scholarly journals A population shift between two heritable cell types of the pathogenCandida albicansis based both on switching and selective proliferation

2019 ◽  
Vol 116 (52) ◽  
pp. 26918-26924 ◽  
Author(s):  
Chiraj K. Dalal ◽  
Ignacio A. Zuleta ◽  
Matthew B. Lohse ◽  
Rebecca E. Zordan ◽  
Hana El-Samad ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Fungal Pathogen ◽  
Cell Types ◽  
White Cell ◽  
Switching Frequency ◽  
Flow Cytometry Assay ◽  
Daughter Cells ◽  
Distinct Cell ◽  
Wide Range

Differentiated cell types often retain their characteristics through many rounds of cell division. A simple example is found inCandida albicans, a member of the human microbiota and also the most prevalent fungal pathogen of humans; here, two distinct cell types (white and opaque) exist, and each one retains its specialized properties across many cell divisions. Switching between the two cell types is rare in standard laboratory medium (2% glucose) but can be increased by signals in the environment, for example, certain sugars. When these signals are removed, switching ceases and cells remain in their present state, which is faithfully passed on through many generations of daughter cells. Here, using an automated flow cytometry assay to monitor white–opaque switching over 96 different sugar concentrations, we observed a wide range of opaque-to-white switching that varied continuously across different sugar compositions of the medium. By also measuring white cell proliferation rates under each condition, we found that both opaque-to-white switching and selective white cell proliferation are required for entire populations to shift from opaque to white. Moreover, the switching frequency correlates with the preference of the resulting cell type for the growth medium; that is, the switching is adjusted to increase in environments that favor white cell proliferation. The widely adjustable, all-or-none nature of the switch, combined with the long-term heritability of each state, is distinct from conventional forms of gene regulation, and we propose that it represents a strategy used byC. albicansto efficiently colonize different niches of its human host.

Noncoding RNAs and RNA Editing in Brain Development, Functional Diversification, and Neurological Disease

2007 ◽  
Vol 87 (3) ◽  
pp. 799-823 ◽  
Author(s):  
Mark F. Mehler ◽  
John S. Mattick
Keyword(s):  
Nervous System ◽  
Rna Editing ◽  
Neurological Diseases ◽  
Cell Types ◽  
State Transitions ◽  
Long Term Memory ◽  
Protein Coding ◽  
Continuous State ◽  
Wide Range

The progressive maturation and functional plasticity of the nervous system in health and disease involve a dynamic interplay between the transcriptome and the environment. There is a growing awareness that the previously unexplored molecular and functional interface mediating these complex gene-environmental interactions, particularly in brain, may encompass a sophisticated RNA regulatory network involving the twin processes of RNA editing and multifaceted actions of numerous subclasses of non-protein-coding RNAs. The mature nervous system encompasses a wide range of cell types and interconnections. Long-term changes in the strength of synaptic connections are thought to underlie memory retrieval, formation, stabilization, and effector functions. The evolving nervous system involves numerous developmental transitions, such as neurulation, neural tube patterning, neural stem cell expansion and maintenance, lineage elaboration, differentiation, axonal path finding, and synaptogenesis. Although the molecular bases for these processes are largely unknown, RNA-based epigenetic mechanisms appear to be essential for orchestrating these precise and versatile biological phenomena and in defining the etiology of a spectrum of neurological diseases. The concerted modulation of RNA editing and the selective expression of non-protein-coding RNAs during seminal as well as continuous state transitions may comprise the plastic molecular code needed to couple the intrinsic malleability of neural network connections to evolving environmental influences to establish diverse forms of short- and long-term memory, context-specific behavioral responses, and sophisticated cognitive capacities.

scholarly journals Ssn6 Defines a New Level of Regulation of White-Opaque Switching inCandida albicansand Is Required For the Stochasticity of the Switch

mBio ◽  
2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Aaron D. Hernday ◽  
Matthew B. Lohse ◽  
Clarissa J. Nobile ◽  
Liron Noiman ◽  
Clement N. Laksana ◽  
...  
Keyword(s):  
Fungal Pathogen ◽  
Transcriptional Profiling ◽  
Transcriptional Regulators ◽  
Opportunistic Pathogen ◽  
Cell Types ◽  
White Cell ◽  
Host Immune System ◽  
Cell Type ◽  
Transcriptional Program ◽  
Epigenetic Switch

ABSTRACTThe human commensal and opportunistic pathogenCandida albicanscan switch between two distinct, heritable cell types, named “white” and “opaque,” which differ in morphology, mating abilities, and metabolic preferences and in their interactions with the host immune system. Previous studies revealed a highly interconnected group of transcriptional regulators that control switching between the two cell types. Here, we identify Ssn6, theC. albicansfunctional homolog of theSaccharomyces cerevisiaetranscriptional corepressor Cyc8, as a new regulator of white-opaque switching. Inaor α mating type strains, deletion ofSSN6results in mass switching from the white to the opaque cell type. Transcriptional profiling ofssn6deletion mutant strains reveals that Ssn6 represses part of the opaque cell transcriptional program in white cells and the majority of the white cell transcriptional program in opaque cells. Genome-wide chromatin immunoprecipitation experiments demonstrate that Ssn6 is tightly integrated into the opaque cell regulatory circuit and that the positions to which it is bound across the genome strongly overlap those bound by Wor1 and Wor2, previously identified regulators of white-opaque switching. This work reveals the next layer in the white-opaque transcriptional circuitry by integrating a transcriptional regulator that does not bind DNA directly but instead associates with specific combinations of DNA-bound transcriptional regulators.IMPORTANCEThe most common fungal pathogen of humans,C. albicans, undergoes several distinct morphological transitions during interactions with its host. One such transition, between cell types named “white” and “opaque,” is regulated in an epigenetic manner, in the sense that changes in gene expression are heritably maintained without any modification of the primary genomic DNA sequence. Prior studies revealed a highly interconnected network of sequence-specific DNA-binding proteins that control this switch. We report the identification of Ssn6, which defines an additional layer of transcriptional regulation that is critical for this heritable switch. Ssn6 is necessary to maintain the white cell type and to properly express the opaque cell transcriptional program. Ssn6 does not bind DNA directly but rather associates with specific combinations of DNA-bound transcriptional regulators to control the switch. This work is significant because it reveals a new level of regulation of an important epigenetic switch in the predominant fungal pathogen of humans.

scholarly journals Factor XIII Subunit A in the Skin: Applications in Diagnosis and Treatment

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Lilla Paragh ◽  
Daniel Törőcsik
Keyword(s):  
Factor Xiii ◽  
Potential Role ◽  
Cell Types ◽  
Subunit A ◽  
Therapeutic Implications ◽  
Inflammatory Conditions ◽  
Dermal Cell ◽  
Wide Range

The role of factor XIII subunit A (FXIII-A) is not restricted to hemostasis. FXIII-A is also present intracellularly in several human cells and serves as a diagnostic marker in a wide range of dermatological diseases from inflammatory conditions to malignancies. In this review, we provide a guide on the still controversial interpretation of dermal cell types expressing FXIII-A and assess the previously described mechanisms behind their accumulation under physiological and pathological conditions of the human skin. We summarize the intracellular functions of FXIII-A as well as its possible sources in the extracellular space of the dermis with a focus on its relevance to skin homeostasis and disease pathogenesis. Finally, the potential role of FXIII-A in wound healing, as a field with long-term therapeutic implications, is also discussed.

scholarly journals Control of Cytokines in Latent Cytomegalovirus Infection

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 858
Author(s):  
Pearley Chinta ◽  
Erica C. Garcia ◽  
Kiran Hina Tajuddin ◽  
Naomi Akhidenor ◽  
Allyson Davis ◽  
...  
Keyword(s):  
Latent Infection ◽  
Cell Types ◽  
Cytokine Signaling ◽  
Host Immune System ◽  
Myeloid Progenitor ◽  
Wide Range ◽  
Latently Infected ◽  
Myeloid Progenitor Cells ◽  
Infected Cells

Human cytomegalovirus (HCMV) has evolved a number of mechanisms for long-term co-existence within its host. HCMV infects a wide range of cell types, including fibroblasts, epithelial cells, monocytes, macrophages, dendritic cells, and myeloid progenitor cells. Lytic infection, with the production of infectious progeny virions, occurs in differentiated cell types, while undifferentiated myeloid precursor cells are the primary site of latent infection. The outcome of HCMV infection depends partly on the cell type and differentiation state but is also influenced by the composition of the immune environment. In this review, we discuss the role of early interactions between HCMV and the host immune system, particularly cytokine and chemokine networks, that facilitate the establishment of lifelong latent infection. A better understanding of these cytokine signaling pathways could lead to novel therapeutic targets that might prevent latency or eradicate latently infected cells.

scholarly journals Unique and distinct identities and functions of leaf phloem cells revealed by single cell transcriptomics

2020 ◽  
Author(s):  
Ji-Yun Kim ◽  
Efthymia Symeonidi ◽  
Tin Yau Pang ◽  
Tom Denyer ◽  
Diana Weidauer ◽  
...  
Keyword(s):  
Amino Acid ◽  
Single Cell ◽  
Cell Types ◽  
Phloem Loading ◽  
Vascular Cells ◽  
Metabolic Pathway Analysis ◽  
Differential Distribution ◽  
Distinct Cell ◽  
Wide Range ◽  
Cell Transcriptome

AbstractThe leaf vasculature plays a key role in solute translocation. Veins consist of at least seven distinct cell types, with specific roles in transport, metabolism, and signaling. Little is known about the vascular cells in leaves, in particular the phloem parenchyma (PP). PP effluxes sucrose into the apoplasm as a basis for phloem loading; yet PP has only been characterized microscopically. Here, we enriched vascular cells from Arabidopsis leaves to generate a single-cell transcriptome atlas of leaf vasculature. We identified ≥19 cell clusters, encompassing epidermis, guard cells, hydathodes, mesophyll, and all vascular cell types, and used metabolic pathway analysis to define their roles. Clusters comprising PP cells were enriched for transporters, including SWEET11 and SWEET12 sucrose and UmamiT amino acid efflux carriers. PP development occurs independently from APL, a transcription factor required for phloem differentiation. PP cells have a unique pattern of amino acid metabolism activity distinct from companion cells (CC), explaining differential distribution/metabolism of amino acids in veins. The kinship relation of the vascular clusters is strikingly similar to the vein morphology, except for a clear separation of CC from the other vascular cells including PP. In summary, our scRNA-seq analysis provides a wide range of information into the leaf vasculature and the role and relationship of the leaf cell types.

scholarly journals DIANA-LncBase v3: indexing experimentally supported miRNA targets on non-coding transcripts

2019 ◽  
Author(s):  
Dimitra Karagkouni ◽  
Maria D Paraskevopoulou ◽  
Spyros Tastsoglou ◽  
Giorgos Skoufos ◽  
Anna Karavangeli ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Cell Types ◽  
Lncrna Expression ◽  
Mirna Targets ◽  
Manual Curation ◽  
Distinct Cell ◽  
Wide Range ◽  
Variant Information ◽  
Cell Type Specific ◽  
Cellular Compartments

Abstract DIANA-LncBase v3.0 (www.microrna.gr/LncBase) is a reference repository with experimentally supported miRNA targets on non-coding transcripts. Its third version provides approximately half a million entries, corresponding to ∼240 000 unique tissue and cell type specific miRNA–lncRNA pairs. This compilation of interactions is derived from the manual curation of publications and the analysis of >300 high-throughput datasets. miRNA targets are supported by 14 experimental methodologies, applied to 243 distinct cell types and tissues in human and mouse. The largest part of the database is highly confident, AGO-CLIP-derived miRNA-binding events. LncBase v3.0 is the first relevant database to employ a robust CLIP-Seq-guided algorithm, microCLIP framework, to analyze 236 AGO-CLIP-Seq libraries and catalogue ∼370 000 miRNA binding events. The database was redesigned from the ground up, providing new functionalities. Known short variant information, on >67,000 experimentally supported target sites and lncRNA expression profiles in different cellular compartments are catered to users. Interactive visualization plots, portraying correlations of miRNA–lncRNA pairs, as well as lncRNA expression profiles in a wide range of cell types and tissues, are presented for the first time through a dedicated page. LncBase v3.0 constitutes a valuable asset for ncRNA research, providing new insights to the understanding of the still widely unexplored lncRNA functions.

scholarly journals MicroRNAs Instruct and Maintain Cell Type Diversity in the Nervous System

2021 ◽  
Vol 14 ◽  
Author(s):  
Norjin Zolboot ◽  
Jessica X. Du ◽  
Federico Zampa ◽  
Giordano Lippi
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Expression Profiles ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Neural Progenitor ◽  
Cell Type ◽  
Mrna Targets ◽  
Distinct Cell ◽  
Wide Range

Characterizing the diverse cell types that make up the nervous system is essential for understanding how the nervous system is structured and ultimately how it functions. The astonishing range of cellular diversity found in the nervous system emerges from a small pool of neural progenitor cells. These progenitors and their neuronal progeny proceed through sequential gene expression programs to produce different cell lineages and acquire distinct cell fates. These gene expression programs must be tightly regulated in order for the cells to achieve and maintain the proper differentiated state, remain functional throughout life, and avoid cell death. Disruption of developmental programs is associated with a wide range of abnormalities in brain structure and function, further indicating that elucidating their contribution to cellular diversity will be key to understanding brain health. A growing body of evidence suggests that tight regulation of developmental genes requires post-transcriptional regulation of the transcriptome by microRNAs (miRNAs). miRNAs are small non-coding RNAs that function by binding to mRNA targets containing complementary sequences and repressing their translation into protein, thereby providing a layer of precise spatial and temporal control over gene expression. Moreover, the expression profiles and targets of miRNAs show great specificity for distinct cell types, brain regions and developmental stages, suggesting that they are an important parameter of cell type identity. Here, we provide an overview of miRNAs that are critically involved in establishing neural cell identities, focusing on how miRNA-mediated regulation of gene expression modulates neural progenitor expansion, cell fate determination, cell migration, neuronal and glial subtype specification, and finally cell maintenance and survival.

Fine Structure of the Malpighian Tubules of the Mosquito, Culex pipiens

1971 ◽  
Vol 29 ◽  
pp. 402-403
Author(s):  
Brendan Clifford
Keyword(s):  
Fine Structure ◽  
Culex Pipiens ◽  
Stellate Cell ◽  
Malpighian Tubule ◽  
Cell Types ◽  
Instar Larva ◽  
Malpighian Tubules ◽  
Calliphora Erythrocephala ◽  
Distinct Cell ◽  
Basal Plasma

An ultrastructural investigation of the Malpighian tubules of the fourth instar larva of Culex pipiens was undertaken as part of a continuing study of the fine structure of transport epithelia.Each of the five Malpighian tubules was found to be morphologically identical and regionally undifferentiated. Two distinct cell types, the primary and stellate, were found intermingled along the length of each tubule. The ultrastructure of the stellate cell was previously described in the Malpighian tubule of the blowfly, Calliphora erythrocephala by Berridge and Oschman.The basal plasma membrane of the primary cell is extremely irregular, giving rise to a complex interconnecting network of basal channels. The compartments of cytoplasm entrapped within this system of basal infoldings contain mitochondria, free ribosomes, and small amounts of rough endoplasmic reticulum. The mitochondria are distinctive in that the cristae run parallel to the long axis of the organelle.

Modern prevention and active longevity programs on the basis of disruptive domestic technologies: positive experience and prospects for application

2020 ◽  
pp. 66-73
Author(s):  
A. Simonova ◽  
S. Chudakov ◽  
R. Gorenkov ◽  
V. Egorov ◽  
A. Gostry ◽  
...  
Keyword(s):  
Personalized Medicine ◽  
Early Detection ◽  
Laboratory Diagnostics ◽  
Positive Experience ◽  
Practical Application ◽  
Wide Range ◽  
Integrated Program ◽  
Long Term Experience ◽  
Early Detection And Prevention

The article summarizes the long-term experience of practical application of domestic breakthrough technologies of preventive personalized medicine for laboratory diagnostics of a wide range of socially significant non-infectious diseases. Conceptual approaches to the formation of an integrated program for early detection and prevention of civilization diseases based on these technologies are given. A vision of the prospects for the development of this area in domestic and foreign medicine has been formed.

To the 70th anniversary of World Meteorological Organization. Scientific and technical cooperation of Hydrometeorological Center of the USSR/Russia in the Programs of World Meteorological Organization

2020 ◽  
pp. 117-138
Author(s):  
S.V. Borshch ◽  
◽  
R.M. Vil’fand ◽  
D.B. Kiktev ◽  
V.M. Khan ◽  
...  
Keyword(s):  
Environmental Monitoring ◽  
High Efficiency ◽  
World Meteorological Organization ◽  
70Th Anniversary ◽  
Technical Level ◽  
Technical Cooperation ◽  
Wide Range

The paper presents the summary and results of long-term and multi-faceted experience of international scientific and technical cooperation of Hydrometeorological Center of Russia in the field of hydrometeorology and environmental monitoring within the framework of WMO programs, which indicates its high efficiency in performing a wide range of works at a high scientific and technical level. Keywords: World Meteorological Organization, major WMO programs, representatives of Hydrometeorological Center of Russia in WMO

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