scholarly journals Ancient Evolutionary Origin and Properties of Universally Produced Natural Exosomes Contribute to Their Therapeutic Superiority Compared to Artificial Nanoparticles

2021 ◽  
Vol 22 (3) ◽  
pp. 1429
Author(s):  
Phillip W. Askenase
Keyword(s):  
Membrane Lipid ◽  
Epigenetic Alterations ◽  
Maternal Milk ◽  
Evolutionary Origins ◽  
Cellular Changes ◽  
Therapeutic Uses ◽  
Intracellular Release ◽  
Experimental Approaches ◽  
Primordial Soup ◽  
Harsh Conditions

Extracellular vesicles (EVs), such as exosomes, are newly recognized fundamental, universally produced natural nanoparticles of life that are seemingly involved in all biologic processes and clinical diseases. Due to their universal involvements, understanding the nature and also the potential therapeutic uses of these nanovesicles requires innovative experimental approaches in virtually every field. Of the EV group, exosome nanovesicles and larger companion micro vesicles can mediate completely new biologic and clinical processes dependent on the intercellular transfer of proteins and most importantly selected RNAs, particularly miRNAs between donor and targeted cells to elicit epigenetic alterations inducing functional cellular changes. These recipient acceptor cells are nearby (paracrine transfers) or far away after distribution via the circulation (endocrine transfers). The major properties of such vesicles seem to have been conserved over eons, suggesting that they may have ancient evolutionary origins arising perhaps even before cells in the primordial soup from which life evolved. Their potential ancient evolutionary attributes may be responsible for the ability of some modern-day exosomes to withstand unusually harsh conditions, perhaps due to unique membrane lipid compositions. This is exemplified by ability of the maternal milk exosomes to survive passing the neonatal acid/enzyme rich stomach. It is postulated that this resistance also applies to their durable presence in phagolysosomes, thus suggesting a unique intracellular release of their contained miRNAs. A major discussed issue is the generally poorly realized superiority of these naturally evolved nanovesicles for therapies when compared to human-engineered artificial nanoparticles, e.g., for the treatment of diseases like cancers.

scholarly journals Ancient Origin Properties of Natural Exosomes Contribute to Their Therapeutic Superiority Compared to Artificial Nanoparticles

2020 ◽  
Author(s):  
Philip Askenase
Keyword(s):  
Membrane Lipid ◽  
Epigenetic Alterations ◽  
Maternal Milk ◽  
Evolutionary Origins ◽  
Therapeutic Uses ◽  
Intracellular Release ◽  
Experimental Approaches ◽  
New Phenomena ◽  
Primordial Soup ◽  
Harsh Conditions

Extracellular vesicles (EV) such as exosomes, are newly recognized fundamental, natural and physiologic particles of life that seemingly are involved all biologic processes and clinical diseases. Due to their universal involvements, understanding the nature and the potential therapeutic uses of these nano-vesicles requires innovative experimental approaches, in virtually every field. Of the EV group, exosome nano-vesicles and larger companion extracellular micro vesicles (MV) can mediate completely new phenomena dependent on intercellular transfer of proteins and selected RNAs; particularly miRNAs, between donor and targeted cells to elicit epigenetic alterations inducing functional cellular changes. These recipient acceptor cells are nearby (paracrine transfers) or far away after distribution via the circulation (endocrine transfers). The major properties of such vesicles seem to have been conserved over eons, suggesting that they may have ancient evolutionary origins arising perhaps even before cells in the primordial soup from which life evolved. Their potential ancient evolutionary attributes may be responsible for the ability of some modern day exosomes to withstand unusually harsh conditions; perhaps due to unusual membrane lipid compositions. This is exemplified by maternal milk exosome survival of the neonatal acid/enzyme rich stomach. It is postulated that this also applies to their durable presence in phagolysosomes; suggesting unique intracellular release of contents. A major issue discussed is the generally poorly realized superiority of these naturally evolved nano vesicles to therapies compared human engineered artificial nanoparticles; say for treatment of cancers.

scholarly journals Dually localized proteins found in both the apicoplast and mitochondrion utilize the Golgi-dependent pathway for apicoplast targeting in Toxoplasma gondii

2020 ◽  
Author(s):  
Aparna Prasad ◽  
Pragati Mastud ◽  
Swati Patankar
Keyword(s):  
Toxoplasma Gondii ◽  
Protein Trafficking ◽  
Secretory Pathway ◽  
Apicomplexan Parasites ◽  
Evolutionary Origins ◽  
Molecular Features ◽  
Experimental Approaches ◽  
Endosymbiotic Organelle ◽  
First Time ◽  
Dependent Pathway

ABSTRACTLike other apicomplexan parasites, Toxoplasma gondii harbours a four-membraned endosymbiotic organelle - the apicoplast. Apicoplast proteins are nuclear-encoded and trafficked to the organelle through the endoplasmic reticulum (ER). From the ER to the apicoplast, two distinct protein trafficking pathways can be used. One such pathway is the cell’s secretory pathway involving the Golgi, while the other is a unique Golgi-independent pathway. Using different experimental approaches, many apicoplast proteins have been shown to utilize the Golgi-independent pathway, while a handful of reports show that a few proteins use the Golgi-dependent pathway. This has led to an emphasis towards the unique Golgi-independent pathway when apicoplast protein trafficking is discussed in the literature. Additionally, the molecular features that drive proteins to each pathway are not known. In this report, we systematically test eight apicoplast proteins, using a C-terminal HDEL sequence to assess the role of the Golgi in their transport. We demonstrate that dually localised proteins of the apicoplast and mitochondrion (TgSOD2, TgTPx1/2 and TgACN) are trafficked through the Golgi while proteins localised exclusively to the apicoplast are trafficked independent of the Golgi. Mutants of the dually localised proteins that localised exclusively to the apicoplast also showed trafficking through the Golgi. Phylogenetic analysis of TgSOD2, TgTPx1/2 and TgACN suggested that the evolutionary origins of TgSOD2, TgTPx1/2 lie in the mitochondrion while TgACN appears to have originated from the apicoplast. Collectively, with these results, for the first time, we establish that the driver of the Golgi-dependent trafficking route to the apicoplast is the dual localisation of the protein to the apicoplast and the mitochondrion.

scholarly journals Strongly asymmetric hybridization barriers shape the origin of a new polyploid species and its hybrid ancestor

2015 ◽  
Author(s):  
Mario Vallejo-Marin ◽  
Arielle Cooley ◽  
Michelle Qi ◽  
Madison Folmer ◽  
Michael McKain ◽  
...  
Keyword(s):  
Natural Populations ◽  
Genomic Data ◽  
Parentage Analysis ◽  
Polyploid Species ◽  
Common Pattern ◽  
Evolutionary Origins ◽  
Allopolyploid Speciation ◽  
Genomic Analyses ◽  
Experimental Approaches ◽  
The Common

Premise of the study: Hybridization between diploids and tetraploids can lead to new allopolyploid species, often via a triploid intermediate. Viable triploids are often produced asymmetrically, with greater success observed for maternal-excess crosses where the mother has a higher ploidy than the father. Here we investigate the evolutionary origins of Mimulus peregrinus, an allopolyploid recently derived from the triploid M. x robertsii, to determine whether reproductive asymmetry has shaped the formation of this new species. Methods: We used reciprocal crosses between the diploid (M. guttatus) and tetraploid (M. luteus) progenitors to determine the viability of triploid hybrids resulting from paternal- versus maternal-excess crosses. To investigate whether experimental results predict patterns seen in the field, we performed parentage analyses comparing natural populations of M. peregrinus to its diploid, tetraploid, and triploid progenitors. Organellar sequences obtained from pre-existing genomic data, supplemented with additional genotyping was used to establish the maternal ancestry of multiple M. peregrinus and M. x robertsii populations. Key results: We find strong evidence for asymmetric origins of M. peregrinus, but opposite to the common pattern, with paternal-excess crosses significantly more successful than maternal-excess crosses. These results successfully predicted hybrid formation in nature: 111 of 114 M. x robertsii individuals, and 27 of 27 M. peregrinus, had an M. guttatus maternal haplotype. Conclusion: This study, which includes assembly of the first Mimulus chloroplast genome, demonstrates the utility of parentage analysis through genome skimming. We highlight the benefits of complementing genomic analyses with experimental approaches to understand asymmetry in allopolyploid speciation.

Osmolarity and Artificial Cell Damage in Ischemic Myocardium

1990 ◽  
Vol 48 (3) ◽  
pp. 262-263
Author(s):  
Richard Montione ◽  
Muhammad Ashraf
Keyword(s):  
Cell Damage ◽  
Uranyl Acetate ◽  
Tissue Preservation ◽  
Rat Myocardium ◽  
En Bloc ◽  
Cellular Changes ◽  
Artificial Cell ◽  
Cacodylate Buffer ◽  
Isotonic Buffer ◽  
Perfusion Fixation

Osmolarity of a fixative vehicle has long been known to have an effect on the tissue preservation. An increase in tissue osmolarity occurs in ischemia-damaged tissue and affects the morphology. In this study, we examined cellular changes in ischemic rat myocardium induced by varying fixative toxicity.Rats were sacrificed by decapitation and the hearts immediately removed and retrogradily perfused through the aorta with anoxic Kurbs-Henseleit medium. Hearts were then placed in a bag with a small amount of medium at 37°C for 90 minutes. Hearts were perfusion-fixed using 2% glutaraldehyde in 0.1 M cacodylate buffer pH -7.3 at three osmolarities. The isotonic buffer was adjusted to 311 mOsm/kg using D-manitol. Hypertonic buffers were adjusted to 375 and 400 mOsm/kg. One-half hour after perfusion fixation, the hearts were sliced and cut into small blocks and allowed to fix overnight at 4°C. Blocks were post fixed in osmium, en bloc stained in uranyl acetate, dehydrated in ethanol and embedded in Spurr medium.

“Part of the Primordial Soup”

1995 ◽  
Vol 64 (1) ◽  
pp. 220-221
Author(s):  
Paul G. McDonough ◽  
Wilfried Feichtinger
Keyword(s):  
Primordial Soup

Learned Placebo Effects in the Immune System

2014 ◽  
Vol 222 (3) ◽  
pp. 148-153 ◽  
Author(s):  
Sabine Vits ◽  
Manfred Schedlowski
Keyword(s):  
Nervous System ◽  
Immune System ◽  
Associative Learning ◽  
Placebo Response ◽  
Immunosuppressive Drug ◽  
Immune Functions ◽  
Placebo Effects ◽  
New Therapeutic Approaches ◽  
Biological Variables ◽  
Experimental Approaches

Associative learning processes are one of the major neuropsychological mechanisms steering the placebo response in different physiological systems and end organ functions. Learned placebo effects on immune functions are based on the bidirectional communication between the central nervous system (CNS) and the peripheral immune system. Based on this “hardware,” experimental evidence in animals and humans showed that humoral and cellular immune functions can be affected by behavioral conditioning processes. We will first highlight and summarize data documenting the variety of experimental approaches conditioning protocols employed, affecting different immunological functions by associative learning. Taking a well-established paradigm employing a conditioned taste aversion model in rats with the immunosuppressive drug cyclosporine A (CsA) as an unconditioned stimulus (US) as an example, we will then summarize the efferent and afferent communication pathways as well as central processes activated during a learned immunosuppression. In addition, the potential clinical relevance of learned placebo effects on the outcome of immune-related diseases has been demonstrated in a number of different clinical conditions in rodents. More importantly, the learned immunosuppression is not restricted to experimental animals but can be also induced in humans. These data so far show that (i) behavioral conditioned immunosuppression is not limited to a single event but can be reproduced over time, (ii) immunosuppression cannot be induced by mere expectation, (iii) psychological and biological variables can be identified as predictors for this learned immunosuppression. Together with experimental approaches employing a placebo-controlled dose reduction these data provide a basis for new therapeutic approaches to the treatment of diseases where a suppression of immune functions is required via modulation of nervous system-immune system communication by learned placebo effects.

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