Many parasite species migrate to another site of infection after entering the host body. Such parasite dynamics are closely related to pathogenicity, but it is not easy to observe such parasite ...behavior deep within the organs. In recent years, technology that can make organs transparent has been developed that enables us to observe deep within organs ex vivo while maintaining their three-dimensional structure. This review describes a series of attempts to apply this technology to understand the behavior of Toxoplasma gondii in the host body. A series of studies has shown that T. gondii tachyzoites that infect leukocytes can reach target organs far from the site of invasion via the circulatory system. In addition, infected leukocytes in the bloodstream adhere more readily to vascular endothelial cells than uninfected leukocytes and are more likely to remain inside the target organs. When infected leukocytes adhere to the vascular endothelial cells of the target organ, the tachyzoites inside the cells immediately escape and infect the parenchyma of the organs. As described above, organ transparency technology is a powerful tool for understanding the internal dynamics of parasites.
Current human pluripotent stem cells lack the transcription factor circuitry that governs the ground state of mouse embryonic stem cells (ESC). Here, we report that short-term expression of two ...components, NANOG and KLF2, is sufficient to ignite other elements of the network and reset the human pluripotent state. Inhibition of ERK and protein kinase C sustains a transgene-independent rewired state. Reset cells self-renew continuously without ERK signaling, are phenotypically stable, and are karyotypically intact. They differentiate in vitro and form teratomas in vivo. Metabolism is reprogrammed with activation of mitochondrial respiration as in ESC. DNA methylation is dramatically reduced and transcriptome state is globally realigned across multiple cell lines. Depletion of ground-state transcription factors, TFCP2L1 or KLF4, has marginal impact on conventional human pluripotent stem cells but collapses the reset state. These findings demonstrate feasibility of installing and propagating functional control circuitry for ground-state pluripotency in human cells.
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•The trigger of Toxomplasma gondii cyst excystation is environmental ion composition.•Excystation occurs in a solution mimicked extracellular ion composition.•A high Na+/K+ ratio is ...required.•The presence of Ca2+ is also required.
Toxoplasma gondii, an obligate intracellular protozoan parasite, infects a wide variety of mammals and birds. Although T. gondii infects the brain and muscles in its latent cyst form containing bradyzoite stage parasites during chronic infection, when a chronically infected host becomes immunodeficient or is preyed upon by a predator, the latent cyst undergoes excystation. However, it is not yet known how T. gondii recognises the triggers of excystation in the microenvironment surrounding the cyst. In this study, we incubated T. gondii cysts from host cells in several solutions containing a variety of ionic compositions. Excystation occurred in a solution with an ionic composition which mimicked that of the extracellular environment. However, excystation did not occur in a solution that mimicked the intracellular environment. We also found that the specific Na+/K+ ratio and the presence of Ca2+, mimicking the extracellular environment, are required to trigger excystation. To examine whether the stage conversion of bradyzoite to tachyzoite occurs prior to egress, we constructed a gene-modified T. gondii strain expressing a green fluorescent protein specifically in the tachyzoite stage. During the process of cyst reactivation of this strain, green fluorescence was detected prior to excystation. This suggests that stage conversion from bradyzoite to tachyzoite occurs prior to cyst disruption. These results indicate that T. gondii bradyzoites monitor the ionic composition of their surroundings to recognise their expulsion from host cells, to effectively time their excystation and stage conversion.
Forty years have passed since the first pluripotent stem cells (PSCs), mouse embryonic stem cells (ESCs), were established. Since then, several PSCs have been reported, including human ESCs in 1998, ...mouse epiblast stem cells (EpiSCs) in 2007, induced PSCs (iPSCs) in 2006 and 2007, and naïve human PSCs in 2014. Naïve PSCs are thought to correspond to pre‐implantation epiblast cells, whereas conventional (or primed) human PSCs correspond to post‐implantation epiblast cells. Thus, naïve and primed PSCs are classified by their developmental stages and have stage‐specific characteristics, despite sharing the common feature of pluripotency. In this review, we discuss the current status of PSCs and their use to model human peri‐implantation development.
Naïve and primed pluripotent stem cells correspond to pre‐implantation and post‐implantation epiblast, respectively. Both show pluripotency but different characteristics and function
Porcine reproductive and respiratory syndrome (PRRS) is an infectious swine disease caused by the PRRS virus (PRRSV) that results in economic loss to the pig-rearing industry. To study PRRSV ...infection in wild boars and pigs, we conducted a serological survey in Gifu Prefecture, Japan, from 2020 to 2021. Three out of 453 (0.7%) wild boar sera were positive for PRRSV antibodies in a commercial ELISA. However, given that PRRSV RNA was not detected in these three wild boars and the specificity and sensitivity of the test kit, these are considered as false positives. Although seropositive pigs were found in multiple pig farms in the study area, the role of wild boars as a source of PRRS to pig farms appeared to be minimal.
Intracellular pathogens have numerous strategies for effective dissemination within the host. Many intracellular pathogens first infect leukocytes, which they use as a vehicle to transport them to ...target organs. Once at the target organ, intracellular parasite Toxoplasma gondii can cross the capillary wall in extracellular form by infecting endothelial cells. However, after egression from leukocytes, extracellular parasites face the risk of host immune attack. In this study, observation of infected mouse organs, using a method that renders tissue transparent, revealed that adhesion of tachyzoite-infected leukocytes to endothelial cells triggers immediate egression of the parasite. This signal enables the parasite to time egression from its vehicle leukocyte to coincide with arrival at a target organ, minimizing the opportunity for immune attack during the transition from a vehicle leukocyte to capillary endothelial cells.
Abstract
Toxoplasma gondii
is a globally wide-spread parasite that infects almost all species of mammals and birds, including humans. We studied the spatial distribution of individual
T. gondii
...-seropositive wild boar in Gifu Prefecture (10,621 km
2
), Japan. Altogether, 744 wild boars were captured at 663 points around human settlements in Gifu Prefecture. Serum samples were collected after recording the exact capture locations, along with each wild boar’s body length and sex. We then used a commercial enzyme-linked immunosorbent assay kit for swine to measure anti-
T. gondii
antibodies in these animals. Among the 744 wild boars, 169 tested positive for
T. gondii
(22.7%). No significant difference in
T. gondii
seroprevalence was observed between the mountainous northern region with high winter snow cover and the mild-wintered geographical plain of the southern part of the prefecture. In contrast, 8 of the 11 wild boars that were captured in a public park surrounded by residential areas showed
T. gondii
seropositivity (72.7%), a value significantly higher than those of the wild boar populations in the other prefecture areas. This in-depth analysis, which spans the big city suburbs and rural areas of a whole prefecture, explains the seroprevalence of zoonotic
T. gondii
in wild boar and has public health implications.
Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) provide new prospects for studying human neurodevelopment and modeling neurological disease. In particular, iPSC-derived ...neural cells permit a direct comparison of disease-relevant molecular pathways in neurons and glia derived from patients and healthy individuals. A prerequisite for such comparative studies are robust protocols that efficiently yield standardized populations of neural cell types. Here we show that long-term self-renewing neuroepithelial-like stem cells (lt-NES cells) derived from 3 hESC and 6 iPSC lines in two independent laboratories exhibit consistent characteristics including i) continuous expandability in the presence of FGF2 and EGF; ii) stable neuronal and glial differentiation competence; iii) characteristic transcription factor profile; iv) hindbrain specification amenable to regional patterning; v) capacity to generate functionally mature human neurons. We further show that lt-NES cells are developmentally distinct from fetal tissue-derived radial glia-like stem cells. We propose that lt-NES cells provide an interesting tool for studying human neurodevelopment and may serve as a standard system to facilitate comparative analyses of hESC and hiPSC-derived neural cells from control and diseased genetic backgrounds.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several protocols have managed to reset human primed PSCs to the naive state. In this issue of Cell Stem Cell, Collier et al. (2017) report a set of surface markers that identify which cells are ...susceptible to resetting and suggest a potential roadmap for the acquisition of naive pluripotency.
Several protocols have managed to reset human primed PSCs to the naive state. In this issue of Cell Stem Cell, Collier et al. (2017) report a set of surface markers that identify which cells are susceptible to resetting and suggest a potential roadmap for the acquisition of naive pluripotency.
Mesenchymal stem cells (MSCs) are defined as cells that undergo sustained in vitro growth and are able to give rise to multiple mesenchymal lineages. Although MSCs are already used in regenerative ...medicine little is known about their in vivo behavior and developmental derivation. Here, we show that the earliest wave of MSC in the embryonic trunk is generated from Sox1
+ neuroepithelium but not from mesoderm. Using lineage marking by direct gfp knock-in and Cre-recombinase mediated lineage tracing, we provide evidence that Sox1
+ neuroepithelium gives rise to MSCs in part through a neural crest intermediate stage. This pathway can be distinguished from the pathway through which Sox1
+ cells give rise to oligodendrocytes by expression of PDGFRβ and A2B5. MSC recruitment from this pathway, however, is transient and is replaced by MSCs from unknown sources. We conclude that MSC can be defined as a definite in vivo entity recruited from multiple developmental origins.
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