Unraveling Liquid-Liquid Phase Separation (LLPS) in Viral Infections to Understand and Treat Viral Diseases.

In the field of virology, liquid-liquid phase separation (LLPS) has emerged as a pivotal mechanism enabling the compartmentalization required for specific steps of the viral replication cycle [...

Per Aspera ad Chaos: Vladimir Uversky's Odyssey through the Strange World of Intrinsically Disordered Proteins.

Until the late 1990s, we believed that protein function required a unique, well-defined 3D structure encrypted in the amino acid sequence [...

: Intrinsic Disorder in Cellular Proteins Recruited to Viral Infection-Related Biocondensates.

Liquid-liquid phase separation (LLPS) is responsible for the formation of so-called membrane-less organelles (MLOs) that are essential for the spatio-temporal organization of the cell. Intrinsically disordered proteins (IDPs) or regions (IDRs), either alone or in conjunction with nucleic acids, are involved in the formation of these intracellular condensates. Notably, viruses exploit LLPS at their own benefit to form viral replication compartments.

Activity and Crystal Structure of the Adherent-Invasive Tle3/Tli3 T6SS Effector/Immunity Complex Determined Using an AlphaFold2 Predicted Model.

The type VI secretion system (T6SS) delivers enzymatic effectors into target cells to destroy them. Cells of the same strain protect themselves against effectors with immunity proteins that specifically inhibit effectors. Here, we report the identification and characterization of a Tle3 phospholipase effector and its cognate immunity protein Tli3-an outer membrane lipoprotein from adherent-invasive (AIEC).

Oral supplementation with selected Lactobacillus acidophilus triggers IL-17-dependent innate defense response, activation of innate lymphoid cells type 3 and improves colitis.

Live biotherapeutic products constitute an emerging therapeutic approach to prevent or treat inflammatory bowel diseases. Lactobacillus acidophilus is a constituent of the human microbiota with probiotic potential, that is illustrated by improvement of intestinal inflammation and antimicrobial activity against several pathogens. In this study, we evaluated the immunomodulatory properties of the L.

Autistic-like behavioral effects of prenatal stress in juvenile Fmr1 mice: the relevance of sex differences and gene-environment interactions.

Fragile X Syndrome (FXS) is the most common heritable form of mental retardation and monogenic cause of autism spectrum disorder (ASD). FXS is due to a mutation in the X-linked FMR1 gene and is characterized by motor, cognitive and social alterations, mostly overlapping with ASD behavioral phenotypes. The severity of these symptoms and their timing may be exacerbated and/or advanced by environmental adversity interacting with the genetic mutation.

The Challenge of Converting "Failed Spinal Cord Stimulation Syndrome" Back to Clinical Success, Using SCS Reprogramming as Salvage Therapy, through Neurostimulation Adapters Combined with 3D-Computerized Pain Mapping Assessment: A Real Life Retrospective Study.

While paresthesia-based Spinal Cord Stimulation (SCS) has been proven effective as treatment for chronic neuropathic pain, its initial benefits may lead to the development of "Failed SCS Syndrome' (FSCSS) defined as decrease over time related to Loss of Efficacy (LoE) with or without Loss of Coverage (LoC). Development of technologies associating new paresthesia-free stimulation waveforms and implanted pulse generator adapters provide opportunities to manage patients with LoE. The main goal of our study was to investigate salvage procedures, through neurostimulation adapters, in patients already implanted with SCS and experiencing LoE.

Datasets for calcium dynamics comparison between the whole-cell and a β-escin based perforated patch configuration in brain slices from adult mice.

Multiple processes shape calcium signals in neurons. The spatial and temporal dynamics of these signals are determined by various cellular parameters, including the calcium influx, calcium buffering, and calcium extrusion. The different Ca handling properties can be estimated using the 'added buffer approach' [1], which is based on a single compartment model of Ca buffering.

A simple method for getting standard error on the ratiometric calcium estimator.

The ratiometric fluorescent calcium indicator Fura-2 plays a fundamental role in the investigation of cellular calcium dynamics. Despite of its widespread use in the last 30 years, only one publication (Joucla et al., 2010)) proposed a way of obtaining confidence intervals on fitted calcium dynamic model parameters from single 'calcium transients'.

Plekhh1, a partner of myosin 1 and an effector of EphB2, controls the cortical actin network during cell repulsion.

EphB2-ephrinB signalling, which plays a major role in cell segregation during embryonic development and tissue homeostasis, induces an important reorganization of the cortical actin network. We have previously reported that myosin 1b contributes to reorganization of the cortical actin network upon EphB2 signalling. In this report, we identify Plekhh1 as a new partner of members of the myosin 1 family and EphB2 receptors.

Machine Learning Algorithms Provide Greater Prediction of Response to SCS Than Lead Screening Trial: A Predictive AI-Based Multicenter Study.

Persistent pain after spinal surgery can be successfully addressed by spinal cord stimulation (SCS). International guidelines strongly recommend that a lead trial be performed before any permanent implantation. Recent clinical data highlight some major limitations of this approach.

Following in Jakobson and Lévi-Strauss' footsteps: A neurocognitive poetics investigation of eye movements during the reading of Baudelaire's 'Les Chats'.

Following Jakobson and Levi-Strauss [1] famous analysis of Baudelaire's poem ', in the present study we investigated the reading of French poetry from a Neurocognitive Poetics perspective. Our study is exploratory and a first attempt in French, most previous work having been done in either German or English (e.g.

Letter and word identification in the fovea and parafovea.

We investigated the extent to which accuracy in word identification in foveal and parafoveal vision is determined by variations in the visibility of the component letters of words. To do so we measured word identification accuracy in displays of three three-letter words, one on fixation and the others to the left and right of the central word. We also measured accuracy in identifying the component letters of these words when presented at the same location in a context of three three-letter nonword sequences.

Spin-resolved atomic orbital model refinement for combined charge and spin density analysis: application to the YTiO perovskite.

A new crystallographic method is proposed in order to refine a spin-resolved atomic orbital model against X-ray and polarized neutron diffraction data. This atomic orbital model is applied to the YTiO perovskite crystal, where orbital ordering has previously been observed by several techniques: X-ray diffraction, polarized neutron diffraction and nuclear magnetic resonance. This method gives the radial extension, orientation and population of outer atomic orbitals for each atom.

Observation of arenavirus nucleoprotein heptamer assembly.

Arenaviruses are enveloped viruses containing a segmented, negative, and ambisense single-stranded RNA genome wrapped with a nucleoprotein (NP). The NP is the most abundant viral protein in infected cells and plays a critical role in both replication/transcription and virion assembly. The NP associates with RNA to form a ribonucleoprotein (RNP) complex, and this implies self-assembly while the exact structure of this polymer is not yet known.

A small-molecule P2RX7 activator promotes anti-tumor immune responses and sensitizes lung tumor to immunotherapy.

Only a subpopulation of non-small cell lung cancer (NSCLC) patients responds to immunotherapies, highlighting the urgent need to develop therapeutic strategies to improve patient outcome. We develop a chemical positive modulator (HEI3090) of the purinergic P2RX7 receptor that potentiates αPD-1 treatment to effectively control the growth of lung tumors in transplantable and oncogene-induced mouse models and triggers long lasting antitumor immune responses. Mechanistically, the molecule stimulates dendritic P2RX7-expressing cells to generate IL-18 which leads to the production of IFN-γ by Natural Killer and CD4 T cells within tumors.

Liquid-Liquid Phase Separation by Intrinsically Disordered Protein Regions of Viruses: Roles in Viral Life Cycle and Control of Virus-Host Interactions.

Intrinsically disordered proteins (IDPs) are unable to adopt a unique 3D structure under physiological conditions and thus exist as highly dynamic conformational ensembles. IDPs are ubiquitous and widely spread in the protein realm. In the last decade, compelling experimental evidence has been gathered, pointing to the ability of IDPs and intrinsically disordered regions (IDRs) to undergo liquid-liquid phase separation (LLPS), a phenomenon driving the formation of membrane-less organelles (MLOs).

Ensemble description of the intrinsically disordered N-terminal domain of the Nipah virus P/V protein from combined NMR and SAXS.

Using SAXS and NMR spectroscopy, we herein provide a high-resolution description of the intrinsically disordered N-terminal domain (PNT, aa 1-406) shared by the Nipah virus (NiV) phosphoprotein (P) and V protein, two key players in viral genome replication and in evasion of the host innate immune response, respectively. The use of multidimensional NMR spectroscopy allowed us to assign as much as 91% of the residues of this intrinsically disordered domain whose size constitutes a technical challenge for NMR studies. Chemical shifts and nuclear relaxation measurements provide the picture of a highly flexible protein.

Fundamental Difficulties Prevent the Reconstruction of the Deep Phylogeny of Viruses.

The extension of virology beyond its traditional medical, veterinary, or agricultural applications, now called environmental virology, has shown that viruses are both the most numerous and diverse biological entities on Earth. In particular, virus isolations from unicellular eukaryotic hosts (heterotrophic and photosynthetic protozoans) revealed numerous viral types previously unexpected in terms of virion structure, gene content, or mode of replication. Complemented by large-scale metagenomic analyses, these discoveries have rekindled interest in the enigma of the origin of viruses, for which a description encompassing all their diversity remains not available.