94 research outputs found
A Draft of the Genome of the Gulf Coast tick, \u3ci\u3eAmblyomma maculatum\u3c/i\u3e
The Gulf Coast tick, Amblyomma maculatum, inhabits the Southeastern states of the USA bordering the Gulf of Mexico, Mexico, and other Central and South American countries. More recently, its U.S. range has extended West to Arizona and Northeast to New York state and Connecticut. It is a vector of Rickettsia parkeri and Hepatozoon americanum. This tick species has become a model to study tick/Rickettsia interactions. To increase our knowledge of the basic biology of A. maculatum we report here a draft genome of this tick and an extensive functional classification of its proteome. The DNA from a single male tick was used as a genomic source, and a 10X genomics protocol determined 28,460 scaffolds having equal or more than 10 Kb, totaling 1.98 Gb. The N50 scaffold size was 19,849 Kb. The BRAKER pipeline was used to find the protein-coding gene boundaries on the assembled A. maculatum genome, discovering 237,921 CDS. After trimming and classifying the transposable elements, bacterial contaminants, and truncated genes, a set of 25,702 were annotated and classified as the core gene products. A BUSCO analysis revealed 83.4% complete BUSCOs. A hyperlinked spreadsheet is provided, allowing browsing of the individual gene products and their matches to several databases
Molecular Pathways in Cancers
This book includes some recent works providing the readers with novel relevant findings about the main signaling pathways that govern the molecular pathogenesis of some of the highest prevalent human tumors, which are the basis for developing alternative therapeutic strategies to improve patient outcomes
An endogenous lentivirus in the germline of a rodent
Lentiviruses (genus Lentivirus) are complex retroviruses that infect a broad range of mammals, including humans. Unlike many other retrovirus genera, lentiviruses have only rarely been incorporated into the mammalian germline. However, a small number of endogenous retrovirus (ERV) lineages have been identified, and these rare genomic “fossils” can provide crucial insights into the long-term history of lentivirus evolution. Here, we describe a previously unreported endogenous lentivirus lineage in the genome of the South African springhare (Pedetes capensis), demonstrating that the host range of lentiviruses has historically extended to rodents (order Rodentia). Furthermore, through comparative and phylogenetic analysis of lentivirus and ERV genomes, considering the biogeographic and ecological characteristics of host species, we reveal broader insights into the long-term evolutionary history of the genus
RNA, the Epicenter of Genetic Information
The origin story and emergence of molecular biology is muddled. The early triumphs in bacterial genetics and the complexity of animal and plant genomes complicate an intricate history. This book documents the many advances, as well as the prejudices and founder fallacies. It highlights the premature relegation of RNA to simply an intermediate between gene and protein, the underestimation of the amount of information required to program the development of multicellular organisms, and the dawning realization that RNA is the cornerstone of cell biology, development, brain function and probably evolution itself. Key personalities, their hubris as well as prescient predictions are richly illustrated with quotes, archival material, photographs, diagrams and references to bring the people, ideas and discoveries to life, from the conceptual cradles of molecular biology to the current revolution in the understanding of genetic information. Key Features Documents the confused early history of DNA, RNA and proteins - a transformative history of molecular biology like no other. Integrates the influences of biochemistry and genetics on the landscape of molecular biology. Chronicles the important discoveries, preconceptions and misconceptions that retarded or misdirected progress. Highlights major pioneers and contributors to molecular biology, with a focus on RNA and noncoding DNA. Summarizes the mounting evidence for the central roles of non-protein-coding RNA in cell and developmental biology. Provides a thought-provoking retrospective and forward-looking perspective for advanced students and professional researchers
Sequence divergence and retrotransposon insertion underlie interspecific epigenetic differences in primates
内在性レトロウイルス配列によってヒトのエピゲノムが変化してきたことを発見! --ヒトとチンパンジーのiPS細胞の比較解析から--. 京都大学プレスリリース. 2022-10-12.Changes in the epigenome can affect the phenotype without the presence of changes in the genomic sequence. Given the high identity of the human and chimpanzee genome sequences, a substantial portion of their phenotypic divergence likely arises from epigenomic differences between the two species. In this study, the transcriptome and epigenome were determined for induced pluripotent stem cells (iPSCs) generated from human and chimpanzee individuals. The transcriptome and epigenomes for trimethylated histone H3 at lysine-4 (H3K4me3) and lysine-27 (H3K27me3) showed high levels of similarity between the two species. However, there were some differences in histone modifications. Although such regions, in general, did not show significant enrichment of interspecies nucleotide variations, gains in binding motifs for pluripotency-related transcription factors, especially POU5F1 and SOX2, were frequently found in species-specific H3K4me3 regions. We also revealed that species-specific insertions of retrotransposons, including the LTR5_Hs subfamily in human and a newly identified LTR5_Pt subfamily in chimpanzee, created species-specific H3K4me3 regions associated with increased expression of nearby genes. Human iPSCs have more species-specific H3K27me3 regions, resulting in more abundant bivalent domains. Only a limited number of these species-specific H3K4me3 and H3K27me3 regions overlap with species-biased enhancers in cranial neural crest cells, suggesting that differences in the epigenetic state of developmental enhancers appear late in development. Therefore, iPSCs serve as a suitable starting material for studying evolutionary changes in epigenome dynamics during development
Identification and Analysis of the Heparan Sulfate-Binding Domain and Cellular Factors Involved in the Entry of Human Endogenous Retrovirus K HERV-K (HML-2)
The human endogenous retroviruses (HERVs) are remnant elements of ancient retroviruses that infected the human ancestors' germline and integrated into their genome, and thereby passed down to their descendants in a mendelian fashion. The HERV-K (HML-2) family includes the most intact and complete sequences of human-specific elements with conserved ORF for most of their proteins and the ability to produce viral particles. The viral envelope protein (Env) promoted the initial endogenization activities and was shown to have a broad tropism. It mediates the viral entry through interaction with the cell surface heparan sulfates (HS).
In this study, we demonstrated first that the specified receptor binding site (RBS) of HML-2 Env is not involved in binding HS. Further, to identify the involved domain in binding HS, we aligned the protein sequence of HML-2 Env to that of the mouse mammary tumor virus (MMTV). This way, we identified an HS-binding domain (HBD) at the N-terminus of the HML-2 Env between residues 216 and 236, corresponding to MMTV HBD. Generated mutations in all positively charged residues of this domain impaired binding to heparin-coated beads and blocked viral entry. Moreover, mutations in the residues R216, K219, and K223, were influential in HS binding and the viral entry.
In the second and third parts of the study, we aimed to identify the cellular factors or requirements for HML-2 Env in its early entry pathway utilizing two approaches. In the first approach, we successfully generated a trimer fusion protein for HML-2 consisting of the SU subunit fused with fibritin, a trimerization domain derived from the bacteriophage T4. The trimer fusion protein bound HS similarly to the native Env. However, it did not block HML-2 Env viral entry. Using this trimer fusion protein, we specifically co-purified the Golgi membrane protein 73 (GP73) as a potential attachment factor for HML-2 Env. The second approach included using HML-2 Env pseudotyped viral particles in conducting a functional screening of a cDNA library for transmembrane proteins in a non-permissive cell line. Screening results identified six transmembrane proteins (TMEM9, C12ORF59, IL1RAP, PSCA, LETMD1, and MPEG1) involved in the entry pathway of HML-2 that confer the susceptibility to it. We also found that only IL1RAP and MPEG1 proteins confer susceptibility in a different non-permissive cell line. Our results affirmed the role of HS in the HML-2 Env attachments and identified the specific HBD involved. They also affirmed the contribution of another molecule(s) that serves as the receptor(s). In those lines seven transmembrane proteins involved in the entry pathway of HML-2 Env were identified.Die Humanen Endogenen Retroviren (HERVs) sind Restbestandteile alter Retroviren, die die Keimbahn der menschlichen Vorfahren infizierten und in ihr Genom integriert wurden. Sie werden seither nach den Mendelschen Regeln an ihre Nachkommen weitergegeben. Die HERV-K (HML-2)-Familie umfasst die intaktesten und vollständigsten Sequenzen mit konservierten Leserahmen für die meisten ihrer Proteine und die Fähigkeit, virale Partikel zu produzieren. Das virale Hüllprotein (Env) förderte die anfängliche Endogenisierung und zeigt einen breiten Tropismus. Es vermittelt die Infektion durch erste Wechselwirkung mit Heparansulfaten (HS) auf der Zelloberfläche. In dieser Studie zeigten wir, dass die Rezeptorbindungsstelle (RBS) von HML-2 Env nicht an der Bindung von HS beteiligt ist. Um die daran beteiligte Domäne zu identifizieren, haben wir die Proteinsequenz von HML-2 Env mit der des Maus-Mammatumorvirus (MMTV) verglichen. Am N-Terminus des HML-2 Env wurde so eine potentielle homologe HS-bindende Domäne (HBD) zwischen den Positionen 216 und 236 identifiziert. Mutationen in allen positiv geladenen Resten dieser Domäne beeinträchtigten die Bindung an Heparin-beschichtete Beads und blockierten die Infektion. Darüber hinaus waren Mutationen an den Positionen R216, K219 und K223 für die HS-Bindung und den viralen Zelleintritt maßgeblich. Im zweiten und dritten Teil der Studie wollten wir die zellulären Faktoren für den HML-2 Env vermittelten Zelleintritt mit zwei Ansätzen identifizieren. Im ersten Ansatz ist es gelungen, ein Trimer-Fusionsprotein für HML-2 zu erzeugen, das aus der SU-Untereinheit besteht, die mit der Trimerisierungs-domäne fusioniert ist. Sie ist vom Fibritin des Bakteriophagen T4 abgeleitet. Das Trimer-Fusionsprotein bindet HS ähnlich wie das native Env. Es blockierte jedoch nicht den Eintritt von HML-2 in die Zellen. Mit diesem Fusionsprotein wurde das Golgi-Membranprotein 37 (GP73) als potenzieller Bindungsfaktor für HML-2 Env gefunden. Der zweite Ansatz umfasste die Verwendung von HML-2 Env-Pseudoviren bei der Durchführung eines funktionellen Screenings einer cDNA-Bibliothek mit einer nicht-permissiven Zelllinie. Damit wurden 6 Transmembranproteine (TMEM9, C12ORF59, IL1RAP, PSCA, LETMD1 und MPEG1) identifiziert, die am Infektionsprozess von HML-2 beteiligt sind. Nur IL1RAP und MPEG1 konnten allerding den Eintritt in eine andere nicht-permissiven Zelllinie vermitteln. Die Arbeiten bestätigen die Rolle von HS bei der Zelladhärenz von HML-2 Env und identifizierten die spezifische HBD. Sie bestätigten auch die Beteiligung eines oder mehrerer anderer Moleküle, die als Rezeptor(en) dienen. In diesem Zusammenhang wurden 7 Transmembranproteine identifiziert, die am Eintrittsweg von HML-2 beteiligt sind
In Memory of Stefan Kunz
This issue of Viruses is a living memorial dedicated to Professor Stefan Kunz, who passed away too early in life, at 54. During his scientific career, Stefan made major contributions to the field of virology. He made seminal contributions to our understanding of how mammarenaviruses gain access to and are trafficked within their target cells. This issue of Viruses contains a collection of articles by leading researchers in different areas of virus–host cell interactions and who crossed pathways with Stefan. The topics covered in the issue include novel insights on mammeranavirus cell entry, host innate and adaptive immune responses to infection, recent developments on therapeutics against human pathogenic arenaviruses, as well as mammarenavirus ecology and molecular pathogenesis. The collection of articles is also a reflection of Stefan’s enthusiasm for exploring new ideas and his very collegial attitude reflected by his many collaborations, including the colleagues who have contributed sections to this memorial issue
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