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Biology subjects

Petrov, A.

Publications and source records attributed to Petrov, A..

5 recordsLinked to original sources

Proximity-Aware Graph Attention Networks for Spatially Resolved Cell-Cell Inference

Cell-cell inference is a fundamental mechanism driving tissue homeostasis, immune regulation, and disease progression. Existing CCC inference tools operate on dissociated single-cell RNA-seq data, discarding the spatial constraints that govern short-range paracrine and juxtacrine signaling. We present SO_SCPLOWPAC_SCPLOWGNN, a proximity-aware graph attention network that jointly encodes physical cell adjacency and ligand-receptor co-expression from spatial transcriptomics data to infer spatially resolved CCC interactions. A heterogeneous cell communication graph is constructed by combining spatial proximity edges with molecular ligand-receptor edges, and a distance-modulated attention mechanism enforces the locality constraint of cell-to-cell signaling. The model is trained with a composite self-supervised objective that integrates spatial co-localization enrichment and downstream target gene activation. We evaluate SO_SCPLOWPAC_SCPLOWGNN on four spatial transcriptomics datasets spanning 10X Visium, MERFISH, and Slide-seq platforms. Compared with state-of-the-art methods including COMMOT, SpaOTsc, CellChat, and NicheNet, our method achieves superior interaction AUROC (0.871 vs. 0.831 for COMMOT), a 3.42x spatial enrichment score, and an F1 of 0.681 in communication hotspot detection. Ablation studies confirm that spatial distance modulation is the single most impactful component, contributing a 0.030 AUROC improvement over a non-spatial baseline.

bioinformatics↗

Sordarin bound eEF2 unlocks spontaneous forward and reverse translocation on CrPV IRES

The Intergenic Region Internal Ribosome Entry Sites (IGR IRESs) of Discistroviridae promote protein synthesis without initiation factors, with IRES translocation by elongation factor 2 (eEF2) being the first factor catalyzed reaction. Here, we developed a system that allows for the observation of intersubunit conformation of eukaryotic ribosomes at the single-molecule level. We use it to follow translation initiation and subsequent translocation of the cricket paralysis virus IRES (CrPV IRES). We observed that pre-translocation 80S-IRES ribosomes spontaneously exchanged between non-rotated and semi-rotated conformations but predominantly occupied a semi-rotated conformation. In the presence of eEF2, ribosomes underwent forward and reverse translocation. Both reactions were eEF2 concentration dependent, indicating that eEF2 promoted both forward and reverse translocation. The antifungal sordarin, stabilizes eEF2 on the ribosome after GTP hydrolysis in an extended conformation. 80S-CrPV IRES-eEF2-sordarin complexes underwent multiple rounds of forward and reverse translocations per eEF2 binding event. In the presence of sordarin, GTP hydrolysis or phosphate release were not required for IRES translocation. Together, these results suggest that in the presence of sordarin, eEF2 promotes the mid and late stages of CrPV IRES translocation by unlocking ribosomal movements, with mid and late stages of translocation being thermally driven.

biochemistry↗

Serological screening in wild ruminants in Germany, 2021/22: No evidence of SARS-CoV-2, bluetongue virus or pestivirus spread but high seroprevalences against Schmallenberg virus

Wildlife animals may be susceptible for multiple infectious agents of public health or veterinary relevance, thereby potentially forming a reservoir that bears the constant risk of re-introduction into the human or livestock population. Here, we serologically investigated 493 wild ruminant samples collected in the 2021/22 hunting season in Germany for the presence of antibodies against the severe acute respiratory coronavirus 2 (SARS-CoV-2) and four viruses pathogenic for domestic ruminants, namely the orthobunyavirus Schmallenberg virus (SBV), the reovirus bluetongue virus (BTV) and ruminant pestiviruses like bovine viral diarrhoea virus or border disease virus. The animal species comprised fallow deer, red deer, roe deer, mouflon and wisent. For coronavirus serology, additional 307 fallow, roe and red deer samples collected between 2017 and 2020 at three military training areas were included. While antibodies against SBV could be detected in about 13.6% of the samples collected in 2021/22, only one fallow deer of unknown age tested positive for anti-BTV antibodies and all samples reacted negative for antibodies against ruminant pestiviruses. In an ELISA based on the receptor-binding domain (RBD) of SARS-CoV-2, 25 out of 493 (5.1%) samples collected in autumn and winter 2021/22 scored positive. This sero-reactivity could not be confirmed by the highly specific virus neutralization test, occurred also in 2017, 2018 and 2019, i.e. prior to the human SARS-CoV-2 pandemic, and was likewise observed against the RBD of the related SARS-CoV-1. Therefore, the SARS-CoV-2-seroreactivity was most likely induced by another, hitherto unknown deer virus belonging to the subgenus Sarbecovirus of betacoronaviruses.

microbiology↗

Scent dog identification of SARS-CoV-2 infections, similar across different body fluids

BackgroundThe main strategy to contain the current SARS-CoV-2 pandemic remains to implement a comprehensive testing, tracing and quarantining strategy until vaccination of the population is adequate. MethodsTen dogs were trained to detect SARS-CoV-2 infections in beta-propiolactone inactivated saliva samples. The subsequent cognitive transfer performance for the recognition of non-inactivated samples were tested on saliva, urine, and sweat in a randomised, double-blind controlled study. ResultsDogs were tested on a total of 5242 randomised sample presentations. Dogs detected non-inactivated saliva samples with a diagnostic sensitivity of 84% and specificity of 95%. In a subsequent experiment to compare the scent recognition between the three non-inactivated body fluids, diagnostic sensitivity and specificity were 95% and 98% for urine, 91% and 94% for sweat, 82%, and 96% for saliva respectively. ConclusionsThe scent cognitive transfer performance between inactivated and non-inactivated samples as well as between different sample materials indicates that global, specific SARS-CoV-2-associated volatile compounds are released across different body secretions, independently from the patients symptoms. FundingThe project was funded as a special research project of the German Armed Forces. The funding source DZIF-Fasttrack 1.921 provided us with means for biosampling.

animal behavior and cognition↗

Partial spontaneous intersubunit rotations in actively translating ribosomes

The ribosome is a molecular machine that adopts at least two global states during translation. Two main steps of translation, peptidyl transfer and translocation, are accompanied by counterclockwise and clockwise rotations of the two ribosomal subunits. However, when and why the ribosome alternates between these states remains unclear, with two well supported but conflicting hypotheses. Ribosomes may undergo a single cycle of forward and backward rotations per codon read. Alternatively, in addition to rotations caused by peptidyl transfer and translocation, ribosomes may undergo multiple full spontaneous rotations, with these rotations playing a critical role in elongation and specifically in translocation mechanism. We applied high-speed single-molecule TIRF microscopy to follow translation in real-time. Actively translating ribosomes undergo partial spontaneous rotations between three different rotational states. Spontaneous rotations are restricted prior to A-site tRNA decoding. Peptidyl transfer unlocks spontaneous rotations. Consequently, translocation proceeds via a novel rotational state induced by EF-G. Our results bridge both models and provide a coherent view of ribosome dynamics during translation.

biochemistry↗