scholarly journals Proinflammatory Caspase A Activation and an Antiviral State Are Induced by a Zebrafish Perforin after Possible Cellular and Functional Diversification from a Myeloid Ancestor

2015 ◽  
Vol 8 (1) ◽  
pp. 43-56 ◽  
Author(s):  
Mónica Varela ◽  
Gabriel Forn-Cuní ◽  
Sonia Dios ◽  
Antonio Figueras ◽  
Beatriz Novoa
Keyword(s):  
Expression Patterns ◽  
Cell Types ◽  
Natural Killer T Cells ◽  
Functional Diversification ◽  
Evolutionary Level ◽  
Dependent Cell ◽  
Different Cell Types ◽  
Killer T Cells

In mammals, perforins play a central role in the granule-dependent cell death induced by natural killer T cells and cytotoxic T lymphocytes, and participate both in the defense against virus-infected and neoplastic cells and in the recognition of nonself molecules by the immune system. Little is known about fish perforin genes. We examined the zebrafish with the aim of increasing our knowledge about the role of perforins. We characterized 6 perforin genes in the zebrafish genome, and we studied them at the evolutionary level in combination with expression patterns in several tissues and cell populations, during both larval development and in the course of a viral infection. Our results suggest the specialization of different cell types in the production of perforins. Moreover, functional diversification during the evolution of these molecules could be inferred from this study. In particular, one of the genes, prf19b, which is mainly produced by myeloid cells, seemed to be involved in antiviral defense, conferring protection after an in vivo infection.

scholarly journals Chronic imaging of mitochondria in the murine cerebral vasculature using in vivo two-photon microscopy

2020 ◽  
Vol 318 (6) ◽  
pp. H1379-H1386
Author(s):  
Ibolya Rutkai ◽  
Wesley R. Evans ◽  
Nikita Bess ◽  
Tomas Salter-Cid ◽  
Siniša Čikić ◽  
...  
Keyword(s):  
Cerebral Circulation ◽  
Three Dimensional ◽  
Cell Types ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Dimensional Reconstruction ◽  
Different Cell Types

We introduce an innovative in vivo approach to study mitochondria in the cerebral circulation in their physiological environment by demonstrating the feasibility of long-term imaging and three-dimensional reconstruction. We postulate that the appropriate combination of Cre/Lox system and two-photon microscopy will contribute to a better understanding of the role of mitochondria in not only endothelium but also the different cell types of the cerebral circulation.

Lymphocyte infiltration into sponge allografts

1991 ◽  
Vol 49 ◽  
pp. 114-115
Author(s):  
A. Suresh ◽  
N. Smith ◽  
O. Martinez ◽  
M. Nieto
Keyword(s):  
T Cells ◽  
Matrix Model ◽  
Cell Types ◽  
Cytotoxic Lymphocytes ◽  
High Endothelial Venules ◽  
Different Cell Types ◽  
Sponge Matrix ◽  
Do So

A sponge matrix model utilized for the study of allograft (graft of tissue between genetically different members of the same species) provides sufficient cell numbers to characterize the cells which infiltrate an allograft in vivo. Circumstantial evidence supports the postulated role of specifically sensitized cytotoxic lymphocytes as the principle mediators of allograft rejection in vivo. The sponge matrix model showed that sponge allografts acquire alloantigenreactive T lymphocytes, whereas sponge isografts (grafts between genetically identical individuals) fail to do so, even though the T cells are continuously circulating in the peripheral blood. High endothelial venules (HEV) are present in the normal lymph nodes and they regulate lymphocyte extravasation from the blood. HEV-like vessels have been identified in the sponge allografts. A correlation has been shown between the formation of HEV-like vessels and the presence of alloantigen-reactive T cells in the sponge matrix. Sponges were examined with the scanning electron microscope (SEM) to study the infiltration of different cell types into the sponge allografts and the development of endothelial venules and neovascularization.

scholarly journals Heterogeneity of Transcription Factor binding specificity models within and across cell lines

2015 ◽  
Author(s):  
Mahfuza Sharmin ◽  
Hector Corrada Bravo ◽  
Sridhar S. Hannenhalli
Keyword(s):  
Expression Patterns ◽  
Specific Interaction ◽  
Cell Types ◽  
Cell Type ◽  
Binding Interaction ◽  
Interaction Partners ◽  
A Cell ◽  
Cell Type Specific ◽  
Different Cell Types

Complex gene expression patterns are mediated by binding of transcription factors (TF) to specific genomic loci. The in vivo occupancy of a TF is, in large part, determined by the TFs DNA binding interaction partners, motivating genomic context based models of TF occupancy. However, the approaches thus far have assumed a uniform binding model to explain genome wide bound sites for a TF in a cell-type and as such heterogeneity of TF occupancy models, and the extent to which binding rules underlying a TFs occupancy are shared across cell types, has not been investigated. Here, we develop an ensemble based approach (TRISECT) to identify heterogeneous binding rules of cell-type specific TF occupancy and analyze the inter-cell-type sharing of such rules. Comprehensive analysis of 23 TFs, each with ChIP-Seq data in 4-12 cell-types, shows that by explicitly capturing the heterogeneity of binding rules, TRISECT accurately identifies in vivo TF occupancy (93%) substantially improving upon previous methods. Importantly, many of the binding rules derived from individual cell-types are shared across cell-types and reveal distinct yet functionally coherent putative target genes in different cell-types. Closer inspection of the predicted cell-type-specific interaction partners provides insights into context-specific functional landscape of a TF. Together, our novel ensemble-based approach reveals, for the first time, a widespread heterogeneity of binding rules, comprising interaction partners within a cell-type, many of which nevertheless transcend cell-types. Notably, the putative targets of shared binding rules in different cell-types, while distinct, exhibit significant functional coherence.

scholarly journals mPRs represent a novel target for PRL inhibition in experimental prolactinomas

2019 ◽  
Vol 26 (5) ◽  
pp. 497-510 ◽  
Author(s):  
María Andrea Camilletti ◽  
Alejandra Abeledo-Machado ◽  
Pablo A Perez ◽  
Erika Y Faraoni ◽  
Fernanda De Fino ◽  
...  
Keyword(s):  
Relative Proportion ◽  
Progesterone Receptors ◽  
Cell Types ◽  
Prolactin Secretion ◽  
Dopaminergic Drugs ◽  
Rat Pituitary ◽  
Novel Target ◽  
Different Cell Types

Membrane progesterone receptors are known to mediate rapid nongenomic progesterone effects in different cell types. Recent evidence revealed that mPRα is highly expressed in the rat pituitary, being primarily localized in lactotrophs, acting as an intermediary of P4-inhibitory actions on prolactin secretion. The role of mPRs in prolactinoma development remains unclear. We hypothesize that mPR agonists represent a novel tool for hyperprolactinemia treatment. To this end, pituitary expression of mPRs was studied in three animal models of prolactinoma. Expression of mPRs and nuclear receptor was significantly decreased in tumoral pituitaries compared to normal ones. However, the relative proportion of mPRα and mPRβ was highly increased in prolactinomas. Interestingly, the selective mPR agonist (Org OD 02-0) significantly inhibited PRL release in both normal and tumoral pituitary explants, displaying a more pronounced effect in tumoral tissues. As P4 also regulates PRL secretion indirectly, by acting on dopaminergic neurons, we studied mPR involvement in this effect. We found that the hypothalamus has a high expression of mPRs. Interestingly, both P4 and OrgOD 02-0 increased dopamine release in hypothalamus explants. Moreover, in an in vivo treatment, that allows both, pituitary and hypothalamus actions, the mPR agonist strongly reduced the hyperprolactinemia in transgenic females carrying prolactinoma. Finally, we also found and interesting gender difference: males express higher levels of pituitary mPRα/β, a sex that does not develop prolactinoma in these mice models. Taken together, these findings suggest mPRs activation could represent a novel tool for hyperprolactinemic patients, especially those that present resistance to dopaminergic drugs.

scholarly journals Overview of the Role of Cell Wall DUF642 Proteins in Plant Development

2019 ◽  
Vol 20 (13) ◽  
pp. 3333 ◽  
Author(s):  
José Erik Cruz-Valderrama ◽  
Ximena Gómez-Maqueo ◽  
Alexis Salazar-Iribe ◽  
Esther Zúñiga-Sánchez ◽  
Alejandra Hernández-Barrera ◽  
...  
Keyword(s):  
Cell Wall ◽  
Plant Development ◽  
Expression Patterns ◽  
Cell Types ◽  
Pectin Methyl Esterase ◽  
Temporal Expression ◽  
Temporal Expression Pattern ◽  
Different Cell Types ◽  
Cell Wall Properties

The DUF642 protein family is found exclusively in spermatophytes and is represented by 10 genes in Arabidopsis and in most of the 24 plant species analyzed to date. Even though the primary structure of DUF642 proteins is highly conserved in different spermatophyte species, studies of their expression patterns in Arabidopsis have shown that the spatial-temporal expression pattern for each gene is specific and consistent with the phenotypes of the mutant plants studied so far. Additionally, the regulation of DUF642 gene expression by hormones and environmental stimuli was specific for each gene, showing both up- and down-regulation depending of the analyzed tissue and the intensity or duration of the stimuli. These expression patterns suggest that the DUF642 genes are involved throughout the development and growth of plants. In general, changes in the expression patterns of DUF642 genes can be related to changes in pectin methyl esterase activity and/or to changes in the degree of methyl-esterified homogalacturonans during plant development in different cell types. Thus, the regulation of pectin methyl esterases mediated by DUF642 genes could contribute to the regulation of the cell wall properties during plant growth.

Role of Transcriptional Read-Through in PRE Activity in Drosophila melanogaster

Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 79-86 ◽  
Author(s):  
P. V. Elizar’ev ◽  
D. V. Lomaev ◽  
D. A. Chetverina ◽  
P. G. Georgiev ◽  
M. M. Erokhin
Keyword(s):  
Dna Sequences ◽  
Cell Types ◽  
Transcription Terminator ◽  
Response Elements ◽  
Polycomb Response Elements ◽  
The Individual ◽  
Multicellular Organisms ◽  
Different Cell Types ◽  
Main Factor

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.

scholarly journals Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3389
Author(s):  
Ishtiaq Ahmed ◽  
Saif Ur Rehman ◽  
Shiva Shahmohamadnejad ◽  
Muhammad Anjum Zia ◽  
Muhammad Ahmad ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Cell Types ◽  
Autoimmune Disorders ◽  
Specific Receptors ◽  
Different Cell Types

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

scholarly journals Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 376
Author(s):  
Chantal B. Lucini ◽  
Ralf J. Braun
Keyword(s):  
Cell Death ◽  
Oxygen Species ◽  
In Vivo Models ◽  
Dependent Cell ◽  
Cell Death Mechanisms ◽  
Sting Pathway ◽  
Mitochondrial Membrane Permeabilization

In the last decade, pieces of evidence for TDP-43-mediated mitochondrial dysfunction in neurodegenerative diseases have accumulated. In patient samples, in vitro and in vivo models have shown mitochondrial accumulation of TDP-43, concomitantly with hallmarks of mitochondrial destabilization, such as increased production of reactive oxygen species (ROS), reduced level of oxidative phosphorylation (OXPHOS), and mitochondrial membrane permeabilization. Incidences of TDP-43-dependent cell death, which depends on mitochondrial DNA (mtDNA) content, is increased upon ageing. However, the molecular pathways behind mitochondrion-dependent cell death in TDP-43 proteinopathies remained unclear. In this review, we discuss the role of TDP-43 in mitochondria, as well as in mitochondrion-dependent cell death. This review includes the recent discovery of the TDP-43-dependent activation of the innate immunity cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway. Unravelling cell death mechanisms upon TDP-43 accumulation in mitochondria may open up new opportunities in TDP-43 proteinopathy research.

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