Entropy Production of Run-and-Tumble Particles.

We analyze the entropy production in run-and-tumble models. After presenting the general formalism in the framework of the Fokker-Planck equations in one space dimension, we derive some known exact results in simple physical situations (free run-and-tumble particles and harmonic confinement). We then extend the calculation to the case of anisotropic motion (different speeds and tumbling rates for right- and left-oriented particles), obtaining exact expressions of the entropy production rate. We conclude by discussing the general case of heterogeneous run-and-tumble motion described by space-dependent parameters and extending the analysis to the case of d-dimensional motions.

Trehalose counteracts the dissociation of tetrameric rabbit lactate dehydrogenase induced by acidic pH conditions.

The lactate dehydrogenase from rabbit skeletal muscle (rbLDH) is a tetrameric enzyme, known to undergo dissociation when exposed to acidic pH conditions. Moreover, it should be mentioned that this dissociation translates into a pronounced loss of enzyme activity. Notably, among the compounds able to stabilize proteins and enzymes, the disaccharide trehalose represents an outperformer. In particular, trehalose was shown to efficiently counteract quite a number of physical and chemical agents inducing protein denaturation. However, no information is available on the effect, if any, exerted by trehalose against the dissociation of protein oligomers. Accordingly, we thought it of interest to investigate whether this disaccharide is competent in preventing the dissociation of rbLDH induced by acidic pH conditions. Further, we compared the action of trehalose with the effects triggered by maltose and cellobiose. Surprisingly, both these disaccharides enhanced the dissociation of rbLDH, with maltose being responsible for a major effect when compared to cellobiose. On the contrary, trehalose was effective in preventing enzyme dissociation, as revealed by activity assays and by Dynamic Light Scattering (DLS) experiments. Moreover, we detected a significant decrease of both K0.5 and Vmax when the rbLDH activity was tested (at pH 7.5 and 6.5) as a function of pyruvate concentration in the presence of trehalose. Further, we found that trehalose induces a remarkable increase of Vmax when the enzyme is exposed to pH 5. Overall, our observations suggest that trehalose triggers conformational rearrangements of tetrameric rbLDH mirrored by resistance to dissociation and peculiar catalytic features.

Entropons as collective excitations in active solids.

The vibrational dynamics of solids is described by phonons constituting basic collective excitations in equilibrium crystals. Here, we consider a non-equilibrium active solid, formed by self-propelled particles, which bring the system into a non-equilibrium steady-state. We identify novel vibrational collective excitations of non-equilibrium (active) origin, which coexist with phonons and dominate over them when the system is far from equilibrium. These vibrational excitations are interpreted in the framework of non-equilibrium physics, in particular, stochastic thermodynamics. We call them "entropons" because they are the modes of spectral entropy production (at a given frequency and wave vector). The existence of entropons could be verified in future experiments on dense self-propelled colloidal Janus particles and granular active matter, as well as in living systems, such as dense cell monolayers.

Production in Escherichia coli of recombinant COVID-19 spike protein fragments fused to CRM197.

During 2020, the COVID-19 pandemic affected almost 108 individuals. Quite a number of vaccines against COVID-19 were therefore developed, and a few recently received authorization for emergency use. Overall, these vaccines target specific viral proteins by antibodies whose synthesis is directly elicited or indirectly triggered by nucleic acids coding for the desired targets. Among these targets, the receptor binding domain (RBD) of COVID-19 spike protein (SP) does frequently occur in the repertoire of candidate vaccines. However, the immunogenicity of RBD per se is limited by its low molecular mass, and by a structural rearrangement of full-length SP accompanied by the detachment of RBD. Here we show that the RBD of COVID-19 SP can be conveniently produced in Escherichia coli when fused to a fragment of CRM197, a variant of diphtheria toxin currently used for a number of conjugated vaccines. In particular, we show that the CRM197-RBD chimera solubilized from inclusion bodies can be refolded and purified to a state featuring the 5 native disulphide bonds of the parental proteins, the competence in binding angiotensin-converting enzyme 2, and a satisfactory stability at room temperature. Accordingly, our observations provide compulsory information for the development of a candidate vaccine directed against COVID-19.

Diffusion properties of self-propelled particles in cellular flows.

We study the dynamics of a self-propelled particle advected by a steady laminar flow. The persistent motion of the self-propelled particle is described by an active Ornstein-Uhlenbeck process. We focus on the diffusivity properties of the particle as a function of persistence time and free-diffusion coefficient, revealing non-monotonic behaviors, with the occurrence of a minimum and a steep growth in the regime of large persistence time. In the latter limit, we obtain an analytical prediction for the scaling of the diffusion coefficient with the parameters of the active force. Our study sheds light on the effect of a flow-field on the diffusion of active particles, such as living microorganisms and motile phytoplankton in fluids.

Active escape dynamics: The effect of persistence on barrier crossing.

We study a system of non-interacting active particles, propelled by colored noises, characterized by an activity time τ, and confined by a double-well potential. A straightforward application of this system is the problem of barrier crossing of active particles, which has been studied only in the limit of small activity. When τ is sufficiently large, equilibrium-like approximations break down in the barrier crossing region. In the model under investigation, it emerges as a sort of "negative temperature" region, and numerical simulations confirm the presence of non-convex local velocity distributions. We propose, in the limit of large τ, approximate equations for the typical trajectories which successfully predict many aspects of the numerical results. The local breakdown of detailed balance and its relation with a recent definition of non-equilibrium heat exchange is also discussed.

Development and characterization of an inducible mouse model for glycogen storage disease type Ib.

BACKGROUND AND AIMS: Glycogen storage disease type Ib (GSD1b) is a rare metabolic and immune disorder caused by a deficiency in the glucose-6-phosphate transporter (G6PT) and characterized by impaired glucose homeostasis, myeloid dysfunction, and long-term risk of hepatocellular adenomas. Despite maximal therapy, based on a strict diet and on granulocyte colony-stimulating factor treatment, long-term severe complications still develop. Understanding the pathophysiology of GSD1b is a prerequisite to develop new therapeutic strategies and depends on the availability of animal models. The G6PT-KO mouse mimics the human disease but is very fragile and rarely survives weaning. We generated a conditional G6PT-deficient mouse as an alternative model for studying the long-term pathophysiology of the disease. We utilized this conditional mouse to develop an inducible G6PT-KO model to allow temporally regulated G6PT deletion by the administration of tamoxifen (TM). METHODS: We generated a conditional G6PT-deficient mouse utilizing the CRElox strategy. Histology, histochemistry, and phenotype analyses were performed at different times after TM-induced G6PT inactivation. Neutrophils and monocytes were isolated and analyzed for functional activity with standard techniques. RESULTS: The G6PT-inducible KO mice display the expected disturbances of G6P metabolism and myeloid dysfunctions of the human disorder, even though with a milder intensity. CONCLUSIONS: TM-induced inactivation of G6PT in these mice leads to a phenotype which mimics that of human GSD1b patients. The conditional mice we have generated represent an excellent tool to study the tissue-specific role of the G6PT gene and the mechanism of long-term complications in GSD1b.

Thermodynamics and Statistical Mechanics of Small Systems.

A challenging frontier in modern statistical physics is concerned with systems with a small number of degrees of freedom, far from the thermodynamic limit.[...].

The Role of Data in Model Building and Prediction: A Survey Through Examples.

The goal of Science is to understand phenomena and systems in order to predict their development and gain control over them. In the scientific process of knowledge elaboration, a crucial role is played by models which, in the language of quantitative sciences, mean abstract mathematical or algorithmical representations. This short review discusses a few key examples from Physics, taken from dynamical systems theory, biophysics, and statistical mechanics, representing three paradigmatic procedures to build models and predictions from available data. In the case of dynamical systems we show how predictions can be obtained in a virtually model-free framework using the methods of analogues, and we briefly discuss other approaches based on machine learning methods. In cases where the complexity of systems is challenging, like in biophysics, we stress the necessity to include part of the empirical knowledge in the models to gain the minimal amount of realism. Finally, we consider many body systems where many (temporal or spatial) scales are at play-and show how to derive from data a dimensional reduction in terms of a Langevin dynamics for their slow components.

Histone chaperone spt16 promotes redeposition of the original h3-h4 histones evicted by elongating RNA polymerase.

Nucleosomes are surprisingly dynamic structures in vivo, showing transcription-independent exchange of histones H2A-H2B genome-wide and exchange of H3-H4 mainly within the promoters of transcribed genes. In addition, nucleosomes are disrupted in front of and reassembled behind the elongating RNA polymerase. Here we show that inactivation of histone chaperone Spt16 in yeast results in rapid loss of H2B and H3 from transcribed genes but also from inactive genes. In all cases, histone loss is blocked by a transcription inhibitor, indicating a transcription-dependent event. Thus, nucleosomes are efficiently evicted by the polymerase but do not reform in the absence of Spt16. Yet exchange of nucleosomal H2B with free histones occurs normally, and, unexpectedly, incorporation of new H3 increases at all loci tested. This points to Spt16 restoring normal nucleosome structure by redepositing the displaced H3-H4 histones, thereby preventing incorporation of new histones and perhaps changes in histone modification patterns associated with ongoing transcription.

Systemic alkalinisation delays prostate cancer cell progression in TRAMP mice.

The microenvironment of solid tumours is extremely acidic and this condition arises since the precancerous stage. This acidic milieu could therefore provide a useful target for both prophylactic and therapeutic approaches. In TRAMP transgenic mice, an in vivo model of prostate adenocarcinoma (AC), oral administration of alkaline water was devoid of unwanted side effects, and when started from an early age was as effective as NaHCO3 in significantly delaying tumour progression, while when started when prostate tumours were already present, a nonstatistically significant trend in the same direction was detected. These findings indicate that the use of alkalinizing drugs should be considered for chemoprevention and, in association with standard chemotherapy, for treatment of human prostate AC.

Thermal Convection in Granular Gases with Dissipative Lateral Walls.

We consider a granular gas under the action of gravity, fluidized by a vibrating base. We show that a horizontal temperature gradient, here induced by limiting dissipative lateral walls (DLW), leads always to a granular thermal convection (DLW TC) that is essentially different from ordinary bulk-buoyancy-driven convection (BBD TC). In an experiment where BBD TC is inhibited, by reducing gravity with an inclined plane, we always observe a DLW TC cell next to each lateral wall. Such a cell squeezes towards the nearest wall as the gravity and/or the number of grains increase. Molecular dynamics simulations reproduce the experimental results and indicate that at large gravity or number of grains the DLW TC is barely detectable.

Transgenic mice overexpressing arginase 1 in monocytic cell lineage are affected by lympho-myeloproliferative disorders and disseminated intravascular coagulation.

Arginase (ARG) is a metabolic enzyme present in two isoforms that hydrolyze l-arginine to urea and ornithine. In humans, ARG isoform 1 is also expressed in cells of the myeloid lineage. ARG activity promotes tumour growth and inhibits T lymphocyte activation. However, the two ARG transgenic mouse lines produced so far failed to show such effects. We have generated, in two different genetic backgrounds, transgenic mice constitutively expressing ARG1 under the control of the CD68 promoter in macrophages and monocytes. Both heterozygous and homozygous transgenic mice showed a relevant increase in mortality at early age, compared with wild-type siblings (67/267 and 48/181 versus 8/149, respectively, both P < 0.005). This increase was due to high incidence of haematologic malignancies, in particular myeloid leukaemia, myeloid dysplasia, lymphomas and disseminated intravascular coagulation (DIC), diseases that were absent in wild-type mice. Atrophy of lymphoid organs due to reduction in T-cell compartment was also detected. Our results indicate that ARG activity may participate in the pathogenesis of lymphoproliferative and myeloproliferative disorders, suggest the involvement of alterations of L-arginine metabolism in the onset of DIC and confirm a role for the enzyme in regulating T-cell homeostasis.

Cages and anomalous diffusion in vibrated dense granular media.

A vertically shaken granular medium hosts a blade rotating around a fixed vertical axis, which acts as a mesorheological probe. At high densities, independently of the shaking intensity, the blade's dynamics shows strong caging effects, marked by transient subdiffusion and a maximum in the velocity power density spectrum, at a resonant frequency ~10 Hz. Interpreting the data through a diffusing harmonic cage model allows us to retrieve the elastic constant of the granular medium and its collective diffusion coefficient. For high frequencies f, a tail ~1/f in the velocity power density spectrum reveals nontrivial correlations in the intracage microdynamics. At very long times (larger than 10 s), a superdiffusive behavior emerges, ballistic in the most extreme cases. Consistently, the distribution of slow velocity inversion times τ displays a power-law decay, likely due to persistent collective fluctuations of the host medium.

An itinerant oscillator model with cage inertia for mesorheological granular experiments.

Recent experiments with a rotating probe immersed in weakly fluidized granular materials show a complex behavior on a wide range of time scales. Viscous-like relaxation at high frequency is accompanied by an almost harmonic dynamical trapping at intermediate times, with possibly anomalous long time behavior in the form of super-diffusion. Inspired by the itinerant oscillator model for diffusion in molecular liquids, and other models with coupled thermostats acting at different time scales, here we discuss a new model able to account for fast viscous relaxation, dynamical trapping, and super-diffusion at long times. The main difference with respect to liquids is a non-negligible cage inertia for the surrounding (granular) fluid, which allows it to sustain a slow but persistent motion for long times. The computed velocity power density spectra and mean-squared displacement qualitatively reproduce the experimental findings. We also discuss the linear response to external perturbations and the tail of the distribution of persistency time, which is associated with superdiffusion, and whose cut-off time is determined by cage inertia.

Brownian ratchet in a thermal bath driven by Coulomb friction.

The rectification of unbiased fluctuations, also known as the ratchet effect, is normally obtained under statistical nonequilibrium conditions. Here we propose a new ratchet mechanism where a thermal bath solicits the random rotation of an asymmetric wheel, which is also subject to Coulomb friction due to solid-on-solid contacts. Numerical simulations and analytical calculations demonstrate a net drift induced by friction. If the thermal bath is replaced by a granular gas, the well-known granular ratchet effect also intervenes, becoming dominant at high collision rates. For our chosen wheel shape the granular effect acts in the opposite direction with respect to the friction-induced torque, resulting in the inversion of the ratchet direction as the collision rate increases. We have realized a new granular ratchet experiment where both these ratchet effects are observed, as well as the predicted inversion at their crossover. Our discovery paves the way to the realization of micro and submicrometer Brownian motors in an equilibrium fluid, based purely upon nanofriction.

Modeling the emergence of universality in color naming patterns.

The empirical evidence that human color categorization exhibits some universal patterns beyond superficial discrepancies across different cultures is a major breakthrough in cognitive science. As observed in the World Color Survey (WCS), indeed, any two groups of individuals develop quite different categorization patterns, but some universal properties can be identified by a statistical analysis over a large number of populations. Here, we reproduce the WCS in a numerical model in which different populations develop independently their own categorization systems by playing elementary language games. We find that a simple perceptual constraint shared by all humans, namely the human Just Noticeable Difference (JND), is sufficient to trigger the emergence of universal patterns that unconstrained cultural interaction fails to produce. We test the results of our experiment against real data by performing the same statistical analysis proposed to quantify the universal tendencies shown in the WCS [Kay P & Regier T. (2003) Proc. Natl. Acad. Sci. USA 100: 9085-9089], and obtain an excellent quantitative agreement. This work confirms that synthetic modeling has nowadays reached the maturity to contribute significantly to the ongoing debate in cognitive science.

A microfluidic method for passive trapping of sperms in microstructures.

Sperm motility is a prerequisite for male fertility. Enhancing the concentration of motile sperms in assisted reproductive technologies - for human and animal reproduction - is typically achieved through aggressive methods such as centrifugation. Here, we propose a passive technique for the amplification of motile sperm concentration, with no externally imposed forces or flows. The technique is based on the disparity between probability rates, for motile cells, of entering and escaping from complex structures. The effectiveness of the technique is demonstrated in microfluidic experiments with microstructured devices, comparing the trapping power in different geometries. In these micro-traps, we observe an enhancement of cells' concentration close to 10, with a contrast between motile and non-motile cells increased by a similar factor. Simulations of suitable interacting model sperms in realistic geometries reproduce quantitatively the experimental results, extend the range of observations and highlight the components that are key to the optimal trap design.

Shaken granular lasers.

Granular materials have been studied for decades, driven by industrial and technological applications. These very simple systems, composed of agglomerations of mesoscopic particles, are characterized, in specific regimes, by a large number of metastable states and an extreme sensitivity (e.g., in sound transmission) to the arrangement of grains; they are not substantially affected by thermal phenomena, but can be controlled by mechanical solicitations. Laser emission from shaken granular matter is so far unexplored. Here we provide experimental evidence that laser emission can be affected and controlled by the status of the motion of the granular material; we also find that competitive random lasers can be observed. We hence demonstrate the potentialities of gravity-affected moving disordered materials for optical applications, and open the road to a variety of novel interdisciplinary investigations, involving modern statistical mechanics and disordered photonics.