 2, cytidine diphosphate-diacylglycerol synthase; 3, phosphatidylinositol synthase; 70 bp, 70 base pair repeats; Ath, Arabidopsis thaliana; DAG, diacylglycerol; ER, endoplasmic reticulum; ES, expression site; ESAG, expression site associated genes; Hsp, Homo sapiens; I, myo-inositol; IMPase, inositol monophosphatase; IP, inositol phosphate; IP1, D-myo-inositol 1-monophosphate; IP2, D-myo-inositol 1,4-diphosphate; IP3, D-myo-inositol 1,4,5-triphosphate; IP4, D-myo-inositol 1,3,4,5-tetrakisphosphate; IP5, D-myo-inositol 1,2,3,4,5-pentakisphosphate; IP5Pase, inositol polyphosphate 5-phosphatase; IP6, D-myo-inositol 1,2,3,4,5,6-hexakisphosphate; IP6K, inositol hexakisphosphate kinase; IP7, D-myo-inositol 5-diphospho 1,2,3,4,6-pentakisphosphate; IPMK, inositol polyphosphate multikinase; Mtb, Mycobacterium tuberculosis; PIP, phosphatidylinositol phosphate; PIP1, phosphatidylinositol 4-phosphate; PIP2, phosphatidylinositol 4,5-biphosphate; PIP3, phosphatidylinositol 3,4,5-triphosphate; PIP5K, phosphatidylinositol phosphate 5-kinase; PIP5Pase, phosphatidylinositol phosphate 5-phosphatase; PIP-Pase, phosphatidylinositol phosphate phosphatases; PLC, Phospholipase C; PM, plasma membrane; Pol I, RNA polymerase I; PP-IP4, D-myo-inositol 5-diphospho 1,3,4,6-tetrakisphosphate; RAP1, repressor-activator protein 1; Sce, Saccharomyces cerevisiae; sn1, unimolecular nucleophilic substitution; Tbr, T. brucei; Ttm, Thermus thermophilus; VSG, variant surface glycoprotein.</p
The phosphoinositide regulatory network in Trypanosoma brucei: Implications for cell-wide regulation in eukaryotes.
No full textThe unicellular eukaryote Trypanosoma brucei undergoes extensive cellular and developmental changes during its life cycle. These include regulation of mammalian stage surface antigen variation and surface composition changes between life stages; switching between glycolysis and oxidative phosphorylation; differential mRNA editing; and changes in posttranscriptional gene expression, protein trafficking, organellar function, and cell morphology. These diverse events are coordinated and controlled throughout parasite development, maintained in homeostasis at each life stage, and are essential for parasite survival in both the host and insect vector. Described herein are the enzymes and metabolites of the phosphatidylinositol (PI) cellular regulatory network, its integration with other cellular regulatory systems that collectively control and coordinate these numerous cellular processes, including cell development and differentiation and the many associated complex processes in multiple subcellular compartments. We conclude that this regulation is the product of the organization of these enzymes within the cellular architecture, their activities, metabolite fluxes, and responses to environmental changes via signal transduction and other processes. We describe a paradigm for how these enzymes and metabolites could function to control and coordinate multiple cellular functions. The significance of the PI system's regulatory functions in single-celled eukaryotes to metazoans and their potential as chemotherapeutic targets are indicated
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