Capture of Totipotency in Mouse Embryonic Stem Cells in the Absence of Pdzk1.

Totipotent cells can differentiate into three lineages: the epiblast, primitive endoderm, and trophectoderm. Naturally, only early fertilized embryos possess totipotency, and they lose this ability as they develop. The expansion of stem cell differentiation potential has been a hot topic in developmental biology for years, particularly with respect to the generation totipotent-like stem cells.

Research on a Method for Measuring the Pile Height of Materials in Agricultural Product Transport Vehicles Based on Binocular Vision.

The advancement of unloading technology in combine harvesting is crucial for the intelligent development of agricultural machinery. Accurately measuring material pile height in transport vehicles is essential, as uneven accumulation can lead to spillage and voids, reducing loading efficiency. Relying solely on manual observation for measuring stack height can decrease harvesting efficiency and pose safety risks due to driver distraction.

Unveiling circRNA-mediated ceRNA networks in ischemic stroke by integrative analysis of multi-source gene expression profiling.

Background: Circular RNAs (circRNAs) are emerging as potential therapeutic targets for ischemic stroke (IS) due to their regulatory roles in inflammation and apoptosis. This study aimed to develop a comprehensive and robust IS-specific competing endogenous RNA (ceRNA) network to facilitate the identification of novel diagnostic and therapeutic targets.

Methods: We integrated expression data from 15 IS studies using the Rank-In algorithm to minimize batch effects.

The transcription factor ZEB2 drives the formation of age-associated B cells.

Age-associated B cells (ABCs) accumulate during infection, aging, and autoimmunity, contributing to lupus pathogenesis. In this study, we screened for transcription factors driving ABC formation and found that zinc finger E-box binding homeobox 2 (ZEB2) is required for human and mouse ABC differentiation in vitro. ABCs are reduced in haploinsufficient individuals and in mice lacking in B cells.

PRMT5 orchestrates EGFR and AKT networks to activate NFκB and promote EMT.

Neuroblastoma remains a formidable challenge in pediatric oncology, representing 15% of cancer-related mortalities in children. Despite advancements in combinatorial and targeted treatments improving survival rates, nearly 50% of patients with high-risk neuroblastoma will ultimately succumb to their disease. Dysregulation of the epithelial-mesenchymal transition (EMT) is a key mechanism of tumor cell dissemination, resulting in metastasis and poor outcomes in many cancers.

Allele-specific binding (ASB) analyzer for annotation of allele-specific binding SNPs.

Background: Allele-specific binding (ASB) events occur when transcription factors (TFs) bind more favorably to one of the two parental alleles at heterozygous single nucleotide polymorphisms (SNPs). Evidence suggests that ASB events could reveal the impact of sequence variations on TF binding and may have implications for the risk of diseases.

Results: Here we present ASB-analyzer, a software platform that enables the users to quickly and efficiently input raw sequencing data to generate individual reports containing the cytogenetic map of ASB SNPs and their associated phenotypes.

TE-TSS: an integrated data resource of human and mouse transposable element (TE)-derived transcription start site (TSS).

Transposable elements (TEs) are abundant in the genome and serve as crucial regulatory elements. Some TEs function as epigenetically regulated promoters, and these TE-derived transcription start sites (TSSs) play a crucial role in regulating genes associated with specific functions, such as cancer and embryogenesis. However, the lack of an accessible database that systematically gathers TE-derived TSS data is a current research gap.

First-principles study of magnetic interactions and excitations in antiferromagnetic van der Waals material MPX(M=Mn, Fe, Co, Ni; X=S, Se).

Transition metal phosphorus trichalcogenides MPX(M = Mn, Fe, Co, Ni; X = S, Se), as layered van der Waals antiferromagnetic (AFM) materials, have emerged as a promising platform for exploring two-dimensional (2D) magnetism. Based on density functional theory, we present a comprehensive investigation of the electronic and magnetic properties of MPX. We calculated the spin exchange interactions as well as magnetocrystalline anisotropy energy.

BCL2 is a major regulator of haploidy maintenance in murine embryonic stem cells.

Mammalian haploid cells are important resources for forward genetic screening and are important in genetic medicine and drug development. However, the self-diploidization of murine haploid embryonic stem cells (haESCs) during daily culture or differentiation jeopardizes their use in genetic approaches. Here, we show that overexpression (OE) of an antiapoptosis gene, BCL2, in haESCs robustly ensures their haploidy maintenance in various situations, even under strict differentiation in vivo (embryonic 10.

Epigenetic and chromosomal features drive transposon insertion in Drosophila melanogaster.

Transposons are mobile genetic elements prevalent in the genomes of most species. The distribution of transposons within a genome reflects the actions of two opposing processes: initial insertion site selection, and selective pressure from the host. By analyzing whole-genome sequencing data from transposon-activated Drosophila melanogaster, we identified 43 316 de novo and 237 germline insertions from four long-terminal-repeat (LTR) transposons, one LINE transposon (I-element), and one DNA transposon (P-element).

Arm Movement Analysis Technology of Wushu Competition Image Based on Deep Learning.

In order to improve the recognition accuracy of action poses for athletes in martial arts competitions, it is considered that a single frame pose does not have the temporal features required for sequential actions. Based on deep learning, this paper proposes an image arm movement analysis technology in martial arts competitions. The motion features of the arm are extracted from the bone sequence.

Arih2 regulates Hedgehog signaling through smoothened ubiquitylation and ER-associated degradation.

During Hedgehog signaling, the ciliary levels of Ptch1 and Smo are regulated by the pathway. At the basal state, Ptch1 localizes to cilia and prevents the ciliary accumulation and activation of Smo. Upon binding a Hedgehog ligand, Ptch1 exits cilia, relieving inhibition of Smo.

PRMT5 activates AKT via methylation to promote tumor metastasis.

Protein arginine methyltransferase 5 (PRMT5) is the primary methyltransferase generating symmetric-dimethyl-arginine marks on histone and non-histone proteins. PRMT5 dysregulation is implicated in multiple oncogenic processes. Here, we report that PRMT5-mediated methylation of protein kinase B (AKT) is required for its subsequent phosphorylation at Thr308 and Ser473.

Integration of high-resolution promoter profiling assays reveals novel, cell type-specific transcription start sites across 115 human cell and tissue types.

Accurate transcription start site (TSS) annotations are essential for understanding transcriptional regulation and its role in human disease. Gene collections such as GENCODE contain annotations for tens of thousands of TSSs, but not all of these annotations are experimentally validated nor do they contain information on cell type-specific usage. Therefore, we sought to generate a collection of experimentally validated TSSs by integrating RNA Annotation and Mapping of Promoters for the Analysis of Gene Expression (RAMPAGE) data from 115 cell and tissue types, which resulted in a collection of approximately 50 thousand representative RAMPAGE peaks.

5'-Modifications improve potency and efficacy of DNA donors for precision genome editing.

Nuclease-directed genome editing is a powerful tool for investigating physiology and has great promise as a therapeutic approach to correct mutations that cause disease. In its most precise form, genome editing can use cellular homology-directed repair (HDR) pathways to insert information from an exogenously supplied DNA-repair template (donor) directly into a targeted genomic location. Unfortunately, particularly for long insertions, toxicity and delivery considerations associated with repair template DNA can limit HDR efficacy.

Deletion and replacement of long genomic sequences using prime editing.

Genomic insertions, duplications and insertion/deletions (indels), which account for ~14% of human pathogenic mutations, cannot be accurately or efficiently corrected by current gene-editing methods, especially those that involve larger alterations (>100 base pairs (bp)). Here, we optimize prime editing (PE) tools for creating precise genomic deletions and direct the replacement of a genomic fragment ranging from ~1 kilobases (kb) to ~10 kb with a desired sequence (up to 60 bp) in the absence of an exogenous DNA template. By conjugating Cas9 nuclease to reverse transcriptase (PE-Cas9) and combining it with two PE guide RNAs (pegRNAs) targeting complementary DNA strands, we achieve precise and specific deletion and repair of target sequences via using this PE-Cas9-based deletion and repair (PEDAR) method.

An organ-on-a-chip model for pre-clinical drug evaluation in progressive non-genetic cardiomyopathy.

Angiotensin II (Ang II) presents a critical mediator in various pathological conditions such as non-genetic cardiomyopathy. Osmotic pump infusion in rodents is a commonly used approach to model cardiomyopathy associated with Ang II. However, profound differences in electrophysiology and pharmacokinetics between rodent and human cardiomyocytes may limit predictability of animal-based experiments.

Genetic and epigenetic features of promoters with ubiquitous chromatin accessibility support ubiquitous transcription of cell-essential genes.

Gene expression is controlled by regulatory elements within accessible chromatin. Although most regulatory elements are cell type-specific, a subset is accessible in nearly all the 517 human and 94 mouse cell and tissue types assayed by the ENCODE consortium. We systematically analyzed 9000 human and 8000 mouse ubiquitously-accessible candidate cis-regulatory elements (cCREs) with promoter-like signatures (PLSs) from ENCODE, which we denote ubi-PLSs.

Investigating the Potential Roles of SINEs in the Human Genome.

Short interspersed nuclear elements (SINEs) are nonautonomous retrotransposons that occupy approximately 13% of the human genome. They are transcribed by RNA polymerase III and can be retrotranscribed and inserted back into the genome with the help of other autonomous retroelements. Because they are preferentially located close to or within gene-rich regions, they can regulate gene expression by various mechanisms that act at both the DNA and the RNA levels.

Optimized RNA-targeting CRISPR/Cas13d technology outperforms shRNA in identifying functional circRNAs.

Short hairpin RNAs (shRNAs) are used to deplete circRNAs by targeting back-splicing junction (BSJ) sites. However, frequent discrepancies exist between shRNA-mediated circRNA knockdown and the corresponding biological effect, querying their robustness. By leveraging CRISPR/Cas13d tool and optimizing the strategy for designing single-guide RNAs against circRNA BSJ sites, we markedly enhance specificity of circRNA silencing.

Expanded encyclopaedias of DNA elements in the human and mouse genomes.

The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development.

YAP1 Withdrawal in Hepatoblastoma Drives Therapeutic Differentiation of Tumor Cells to Functional Hepatocyte-Like Cells.

Background And Aims: Despite surgical and chemotherapeutic advances, the 5-year survival rate for stage IV hepatoblastoma (HB), the predominant pediatric liver tumor, remains at 27%. Yes-associated protein 1 (YAP1) and β-catenin co-activation occurs in 80% of children's HB; however, a lack of conditional genetic models precludes tumor maintenance exploration. Thus, the need for a targeted therapy remains unmet.

Mitochondrial DNA Stress Signalling Protects the Nuclear Genome.

The mammalian genome comprises nuclear DNA (nDNA) derived from both parents and mitochondrial DNA (mtDNA) that is maternally inherited and encodes essential proteins required for oxidative phosphorylation. Thousands of copies of the circular mtDNA are present in most cell types that are packaged by TFAM into higher-order structures called nucleoids1. Mitochondria are also platforms for antiviral signalling2 and, due to their bacterial origin, mtDNA and other mitochondrial components trigger innate immune responses and inflammatory pathology.

Chemical modifications of adenine base editor mRNA and guide RNA expand its application scope.

CRISPR-Cas9-associated base editing is a promising tool to correct pathogenic single nucleotide mutations in research or therapeutic settings. Efficient base editing requires cellular exposure to levels of base editors that can be difficult to attain in hard-to-transfect cells or in vivo. Here we engineer a chemically modified mRNA-encoded adenine base editor that mediates robust editing at various cellular genomic sites together with moderately modified guide RNA, and show its therapeutic potential in correcting pathogenic single nucleotide mutations in cell and animal models of diseases.