scholarly journals Evolutionary history and origin of Tre1 superfamily shed light on its role in regulating blood brain barrier

2021 ◽  
Author(s):  
Norwin Kubick ◽  
Pavel Klimovich ◽  
Irmina Bieńkowska ◽  
Mariusz Sacharczuk ◽  
Michel-Edwar Mickael
Keyword(s):  
Positive Selection ◽  
Immune Cells ◽  
Evolutionary History ◽  
Evolutionary Relationship ◽  
Drosophila Genome ◽  
Dependent Manner ◽  
Ancestral Reconstruction ◽  
Critical Function ◽  
Blood Brain ◽  
Drosophila Brain

Understanding how the evolutionary relationship between immune cells and the blood-brain is important to devise therapeutic strategies that can regulate their critical function. In vertebrates, immune cells follow either a paracellular or transcellular pathway to infiltrate the BBB. In drosophila glial cells form the BBB that regulates the access of immune-like cells to the drosophila brain. However, it is still not known which route immune-like cells follow to infiltrate the drosophila brain. In vertebrates, paracellular migration is dependent on PECAM1, while transcellular migration is dependent on the expression of CAV1. Interestingly drosophila genome lacks both genes. Tre1 superfamily (Tre1, Moody, and Dmel_CG4313) play a diverse role in regulating transepithelial migration in drosophila. However, its evolutionary history and origin are not yet known. We performed phylogenetic analysis, together with HH search, positive selection, and ancestral reconstruction to investigate the Tre1 family Interestingly we found that Tre1 exists in mollusks, insects, ambulacria, and sclaidphora. Moody is shown to be a more ancient protein and it existed since cnidaria emergence and has a homolog (GPCR84) in mammals. The third family member (Dmel_CG4313) only exists in insects. The origin of the family seems to be related to the rhodopsin-like family and in particular family α. We found that opsin is the nearest receptor to have a common ancestor with the Tre1 superfamily that seems to have diverged in sponges. We investigated the positive selection of the Tre1 family using PAML. Tre1 seems to have evolved under negative selection, whereas Moody has evolved during positive selection. The sites that we found under positive selection are Likely to play a role in the speciation of function in the case of Moody. We have identified an SH3, in Tre1 and, moody and Dmel_CG4313. Sh3 is known to play a fundamental role in regulating actin movement in a Rho-dependent manner. We suggest that Tre1 could be playing an important role in paracellular diapedesis in drosophila.

scholarly journals Investigation of Evolutionary History and Origin of the Tre1 Family Suggests a Role in Regulating Hemocytes Cells Infiltration of the Blood–Brain Barrier

Insects ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 882
Author(s):  
Norwin Kubick ◽  
Pavel Klimovich ◽  
Irmina Bieńkowska ◽  
Piotr Poznanski ◽  
Marzena Łazarczyk ◽  
...  
Keyword(s):  
Positive Selection ◽  
Blood Brain Barrier ◽  
Immune Cells ◽  
Evolutionary History ◽  
Evolutionary Relationship ◽  
Brain Barrier ◽  
Drosophila Genome ◽  
Dependent Manner ◽  
Ancestral Reconstruction ◽  
Blood Brain

Understanding the evolutionary relationship between immune cells and the blood–brain barrier (BBB) is important to devise therapeutic strategies. In vertebrates, immune cells follow either a paracellular or a transcellular pathway to infiltrate the BBB. In Drosophila, glial cells form the BBB that regulates the access of hemocytes to the brain. However, it is still not known which diapedesis route hemocytes cells follow. In vertebrates, paracellular migration is dependent on PECAM1, while transcellular migration is dependent on the expression of CAV1. Interestingly Drosophila genome lacks both genes. Tre1 family (Tre1, moody, and Dmel_CG4313) play a diverse role in regulating transepithelial migration in Drosophila. However, its evolutionary history and origin are not yet known. We performed phylogenetic analysis, together with HH search, positive selection, and ancestral reconstruction to investigate the Tre1 family. We found that Tre1 exists in Mollusca, Arthropoda, Ambulacraria, and Scalidophora. moody is shown to be a more ancient protein and it has existed since Cnidaria emergence and has a homolog (e.g., GPCR84) in mammals. The third family member (Dmel_CG4313) seems to only exist in insects. The origin of the family seems to be related to the rhodopsin-like family and in particular family α. We found that opsin is the nearest receptor to have a common ancestor with the Tre1 family that has diverged in sponges. We investigated the positive selection of the Tre1 family using PAML. Tre1 seems to have evolved under negative selection, whereas moody has evolved during positive selection. The sites that we found under positive selection are likely to play a role in the speciation of function in the case of moody. We have identified an SH3 motif, in Tre1 and, moody and Dmel_CG4313. SH3 is known to play a fundamental role in regulating actin movement in a Rho-dependent manner in PECAM1. Our results suggest that the Tre1 family could be playing an important role in paracellular diapedesis in Drosophila.

scholarly journals Interleukins and Interleukin Receptors Evolutionary History and Origin in Relation to CD4+ T Cell Evolution

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 813
Author(s):  
Norwin Kubick ◽  
Pavel Klimovich ◽  
Patrick Henckell Flournoy ◽  
Irmina Bieńkowska ◽  
Marzena Łazarczyk ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Positive Selection ◽  
Cd4 T Cells ◽  
Cell Function ◽  
Single Gene ◽  
Ancestral Reconstruction ◽  
Critical Function ◽  
Interleukin Receptors

Understanding the evolution of interleukins and interleukin receptors is essential to control the function of CD4+ T cells in various pathologies. Numerous aspects of CD4+ T cells’ presence are controlled by interleukins including differentiation, proliferation, and plasticity. CD4+ T cells have emerged during the divergence of jawed vertebrates. However, little is known about the evolution of interleukins and their origin. We traced the evolution of interleukins and their receptors from Placozoa to primates. We performed phylogenetic analysis, ancestral reconstruction, HH search, and positive selection analysis. Our results indicated that various interleukins' emergence predated CD4+ T cells divergence. IL14 was the most ancient interleukin with homologs in fungi. Invertebrates also expressed various interleukins such as IL41 and IL16. Several interleukin receptors also appeared before CD4+ T cells divergence. Interestingly IL17RA and IL17RD, which are known to play a fundamental role in Th17 CD4+ T cells first appeared in mollusks. Furthermore, our investigations showed that there is not any single gene family that could be the parent group of interleukins. We postulate that several groups have diverged from older existing cytokines such as IL4 from TGFβ, IL10 from IFN, and IL28 from BCAM. Interleukin receptors were less divergent than interleukins. We found that IL1R, IL7R might have diverged from a common invertebrate protein that contained TIR domains, conversely, IL2R, IL4R and IL6R might have emerged from a common invertebrate ancestor that possessed a fibronectin domain. IL8R seems to be a GPCR that belongs to the rhodopsin-like family and it has diverged from the Somatostatin group. Interestingly, several interleukins that are known to perform a critical function for CD4+ T cells such as IL6, IL17, and IL1B have gained new functions and evolved under positive selection. Overall evolution of interleukin receptors was not under significant positive selection. Interestingly, eight interleukin families appeared in lampreys, however, only two of them (IL17B, IL17E) evolved under positive selection. This observation indicates that although lampreys have a unique adaptive immune system that lacks CD4+ T cells, they could be utilizing interleukins in homologous mode to that of the vertebrates' immune system. Overall our study highlights the evolutionary heterogeneity within the interleukins and their receptor superfamilies and thus does not support the theory that interleukins evolved solely in jawed vertebrates to support T cell function. Conversely, some of the members are likely to play conserved functions in the innate immune system.

A Phenotype–Genotype Codon Model for Detecting Adaptive Evolution

2019 ◽  
Vol 69 (4) ◽  
pp. 722-738 ◽  
Author(s):  
Christopher T Jones ◽  
Noor Youssef ◽  
Edward Susko ◽  
Joseph P Bielawski
Keyword(s):  
Positive Selection ◽  
Adaptive Evolution ◽  
Evolutionary History ◽  
Life History Trait ◽  
Molecular Adaptation ◽  
Simulation Studies ◽  
Site Model ◽  
Branch Site ◽  
A Site ◽  
Post Hoc

Abstract A central objective in biology is to link adaptive evolution in a gene to structural and/or functional phenotypic novelties. Yet most analytic methods make inferences mainly from either phenotypic data or genetic data alone. A small number of models have been developed to infer correlations between the rate of molecular evolution and changes in a discrete or continuous life history trait. But such correlations are not necessarily evidence of adaptation. Here, we present a novel approach called the phenotype–genotype branch-site model (PG-BSM) designed to detect evidence of adaptive codon evolution associated with discrete-state phenotype evolution. An episode of adaptation is inferred under standard codon substitution models when there is evidence of positive selection in the form of an elevation in the nonsynonymous-to-synonymous rate ratio $\omega$ to a value $\omega > 1$. As it is becoming increasingly clear that $\omega > 1$ can occur without adaptation, the PG-BSM was formulated to infer an instance of adaptive evolution without appealing to evidence of positive selection. The null model makes use of a covarion-like component to account for general heterotachy (i.e., random changes in the evolutionary rate at a site over time). The alternative model employs samples of the phenotypic evolutionary history to test for phenomenological patterns of heterotachy consistent with specific mechanisms of molecular adaptation. These include 1) a persistent increase/decrease in $\omega$ at a site following a change in phenotype (the pattern) consistent with an increase/decrease in the functional importance of the site (the mechanism); and 2) a transient increase in $\omega$ at a site along a branch over which the phenotype changed (the pattern) consistent with a change in the site’s optimal amino acid (the mechanism). Rejection of the null is followed by post hoc analyses to identify sites with strongest evidence for adaptation in association with changes in the phenotype as well as the most likely evolutionary history of the phenotype. Simulation studies based on a novel method for generating mechanistically realistic signatures of molecular adaptation show that the PG-BSM has good statistical properties. Analyses of real alignments show that site patterns identified post hoc are consistent with the specific mechanisms of adaptation included in the alternate model. Further simulation studies show that the covarion-like component of the PG-BSM plays a crucial role in mitigating recently discovered statistical pathologies associated with confounding by accounting for heterotachy-by-any-cause. [Adaptive evolution; branch-site model; confounding; mutation-selection; phenotype–genotype.]

scholarly journals Evolutionary Relationship between Two Firefly Species,Curtos costipennisandC. okinawanus(Coleoptera, Lampyridae), in the Ryukyu Islands of Japan Revealed by the Mitochondrial and Nuclear DNA Sequences

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Masahiko Muraji ◽  
Norio Arakaki ◽  
Shigeo Tanizaki
Keyword(s):  
Dna Sequences ◽  
Evolutionary History ◽  
Nuclear Dna ◽  
Evolutionary Relationship ◽  
Early Pleistocene ◽  
Ryukyu Islands ◽  
Mtdna Sequences ◽  
Northern Half ◽  
The Ryukyu Islands ◽  
History Of

The phylogenetic relationship, biogeography, and evolutionary history of closely related two firefly species,Curtos costipennisandC. okinawanus, distributed in the Ryukyu Islands of Japan were examined based on nucleotide sequences of mitochondrial (2.2 kb long) and nuclear (1.1-1.2 kb long) DNAs. In these analyses, individuals were divided among three genetically distinct local groups,C. costipennisin the Amami region,C. okinawanusin the Okinawa region, andC. costipennisin the Sakishima region. Their mtDNA sequences suggested that ancestralC. costipennispopulation was first separated between the Central and Southern Ryukyu areas, and the northern half was then subdivided betweenC. costipennisin the Amami andC. okinawanusin the Okinawa. The application of the molecular evolutionary clocks of coleopteran insects indicated that their vicariance occurred 1.0–1.4 million years ago, suggesting the influence of submergence and subdivision of a paleopeninsula extending between the Ryukyu Islands and continental China through Taiwan in the early Pleistocene.

scholarly journals INTEGRINS MEDIATE PLACENTAL EXTRACELLULAR VESICLE TRAFFICKING TO LUNG AND LIVER IN VIVO

2020 ◽  
Author(s):  
Sean L. Nguyen ◽  
Soo Hyun Ahn ◽  
Jacob W. Greenberg ◽  
Benjamin W. Collaer ◽  
Dalen W. Agnew ◽  
...  
Keyword(s):  
Immune Cells ◽  
Extracellular Vesicle ◽  
Dependent Manner ◽  
Cellular Phenotype ◽  
Reporter Mouse ◽  
Membrane Bound ◽  
First Time

ABSTRACTMembrane-bound extracellular vesicles (EVs) mediate intercellular communication in all organisms, and those produced by placental mammals have become increasingly recognized as significant mediators of fetal-maternal communication. Here, we aimed to identify maternal cells targeted by placental EVs and elucidate the mechanisms by which they traffic to these cells. Exogenously administered pregnancy-associated EVs traffic specifically to the lung; further, placental EVs associate with lung interstitial macrophages and liver Kupffer cells in an integrin-dependent manner. Localization of EV to maternal lungs was confirmed in unmanipulated pregnancy using a transgenic reporter mouse model, which also provided in situ and in vitro evidence that fetally-derived EVs, rarely, may cause genetic alteration of maternal cells. These results provide for the first time direct in vivo evidence for targeting of placental EVs to maternal immune cells, and further, evidence that EVs can alter cellular phenotype.

scholarly journals Evolution and lineage dynamics of a transmissible cancer in Tasmanian devils

PLoS Biology ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. e3000926 ◽  
Author(s):  
Young Mi Kwon ◽  
Kevin Gori ◽  
Naomi Park ◽  
Nicole Potts ◽  
Kate Swift ◽  
...  
Keyword(s):  
Positive Selection ◽  
Cancer Cells ◽  
Cell Lines ◽  
Copy Number ◽  
Convergent Evolution ◽  
Evolutionary History ◽  
Genome Instability ◽  
Copy Number Variants ◽  
Tasmanian Devil ◽  
Transmissible Cancer

Devil facial tumour 1 (DFT1) is a transmissible cancer clone endangering the Tasmanian devil. The expansion of DFT1 across Tasmania has been documented, but little is known of its evolutionary history. We analysed genomes of 648 DFT1 tumours collected throughout the disease range between 2003 and 2018. DFT1 diverged early into five clades, three spreading widely and two failing to persist. One clade has replaced others at several sites, and rates of DFT1 coinfection are high. DFT1 gradually accumulates copy number variants (CNVs), and its telomere lengths are short but constant. Recurrent CNVs reveal genes under positive selection, sites of genome instability, and repeated loss of a small derived chromosome. Cultured DFT1 cell lines have increased CNV frequency and undergo highly reproducible convergent evolution. Overall, DFT1 is a remarkably stable lineage whose genome illustrates how cancer cells adapt to diverse environments and persist in a parasitic niche.

scholarly journals Time-dependent dual effect of NLRP3 inflammasome in brain ischemia

2020 ◽  
Author(s):  
Alejandra Palomino-Antolin ◽  
Paloma Narros-Fernández ◽  
Víctor Farré-Alins ◽  
Javier Sevilla-Montero ◽  
Celine Decouty-Pérez ◽  
...  
Keyword(s):  
Brain Injury ◽  
Blood Brain Barrier ◽  
Inflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Neurovascular Unit ◽  
Time Dependent ◽  
Brain Barrier ◽  
Dependent Manner ◽  
Dual Effect ◽  
Blood Brain

AbstractBackground and purposePost-ischemic inflammation contributes to worsening of ischemic brain injury and in this process, the inflammasomes play a key role. Inflammasomes are cytosolic multiprotein complexes which upon assembly activate the maturation and secretion of the inflammatory cytokines IL-1β and IL-18. However, participation of the NLRP3 inflammasome in ischemic stroke remains controversial. Our aims were to determine the role of NLRP3 in ischemia and to explore the mechanism involved in the potential protective effect of the neurovascular unit.MethodsWT and NLRP3 knock-out mice were subjected to ischemia by middle cerebral artery occlusion (60 minutes) with or without treatment with MCC950 at different time points post-stroke. Brain injury was measured histologically with 2,3,5-triphenyltetrazolium chloride (TTC) staining.ResultsWe identified a time-dependent dual effect of NLRP3. While neither the pre-treatment with MCC950 nor the genetic approach (NLRP3 KO) proved to be neuroprotective, post-reperfusion treatment with MCC950 significantly reduced the infarct volume in a dose-dependent manner. Importantly, MCC950 improved the neuro-motor function and reduced the expression of different pro-inflammatory cytokines (IL-1β, TNF-α), NLRP3 inflammasome components (NLRP3, pro-caspase-1), protease expression (MMP9) and endothelial adhesion molecules (ICAM, VCAM). We observed a marked protection of the blood-brain barrier (BBB), which was also reflected in the recovery of the tight junctions proteins (ZO-1, Claudin-5). Additionally, MCC950 produced a reduction of the CCL2 chemokine in blood serum and in brain tissue, which lead to a reduction in the immune cell infiltration.ConclusionsThese findings suggest that post-reperfusion NLRP3 inhibition may be an effective acute therapy for protecting the blood-brain barrier in cerebral ischemia with potential clinical translation.

scholarly journals Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage

2021 ◽  
Vol 16 (1) ◽  
pp. 845-855
Author(s):  
Huaxu Yu ◽  
Bin He ◽  
Xu Han ◽  
Ting Yan
Keyword(s):  
Kainic Acid ◽  
Blood Brain Barrier ◽  
Neuronal Damage ◽  
Brain Barrier ◽  
Protective Mechanism ◽  
Dependent Manner ◽  
Nissl Staining ◽  
Microglia Cell ◽  
Protein Levels ◽  
Blood Brain

Abstract Rufinamide (RUF) is a structurally unique anti-epileptic drug, but its protective mechanism against brain injury remains unclear. In the present study, we validated how the RUF protected mice with kainic acid (KA)-induced neuronal damage. To achieve that, a mouse epilepsy model was established by KA intraperitoneal injection. After Nissl staining, although there was a significant reduction in Nissl bodies in mice treated with KA, 40, 80, and 120 mg/kg, RUF significantly reduced KA-induced neuronal damage, in a dose-dependent manner. Among them, 120 mg/kg RUF was most pronounced. Immunohistochemistry (IHC) and western blot analysis showed that RUF inhibited the IBA-1 overexpression caused by KA to block microglia cell overactivation. Further, RUF treatment partially reversed neuroinflammatory cytokine (IL-1β, TNFα, HMGB1, and NLRP3) overexpression in mRNA and protein levels in KA mice. Moreover, although KA stimulation inhibited the expression of tight junctions, RUF treatment significantly upregulated expression of tight junction proteins (occludin and claudin 5) in both mRNA and protein levels in the brain tissues of KA mice. RUF inhibited the overactivation of microglia, suppressed the neuroinflammatory response, and reduced the destruction of blood–brain barrier, thereby alleviating the excitatory nerve damage of the KA-mice.

scholarly journals Flavonoid transport across RBE4 cells: A blood-brain barrier model

2010 ◽  
Vol 15 (2) ◽  
Author(s):  
Ana Faria ◽  
Diogo Pestana ◽  
Diana Teixeira ◽  
Joana Azevedo ◽  
Victor Freitas ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Cerebrovascular Diseases ◽  
Brain Barrier ◽  
Array Detector ◽  
Dependent Manner ◽  
Blood Brain ◽  
Parkinson’S Diseases ◽  
Blood Brain Barrier Model ◽  
Immortalized Cell ◽  
Barrier Model

AbstractThere is a growing interest in dietary therapeutic strategies to combat oxidative stress-induced damage to the Central Nervous System (CNS), which is associated with a number of pathophysiological processes, including Alzheimer’s and Parkinson’s diseases and cerebrovascular diseases. Identifying the mechanisms associated with phenolic neuroprotection has been delayed by the lack of information concerning the ability of these compounds to enter the CNS. The aim of this study was to evaluate the transmembrane transport of flavonoids across RBE-4 cells (an immortalized cell line of rat cerebral capillary endothelial cells) and the effect of ethanol on this transport. The detection and quantification of all of the phenolic compounds in the studied samples (basolateral media) was performed using a HPLC-DAD (Diode Array Detector). All of the tested flavonoids (catechin, quercetin and cyanidin-3-glucoside) passed across the RBE-4 cells in a time-dependent manner. This transport was not influenced by the presence of 0.1% ethanol. In conclusion, the tested flavonoids were capable of crossing this blood-brain barrier model.

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