Biology subjects

Nagy, G. A.

Publications and source records attributed to Nagy, G. A..

5 recordsLinked to original sources

bioRxiv2026

Isoform-Resolved Temporal Remodeling of Transcriptome Architecture in Monkeypox Virus

We reanalyzed previously generated replicated Oxford Nanopore direct cDNA sequencing data from six infection time points, together with cap analysis of gene expression and native direct RNA sequencing, to reconstruct full-length monkeypox virus transcripts and characterize their temporal regulation. A broad catalogue of candidate transcript models, including candidate 5' poly(A)-associated structures, was filtered with independent 5'- and 3'-end evidence to define conservative analysis sets. Transcript-resolved profiles revealed a structured temporal program extending beyond gene-level abundance. Host-virus interaction, transcription, and nucleotide-metabolism genes contributed strongly early, whereas virion structure and morphogenesis genes dominated later. Transcription start and end site abundance profiles changed extensively over time, and many genes redistributed among alternative full-length transcript structures. Differential transcript usage was particularly prominent among host-virus interaction genes but depleted among virion structure and morphogenesis genes. Candidate 5' poly(A)-associated transcripts also increased in relative contribution and showed locus-specific patterns. Building on our previous endpoint map, the replicated direct cDNA time course enabled temporal quantification of gene abundance, transcript-end dynamics, and isoform composition. Together, these results show that Monkeypox virus gene regulation involves coordinated remodeling of gene output, transcript boundaries, and full-length transcriptome architecture.

microbiology↗

bioRxiv2026

Sensory stimulation triggers different spike responses in serotonin and dopamine neurons in the dorsal midbrain tegmentum.

The dorsal midbrain tegmentum, including the dorsal raphe nucleus (DRN) and the ventrolateral periaqueductal gray (vlPAG), contains diverse neuronal populations. Within this region, serotonin (5-HT) and dopamine (DA) neurons are the principal monoaminergic cell types and exert widespread influence on brain circuits. While the role of 5-HT and DA neurons in sensory integration is well established, their stimulus-driven spiking activity remains incompletely characterized. Using silicon probe recordings in mice, we found that >57% of DRN/vlPAG neurons responded to foot shock and mechanical stimulation, whereas <15% showed changes in spiking activity following light or acoustic stimulation. At the population level, similar results were obtained using juxtacellular recordings, a method that allowed post hoc identification of 5-HT and DA neurons. Upon foot shock delivery, 5-HT neurons exhibited heterogeneous responses, including both excitation and inhibition, whereas DA neurons typically increased their firing rates. We found that DA neurons lacking vasoactive intestinal polypeptide (VIP) fired within the first second after foot shocks, while VIP-expressing DA neurons were most active later. Together, our results demonstrate that DRN/vlPAG neurons are most responsive to foot shock and mechanical stimuli. Moreover, 5-HT and DA neurons exhibit distinct patterns of activation following aversive inputs, suggesting that they play different roles in sensory information processing.

neuroscience↗

bioRxiv2025

Large sharp-wave ripples promote hippocampo-cortical memory reactivation and consolidation

During sleep, ensemble activity patterns encoding recent experiences are reactivated in the hippocampus and cortex. This reactivation is coordinated by hippocampal sharp-wave ripples (SWRs) and is believed to support the early stages of memory consolidation. However, only a minority of sleep SWRs are associated with memory reactivation in the hippocampus and its downstream areas. Whether that subset of SWRs have specific physiological characteristics and directly contribute to memory performance is not known. We identified a specific subset of large SWRs linked to memory reactivation in both the hippocampus and prefrontal cortex (PFC) of mice, and found that their occurrence selectively increased during sleep following new learning. Closed-loop optogenetic SWR boosting during sleep was sufficient to enhance ensemble memory reactivation in hippocampus and PFC. This manipulation also improved subsequent memory retrieval and hippocampal-PFC coordination during waking, causally linking both phenomena to SWR-associated ensemble reactivation during sleep.

neuroscience↗

bioRxiv2024

Exploring the Transcriptomic Profile of Human Monkeypox Virus via CAGE and Native RNA Sequencing Approaches

In this study, we employed short- and long-read sequencing technologies to delineate the transcriptional architecture of the human monkeypox virus and to identify key regulatory elements that govern its gene expression. Specifically, we conducted a transcriptomic analysis to annotate the transcription start sites (TSSs) and transcription end sites (TESs) of the virus by utilizing cap analysis of gene expression sequencing on the Illumina platform and direct RNA sequencing on the Oxford Nanopore technology device. Our investigations uncovered significant complexity in the use of alternative TSSs and TESs in viral genes. In this research, we also detected the promoter elements and poly(A) signals associated with the viral genes. Additionally, we identified novel genes in both the left and right variable regions of the viral genome. ImportanceGenerally, gaining insight into how the transcription of a virus is regulated offers insights into the key mechanisms that control its life cycle. The recent outbreak of the human monkeypox virus has underscored the necessity of understanding the basic biology of its causative agent. Our results are pivotal for constructing a comprehensive transcriptomic atlas of the human monkeypox virus, providing valuable resources for future studies.

microbiology↗

bioRxiv2023

Novel Herpesvirus Transcripts with Putative Regulatory Roles in DNA Replication and Global Transcription

In the last couple of years, the rapid advances and decreasing costs of sequencing technologies have revolutionized transcriptomic research. Long-read sequencing (LRS) techniques are able to detect full-length RNA molecules in a single run without the need for additional assembly steps. LRS studies have revealed an unexpected transcriptomic complexity in a variety of organisms, including viruses. A number of transcripts with proven or putative regulatory role, mapping close to or overlapping the replication origins (Oris) and the nearby transcription activator genes, have been described in herpesviruses. In this study, we applied both newly generated and previously published LRS and short-read sequencing datasets to discover additional Ori-proximal transcripts in nine herpesviruses belonging to all of the three subfamilies (alpha, beta and gamma). We identified novel long non-coding RNAs (lncRNAs), as well as splice and length isoforms of mRNAs and lncRNAs. Furthermore, our analysis disclosed an intricate meshwork of transcriptional overlaps at the examined genomic regions. Our results suggest the existence of a super regulatory center, which controls both the replication and the global transcription through multilevel interactions between the molecular machineries.

molecular biology↗