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Retrotransposon instability dominates the acquired mutation landscape of mouse induced pluripotent stem cells

Induced pluripotent stem cells (iPSCs) can in principle differentiate into any cell of the body, and have revolutionized biomedical research and regenerative medicine. Unlike their human counterparts, mouse iPSCs (miPSCs) are reported to silence transposable elements and prevent transposable element-mediated mutagenesis. Here we apply short-read or Oxford Nanopore Technologies long-read genome seq

Somatic retrotransposition in the developing rhesus macaque brain

The retrotransposon LINE-1 (L1) is central to the recent evolutionary history of the human genome and continues to drive genetic diversity and germline pathogenesis. However, the spatiotemporal extent and biological significance of somatic L1 activity are poorly defined and are virtually unexplored in other primates. From a single L1 lineage active at the divergence of apes and Old World monkeys,

LINE-1 retrotransposons contribute to mouse PV interneuron development

Retrotransposons are mobile DNA sequences duplicated via transcription and reverse transcription of an RNA intermediate. Cis-regulatory elements encoded by retrotransposons can also promote the transcription of adjacent genes. Somatic LINE-1 (L1) retrotransposon insertions have been detected in mammalian neurons. It is, however, unclear whether L1 sequences are mobile in only some neuronal lineage

Primary healthcare professionals’ attitudes toward patients with current or previous drug use

Objective: People with current or previous drug use (PCPDU) often lack long-term healthcare contacts in primary healthcare (PHC). While international research has shown negative attitudes toward PCPDU in healthcare, PHC professionals’ attitudes toward PCPDU have not been assessed in Sweden. The aim of this study was to investigate PHC professionals’ attitudes to PCPDU, and to compare attitudes tow

Rethinking peatlands : Exploring diverging care practices within Danish agricultural peatlands

Positioned as a pivotal element in achieving up to 50% in emissions reduction from theagricultural sector, peatlands assume a paramount role in Denmark's green transition of thesector. Historically cultivated and drained by farmers, the current transformative process ofrestoring and rewetting peatlands is characterized by inherent controversies in knowledge,practices, and perceptions. Tensions eme

No evidence of human genome integration of SARS-CoV-2 found by long-read DNA sequencing

A recent study proposed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we apply deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2 and do not fin

LINE-1 Evasion of Epigenetic Repression in Humans

Epigenetic silencing defends against LINE-1 (L1) retrotransposition in mammalian cells. However, the mechanisms that repress young L1 families and how L1 escapes to cause somatic genome mosaicism in the brain remain unclear. Here we report that a conserved Yin Yang 1 (YY1) transcription factor binding site mediates L1 promoter DNA methylation in pluripotent and differentiated cells. By analyzing 2

L1 retrotransposition is a common feature of mammalian hepatocarcinogenesis

The retrotransposon Long Interspersed Element 1 (LINE-1 or L1) is a continuing source of germline and somatic mutagenesis in mammals. Deregulated L1 activity is a hallmark of cancer, and L1 mutagenesis has been described in numerous human malignancies. We previously employed retrotransposon capture sequencing (RC-seq) to analyze hepatocellular carcinoma (HCC) samples from patients infected with he

Heritable L1 retrotransposition in the mouse primordial germline and early embryo

LINE-1 (L1) retrotransposons are a noted source of genetic diversity and disease in mammals. To expand its genomic footprint, L1 must mobilize in cells that will contribute their genetic material to subsequent generations. Heritable L1 insertions may therefore arise in germ cells and in pluripotent embryonic cells, prior to germline specification, yet the frequency and predominant developmental ti

TET enzymes : double agents in the transposable element-host genome conflict

The mouse genome is replete with retrotransposon sequences, from evolutionarily young elements with mutagenic potential that must be controlled, to inactive molecular fossils whose sequences can be domesticated over evolutionary time to benefit the host genome. In an exciting new study, de la Rica and colleagues have uncovered a complex relationship between ten-eleven translocation (TET) proteins

Evidence for L1-associated DNA rearrangements and negligible L1 retrotransposition in glioblastoma multiforme

BACKGROUND: LINE-1 (L1) retrotransposons are a notable endogenous source of mutagenesis in mammals. Notably, cancer cells can support unusual L1 retrotransposition and L1-associated sequence rearrangement mechanisms following DNA damage. Recent reports suggest that L1 is mobile in epithelial tumours and neural cells but, paradoxically, not in brain cancers.RESULTS: Here, using retrotransposon capt

Transposable elements in the mammalian embryo : pioneers surviving through stealth and service

Transposable elements (TEs) are notable drivers of genetic innovation. Over evolutionary time, TE insertions can supply new promoter, enhancer, and insulator elements to protein-coding genes and establish novel, species-specific gene regulatory networks. Conversely, ongoing TE-driven insertional mutagenesis, nonhomologous recombination, and other potentially deleterious processes can cause sporadi

Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells

Human induced pluripotent stem cells (hiPSCs) are capable of unlimited proliferation and can differentiate in vitro to generate derivatives of the three primary germ layers. Genetic and epigenetic abnormalities have been reported by Wissing and colleagues to occur during hiPSC derivation, including mobilization of engineered LINE-1 (L1) retrotransposons. However, incidence and functional impact of

Protest and the Opacity of Literature : James Baldwin and Paul Celan

This article analyzes Paul Celan’s translation of James Baldwin’s “Everybody’s Protest Novel” and considers the connections between the poetics of these two writers. In addition to their shared preoccupation with and rearticulation of terms such as human, creature, and darkness, the translation reveals how they explored the relationship between literature and reality at early and transitional mome

Superporous agarose as an affinity chromatography support

Superporous agarose beads were used as an affinity support in column chromatography. These beads characteristically possess two sets of pores, normal diffusion pores and flow pores, so-called superpores. The superpores, whose diameter is a substantial fraction of the particle diameter (i.e. 1/3 to 1/10 of the particle diameter), allow part of the chromatographic flow to pass through each individua

Off-Translation: Bertha Pappenheim's Yiddish-German

This article centres on Bertha Pappenheim’s translations of Old Yiddish literature, with particular focus on Die Memoiren der Gl€uckel von Hameln, which was published as a private edition in Vienna in 1910. While the fact that Pappenheim translated Glikl’s Yiddish-language writings into German is well known, little attention has been paid to the particular language of the translated text or to Pap