scholarly journals Involvement of non-LTR retrotransposons in the cancer incidence and lifespan of mammals

2021 ◽  
Author(s):  
Marco Ricci ◽  
Valentina Peona ◽  
Cristian Taccioli
Keyword(s):  
Cancer Incidence ◽  
Viral Infections ◽  
Cancer Susceptibility ◽  
Sterile Inflammation ◽  
Natural Occurrence ◽  
Ltr Retrotransposons ◽  
Strong Suppression ◽  
Pteropus Vampyrus ◽  
Molossus Molossus ◽  
Retrotransposon Activity

The natural occurrence of closely related species that show drastic differences in lifespan and cancer incidence raised the interest in finding the particular adaptations and genomic characteristics underlying the evolution of long lifespans. Studies on transposable elements (TEs) have more and more linked them to ageing and cancer development. In this study, we compared the TE content and dynamics in the genomes of four Rodent and six Chiroptera species that show very different lifespans and cancer susceptibility including the long-lived and refractory to cancer naked mole rat (Heterocephalus glaber), the long-lived fruit bats (Pteropus vampyrus, Rousettus aegypticaus) and the short-lived velvety free-tailed bat (Molossus molossus). By analysing the patterns of recent TE accumulation (TEs that are potentially currently active) in high-quality genome assemblies, we found that the shared genomic characteristics between long-lived species that are refractory to cancer, is the strong suppression, or negative selection against the accumulation, of non-LTR retrotransposons. All the short-lived species did show a recent accumulation of these TEs. Non-LTR retrotransposons have been often found to take part in the immune response of the host against viral infections, but their dysregulation can lead to phenomena of "sterile inflammation" and "inflammageing". Therefore, we hypothesise that the uncontrolled non-LTR retrotransposon activity is an important factor explaining the evolution of shorter lifespans in both Rodents and Chiroptera species and potentially in all mammals. Finally, these results suggest that non-LTR retrotransposons can be agents promoting cancer and ageing in mammals thus they may be targets of future oncological therapies.

scholarly journals Genome-wide characterization of LTR retrotransposons in the non-model deep-sea annelid Lamellibrachia luymesi

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Oluchi Aroh ◽  
Kenneth M. Halanych
Keyword(s):  
Deep Sea ◽  
Long Terminal Repeat Retrotransposons ◽  
Marine Organisms ◽  
Model Systems ◽  
Ltr Retrotransposons ◽  
Genome Wide ◽  
Lamellibrachia Luymesi ◽  
Vestimentiferan Tubeworm ◽  
Retrotransposon Activity

Abstract Background Long Terminal Repeat retrotransposons (LTR retrotransposons) are mobile genetic elements composed of a few genes between terminal repeats and, in some cases, can comprise over half of a genome’s content. Available data on LTR retrotransposons have facilitated comparative studies and provided insight on genome evolution. However, data are biased to model systems and marine organisms, including annelids, have been underrepresented in transposable elements studies. Here, we focus on genome of Lamellibrachia luymesi, a vestimentiferan tubeworm from deep-sea hydrocarbon seeps, to gain knowledge of LTR retrotransposons in a deep-sea annelid. Results We characterized LTR retrotransposons present in the genome of L. luymesi using bioinformatic approaches and found that intact LTR retrotransposons makes up about 0.1% of L. luymesi genome. Previous characterization of the genome has shown that this tubeworm hosts several known LTR-retrotransposons. Here we describe and classify LTR retrotransposons in L. luymesi as within the Gypsy, Copia and Bel-pao superfamilies. Although, many elements fell within already recognized families (e.g., Mag, CSRN1), others formed clades distinct from previously recognized families within these superfamilies. However, approximately 19% (41) of recovered elements could not be classified. Gypsy elements were the most abundant while only 2 Copia and 2 Bel-pao elements were present. In addition, analysis of insertion times indicated that several LTR-retrotransposons were recently transposed into the genome of L. luymesi, these elements had identical LTR’s raising possibility of recent or ongoing retrotransposon activity. Conclusions Our analysis contributes to knowledge on diversity of LTR-retrotransposons in marine settings and also serves as an important step to assist our understanding of the potential role of retroelements in marine organisms. We find that many LTR retrotransposons, which have been inserted in the last few million years, are similar to those found in terrestrial model species. However, several new groups of LTR retrotransposons were discovered suggesting that the representation of LTR retrotransposons may be different in marine settings. Further study would improve understanding of the diversity of retrotransposons across animal groups and environments.

APOBEC3 proteins: major players in intracellular defence against LINE-1-mediated retrotransposition

2007 ◽  
Vol 35 (3) ◽  
pp. 637-642 ◽  
Author(s):  
G.G. Schumann
Keyword(s):  
Transposable Elements ◽  
Tandem Repeats ◽  
Genetic Disorders ◽  
Single Copy ◽  
Long Terminal Repeat Retrotransposons ◽  
Variable Number ◽  
Ltr Retrotransposons ◽  
Negative Effects ◽  
Processed Pseudogenes ◽  
Retrotransposon Activity

Mammalian genomes are littered with enormous numbers of transposable elements interspersed within and between single-copy endogenous genes. The only presently spreading class of human transposable elements comprises non-LTR (long terminal repeat) retrotransposons, which cover approx. 34% of the human genome. Non-LTR retrotransposons include the widespread autonomous LINEs (long interspersed nuclear elements) and non-autonomous elements such as processed pseudogenes, SVAs [named after SINE (short interspersed nuclear element), VNTR (variable number of tandem repeats) and Alu] and SINEs. Mobilization of these elements affects the host genome, can be deleterious to the host cell, and cause genetic disorders and cancer. In order to limit negative effects of retrotransposition, host genomes have adopted several strategies to curb the proliferation of transposable elements. Recent studies have demonstrated that members of the human APOBEC3 (apolipoprotein B mRNA editing enzyme catalytic polypeptide 3) protein family inhibit the mobilization of the non-LTR retrotransposons LINE-1 and Alu significantly and participate in the intracellular defence against retrotransposition by mechanisms unknown to date. The striking coincidence between the expansion of the APOBEC3 gene cluster and the abrupt decline in retrotransposon activity in primates raises the possibility that these genes may have been expanded to prevent genomic instability caused by endogenous retroelements.

scholarly journals Extracellular RNA as a Versatile DAMP and Alarm Signal That Influences Leukocyte Recruitment in Inflammation and Infection

2020 ◽  
Vol 8 ◽  
Author(s):  
Klaus T. Preissner ◽  
Silvia Fischer ◽  
Elisabeth Deindl
Keyword(s):  
Tissue Damage ◽  
Viral Infections ◽  
Vasogenic Edema ◽  
Immune Defense ◽  
Leukocyte Recruitment ◽  
Host Cells ◽  
Sterile Inflammation ◽  
Vegf Receptor ◽  
Extracellular Rna ◽  
Microbial Invasion

Upon vascular injury, tissue damage, ischemia, or microbial infection, intracellular material such as nucleic acids and histones is liberated and comes into contact with the vessel wall and circulating blood cells. Such “Danger-associated molecular patterns” (DAMPs) may thus have an enduring influence on the inflammatory defense process that involves leukocyte recruitment and wound healing reactions. While different species of extracellular RNA (exRNA), including microRNAs and long non-coding RNAs, have been implicated to influence inflammatory processes at different levels, recent in vitro and in vivo work has demonstrated a major impact of ribosomal exRNA as a prominent DAMP on various steps of leukocyte recruitment within the innate immune response. This includes the induction of vascular hyper-permeability and vasogenic edema by exRNA via the activation of the “vascular endothelial growth factor” (VEGF) receptor-2 system, as well as the recruitment of leukocytes to the inflamed endothelium, the M1-type polarization of inflammatory macrophages, or the role of exRNA as a pro-thrombotic cofactor to promote thrombosis. Beyond sterile inflammation, exRNA also augments the docking of bacteria to host cells and the subsequent microbial invasion. Moreover, upon vessel occlusion and ischemia, the shear stress-induced release of exRNA initiates arteriogenesis (i.e., formation of natural vessel bypasses) in a multistep process that resembles leukocyte recruitment. Although exRNA can be counteracted for by natural circulating RNase1, under the conditions mentioned, only the administration of exogenous, thermostable, non-toxic RNase1 provides an effective and safe therapeutic regimen for treating the damaging activities of exRNA. It remains to be investigated whether exRNA may also influence viral infections (including COVID-19), e.g., by supporting the interaction of host cells with viral particles and their subsequent invasion. In fact, as a consequence of the viral infection cycle, massive amounts of exRNA are liberated, which can provoke further tissue damage and enhance virus dissemination. Whether the application of RNase1 in this scenario may help to limit the extent of viral infections like COVID-19 and impact on leukocyte recruitment and emigration steps in immune defense in order to limit the extent of associated cardiovascular diseases remains to be studied.

scholarly journals The Mutual Relation of Platelet Activation and Innate Immunity

2018 ◽  
Vol 38 (04) ◽  
pp. 186-202 ◽  
Author(s):  
Felix Eisinger ◽  
Harald Langer
Keyword(s):  
Innate Immunity ◽  
Viral Infections ◽  
Immune Cell ◽  
Sterile Inflammation ◽  
Immune Defence ◽  
Central Importance ◽  
Free Process ◽  
Close Relationship ◽  
Pathogen Clearance ◽  
The Complement System

AbstractPlatelets are known to be central regulators of haemostasis, inflammation and immune response. Formed by megakaryocytes in the bone marrow and the lungs, platelets express a broad range of adhesion receptors and release cytokines and platelet microparticles which enable them to interact with both immune cells and pathogens. In bacterial and viral infections, thrombophilia and thrombocytopenia are commonly seen symptoms, indicating the close relationship between haemostasis and immune defence. Indeed, platelets contribute both directly and via immune mediation to pathogen clearance. In sterile inflammation, a pathogen-free process which is often triggered by cell necrosis and autoimmune reactions, platelets are also of central importance. Recently, platelet inflammasome has been extensively studied in this context. Both sterile inflammation and infection are affected by the interactions of platelets and innate immunity, notably the complement system. Although the general elements of this interplay have been known for long, more and more insights into disease-specific mechanisms could be gained recently. This review gives an outline of the current findings in the field of platelet–immune cell interactions and points out possible implications for clinical therapy.

scholarly journals Reprogramming of retrotransposon activity during speciation of the genus Citrus

2019 ◽  
Author(s):  
Carles Borredá ◽  
Estela Pérez-Román ◽  
Victoria Ibanez ◽  
Javier Terol ◽  
Manuel Talon
Keyword(s):  
Common Ancestor ◽  
General Pattern ◽  
Specific Pattern ◽  
Regulatory Mechanisms ◽  
Ltr Retrotransposons ◽  
Genetic Response ◽  
Citrus Species ◽  
Pure Species ◽  
Retrotransposon Activity ◽  
Species Specific

Abstract Speciation of the genus Citrus from a common ancestor has recently been established to begin approximately 8 Mya during the late Miocene, a period of major climatic alterations. Here, we report the changes in activity of Citrus LTR retrotransposons during the process of diversification that gave rise to the current Citrus species. To reach this goal, we analyzed four pure species that diverged early during Citrus speciation, three recent admixtures derived from those species and an outgroup of the Citrus clade. More than thirty thousand retrotransposons were grouped in 10 linages. Estimations of LTR insertion times revealed that retrotransposon activity followed a species-specific pattern of change that could be ascribed to one of three different models. In some genomes, the expected pattern of gradual transposon accumulation was suddenly arrested during the radiation of the ancestor that gave birth to the current Citrus species. The individualized analyses of retrotransposon lineages showed that in each and every species studied, not all lineages follow the general pattern of the species itself. For instance, in most of the genomes, the retrotransposon activity of elements from the SIRE lineage reached its highest level just before Citrus speciation while for Retrofit elements it has been steadily growing. Based on these observations we propose that Citrus retrotransposons may respond to stressful conditions driving speciation as a part of the genetic response involved in adaptation. This proposal implies that the evolving conditions of each species interacts with the internal regulatory mechanisms of the genome controlling the proliferation of mobile elements.

scholarly journals Prevalence of germline pathogenic variants in 22 cancer susceptibility genes in Swedish pediatric cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kristoffer von Stedingk ◽  
Karl-Johan Stjernfelt ◽  
Anders Kvist ◽  
Cecilia Wahlström ◽  
Ulf Kristoffersson ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cancer Incidence ◽  
Pediatric Cancer ◽  
Cancer Susceptibility ◽  
Familial Cancer ◽  
Susceptibility Genes ◽  
Pathogenic Variants ◽  
Cancer Susceptibility Genes ◽  
Significant Difference ◽  
Pediatric Cancer Patients

AbstractUp to 10% of pediatric cancer patients harbor pathogenic germline variants in one or more cancer susceptibility genes. A recent study from the US reported pathogenic variants in 22 out of 60 analyzed autosomal dominant cancer susceptibility genes, implicating 8.5% of pediatric cancer patients. Here we aimed to assess the prevalence of germline pathogenic variants in these 22 genes in a population-based Swedish cohort and to compare the results to those described in other populations. We found pathogenic variants in 10 of the 22 genes covering 3.8% of these patients. The prevalence of TP53 mutations was significantly lower than described in previous studies, which can largely be attributed to differences in tumor diagnosis distributions across the three cohorts. Matched family history for relatives allowed assessment of familial cancer incidence, however, no significant difference in cancer incidence was found in families of children carrying pathogenic variants compared to those who did not.

scholarly journals Etiological Value of Sterile Inflammation in Preeclampsia: Is It a Non-Infectious Pregnancy Complication?

2021 ◽  
Vol 11 ◽  
Author(s):  
Sayani Banerjee ◽  
Zheping Huang ◽  
Zhengke Wang ◽  
Akitoshi Nakashima ◽  
Shigeru Saito ◽  
...  
Keyword(s):  
Er Stress ◽  
Pregnancy Complications ◽  
Viral Infections ◽  
High Mobility ◽  
Sterile Inflammation ◽  
Contributory Factor ◽  
Cell Free Fetal Dna ◽  
Molecular Patterns ◽  
Key Events ◽  
Damage Associated Molecular Patterns

Understanding of sterile inflammation and its associated biological triggers and diseases is still at the elementary stage. This becomes more warranted in cases where infections are not associated with the pathology. Detrimental effects of bacterial and viral infections on the immune responses at the maternal-fetal interface as well as pregnancy outcomes have been well documented. However, an infection-induced etiology is not thought to be a major contributing component to severe pregnancy complications such as preeclampsia (PE) and gestational diabetes. How is then an inflammatory signal thought to be associated with these pregnancy complications? It is not clear what type of inflammation is involved in the onset of PE-like features. We opine that sterile inflammation regulated by the inflammasome-gasdermins-caspase-1 axis is a contributory factor to the onset of PE. We hypothesize that increased production and release of damage-associated molecular patterns (DAMPs) or Alarmins such as high-mobility group box1 (HMGB1), cell-free fetal DNA, uric acid, the NOD-like receptor pyrin-containing receptor 3 (NLRP3) inflammasome, IL-1β and IL-18 occur in the PE placenta. Some of these molecules have already been observed in the placenta from women with PE. Mechanistically, emerging evidence has demonstrated that excessive placental endoplasmic reticulum (ER) stress, impaired autophagy and gasdermine D (GSDMD)-mediated intrinsic pyroptosis are key events that contribute to systemic sterile inflammation in patients with PE, especially early-onset PE (e-PE). In this review, we highlight the advances on the roles of sterile inflammation and inflammatory signaling cascades involving ER stress, autophagy deficiency and pyroptosis in PE pathophysiology. Deciphering the mechanisms underlying these inflammatory pathways may provide potential diagnostic biomarkers and facilitate the development of therapeutic strategies to treat this devastating disease.

The growth of mica polytypes as studied by conventional and high-resolution TEM

1983 ◽  
Vol 41 ◽  
pp. 174-177
Author(s):  
A. Baronnet ◽  
M. Amouric
Keyword(s):  
Water Pressure ◽  
Point Of View ◽  
Temperature Fields ◽  
Natural Occurrence ◽  
Growth Mechanisms ◽  
Long Period ◽  
High Resolution Tem ◽  
Layer Stacking ◽  
Experimental Works ◽  
Potential Use

The origin of mica polytypes has long been a challenging problem for crystal- lographers, mineralogists and petrologists. From the petrological point of view, interest in this field arose from the potential use of layer stacking data to furnish further informations about equilibrium and/or kinetic conditions prevailing during the crystallization of the widespread mica-bearing rocks. From the compilation of previous experimental works dealing with the occurrence domains of the various mica "polymorphs" (1Mr, 1M, 2M1, 2M2 and 3T) within water-pressure vs temperature fields, it became clear that most of these modifications should be considered as metastable for a fixed mica species. Furthermore, the natural occurrence of long-period (or complex) polytypes could not be accounted for by phase considerations. This highlighted the need of a more detailed kinetic approach of the problem and, in particular, of the role growth mechanisms of basal faces could play in this crystallographic phenomenon.

The Diagnosis of Viral Disease by Electron Microscopy

1982 ◽  
Vol 40 ◽  
pp. 270-273
Author(s):  
William B. McCombs ◽  
Cameron E. McCoy
Keyword(s):  
Electron Microscopy ◽  
Hospital Stay ◽  
Viral Infections ◽  
Medical Profession ◽  
Bacterial Pathogens ◽  
Viral Disease ◽  
Viral Pathogens ◽  
Academic Interest ◽  
The Past

Recent years have brought a reversal in the attitude of the medical profession toward the diagnosis of viral infections. Identification of bacterial pathogens was formerly thought to be faster than identification of viral pathogens. Viral identification was dismissed as being of academic interest or for confirming the presence of an epidemic, because the patient would recover or die before this could be accomplished. In the past 10 years, the goal of virologists has been to present the clinician with a viral identification in a matter of hours. This fast diagnosis has the potential for shortening the patient's hospital stay and preventing the administering of toxic and/or expensive antibiotics of no benefit to the patient.

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