Browse Articles
Discover research articles across all indexed journals
RNA-mediated condensation of TFE3 oncofusions facilitates transcriptional hub formation to promote translocation renal cell carcinoma
Abstract Transcription factor E3 (TFE3) oncofusions are frequently detected in the Microphthalmia transcription factor (MiT) family translocation renal cell carcinoma (tRCC), a rare pediatric renal cancer with limited treatment options. The mechanisms by which TFE3 oncofusions promote tRCC malignancy remain inadequately defined. Here, we demonstrate that the RNA-binding capability conferred by TFE3 fusion partners drives the formation of TFE3 condensates. This further enables TFE3 oncofusions to co-condensate with RNA polymerase II (RNAPII) and other RNA-binding proteins, such as paraspeckle component 1 (PSPC1), ultimately driving the formation of transcriptional hubs to promote pro-oncogenic transcription. Dissolution of oncofusion condensates through nanobody-based chemogenetic manipulation effectively curtails tRCC cell growth both in vitro and in vivo, suggesting the therapeutic potential for targeting oncofusion condensation in tRCC. Collectively, our study establishes the causal role of RNA and RNA-binding proteins in facilitating oncofusion condensation to promote renal cancer progression.
DNA barcode reference library of bush-crickets (Orthoptera, Tettigoniidae) from the Iberian Peninsula
Abstract Curated DNA barcode reference libraries are crucial for advancing environmental DNA (eDNA) studies, monitoring biological invasions, reliable biodiversity assessments, accurate species identification, etc. However, DNA barcode databases remain highly incomplete for most invertebrate taxa. In this study, we present the most comprehensive reference library to date for the family Tettigoniidae (Orthoptera) from the Iberian Peninsula—the most species-rich orthopteran family globally, with over 8,000 valid species. We generated 402 new DNA barcodes from at least 121 tettigoniid species from the Iberian Peninsula and integrated these with 169 previously published sequences. The resulting dataset comprises 571 barcoded specimens, representing 49 genera and 123 species, including many recently described taxa. Notably, we provide DNA barcodes for at least 68 described species that previously lacked them. Our dataset covers 85% of the tettigoniid species in the Iberian Peninsula and approximately 25% of European bush-cricket species. Furthermore, our analyses show that most tettigoniid species (95%) can be reliably identified using DNA barcoding. However, mitochondrial introgression events were detected in several species of the subfamilies Bradyporinae and Tettigoniinae, highlighting the need for cautious application of this molecular identification tool.
Optimized FOC control strategy for dual stators permanent magnet machine
Daily briefing: Tiny charged bubbles of methane could explain will-o’-the-wisps
CXCR4 mediated recognition of HIV envelope spike and inhibition by CXCL12
Abstract CCR5 and CXCR4 both act as HIV co-receptors, though CXCR4 is less explored. CXCR4 binds the chemokine CXCL12 to regulate cellular processes and mediate HIV entry, a process that CXCL12 inhibits. Using cryo-EM, we investigate HIV-2 envelope (Env) spike recognition by CXCR4 and how CXCL12 inhibit this interaction. We discover that CXCR4 unexpected forms a tetramer, both alone and in complex. It binds CXCL12 with 4:8 and 8:8 stoichiometries, with the CXCL12 N-terminus inserting into the CXCR4 pocket. Structures of CXCR4-gp120HIV-2 complex show one or two gp120 molecules per CXCR4 tetramer, with the V3 loop occupying the major sub-pocket of CXCR4 through deep embedment of its GFKF motif. The CXCL12 N-terminus chashes with gp120HIV-2 V3 loops, explain its inhibitory effect. Docking analyses of other HIV antagonists further clarify their mechanisms. The CXCR4-gp120HIV-1 model illustrate how V3 loop residues define co-receptor specificity, offering insights into co-receptor switching and therapeutic design.
Aerodynamic simulation and control analysis of an aircraft emergency tailplane system
Association of serum copper, zinc and copper to zinc ratio in patients with acute myeloid leukemia
Genetic tuning of retinal ganglion cell subtype identity to drive visual behavior
Abstract The distinct blend of molecular and cellular features that define neuronal subtype identity are central to shaping how individual subtypes impact animal behavior. The diversity of the mammalian nervous system is vast — the retina alone contains over 100 neuronal subtypes. Yet, the genetic processes giving rise to this stunning structural and functional diversity remain poorly understood. Here, we uncover a graded expression pattern of the transcription factor BRN3B that tunes and maintains multiple, subtype-defining transcriptional and morphophysiological features of the melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) in mice. Disruption of BRN3B expression levels causes the transcriptional and morphophysiological identity of ipRGC subtypes to begin to converge, leading to dysfunction in multiple ipRGC-dependent behaviors. These findings show that graded levels of a single transcription factor can tune a diverse array of features to shape neuronal identity and circuit function to drive behavior.