Trypanosoma cruzi Vps34 colocalizes with Beclin1 and plays a role in parasite invasion of the host cell by modulating the expression of a sub-group of trans-sialidases.

Trypanosoma cruzi, the etiological agent of Chagas' disease, can infect both phagocytic and non-phagocytic cells. T. cruzi gp82 and gp90 are cell surface proteins belonging to Group II trans-sialidases known to be involved in host cell binding and invasion.

Depletion of Na/H Exchanger Isoform 1 Increases the Host Cell Resistance to Invasion.

Na/H exchanger isoform 1 (NHE1), a member of a large family of integral membrane proteins, plays a role in regulating the cortical actin cytoskeleton. , the agent of Chagas disease, depends on F-actin rearrangement and lysosome mobilization to invade host cells. To determine the involvement of NHE1 in metacyclic trypomastigote (MT) internalization, the effect of treatment in cells with NHE1 inhibitor amiloride or of NHE1 depletion was examined in human epithelial cells.

Gp35/50 mucin molecules of Trypanosoma cruzi metacyclic forms that mediate host cell invasion interact with annexin A2.

Host cell invasion is a critical step for infection by Trypanosoma cruzi, the agent of Chagas disease. In natural infection, T. cruzi metacyclic trypomastigote (MT) forms establish the first interaction with host cells.

Shedding of Surface Molecules That Regulate Host Cell Invasion Involves Phospholipase C and Increases Upon Sterol Depletion.

Metacyclic trypomastigote (MT) forms of have been shown to release into medium gp82 and gp90, the stage-specific surface molecules that regulate host cell invasion, either in vesicles or in soluble form. Here, we found that during interaction of poorly invasive G strain with the host cell, gp82 and gp90 were released in vesicle-like forms, whereas no such release by highly invasive CL strain was observed. Shedding of vesicles of varying sizes by CL and G strains was visualized by scanning electron microscopy, and the protein profile of conditioned medium (CM) of the two strains was similar, but the content of gp82 and gp90 differed, with both molecules being detected in G strain as bands of high intensity in Western blotting, whereas in CL strain, they were barely detectable.

Hospital performance in a large urban acute myocardial infarction emergency care system: Tokyo Cardiovascular Care Unit network.

Background: An ideal urban network system for improving regional acute myocardial infarction (AMI) outcomes should be geographically balanced and uniform according to regional population in performance of participating hospitals. The objective of our study is to evaluate whether there is a major difference in risk-adjusted in-hospital mortality between the Tokyo Cardiovascular Care Unit (CCU) network hospitals, which cover the whole population of large cities.

Methods: The study subjects were all AMI patients without cardiac arrest on arrival admitted to the Tokyo CCU network hospitals from 2009 to 2017.

Interaction of Gp82 With Host Cell LAMP2 Induces Protein Kinase C Activation and Promotes Invasion.

The surface molecule gp82 of metacyclic trypomastigote (MT) forms of , the protozoan parasite that causes Chagas disease, mediates the host cell invasion, a process critical for the establishment of infection. Gp82 is known to bind to the target cell in a receptor-dependent manner, triggering Ca signal, actin cytoskeleton rearrangement and lysosome spreading. The host cell receptor for gp82 was recently identified as LAMP2, the major lysosome membrane-associated protein.

Engineering a single-chain antibody against Trypanosoma cruzi metacyclic trypomastigotes to block cell invasion.

Trypanosoma cruzi is a flagellate protozoan pathogen that causes Chagas disease. Currently there is no preventive treatment and the efficiency of the two drugs available is limited to the acute phase. Therefore, there is an unmet need for innovative tools to block transmission in endemic areas.

Depletion of Host Cell Focal Adhesion Kinase Increases the Susceptibility to Invasion by Metacyclic Forms.

Focal adhesion kinase (FAK), a cytoplasmic protein tyrosine kinase (PTK), is implicated in diverse cellular processes, including the regulation of F-actin dynamics. Host cell F-actin rearrangement is critical for invasion of , the protozoan parasite that causes Chagas disease. It is unknown whether FAK is involved in the internalization process of metacyclic trypomastigote (MT), the parasite form that is important for vectorial transmission.

Signal peptide recognition in Trypanosoma cruzi GP82 adhesin relies on its localization at protein N-terminus.

Trypanosoma cruzi, the causative agent of Chagas disease, has a dense coat of GPI-anchored virulence factors. T. cruzi GPI-anchored adhesin GP82 is encoded by a repertoire of transcripts containing several in-frame initiation codons located up-stream from that adjacent to the predicted signal peptide (SP).

Is systolic blood pressure high in patients with acute aortic dissection on first medical contact before hospital transfer?

Acute aortic dissection (AAD) cases are thought to have high blood pressure (BP) on admission; however, little data are available on BP prior to admission. The purpose of this study was to investigate systolic blood pressure (SBP) very early after symptom onset and before hospital transfer in patients with AAD to determine whether SBPs were high, and also whether SBPs were higher or lower compared with SBPs at hospital admission. We obtained results using three-year data derived from the Tokyo Acute Aortic Super Network Database.

Temporal Trends in Acute Myocardial Infarction Incidence and Mortality Between 2006 and 2016 in Tokyo - Report From the Tokyo CCU Network.

Background: Temporal trends in the incidence and mortality of acute myocardial infarction (AMI) have not been fully clarified in Japan.

Methods and results: The Tokyo CCU network collects information every 3 months regarding the number of AMI cases, age of patients and in-hospital mortality. Age-adjusted hospitalized AMI numbers were unchanged from 2006 to 2016 (40.

Oral infection of mice and host cell invasion by Trypanosoma cruzi strains from Mexico.

Oral infection by Trypanosoma cruzi has been responsible for frequent outbreaks of acute Chagas disease in the north of South America and in the Amazon region, where T. cruzi genetic group TcI predominates. TcI strains from different geographical regions have been used in oral infection in mice, but there is no information about strains from Mexico where TcI is prevalent.

Host cell protein LAMP-2 is the receptor for Trypanosoma cruzi surface molecule gp82 that mediates invasion.

Host cell invasion by Trypanosoma cruzi metacyclic trypomastigote (MT) is mediated by MT-specific surface molecule gp82, which binds to a still unidentified receptor, inducing lysosome spreading and exocytosis required for the parasitophorous vacuole formation. We examined the involvement of the major lysosome membrane-associated LAMP proteins in MT invasion. First, human epithelial HeLa cells were incubated with MT in the presence of antibody to LAMP-1 or LAMP-2.

Inhibition of Host Cell Lysosome Spreading by Trypanosoma cruzi Metacyclic Stage-Specific Surface Molecule gp90 Downregulates Parasite Invasion.

Successful infection by , the agent of Chagas' disease, is critically dependent on host cell invasion by metacyclic trypomastigote (MT) forms. Two main metacyclic stage-specific surface molecules, gp82 and gp90, play determinant roles in target cell invasion and in oral infection in mice. The structure and properties of gp82, which is highly conserved among strains, are well known.

Beta-adrenergic antagonist propranolol inhibits mammalian cell lysosome spreading and invasion by Trypanosoma cruzi metacyclic forms.

The involvement of β-adrenergic receptor (β-AR) in host cell invasion by Trypanosoma cruzi metacyclic trypomastigote (MT) is not known. We examined whether isoproterenol, an agonist of β-AR, or nonselective β-blocker propranolol affected MT internalization mediated the stage-specific surface molecule gp82. Treatment of HeLa cells with propranolol significantly inhibited MT invasion whereas isoproterenol had no effect.

Characteristic bisimulation for higher-order session processes.

For higher-order (process) languages, characterising contextual equivalence is a long-standing issue. In the setting of a higher-order -calculus with , we develop , a typed bisimilarity which fully characterises contextual equivalence. To our knowledge, ours is the first characterisation of its kind.

Surface Molecules Released by Trypanosoma cruzi Metacyclic Forms Downregulate Host Cell Invasion.

Background: The question whether metacylic trypomastigote (MT) forms of different T. cruzi strains differentially release surface molecules, and how they affect host cell invasion, remains to be fully clarified. We addressed that question using T.

Unique behavior of Trypanosoma cruzi mevalonate kinase: A conserved glycosomal enzyme involved in host cell invasion and signaling.

Mevalonate kinase (MVK) is an essential enzyme acting in early steps of sterol isoprenoids biosynthesis, such as cholesterol in humans or ergosterol in trypanosomatids. MVK is conserved from bacteria to mammals, and localizes to glycosomes in trypanosomatids. During the course of T.

Host cell invasion and oral infection by Trypanosoma cruzi strains of genetic groups TcI and TcIV from chagasic patients.

Background: Outbreaks of acute Chagas disease by oral infection have been reported frequently over the last ten years, with higher incidence in northern South America, where Trypanosoma cruzi lineage TcI predominates, being responsible for the major cause of resurgent human disease, and a small percentage is identified as TcIV. Mechanisms of oral infection and host-cell invasion by these parasites are poorly understood. To address that question, we analyzed T.

Lysosome biogenesis/scattering increases host cell susceptibility to invasion by Trypanosoma cruzi metacyclic forms and resistance to tissue culture trypomastigotes.

A fundamental question to be clarified concerning the host cell invasion by Trypanosoma cruzi is whether the insect-borne and mammalian-stage parasites use similar mechanisms for invasion. To address that question, we analysed the cell invasion capacity of metacyclic trypomastigotes (MT) and tissue culture trypomastigotes (TCT) under diverse conditions. Incubation of parasites for 1 h with HeLa cells in nutrient-deprived medium, a condition that triggered lysosome biogenesis and scattering, increased MT invasion and reduced TCT entry into cells.

Molecular Characterization of a Novel Family of Trypanosoma cruzi Surface Membrane Proteins (TcSMP) Involved in Mammalian Host Cell Invasion.

Background: The surface coat of Trypanosoma cruzi is predominantly composed of glycosylphosphatidylinositol-anchored proteins, which have been extensively characterized. However, very little is known about less abundant surface proteins and their role in host-parasite interactions.

Methodology/ Principal Findings: Here, we described a novel family of T.

Characterization of Trypanosoma cruzi Sirtuins as Possible Drug Targets for Chagas Disease.

Acetylation of lysine is a major posttranslational modification of proteins and is catalyzed by lysine acetyltransferases, while lysine deacetylases remove acetyl groups. Among the deacetylases, the sirtuins are NAD(+)-dependent enzymes, which modulate gene silencing, DNA damage repair, and several metabolic processes. As sirtuin-specific inhibitors have been proposed as drugs for inhibiting the proliferation of tumor cells, in this study, we investigated the role of these inhibitors in the growth and differentiation of Trypanosoma cruzi, the agent of Chagas disease.

Fibronectin-degrading activity of Trypanosoma cruzi cysteine proteinase plays a role in host cell invasion.

Trypanosoma cruzi, the agent of Chagas disease, binds to diverse extracellular matrix proteins. Such an ability prevails in the parasite forms that circulate in the bloodstream and contributes to host cell invasion. Whether this also applies to the insect-stage metacyclic trypomastigotes, the developmental forms that initiate infection in the mammalian host, is not clear.