The functions and unique features of long intergenic non-coding RNA.

Long intergenic non-coding RNA (lincRNA) genes have diverse features that distinguish them from mRNA-encoding genes and exercise functions such as remodelling chromatin and genome architecture, RNA stabilization and transcription regulation, including enhancer-associated activity. Some genes currently annotated as encoding lincRNAs include small open reading frames (smORFs) and encode functional peptides and thus may be more properly classified as coding RNAs. lincRNAs may broadly serve to fine-tune the expression of neighbouring genes with remarkable tissue specificity through a diversity of mechanisms, highlighting our rapidly evolving understanding of the non-coding genome.

Clonal inactivation of TERT impairs stem cell competition.

Telomerase is intimately associated with stem cells and cancer, because it catalytically elongates telomeres-nucleoprotein caps that protect chromosome ends1. Overexpression of telomerase reverse transcriptase (TERT) enhances the proliferation of cells in a telomere-independent manner2-8, but so far, loss-of-function studies have provided no evidence that TERT has a direct role in stem cell function. In many tissues, homeostasis is shaped by stem cell competition, a process in which stem cells compete on the basis of inherent fitness. Here we show that conditional deletion of Tert in the spermatogonial stem cell (SSC)-containing population in mice markedly impairs competitive clone formation. Using lineage tracing from the Tert locus, we find that TERT-expressing SSCs yield long-lived clones, but that clonal inactivation of TERT promotes stem cell differentiation and a genome-wide reduction in open chromatin. This role for TERT in competitive clone formation occurs independently of both its reverse transcriptase activity and the canonical telomerase complex. Inactivation of TERT causes reduced activity of the MYC oncogene, and transgenic expression of MYC in the TERT-deleted pool of SSCs efficiently rescues clone formation. Together, these data reveal a catalytic-activity-independent requirement for TERT in enhancing stem cell competition, uncover a genetic connection between TERT and MYC and suggest that a selective advantage for stem cells with high levels of TERT contributes to telomere elongation in the male germline during homeostasis and ageing.

Alpha-kinase 1 (ALPK1) agonist DF-006 demonstrates potent efficacy in mouse and primary human hepatocyte (PHH) models of hepatitis B.

BACKGROUND AND AIMS: In the treatment of chronic hepatitis B (CHB) infection, stimulation of innate immunity may lead to hepatitis B virus (HBV) cure. Alpha-kinase 1 (ALPK1) is a pattern recognition receptor (PRR) that activates the NF-κB pathway and stimulates innate immunity. Here we characterized the preclinical anti-HBV efficacy of DF-006, an orally active agonist of ALPK1 currently in clinical development for CHB. APPROACH AND RESULTS: In adeno-associated virus (AAV)-HBV mouse models and primary human hepatocytes (PHHs) infected with HBV, we evaluated the antiviral efficacy of DF-006. In the mouse models, DF-006 rapidly reduced serum HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen levels using doses as low as 0.08 µg/kg, 1 µg/kg, and 5 µg/kg, respectively. DF-006 in combination with the HBV nucleoside reverse transcriptase inhibitor, entecavir, further reduced HBV DNA. Antiviral efficacy in mice was associated with an increase in immune cell infiltration and decrease of hepatitis B core antigen, encapsidated pregenomic RNA, and covalently closed circular DNA in liver. At subnanomolar concentrations, DF-006 also showed anti-HBV efficacy in PHH with significant reductions of HBV DNA. Following dosing with DF-006, there was upregulation of NF-κB-targeted genes that are involved in innate immunity. CONCLUSION: DF-006 was efficacious in mouse and PHH models of HBV without any indications of overt toxicity. In mice, DF-006 localized primarily to the liver where it potently activated innate immunity. The transcriptional response in mouse liver provides insights into mechanisms that mediate anti-HBV efficacy by DF-006.

Mechanoresponsive stem cells acquire neural crest fate in jaw regeneration.

During both embryonic development and adult tissue regeneration, changes in chromatin structure driven by master transcription factors lead to stimulus-responsive transcriptional programs. A thorough understanding of how stem cells in the skeleton interpret mechanical stimuli and enact regeneration would shed light on how forces are transduced to the nucleus in regenerative processes. Here we develop a genetically dissectible mouse model of mandibular distraction osteogenesis-which is a process that is used in humans to correct an undersized lower jaw that involves surgically separating the jaw bone, which elicits new bone growth in the gap. We use this model to show that regions of newly formed bone are clonally derived from stem cells that reside in the skeleton. Using chromatin and transcriptional profiling, we show that these stem-cell populations gain activity within the focal adhesion kinase (FAK) signalling pathway, and that inhibiting FAK abolishes new bone formation. Mechanotransduction via FAK in skeletal stem cells during distraction activates a gene-regulatory program and retrotransposons that are normally active in primitive neural crest cells, from which skeletal stem cells arise during development. This reversion to a developmental state underlies the robust tissue growth that facilitates stem-cell-based regeneration of adult skeletal tissue.

Fermi-Level Depinning in Metal/Ge Junctions by Inserting a Carbon Nanotube Layer.

Germanium (Ge)-based devices are recognized as one of the most promising next-generation technologies for extending Moore's law. However, one of the critical issues is Fermi-level pinning (FLP) at the metal/n-Ge interface, and the resulting large contact resistance seriously degrades their performance. The insertion of a thin layer is one main technique for FLP modulation; however, the contact resistance is still limited by the remaining barrier height and the resistance induced by the insertion layer. In addition, the proposed depinning mechanisms are also controversial. Here, the authors report a wafer-scale carbon nanotube (CNT) insertion method to alleviate FLP. The inserted conductive film reduces the effective Schottky barrier height without inducing a large resistance, leading to ohmic contact and the smallest contact resistance between a metal and a lightly doped n-Ge. These devices also indicate that the metal-induced gap states mechanism is responsible for the pinning. Based on the proposed technology, a wafer-scale planar diode array is fabricated at room temperature without using the traditional ion-implantation and annealing technology, achieving an on-to-off current ratio of 4.59 × 104 . This work provides a new way of FLP modulation that helps to improve device performance with new materials.

High-performance gold/graphene/germanium photodetector based on a graphene-on-germanium wafer.

The metal/germanium (Ge) photodetectors have attracted much attention for their potential applications in on-chip optoelectronics. One critical issue is the relatively large dark current due to the limited Schottky potential barrier height of the metal/germanium junction, which is mainly caused by the small bandgap of Ge and the Fermi energy level pinning effect between the metal and Ge. The main technique to solve this problem is to insert a thin interlayer between the metal and Ge. However, so far, the dark current of the photodetectors is still large when using a bulk-material insertion layer, while when using a two-dimensional insertion layer, the area of the insertion layer is too small to support a mass production. Here, we report a gold/graphene/germanium photodetector with a wafer-scale graphene insertion layer using a 4 inch graphene-on-germanium wafer. The insertion layer significantly increases the potential barrier height, leading to a dark current as low as 1.6 mA cm-2, and a responsivity of 1.82 A W-1which are the best results for metal/Ge photodetectors reported so far. Our work contributes to the mass production of high-performance metal/Ge photodetectors.

Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness.

Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.

A Zinc Oxide Nanoflower-Based Electrochemical Sensor for Trace Detection of Sunset Yellow.

Zinc oxide nanoflower (ZnONF) was synthesized by a simple process and was used to construct a highly sensitive electrochemical sensor for the detection of sunset yellow (SY). Due to the large surface area and high accumulation efficiency of ZnONF, the ZnONF-modified carbon paste electrode (ZnONF/CPE) showed a strong enhancement effect on the electrochemical oxidation of SY. The electrochemical behaviors of SY were investigated using voltammetry with the ZnONF-based sensor. The optimized parameters included the amount of ZnONF, the accumulation time, and the pH value. Under optimal conditions, the oxidation peak current was linearly proportional to SY concentration in the range of 0.50-10 µg/L and 10-70 µg/L, while the detection limit was 0.10 µg/L (signal-to-noise ratio = 3). The proposed method was used to determine the amount of SY in soft drinks with recoveries of 97.5%-103%, and the results were in good agreement with the results obtained by high-performance liquid chromatography.

The Role of Nanoparticle Morphology on Enhancing Delivery of Budesonide for Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that affects the gastrointestinal tract. The major hurdles impeding IBD treatment are the low targeting efficiency and short retention time of drugs in IBD sites. Nanoparticles with specific shapes have demonstrated the ability to improve mucus retention and cellular uptake. Herein, mesoporous silica nanoparticles (MSNs) with various morphologies were used to deliver budesonide (BUD) for the treatment of IBD. The therapeutic efficacy is strongly dependent on their shapes. The system comprises different shapes of MSNs as carriers for budesonide (BUD), along with Eudragit S100 as the enteric release shell. The encapsulation of Eudragit S100 not only improved the stability of MSNs-BUD in the gastrointestinal tract but also conferred pH-responsive drug release properties. Then, MSNs efficiently deliver BUD to the colon site, and the special shape of MSNs plays a critical role in enhancing their permeability and retention in the mucus layer. Among them, dendritic MSNs (MSND) effectively reduced myeloperoxidase (MPO) activity and levels of inflammatory cytokines in the colon due to long retention time and rapid release in IBD sites, thereby enhancing the therapeutic efficacy against colitis. Given the special shapes of MSNs and pH-responsivity of Eudragit S100, BUD loaded in the voids of MSND (E@MSNs-BUD) could penetrate the mucous layer and be accurately delivered to the colon with minor side effects. This system is expected to complement current treatment strategies for the IBD.

A fluorescence aptamer sensor utilizing WS2 nanosheets for sensitive detection of patulin: enhanced specificity and wide applicability.

A tungsten disulfide (WS2) nanosheet-based aptamer sensor was developed to detect patulin (PAT). The 5'-end of the PAT aptamer was modified with a cyanine 3 (Cy3) fluorophore, which self-assembled on WS2 nanosheets. The interaction between the Cy3 fluorophore at the 5'-end of the PAT aptamer and the WS2 nanosheets resulted in reduced fluorescence (FL) intensity due to fluorescence resonance energy transfer (FRET). The introduction of PAT into this sensing system led to hybridization with the PAT aptamer, forming a G-quadruplex/PAT complex with low affinity for the WS2 nanosheet surface. This hybridization increased the distance between the Cy3 fluorophore and the WS2 nanosheets, inhibiting FRET and producing a strong FL signal. Under optimal experimental conditions, the FL intensity of the sensing system demonstrated an excellent linear correlation with PAT concentrations ranging from 0.5 to 40.0 ng mL-1, and it achieved a detection limit (S/N = 3) of 0.23 ng mL-1. This sensing system offers enhanced specificity for PAT detection and has the potential for broad application in detecting other toxins by substituting the sequence of the recognition aptamer.

GBT: Two-stage transformer framework for non-stationary time series forecasting.

This paper shows that time series forecasting Transformer (TSFT) suffers from severe over-fitting problem caused by improper initialization method of unknown decoder inputs, especially when handling non-stationary time series. Based on this observation, we propose GBT, a novel two-stage Transformer framework with Good Beginning. It decouples the prediction process of TSFT into two stages, including Auto-Regression stage and Self-Regression stage to tackle the problem of different statistical properties between input and prediction sequences. Prediction results of Auto-Regression stage serve as a 'Good Beginning', i.e., a better initialization for inputs of Self-Regression stage. We also propose the Error Score Modification module to further enhance the forecasting capability of the Self-Regression stage in GBT. Extensive experiments on seven benchmark datasets demonstrate that GBT outperforms SOTA TSFTs (FEDformer, Pyraformer, ETSformer, etc.) and many other forecasting models (SCINet, N-HiTS, etc.) with only canonical attention and convolution while owning less time and space complexity. It is also general enough to couple with these models to strengthen their forecasting capability. The source code is available at: https://github.com/OrigamiSL/GBT.

Vibration comfort assessment of tractor drivers based on sEMG and vibration signals.

In order to comprehensively evaluate the driver's vibration comfort under different vibration conditions, eighteen subjects were required to drive a tractor at different speeds on field and asphalt roads respectively in the real vehicle experiment. The sEMG signals and vibration acceleration signals of the subjects were recorded. And the time-frequency domain analysis of sEMG signals and acceleration signals were used to determine the relationship among the characteristic indexes, tractor speed and road surfaces. The relevance analysis showed that there was a significant correlation between the integral electromyography (iEMG) and median frequency (MF) of the middle scalene muscle, erector spinae muscle and gastrocnemius muscle, the RMS of weighted acceleration (aw) of the neck, waist and legs, and the subjective comfort feelings. It was proven that the tractor speed had a significant impact on human body vibration based on the ANOVA result (p < 0.05). With the increase of running speed, the time domain indexes of sEMG signals including iEMG, RMS and the vibration acceleration signals of the testing body parts increased significantly, while the amplitudes of frequency domain indexes decreased. Therefore, a quantitative regression evaluation model for the comfort of the neck, waist and legs integrating the sEMG and vibration signals was established, and its relative errors were 5.05, 4.38 and 6.12% respectively. This proposed assessment model can combine characteristics of the partial and overall vibration response of human body effectively, predict the tractor driver's vibration comfort accurately, provide a theoretical basis for the evaluation of tractor cab vibration comfort.

Biocontrol ability of Bacillus velezensis T9 against Apiospora arundinis causing Apiospora mold on sugarcane.

Sugarcane (Saccharum officinarum L.) may be infected with Apiospora, which can produce the toxin 3-nitropropionic acid (3-NPA) during improper transportation and storage. The consumption of sugarcane that contains 3-NPA can lead to food poisoning. Therefore, this study sought to explore a novel biocontrol agent to prevent and control Apiospora mold. Bacteria were isolated from the soil of healthy sugarcane and identified as Bacillus velezensis T9 through colony morphological, physiological and biochemical characterization and molecular identification. The inhibitory effect of B. velezensis T9 on Apiospora mold on sugarcane was analyzed. Assays of the cell suspension of strain T9 and its cell-free supernatant showed that T9 had significant in vitro antifungal activities against Apiospora arundinis and thus, would be a likely antagonist. Scanning electron microscopy and transmission electron microscopy showed that treatment with T9 significantly distorted the A. arundinis mycelia, perforated the membrane, contracted the vesicles, and decomposed most organelles into irregular fragments. A re-isolation experiment demonstrates the ability of T9 to colonize the sugarcane stems and survive in them. This strain can produce volatile organic compounds (VOCs) that are remarkably strong inhibitors, and it can also form biofilms. Additionally, the cell-free supernatant significantly reduced the ability of A. arundinis to produce 3-NPA and completely inhibited its production at 10%. Therefore, strain T9 is effective at controlling A. arundinis and has the potential for further development as a fungal prevention agent for agricultural products.

A polymer electrolyte design enables ultralow-work-function electrode for high-performance optoelectronics.

Ambient solution-processed conductive materials with a sufficient low work function are essential to facilitate electron injection in electronic and optoelectronic devices but are challenging. Here, we design an electrically conducting and ambient-stable polymer electrolyte with an ultralow work function down to 2.2 eV, which arises from heavy n-doping of dissolved salts to polymer matrix. Such materials can be solution processed into uniform and smooth films on various conductors including graphene, conductive metal oxides, conducting polymers and metals to substantially improve their electron injection, enabling high-performance blue light-emitting diodes and transparent light-emitting diodes. This work provides a universal strategy to design a wide range of stable charge injection materials with tunable work function. As an example, we also synthesize a high-work-function polymer electrolyte material for high-performance solar cells.

A sensitive MnO2 nanosheet sensing platform based on a fluorescence aptamer sensor for the detection of zearalenone.

An aptamer sensor based on manganese dioxide (MnO2) nanosheets was developed for the detection of zearalenone (ZEN). The ZEN aptamer was modified at the 5'-end by a 6-carboxyfluorescein (6-FAM) fluorophore with self-assembly on MnO2 nanosheets. Interaction of the 6-FAM fluorophore at the 5'-end of the ZEN aptamer with the MnO2 nanosheet lowered fluorescence (FL) intensity due to fluorescence resonance energy transfer (FRET). The introduction of ZEN into the sensing system resulted in hybridization with the ZEN aptamer, forming a stable G-quadruplex/ZEN, which exhibited a low affinity for the MnO2 nanosheet surface. The distance between the 6-FAM fluorophore and MnO2 nanosheet hampered FRET, with a consequent strong FL signal. Under the optimal experimental conditions, the FL intensity of the sensing system showed a good linear correlation with ZEN concentration in the range of 1.5-10.0 ng mL-1, and a detection limit (S/N = 3) of 0.68 ng mL-1. The sensing system delivered enhanced specificity for the detection of ZEN, and can find wide application in the detection of other toxins by replacing the sequence of the recognition aptamer.

Effects of Atrazine on Chernozem Microbial Communities Evaluated by Traditional Detection and Modern Sequencing Technology.

Atrazine is a long residual herbicide commonly used in maize fields. Although atrazine can effectively control weeds and improve crop yield, long-term application leads to continuous pollution in the agricultural ecological environment, especially in the soil ecosystem, and its impact on soil microorganisms is still not clear. Four methods were used in the experiment to clarify the effect of atrazine on the bacterial populations of cultivated soil layers of chernozem in a cold region in different periods: high-performance liquid chromatography (HPLC), colorimetry, microplate, and high-throughput sequencing. The level of residual atrazine in cold chernozem decreased from 4.645 to 0.077 mg/kg soil over time, and the residue gradually leached into deep soil and then decreased after accumulating to a maximum value. Atrazine significantly affected the activities of urease and polyphenol oxidase activity in the soil layers at different periods but had no significant effect on sucrase and phosphatase activity. Atrazine significantly reduced the diversity of microbial carbon source utilization and total activity in soil layers of 0-10 and 20-30 cm but only reduced the diversity of microbial carbon source utilization in the 10-20 cm layer. Atrazine had no significant effect on bacterial populations (10-12 phyla, 29-34 genera), but had a slight effect on the relative abundance of various groups. Atrazine significantly reduced the diversity of bacterial populations in cultivated soil layers of chernozem in a cold region, and the diversity of bacterial populations decreased with decreased residue. This lays a foundation for guiding the safe use of herbicides on farmland in Northeast China.

JUN promotes hypertrophic skin scarring via CD36 in preclinical in vitro and in vivo models.

Pathologic skin scarring presents a vast economic and medical burden. Unfortunately, the molecular mechanisms underlying scar formation remain to be elucidated. We used a hypertrophic scarring (HTS) mouse model in which Jun is overexpressed globally or specifically in α-smooth muscle or collagen type I­expressing cells to cause excessive extracellular matrix deposition by skin fibroblasts in the skin after wounding. Jun overexpression triggered dermal fibrosis by modulating distinct fibroblast subpopulations within the wound, enhancing reticular fibroblast numbers, and decreasing lipofibroblasts. Analysis of human scars further revealed that JUN is highly expressed across the wide spectrum of scars, including HTS and keloids. CRISPR-Cas9­mediated JUN deletion in human HTS fibroblasts combined with epigenomic and transcriptomic analysis of both human and mouse HTS fibroblasts revealed that JUN initiates fibrosis by regulating CD36. Blocking CD36 with salvianolic acid B or CD36 knockout model counteracted JUN-mediated fibrosis efficacy in both human fibroblasts and mouse wounds. In summary, JUN is a critical regulator of pathological skin scarring, and targeting its downstream effector CD36 may represent a therapeutic strategy against scarring.

[Microdialysis and HPLC method for determination of concentration of pantoprazole in rat striatum aftercombined administration with borneol].

OBJECTIVE: To observe the influence of borneol, a traditional Chinese medicine, on the concentration of ceftriaxone in the rat brain striatum and evaluate the relativity. METHOD: The sample of cerebrospinal fluid in the rat brain striatum was collected via brain microdialysis technology, and then the contents of ceftriaxone in standard preparation and sample were detected by high efficiency liquid chromatography combined with diode array detector respectively and analyzed statistically. The concentration of ceftriaxone in rat brain striatum in the ceftriaxone + Borneol group was compared with that in the ceftriaxone-only group. RESULT: The concentration of ceftriaxone in the rat brain in the ceftriaxone + Borneol group (13.01-4.43 mg x L(-1)) is significantly higher than that in the ceftriaxone-only group (2.41-0.94 mg x L(-1)). CONCLUSION: Borneol can promote ceftriaxone through blood-brain barrier, and increase the concentration thereof in striatum.

Structural modularity of the XIST ribonucleoprotein complex.

Long noncoding RNAs are thought to regulate gene expression by organizing protein complexes through unclear mechanisms. XIST controls the inactivation of an entire X chromosome in female placental mammals. Here we develop and integrate several orthogonal structure-interaction methods to demonstrate that XIST RNA-protein complex folds into an evolutionarily conserved modular architecture. Chimeric RNAs and clustered protein binding in fRIP and eCLIP experiments align with long-range RNA secondary structure, revealing discrete XIST domains that interact with distinct sets of effector proteins. CRISPR-Cas9-mediated permutation of the Xist A-repeat location shows that A-repeat serves as a nucleation center for multiple Xist-associated proteins and m6A modification. Thus modular architecture plays an essential role, in addition to sequence motifs, in determining the specificity of RBP binding and m6A modification. Together, this work builds a comprehensive structure-function model for the XIST RNA-protein complex, and suggests a general strategy for mechanistic studies of large ribonucleoprotein assemblies.

Spen links RNA-mediated endogenous retrovirus silencing and X chromosome inactivation.

The Xist lncRNA mediates X chromosome inactivation (XCI). Here we show that Spen, an Xist-binding repressor protein essential for XCI , binds to ancient retroviral RNA, performing a surveillance role to recruit chromatin silencing machinery to these parasitic loci. Spen loss activates a subset of endogenous retroviral (ERV) elements in mouse embryonic stem cells, with gain of chromatin accessibility, active histone modifications, and ERV RNA transcription. Spen binds directly to ERV RNAs that show structural similarity to the A-repeat of Xist, a region critical for Xist-mediated gene silencing. ERV RNA and Xist A-repeat bind the RRM domains of Spen in a competitive manner. Insertion of an ERV into an A-repeat deficient Xist rescues binding of Xist RNA to Spen and results in strictly local gene silencing in cis. These results suggest that Xist may coopt transposable element RNA-protein interactions to repurpose powerful antiviral chromatin silencing machinery for sex chromosome dosage compensation.

The genetic material inside cells is often packaged into thread-like structures called chromosomes. In humans, mice and other mammals, a pair of sex chromosomes determines the genetic or chromosomal sex of each individual. Those who inherit two "X" chromosomes are said to be chromosomally female, while chromosomal males have one "X" and one "Y" chromosome. This means females have twice as many copies of genes on the X chromosome as a male does, which turns out to be double the number that the body needs. To solve this problem, mammals have developed a strategy known as dosage compensation. The second X chromosome in females becomes "silent": its DNA remains unchanged, but none of the genes are active. A long noncoding RNA molecule called Xist is responsible for switching off the extra X genes in female cells. It does this by coating the entirety of the second X chromosome. Normally, RNA molecules transmit the coded instructions in genes to the cellular machinery that manufactures proteins. "Noncoding" RNAs like Xist, however, are RNAs that have taken on different jobs inside the cell. Researchers believe that the ancestral Xist gene may have once encoded a protein but changed over time to produce only a noncoding RNA. Carter, Xu et al. therefore set out to find out how exactly this might have happened, and also how Xist might have acquired its ability to switch genes off. Initial experiments used mouse cells grown in the laboratory, in which a protein called Spen was deleted. Spen is known to help Xist silence the X chromosome. In female cells lacking Spen, the second X chromosome remained active. Other chromosomes in male and female cells also had stretches of DNA that became active upon Spen's removal. These DNA sequences, termed endogenous retroviruses, were remnants of ancestral viral infections. In other words, Spen normally acted as an antiviral defense. Analysis of genetic sequences showed that Spen recognized endogenous retrovirus sequences resembling a key region in Xist, a region which was needed for Xist to work properly. Inserting fragments of endogenous retroviruses into a defective version of Xist lacking this region also partially restored its ability to inactivate genes, suggesting that X chromosome silencing might work by hijacking cellular defenses against viruses. That is, female cells essentially 'pretend' there is a viral infection on the second X chromosome by coating it with Xist (which mimics endogenous retroviruses), thus directing Spen to shut it down. This research is an important step towards understanding how female cells carry out dosage compensation in mammals. More broadly, it sheds new light on how ancient viruses may have shaped the evolution of noncoding RNAs in the human genome.