Fungal Extracellular Vesicles Are Involved in Intraspecies Intracellular Communication

Here, we report a study about extracellular vesicles (EVs) as communication mediators in fungi. Our results demonstrated the role of EVs from Candida albicans , Aspergillus fumigatus , and Paracoccidioides brasiliensis regulating the expression of target genes and phenotype features.

ceRNAs in Cancer: Mechanism and Functions in a Comprehensive Regulatory Network

Noncoding RNAs have been shown with powerful ability in post-transcriptional regulation, enabling intertwined RNA crosstalk and global molecular interaction in a large amount of dysfunctional conditions including cancer. Competing endogenous RNAs (ceRNAs) are those competitively binding with shared microRNAs (miRNAs), freeing their counterparts from miRNA-induced degradation, thus actively influencing and connecting with each other. Constantly updated analytical approaches boost outstanding advancement achieved in this burgeoning hotspot in multilayered intracellular communication, providing new insights into pathogenesis and clinical treatment. Here, we summarize the mechanisms and correlated factors under this RNA interplay and deregulated transcription profile in neoplasm and tumor progression, underscoring the great significance of ceRNAs for diagnostic values, monitoring biomarkers, and prognosis evaluation in cancer.

First person – Kazuko Okamoto

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. Kazuko Okamoto is first author on ‘ Pressure-induced changes on the morphology and gene expression in mammalian cells’, published in BiO. Kazuko conducted the research described in this article while a research scientist in Tomonobu M. Watanabe's lab at RIKEN Center for Biosystems Dynamics Research, Kobe, Japan. She is now an assistant professor in the lab of Satoru Okuda at Nano Life Science Institute, Kanazawa University, Japan, investigating intracellular communication and transcription regulation.

P–267 Characterising a novel embryo grading system for 4-cell embryos including symmetry, fragmentation, cell configuration, cell contacts per cell, distance between cells, and cell adhesion strength

Study question What other cell junction factors can be easily characterised from imagery of 4-cell embryos to assist in embryo classification and prediction of viability? Summary answer 4-cell embryo grading should not only account for symmetry and fragmentation, but also cell configuration and cell adhesion quality. What is known already 4-cell embryos are clinically classified according to cell number, symmetry and fragmentation without accounting for cell orientation or quality of cell junctions. Our previous work has focused on classification of 4-cell embryos according to overall embryo shape (“tetrahedral” versus “planar”) using artificial intelligence. Our work, as confirmed by others, has demonstrated that embryo shape at the 4-cell stage is an important determinant of the ability of the embryo to reach blastocyst, utilisation, pregnancy and live birth. This is thought to be because of variations in intracellular communication between cells in embryos with different orientations, and consequently, different intracellular junction phenotypes. Study design, size, duration Using geometrical principles, possible permutations of 4-cell embryos (excluding redundant mirrored permutations) were identified and further classified based on shape and number of cell junctions. For ease of calculations, cells were assumed to be spherical, with at least one intracellular cell contact and symmetrical in size with other cells in the same embryo. Participants/materials, setting, methods The six distances between centroids of permutations for each configuration were calculated relative to the size of the cell, and the shortest distance between cell membranes. Adhesion was characterised from embryo imagery based on the overall shape of the cell, external angle between cells and the length of cell contact (the more spherical the cell, the larger the angle and the longer the cell contact point, the stronger the adhesion, adapted from Winklbauer,2015). Main results and the role of chance 4-cell embryos may be classified into 13 variant configurations: 1 typical Tetrahedral, 2 quasi-tetrahedral, 10 planar. These variants were classified according to number of cells with 0,1,2 and 3 intracellular contacts, leading to six possible configurations: 0004(tetrahedral), 0022(quasi tetrahedral/planar), 0040 (planar), 0121(quasi tetrahedral/planar), 0301(planar), 0220(planar). The number of total cell junctions in the embryo in each of these configurations was 12,10,8,8,6,6 respectively, with tetrahedral embryos (0004) having twice the cell contacts compared to planar embryos (p < 0.001). Tetrahedral embryos have an advantage over the other embryo configurations in terms of better embryo communication, as demonstrated by the lower average and variation in distance and shorter sum of all intracellular distances between centroids (mean: 0.78 vs 0.94,0.98,1.04,1.09,1.19; stdev:0.06 vs 0.2,0.3,0.3,0.4,0.4,0.3; sum:4.7 vs 5.2,6.3,6.1,6.7,7.0,6.0 cell lengths) and between cells (mean: 0 vs 0.34,0.07,0.39,0.42,0.56; stdev: 0 vs 0.56,0.11,0.51,0.53,0.66; sum: 0 vs 2.71,0.43,3.13,3.38,4.46 cell lengths) observed in tetrahedral embryos versus other five configurations respectively (p < 0.001). Cell junctions were classified according to degree of cell adhesion: A:none (cells remain spherical in shape); B:weak (external angle between the cells is acute, there is a narrow visible cell junction); C:strong (external angle between the cells is obtuse with a wide visible cell junction). Limitations, reasons for caution: Follow-up studies will evaluate the impact of different cell shapes,cells without intracellular contact,and asymmetrical embryos. The proposed classification will be validated against a database of known outcome from 8 clinics from 6 countries to quantify the clinical implications of this classification,and the consistency of assessment by humans and AI . Wider implications of the findings: It is clear that differences in intracellular communication between cells in embryos with different orientations, and different intracellular junction phenotypes is an important determinant of embryo viability. Our classification system allows for an easy to use and mathematically sound criteria for classifying 4-cell embryo cell junction quality. Trial registration number NA

Means of intracellular communication: touching, kissing, fusing

Eukaryotic cells are complicated factories that need ensure productivity and functionality on the cellular level as well as being able to communicate with their environment. In order to do so cells developed intracellular communication systems. For a long time, research focused mainly on the secretory/biosynthetic and endocytic routes for communication, leaving the communication with other organelles apart. In the last decade, this view has changed dramatically and a more holistic view of intracellular communication is emerging. We are still at the tip of the iceberg, but a common theme of touching, kissing, fusing is emerging as general principles of communication.

The Multifunctionality of Exosomes; from the Garbage Bin of the Cell to a Next Generation Gene and Cellular Therapy

Exosomes are packaged with a variety of cellular cargo including RNA, DNA, lipids and proteins. For several decades now there has been ongoing debate as to what extent exosomes are the garbage bin of the cell or if these entities function as a distributer of cellular cargo which acts in a meaningful mechanistic way on target cells. Are the contents of exosomes unwanted excess cellular produce or are they selective nucleic acid packaged nanoparticles used to communicate in a paracrine fashion? Overexpressed RNAs and fragments of DNA have been shown to collect into exosomes which are jettisoned from cells in response to particular stimuli to maintain homeostasis suggesting exosomes are functional trash bins of the cell. Other studies however have deciphered selective packaging of particular nucleic acids into exosomes. Nucleic acids packaged into exosomes are increasingly reported to exert transcriptional control on recipient cells, supporting the notion that exosomes may provide a role in signaling and intracellular communication. We survey the literature and conclude that exosomes are multifunctional entities, with a plethora of roles that can each be taken advantage to functionally modulate cells. We also note that the potential utility of developing exosomes as a next generation genetic therapy may in future transform cellular therapies. We also depict three models of methodologies which can be adopted by researchers intending to package nucleic acid in exosomes for developing gene and cell therapy.

Mitochondrial Membrane Intracellular Communication in Healthy and Diseased Myocardium

Research efforts in the twenty-first century have been paramount to the discovery and development of novel pharmacological treatments in a variety of diseases resulting in improved life expectancy. Yet, cardiac disease remains a leading cause of morbidity and mortality worldwide. Over time, there has been an expansion in conditions such as atrial fibrillation (AF) and heart failure (HF). Although past research has elucidated specific pathways that participate in the development of distinct cardiac pathologies, the exact mechanisms of action leading to disease remain to be fully characterized. Protein turnover and cellular bioenergetics are integral components of cardiac diseases, highlighting the importance of mitochondria and endoplasmic reticulum (ER) in driving cellular homeostasis. More specifically, the interactions between mitochondria and ER are crucial to calcium signaling, apoptosis induction, autophagy, and lipid biosynthesis. Here, we summarize mitochondrial and ER functions and physical interactions in healthy physiological states. We then transition to perturbations that occur in response to pathophysiological challenges and how this alters mitochondrial–ER and other intracellular organelle interactions. Finally, we discuss lifestyle interventions and innovative therapeutic targets that may be used to restore beneficial mitochondrial and ER interactions, thereby improving cardiac function.

Targeting Tumor-derived exosomes expressing CD73: new opportunities in the pathogenesis and treatment of cancer

: Tumor-derived exosomes contain biological contents such as proteins, lipids, RNA (miRNAs, mRNAs, lncRNA), and DNA for intracellular communication. Meanwhile, studies have shown the role of exosomes in cancer progression, metastasis, and therapeutic resistance. Furthermore, tumor exosomes have received growing attention due to their potential as novel therapeutic protocols for the treatment of cancers. Adenosine nucleoside, which is a derivative of ATP, is highly elevated in the tumor microenvironment by CD39 and CD73 enzymatic activity. Recently, it is distinguished that cancer cellderived exosomes carry CD39 and CD73 on their surface and may contribute to rising adenosine levels in the tumor microenvironment. In this review, we summarize the evidence of CD39/CD73-bearing exosomes and their role in cancer development, progression, invasion, angiogenesis, metastasis and their application in the selection of the appropriate strategy to treat different types of cancer.

Extracellular vesicles as potential biomarkers and therapeutic approaches in autoimmune diseases

Extracellular vesicles are heterogeneous populations of naturally occurring secreted small vesicles. EVs function as signaling platforms to facilitate intracellular communication, which indicates the physiological or pathophysiological conditions of cells or tissues. Considering that EVs can be isolated from most body fluids and that molecular constituents could be reprogrammed according to the physiological status of the secreting cells, EVs are regarded as novel diagnostic and prognostic biomarkers for many diseases. The ability to protect encapsulated molecules from degradation in body fluids suggests the potential of EVs as biological medicines or drug delivery systems. This article focuses on the EV-associated biomarkers and therapeutic approaches in autoimmune diseases.