Hypermigration of macrophages through the concerted action of GRA effectors on NF-κB/p38 signaling and host chromatin accessibility potentiates dissemination.

Unlabelled: Mononuclear phagocytes facilitate the dissemination of the obligate intracellular parasite . Here, we report how a set of secreted parasite effector proteins from dense granule organelles (GRA) orchestrates dendritic cell-like chemotactic and pro-inflammatory activation of parasitized macrophages. These effects enabled efficient dissemination of the type II lineage, a highly prevalent genotype in humans.

Hypermigration of macrophages through the concerted action of GRA effectors on NF-κB/p38 signaling and host chromatin accessibility potentiates dissemination.

Mononuclear phagocytes facilitate the dissemination of the obligate intracellular parasite Here, we report how a set of secreted parasite effector proteins from dense granule organelles (GRA) orchestrates dendritic cell-like chemotactic and pro-inflammatory activation of parasitized macrophages. These effects enabled efficient dissemination of the type II lineage, a highly prevalent genotype in humans. We identify novel functions for effectors GRA15 and GRA24 in promoting CCR7-mediated macrophage chemotaxis by acting on NF-κB and p38 MAPK signaling pathways, respectively, with contributions of GRA16/18 and counter-regulation by effector TEEGR.

The Toxoplasma effector GRA28 promotes parasite dissemination by inducing dendritic cell-like migratory properties in infected macrophages.

Upon pathogen detection, macrophages normally stay sessile in tissues while dendritic cells (DCs) migrate to secondary lymphoid tissues. The obligate intracellular protozoan Toxoplasma gondii exploits the trafficking of mononuclear phagocytes for dissemination via unclear mechanisms. We report that, upon T.

In vitro evaluation of Resveratrol as a potential pre-exposure prophylactic drug against Trypanosoma cruzi infection.

Chagas' disease or American trypanosomiasis, caused by Trypanosoma cruzi infection, is an endemic disease in Latin America, which has spread worldwide in the past years. The drugs presently used for treatment have shown limited efficacy due to the appearance of resistant parasites and severe side effects. Some of the most recent studies on anti-parasitic drugs have been focused on protein acetylation, a reversible reaction modulated by Acetyl Transferases (KATs) and Deacetylases (KDACs).

Biological features of TcM: A new isolate from Argentina classified into TcV lineage.

, the etiologic agent of Chagas disease (CD) presents a wide genetic and phenotypic diversity that is classified into seven lineages or discrete typing units (DTU: TcI to TcVI and Tcbat). Although isolates and strains that belong to a particular group can share some attributes, such as geographic distribution, others like growth rate, cell tropism, and response to treatment can be highly variable. In addition, studies that test new trypanocidal drugs are frequently conducted on strains maintained for a long time in axenic culture, resulting in changes in parasite virulence and other important features.

Mobilome of Apicomplexa Parasites.

Transposable elements (TEs) are mobile genetic elements found in the majority of eukaryotic genomes. Genomic studies of protozoan parasites from the phylum Apicomplexa have only reported a handful of TEs in some species and a complete absence in others. Here, we studied sixty-four Apicomplexa genomes available in public databases, using a 'de novo' approach to build candidate TE models and multiple strategies from known TE sequence databases, pattern recognition of TEs, and protein domain databases, to identify possible TEs.

Software evaluation for de novo detection of transposons.

Transposable elements (TEs) are major genomic components in most eukaryotic genomes and play an important role in genome evolution. However, despite their relevance the identification of TEs is not an easy task and a number of tools were developed to tackle this problem. To better understand how they perform, we tested several widely used tools for de novo TE detection and compared their performance on both simulated data and well curated genomic sequences.

From telomere to telomere: The transcriptional and epigenetic state of human repeat elements.

Mobile elements and repetitive genomic regions are sources of lineage-specific genomic innovation and uniquely fingerprint individual genomes. Comprehensive analyses of such repeat elements, including those found in more complex regions of the genome, require a complete, linear genome assembly. We present a de novo repeat discovery and annotation of the T2T-CHM13 human reference genome.

Different kinetoplast degradation patterns in American Trypanosoma vivax strains: Multiple independent origins or fast evolution?

We analyzed the kinetoplast (mitochondrial genome) of Trypanosoma vivax strains from America and Africa to determine their precise architecture and to understand their adaptive response to mechanical transmission. The use of long-read based assemblies that retain individuality of tandem repeats, without erasing inter-copy variability, allowed us to investigate the evolutionary dynamics of repetitive kinetoplast-DNA. This analysis revealed that repeat elements located in edges of repeat clusters are less active in terms of renewal, whereas internal copies appear to undergo a permanent process of birth-and-death.

The Trypanosoma cruzi TcTASV-C protein subfamily administrated with U-Omp19 promotes a protective response against a lethal challenge in mice.

The development of a Chagaś disease vaccine has yet the need for the identification of novel combinations of antigens and adjuvants. Here, the performance of TcTASV-C proteins that are virulence factors of trypomastigotes and belong to a novel surface protein family specific for T. cruzi, have been evaluated as antigens for a prophylactic vaccine.

Transmigration of Trypanosoma cruzi trypomastigotes through 3D cultures resembling a physiological environment.

To disseminate and colonise tissues in the mammalian host, Trypanosoma cruzi trypomastogotes should cross several biological barriers. How this process occurs or its impact in the outcome of the disease is largely speculative. We examined the in vitro transmigration of trypomastigotes through three-dimensional cultures (spheroids) to understand the tissular dissemination of different T.

Transmigration of Trypanosoma cruzi Trypomastigotes through 3D Spheroids Mimicking Host Tissues.

While cellular invasion by T. cruzi trypomastigotes and intracellular amastigote replication are well-characterized events that have been described by using 2D monolayer cultures, other relevant parasite-host interactions, like the dynamics of tissue invasiveness, cannot be captured using monolayer cultures. Spheroids constitute a valuable three-dimensional (3D) culture system because they mimic the microarchitecture of tissues and provide an environment similar to the encountered in natural infections, which includes the presence of extracellular matrix as well as 3D cell-cell interactions.

Heat shock protein 27 modulates autophagy and promotes cell survival after photodynamic therapy.

Photodynamic therapy (PDT) is a clinically approved treatment that exerts a selective cytotoxic activity toward cancer cells. The procedure involves the administration of a photosensitizer drug followed by its activation by visible light. In the presence of oxygen, a series of events lead to tumor cell death.

Expanding an expanded genome: long-read sequencing of Trypanosoma cruzi.

Although the genome of Trypanosoma cruzi, the causative agent of Chagas disease, was first made available in 2005, with additional strains reported later, the intrinsic genome complexity of this parasite (the abundance of repetitive sequences and genes organized in tandem) has traditionally hindered high-quality genome assembly and annotation. This also limits diverse types of analyses that require high degrees of precision. Long reads generated by third-generation sequencing technologies are particularly suitable to address the challenges associated with T.

[The association of schizophrenia with chronic non transmissible diseases].

The life expectancy of patients with schizophrenia (SCH) is 11 to 20 years less than the general population. There is an association between SCH and various diseases and chronic conditions, highlighting the cardio-metabolic diseases. This association has been attributed to the use of antipsychotics, however, evidence has also shown intrinsic susceptibility of schizophrenic patients the development of chronic conditions.

Transcriptomic analysis reveals metabolic switches and surface remodeling as key processes for stage transition in .

American trypanosomiasis is a chronic and endemic disease which affects millions of people. , its causative agent, has a life cycle that involves complex morphological and functional transitions, as well as a variety of environmental conditions. This requires a tight regulation of gene expression, which is achieved mainly by post-transcriptional regulation.

Effect of tracheostomy tube on work of breathing: Comparison of pre- and post-decannulation.

Objective: To describe and compare the work of breathing (WOB) during spontaneous breathing under four conditions: (1) breathing through a tracheostomy tube with an inflated cuff, (2) breathing through the upper airway (UA) with a deflated cuff and occluded tube, (3) breathing through the UA with an occluded cuffless tube, and (4) postdecannulation.

Patients And Methods: Patients who tolerated an occluded cuffless tube were included. Ventilatory variables and esophageal pressure were recorded.

Heat shock proteins in the context of photodynamic therapy: autophagy, apoptosis and immunogenic cell death.

Photodynamic therapy (PDT) is an anti-tumor treatment administered for the elimination of early-stage malignancies and the palliation of symptoms in patients with late-stage tumors, which involves the activation of a photosensitizer (PS) using light of a specific wavelength, which also generates singlet oxygen and other reactive oxygen species (ROS) that cause tumor cell death. Several mechanisms are involved in the protective responses to PDT including the expression of chaperone/heat shock proteins (HSPs). The HSPs are a family of proteins that are induced by cells in response to exposure to stressful conditions.

Shape manipulation of ion irradiated Ag nanoparticles embedded in lithium niobate.

Spherical silver nanoparticles were prepared by means of ion beam synthesis in lithium niobate. The embedded nanoparticles were then irradiated with energetic (84)Kr and (197)Au ions, resulting in different electronic energy losses between 8.1 and 27.

Kinetoplast adaptations in American strains from Trypanosoma vivax.

The mitochondrion role changes during the digenetic life cycle of African trypanosomes. Owing to the low abundance of glucose in the insect vector (tsetse flies) the parasites are dependent upon a fully functional mitochondrion, capable of performing oxidative phosphorylation. Nevertheless, inside the mammalian host (bloodstream forms), which is rich in nutrients, parasite proliferation relies on glycolysis, and the mitochondrion is partially redundant.

Elaeodendron orientale as a source of cytotoxic cardenolides.

In the present study, we report six cardiac glycosides (1-6) along with four known ones (7-10) isolated from the leaves and fruits of Elaeodendron orientale. Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR, and the absolute configuration of 1 was determined by X-ray diffraction analysis. The compounds were evaluated for growth inhibitory activity against a panel of human cancer cell lines, HeLa, A-549, MCF-7 and HL-60, and normal Vero cells.

[Cultural adaptation and Argentine validation of the Northwick Park Neck Pain Questionnaire in the hospitals of the Autonomous City of Buenos Aires].

Objective: [corrected] To make cultural adaptation and validation of the Northwick Park Neck Pain Questionnaire (NPQ) in Argentina, determining its psychometric properties in patients with neck pain of mechanical origin referred to the physiotherapy Service at D. F. Santojanni Hospital.