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Generation and characterization of a Cre-inducible ZNF768 overexpression mouse model
Abstract Zinc-finger protein 768 (ZNF768) is an emerging transcription factor regulating cell proliferation and senescence. Although the role of ZNF768 in regulating cell fate decision has been demonstrated in vitro, its importance in controlling physiological and pathophysiological processes in vivo is still unclear. Here, we report the generation of a transgenic mouse model allowing the conditional overexpression of ZNF768. This was achieved by inserting an inverted Znf768 coding sequence surrounded by heterologous Cre recognition sites in the Gt(ROSA)26Sor mouse locus (FLExZnf768). To study the impact linked to systemic overexpression of ZNF768, mice carrying the FLExZnf768 allele were crossed with CMV-Cre mice to produce a whole-body ZNF768 transgenic mouse (WB-ZNF768-Tg). As expected, WB-ZNF768-Tg mice showed higher ZNF768 levels in various tissues. These mice were born at the expected Mendelian ratio and did not display apparent phenotypes. Because ZNF768 levels are often overexpressed in cancer, we assessed tumor development in WB-ZNF768-Tg mice. However, ZNF768 overexpression was not sufficient to promote 3-methylcholantrene-induced fibrosarcoma and KRASG12D-induced lung adenocarcinoma in mice. Overall, we report the generation of a conditional mouse for ZNF768 overexpression and reveal that forcing ZNF768 expression is not sufficient to alter tumour development in mice.
Bio-inspired mid-infrared neuromorphic transistors for dynamic trajectory perception using PdSe2/pentacene heterostructure
Security analysis of qutrit quantum secret sharing with linear optical correlation measurement
An archaeal nucleoid-associated protein binds an essential motif in DNA replication origins
Abstract DNA replication typically has defined start sites, or replication origins, which are designated by their recognition by specific initiator proteins. In addition to initiators, general chromatin or nucleoid-associated proteins have been shown to play roles in modulating origin efficiency in eukaryotes and bacteria. The role of chromatin proteins in origin function in the archaeal domain of life is poorly understood. Here, we describe a dissection of sequences elements required for in vivo function of an archaeal DNA replication origin. Our data reveal a hitherto uncharacterized sequence element, the ucm, is required for origin activity. We identify a protein, UBP, that interacts with the ucm and additionally with hundreds of other sites on the genome. We solve the crystal structure of UBP alone and in complex with ucm DNA, and further show that UBP interacts with the MCM replicative helicase. Taken together, our data provide evidence that UBP functions as a general nucleoid-associated protein that plays a key role in facilitating the egress of the MCM replicative helicase from DNA replication origins.
Thiol-disulfide homeostasis and ischemia modified albumin levels in patients diagnosed with ovary carcinoma
Abstract In our study, we determined the changes in the oxidative stress (OxS) biomarkers, thiol-disulfide (TD) homeostasis and ischemia-modified albumin (IMA) levels, in patients diagnosed with ovarian carcinoma before and after chemotherapy. We will examine the indirect effects of chemotherapy on OxS and antioxidant capacity by measuring changes in these blood biomarkers and compare the results with those of the healthy control group. This case–control study, which was conducted in a single-center, prospective design, included 42 patients diagnosed with ovarian cancer and 51 healthy volunteers. Venous blood samples were taken from all participants after 8 h of fasting, their serum was separated, and the serum total thiol, native thiol, disulfide, and IMA values were measured. In the comparison of the blood samples taken before the chemotherapy treatment of the patient group with the healthy control group, the native thiol (p < 0.001), total thiol (p < 0.001), and native thiol/total thiol (p < 0.001) values were found to be statistically significantly lower, and the disulfide (p = 0.001), disulfide/native (p < 0.001), and disulfide/total thiol (p < 0.001) levels were found to be statistically significantly greater. In the patient group diagnosed with ovarian cancer, a statistically significant difference was detected between the measurements of cancer antigen-125 (CA-125) (p < 0.001), native thiol (p = 0.019), and total thiol (p = 0.025) values at the 0th month before chemotherapy treatment and the third month after chemotherapy treatment. In the group that received adjuvant chemotherapy after the operation, the native thiol (p = 0.035), total thiol (p = 0.043), disulfide/native thiol (p = 0.035), disulfide total thiol (p = 0.035), native thiol/total thiol (p = 0.035) and IMA (p = 0.026) values were statistically significantly different between the diagnosis and third-month values. Our study suggests that TD homeostasis may be an important guide in terms of disease progression, complications during chemotherapy treatment, appropriate dose reductions, and modifications in chemotherapy depending on the toxicities experienced and the goals of the treatment.
Lysosomal TMEM165 controls cellular ion homeostasis and survival by mediating lysosomal Ca2+ import and H+ efflux
Biocontrol efficacy of formulated probiotic bacteria against Meloidogyne incognita in Kiwifruit under greenhouse and field conditions
Optimizing enzyme inhibition analysis: precise estimation with a single inhibitor concentration
The environmental effects of monocentric urban spatial structure with city-level evidence from China
[1,n]-Metal migrations for directional translational motion at the molecular level
Abstract The controlled translational motion displayed by nature’s motor proteins underpins a wealth of processes integral to life, from organelle transport to muscle contraction. The motor proteins move along one dimensional cytoskeletal tracks, with their motion characterised by high association of the enzyme to the biopolymer combined with highly dynamic motion along the track. Here we introduce carbon-to-carbon metal migration as a platform for dynamic association and show how such migrations, in combination with the incorporation of a simple hydrocarbon, can be harnessed to achieve autonomous directional translational motion of a metal centre along the length of a polyaromatic track.
Decentralized Proof-of-Location systems for trust, scalability, and privacy in digital societies
Abstract Verifying physical presence in digital systems is essential for secure authentication, authorization, and accountability. Proof-of-Location (PoL) systems address this need by enabling verifiable, tamper-resistant claims of location and time, particularly in adversarial environments where traditional localization methods such as GPS fall short. While recent efforts have explored decentralized PoL architectures, existing systems often lack a unified model that integrates spatio-temporal synchronization, distributed consensus, and cryptographic attestation. In this paper, we formalize the architectural foundations of decentralized PoL systems by introducing a composable model based on fault-tolerant witnessing zones. We define core components for synchronization and collective attestation, integrating primitives such as distributed digital signatures, distance bounding protocols, and consensus mechanisms. We contextualize the model across diverse application domains that necessitate digital trust-such as civic processes, content authentication, infrastructure auditing, and supply chain tracking-and argue for a shared, interoperable decentralized PoL infrastructure. To validate our design, we implement and emulate a reference protocol instance, analysing scalability, synchronization behaviour, and timing misalignment under varied conditions. We also outline its security model and discuss limitations and future directions in privacy, interoperability, and real-world deployment. Our contributions lay a formal and practical foundation for scalable, secure, and general-purpose decentralized PoL systems.
Bulk superconductivity near 40 K in hole-doped SmNiO2 at ambient pressure
C. elegans SSNA-1 is required for the structural integrity of centrioles and bipolar spindle assembly
Abstract Centrioles play key roles in mitotic spindle assembly. Once assembled, centrioles exhibit long-term stability, but how stability is achieved and how it is regulated are not completely understood. In this study we show that SSNA-1, the Caenorhabditis elegans ortholog of Sjogren’s Syndrome Nuclear Antigen 1, is a constituent of centrioles and centriole satellite-like structures. A deletion of ssna-1 results in the formation of extra centrioles. We show that SSNA-1 genetically interacts with the centriole stability factor SAS-1 and is required post assembly for centriole structural integrity. In SSNA-1’s absence, centrioles assemble but fracture leading to extra spindle poles. However, if the efficiency of cartwheel assembly is reduced, the absence of SSNA-1 results in daughter centriole loss and monopolar spindles, indicating that the cartwheel and SSNA-1 cooperate to stabilize centrioles during assembly. Our work thus shows that SSNA-1 contributes to centriole stability during and after assembly, thereby ensuring proper centriole number.
Pyrite morphology and sulfur isotopes refine taphonomic models for the 2.1 Ga Francevillian biota, Gabon
Serotonin and neurotensin inputs in the vCA1 dictate opposing social valence
Multimodal cell maps as a foundation for structural and functional genomics
Abstract Human cells consist of a complex hierarchy of components, many of which remain unexplored1,2. Here we construct a global map of human subcellular architecture through joint measurement of biophysical interactions and immunofluorescence images for over 5,100 proteins in U2OS osteosarcoma cells. Self-supervised multimodal data integration resolves 275 molecular assemblies spanning the range of 10−8 to 10−5 m, which we validate systematically using whole-cell size-exclusion chromatography and annotate using large language models3. We explore key applications in structural biology, yielding structures for 111 heterodimeric complexes and an expanded Rag–Ragulator assembly. The map assigns unexpected functions to 975 proteins, including roles for C18orf21 in RNA processing and DPP9 in interferon signalling, and identifies assemblies with multiple localizations or cell type specificity. It decodes paediatric cancer genomes4, identifying 21 recurrently mutated assemblies and implicating 102 validated new cancer proteins. The associated Cell Visualization Portal and Mapping Toolkit provide a reference platform for structural and functional cell biology.