Biology subjects

Torrent, J.

Publications and source records attributed to Torrent, J..

3 recordsLinked to original sources

bioRxiv2026

Non-fibrillar prion protein oligomers transmit structural information during early assembly

The prion paradigm is founded on the transmission of structural information from aggregated assemblies to soluble protein substrates, a process classically attributed to fibril-end-mediated templating. Whether non-fibrillar assemblies or transient oligomeric states can also participate in folding information transfer remains unclear. Here, using recombinant prion protein (PrP), rational mutagenesis, hetero-oligomerization assays, arrested reaction conditions, and single-particle atomic force microscopy coupled to infrared nano-spectroscopy (AFM-IR), we examine the earliest stages of PrP assembly from the perspective of folding information transmission. We show that polymerization-defective PrP variants can be incorporated into oligomeric assemblies through structural complementation, in which folding information supplied by wild-type PrP restores their assembly competence. Under arrested reaction conditions, transient polymerization-competent conformers further contribute to folding information transfer at subcritical concentrations. Domain-resolved analyses reveal a modular oligomeric architecture in which a {beta}-sheet-rich B domain constitutes the primary scaffold for folding information transfer. Preformed O1 oligomers then act as autonomous conformational templates that promote mutant incorporation and undergo hierarchical condensation through accretion of a structurally distinct E domain. Together, these findings demonstrate that non-fibrillar PrP oligomers and transient assembly intermediates can store and transmit folding information and may function as oligomer-based secondary nucleation platforms, expanding the conceptual framework of prion assembly beyond fibril-end elongation alone.

biochemistry↗

bioRxiv2025

From Stability to Complexity: A Systematic Review of Long-term Divergence Exponents in Nonlinear Gait Analysis

Divergence exponents (DEs), also termed maximum Lyapunov exponents, computed from stride-to-stride fluctuations have traditionally been interpreted as measures of gait stability. We evaluated empirical evidence for reinterpreting long-term DE as a measure of gait complexity and automaticity. We systematically searched Web of Science databases through January 2026 for studies applying Rosensteins algorithm to human gait, extracting experimental conditions, and participant characteristics from each study. Study quality was assessed across analytical rigor, outcome reporting, and sample size adequacy. We conducted a meta-analysis examining correlations between long-term DE and detrended fluctuation analysis (DFA) scaling exponents, and synthesized evidence from perturbation, cueing, and between-subject studies. Sixty-two studies published between 2000 and 2026 met inclusion criteria, with 44% achieving high overall quality scores. Meta-analysis from six datasets (209 participants) revealed a positive correlation between long-term DE and DFA scaling exponents (r=0.64, 95% CI 0.34 to 0.82; I{superscript 2}=82%). Perturbation studies consistently increased short-term DE while decreasing long-term DE by up to 51%. Auditory and visual cueing reduced long-term DE (up to -86%) while minimally affecting short-term DE. Between-subject comparisons revealed heterogeneous patterns, with clinical populations exhibiting pathology-dependent long-term DE changes. Converging meta-analytic and experimental evidence supports reinterpreting long-term DE as the Attractor Complexity Index--a measure of gait complexity and automaticity rather than stability. Reduced long-term DE during controlled gait conditions reflects suppression of low-frequency variability, which constrains phase space exploration and accelerates divergence curve saturation. The measures sensitivity to prefrontal cortex engagement and attentional demands indicates that long-term DE reflects gait automaticity: lower values mark a shift from subcortical to executive control. This attention-dependent reorganization explains patterns observed in aging, clinical populations, and experimental perturbations, and establishes long-term DE as a complementary biomarker for motor-cognitive aspects of gait control, with implications for fall risk assessment, disease monitoring, and rehabilitation evaluation.

neuroscience↗

bioRxiv2023

Pathogenicity, strain properties and interspecies transmission capacity of pure recombinant prion protein assemblies

The pathogenicity of fibrillar assemblies derived from bacterially expressed recombinant prion protein (rPrP) has been key to the demonstration that prions are infectious proteins responsible for human and animal transmissible spongiform encephalopathies. Yet, their use in identifying which structural PrP features are important for prion biology, including strain properties and capacity to transmit between species, has been hampered by their limited transmissibility de novo. We report the generation of prions with distinct biological characteristics from rPrP assemblies differing only in their primary structure (hamster, mouse and human amino acid sequence). These rPrP assemblies were transmissible to transgenic mice expressing hamster PrP, causing a clinical disease at full attack rate, brain deposition of pathological prion protein PrPSc and spongiform degeneration. Their adaptation process on serial sub-passaging seemed to depend, as for genuine prions, on the presence of a species/transmission barrier, due notably to PrP sequence mismatch. Remarkably, one of the strains obtained is an unprecedented shortened prion, lacking the 90-140 amino-acid region which is believed to be key to infectivity and structural stability of disease-associated PrP assemblies. Finally, we provide evidence that rPrP prionogenicity lies in the structural organization and/or heterogeneity of the rPrP assemblies. These preparations of rPrP offer unprecedented opportunities for meaningful studies correlating the dynamicity and structures of PrPSc assemblies to prion pathobiology. Author summaryPrions are infectious proteins, causing rapidly progressive neurodegenerative diseases in animals and humans. They are formed from the assisted-refolding and aggregation of the host-encoded prion protein (PrP). During the propagation of the disease, pathological PrP forces normal PrP to adopt its own conformation by a self-templating process. In infected host, different pathological structures of PrP or strains are found, causing diseases with specific biological phenotypes. Prions can also transmit between species. This capacity is limited by a species barrier, which critically depends on the infecting strain and PrP primary structure. How strain biological information is encoded in PrP structural fold remains unknown. We describe here the generation of different bona fide prion strains with markedly distinct adaptation capacities by transmission of refolded assemblies derived from bacterially-derived recombinant PrP (rPrP) of different species. We provide evidence that pathogenicity lies in the structural organization and/or heterogeneity of rPrP assemblies. Pathological PrP from one of the generated strains exhibited unique molecular features, including absence of domains that are thought to be key to prion infectivity, according to most recent ultrastructural studies. Our findings provide new insights for generating prion infectious material and resolving mechanisms of infectivity acquisition during PrP conversion process.

microbiology↗