Biophysical characterization of high-confidence, small human proteins.

Significant efforts have been made to characterize the biophysical properties of proteins. Small proteins have received less attention because their annotation has historically been less reliable. However, recent improvements in sequencing, proteomics, and bioinformatics techniques have led to the high-confidence annotation of small open reading frames (smORFs) that encode for functional proteins, producing smORF-encoded proteins (SEPs).

Biophysical characterization of high-confidence, small human proteins.

Significant efforts have been made to characterize the biophysical properties of proteins. Small proteins have received less attention because their annotation has historically been less reliable. However, recent improvements in sequencing, proteomics, and bioinformatics techniques have led to the high-confidence annotation of small open reading frames (smORFs) that encode for functional proteins, producing smORF-encoded proteins (SEPs).

Coiled-coil domains are sufficient to drive liquid-liquid phase separation in protein models.

Liquid-liquid phase separation (LLPS) is thought to be a main driving force in the formation of membraneless organelles. Examples of such organelles include the centrosome, central spindle, and stress granules. Recently, it has been shown that coiled-coil (CC) proteins, such as the centrosomal proteins pericentrin, spd-5, and centrosomin, might be capable of LLPS.

Programmable de novo designed coiled coil-mediated phase separation in mammalian cells.

Membraneless liquid compartments based on phase-separating biopolymers have been observed in diverse cell types and attributed to weak multivalent interactions predominantly based on intrinsically disordered domains. The design of liquid-liquid phase separated (LLPS) condensates based on de novo designed tunable modules that interact in a well-understood, controllable manner could improve our understanding of this phenomenon and enable the introduction of new features. Here we report the construction of CC-LLPS in mammalian cells, based on designed coiled-coil (CC) dimer-forming modules, where the stability of CC pairs, their number, linkers, and sequential arrangement govern the transition between diffuse, liquid and immobile condensates and are corroborated by coarse-grained molecular simulations.

ParSe 2.0: A web tool to identify drivers of protein phase separation at the proteome level.

We have developed an algorithm, ParSe, which accurately identifies from the primary sequence those protein regions likely to exhibit physiological phase separation behavior. Originally, ParSe was designed to test the hypothesis that, for flexible proteins, phase separation potential is correlated to hydrodynamic size. While our results were consistent with that idea, we also found that many different descriptors could successfully differentiate between three classes of protein regions: folded, intrinsically disordered, and phase-separating intrinsically disordered.

Coiled-coil domains are sufficient to drive liquid-liquid phase separation of proteins in molecular models.

Liquid-liquid phase separation (LLPS) is thought to be a main driving force in the formation of membraneless organelles. Examples of such organelles include the centrosome, central spindle, and stress granules. Recently, it has been shown that coiled-coil (CC) proteins, such as the centrosomal proteins pericentrin, spd-5, and centrosomin, might be capable of LLPS.

Recommendations for Canada's National Action Plan to End Gender-Based Violence: perspectives from leaders, service providers and survivors in Canada's largest city during the COVID-19 pandemic.

Introduction: The Canadian government has committed to a national action plan (NAP) to address violence against women (VAW). However, a formalized plan for implementation has not been published. Building on existing recommendations and consultations, we conducted the first formal and peer-reviewed qualitative analysis of the perspectives of leaders, service providers and survivors on what should be considered in Canada's NAP on VAW.

Physics of the Nuclear Pore Complex: Theory, Modeling and Experiment.

The hallmark of eukaryotic cells is the nucleus that contains the genome, enclosed by a physical barrier known as the nuclear envelope (NE). On the one hand, this compartmentalization endows the eukaryotic cells with high regulatory complexity and flexibility. On the other hand, it poses a tremendous logistic and energetic problem of transporting millions of molecules per second across the nuclear envelope, to facilitate their biological function in all compartments of the cell.

Beta turn propensity and a model polymer scaling exponent identify intrinsically disordered phase-separating proteins.

The complex cellular milieu can spontaneously demix, or phase separate, in a process controlled in part by intrinsically disordered (ID) proteins. A protein's propensity to phase separate is thought to be driven by a preference for protein-protein over protein-solvent interactions. The hydrodynamic size of monomeric proteins, as quantified by the polymer scaling exponent (v), is driven by a similar balance.

Examining Cultural Structures and Functions in Biology.

Scientific culture and structure organize biological sciences in many ways. We make choices concerning the systems and questions we study. Our research then amplifies these choices into factors that influence the directions of future research by shaping our hypotheses, data analyses, interpretation, publication venues, and dissemination via other methods.

Enhanced diffusion by reversible binding to active polymers.

Cells are known to use reversible binding to active biopolymer networks to allow diffusive transport of particles in an otherwise impenetrable mesh. We here determine the motion of a particle that experiences random forces during binding and unbinding events while being constrained by attached polymers. Using Monte-Carlo simulations and a statistical mechanics model, we find that enhanced diffusion is possible with active polymers.

Moving while you're stuck: a macroscopic demonstration of an active system inspired by binding-mediated transport in biology.

Diffusive motion is typically constrained when particles bind to the medium through which they move. However, when binding is transient and the medium is made of flexible filaments, each association or dissociation event produces a stochastic force that can overcome the medium stickiness and enable motion. This mechanism is amply used by biological systems where the act of balancing binding and displacement robustly achieves key functionalities, including bacterial locomotion or selective active filtering in cells.

C-Terminal Tail Polyglycylation and Polyglutamylation Alter Microtubule Mechanical Properties.

Microtubules are biopolymers that perform diverse cellular functions. Microtubule behavior regulation occurs in part through post-translational modification of both the α- and β-subunits of tubulin. One class of modifications is the heterogeneous addition of glycine and/or glutamate residues to the disordered C-terminal tails (CTTs) of tubulin.

Bound-State Diffusion due to Binding to Flexible Polymers in a Selective Biofilter.

Selective biofilters are used by cells to control the transport of proteins, nucleic acids, and other macromolecules. Biological filters demonstrate both high specificity and rapid motion or high flux of proteins. In contrast, high flux comes at the expense of selectivity in many synthetic filters.

Design principles of selective transport through biopolymer barriers.

In biological systems, polymeric materials block the movement of some macromolecules while allowing the selective passage of others. In some cases, binding enables selective transport, while in others the most inert particles appear to transit most rapidly. To study the general principles of filtering, we develop a model motivated by features of the nuclear pore complex (NPC) which are highly conserved and could potentially be applied to other biological systems.

Preferential Root Tropisms in 2D Wet Granular Media with Structural Inhomogeneities.

We investigate certain aspects of the physical mechanisms of root growth in a granular medium and how these roots adapt to changes in water distribution induced by the presence of structural inhomogeneities in the form of solid intrusions. Physical intrusions such as a square rod added into the 2D granular medium maintain robust capillary action, pumping water from the more saturated areas at the bottom of the cell towards the less saturated areas near the top of the cell while the rest of the medium is slowly devoid of water via evaporation. The intrusion induces "preferential tropism" of roots by first generating a humidity gradient that attracts the root to grow towards it.

Stereological Investigation of the Rat Ventral Thalamic Nuclei Following Developmental Hyperserotonemia.

Elevated blood serotonin in perinatal development is the most consistent neurochemical finding reported in Autism Spectrum Disorder (ASD), and has been implicated in the pathogenesis of the disorder. Accordingly, pre- and postnatal administration of the non-selective serotonin agonist, 5-methoxytryptamine (5-MT), is hypothesized as a model of developmental hyperserotonemia (DHS) to investigate the behavioral and morphological implications in ASD. Our previous study, examining the effects of DHS, found significant neuroanatomical changes in the dendritic architecture and connectivity of neurons in the dentate nucleus of the cerebellum.

Study protocol for targeted interventions to prevent chronic low back pain in high-risk patients: A multi-site pragmatic cluster randomized controlled trial (TARGET Trial).

Background: Low back pain (LBP) is one of the most prevalent and potentially disabling conditions for which people seek health care. Patients, providers, and payers agree that greater effort is needed to prevent acute LBP from transitioning to chronic LBP.

Methods And Study Design: The TARGET (Targeted Interventions to Prevent Chronic Low Back Pain in High-Risk Patients) Trial is a primary care-based, multisite, cluster randomized, pragmatic trial comparing guideline-based care (GBC) to GBC + referral to Psychologically Informed Physical Therapy (PIPT) for patients presenting with acute LBP and identified as high risk for persistent disabling symptoms.

In-Cell NMR within Budding Yeast Reveals Cytoplasmic Masking of Hydrophobic Residues of FG Repeats.

In-cell NMR spectroscopy is a powerful tool to determine the properties of proteins and nucleic acids within living cells. In-cell NMR can give site-specific measurements of interactions, modifications, and dynamics as well as their modulation by the cellular environment. In-cell NMR requires selective incorporation of heavy isotopes into a protein of interest, either through the introduction of exogenously produced protein to a cell's interior or the selective overexpression of a protein.

Effect of geometry on the dewetting of granular chains by evaporation.

Understanding evaporation or drying in granular media still remains complex despite recent advancements. Evaporation depends on liquid transport across a connected film network from the bulk to the surface. In this study, we investigate the stability of film networks as a function of the geometry of granular chains of spherical grains.

Challenging the Hidden Curriculum through Problem Based Learning: A reflection on Curricular Design.

This article was migrated. The article was marked as recommended. Problem-Based Learning pedagogy has been around since the late 1960s.

Experimental investigation of water distribution in a two-phase zone during gravity-dominated evaporation.

We characterize the water repartition within the partially saturated (two-phase) zone (PSZ) during evaporation from mixed wettable porous media by controlling the wettability of glass beads, their sizes, and as well the surrounding relative humidity. Here, capillary numbers are low and under these conditions, the percolating front is stabilized by gravity. Using experimental and numerical analyses, we find that the PSZ saturation decreases with the Bond number, where packing of smaller particles have higher saturation values than packing made of larger particles.

Effects of soft interactions and bound mobility on diffusion in crowded environments: a model of sticky and slippery obstacles.

Crowded environments modify the diffusion of macromolecules, generally slowing their movement and inducing transient anomalous subdiffusion. The presence of obstacles also modifies the kinetics and equilibrium behavior of tracers. While previous theoretical studies of particle diffusion have typically assumed either impenetrable obstacles or binding interactions that immobilize the particle, in many cellular contexts bound particles remain mobile.