Conformations of confined biopolymers

Nanoscale and microscale confinement of biopolymers naturally occurs in cells and has been recently achieved in artificial structures designed for nanotechnological applications. Here, we present an extensive theoretical investigation of the conformations and shape of a biopolymer with varying stiffness confined to a narrow channel. Combining scaling arguments, analytical calculations, and Monte Carlo simulations, we identify various scaling regimes where master curves quantify the functional dependence of the polymer conformations on the chain stiffness and strength of confinement.Comment: 5 pages, 4 figures, minor correction

Fluctuation-Dissipation Theorem for the Microcanonical Ensemble

A derivation of the Fluctuation-Dissipation Theorem for the microcanonical ensemble is presented using linear response theory. The theorem is stated as a relation between the frequency spectra of the symmetric correlation and response functions. When the system is not in the thermodinamic limit, this result can be viewed as an extension of the fluctuation-dissipation relations to a situation where dynamical fluctuations determine the response. Therefore, the relation presented here between equilibrium fluctuations and response can have a very different physical nature from the usual one in the canonical ensemble. These considerations imply that the Fluctuation-Dissipation Theorem is not restricted to the context of thermal equilibrium, where it is usually derived. Dispersion relations and sum rules are also obtained and discussed in the present case. Although analogous to the Kramers-Kronig relations, they are not related to the frequency spectrum but to the energy dependence of the response function.Comment: 15 pages, v3: final version, new text added, new reference

Effects of membrane and biological target on the structural and allosteric properties of recoverin: a computational approach

Recoverin (Rec) is a prototypical calcium sensor protein primarily expressed in the vertebrate retina. The binding of two Ca2+ ions to the functional EF-hand motifs induces the extrusion of a myristoyl group that increases the affinity of Rec for the membrane and leads to the formation of a complex with rhodopsin kinase (GRK1). Here, unbiased all-atom molecular dynamics simulations were performed to monitor the spontaneous insertion of the myristoyl group into a model multicomponent biological membrane for both isolated Rec and for its complex with a peptide from the GRK1 target. It was found that the functional membrane anchoring of the myristoyl group is triggered by persistent electrostatic protein-membrane interactions. In particular, salt bridges between Arg43, Arg46 and polar heads of phosphatidylserine lipids are necessary to enhance the myristoyl hydrophobic packing in the Rec-GRK1 assembly. The long-distance communication between Ca2+-binding EF-hands and residues at the interface with GRK1 is significantly influenced by the presence of the membrane, which leads to dramatic changes in the connectivity of amino acids mediating the highest number of persistent interactions (hubs). In conclusion, specific membrane composition and allosteric interactions are both necessary for the correct assembly and dynamics of functional Rec-GRK1 complex

On the impact of large angle CMB polarization data on cosmological parameters

(abridged) We study the impact of the large-angle CMB polarization datasets publicly released by the WMAP and Planck satellites on the estimation of cosmological parameters of the $\Lambda$CDM model. To complement large-angle polarization, we consider the high-resolution CMB datasets from either WMAP or Planck, as well as CMB lensing as traced by Planck. In the case of WMAP, we compute the large-angle polarization likelihood starting over from low-resolution frequency maps and their covariance matrices, and perform our own foreground mitigation technique, which includes as a possible alternative Planck 353 GHz data to trace polarized dust. We find that the latter choice induces a downward shift in the optical depth $\tau$, of order ~$2\sigma$, robust to the choice of the complementary high-l dataset. When the Planck 353 GHz is consistently used to minimize polarized dust emission, WMAP and Planck 70 GHz large-angle polarization data are in remarkable agreement: by combining them we find $\tau = 0.066 ^{+0.012}_{-0.013}$, again very stable against the particular choice for high-$\ell$ data. We find that the amplitude of primordial fluctuations $A_s$, notoriously degenerate with $\tau$, is the parameter second most affected by the assumptions on polarized dust removal, but the other parameters are also affected, typically between $0.5$ and $1\sigma$. In particular, cleaning dust with \planck's 353 GHz data imposes a $1\sigma$ downward shift in the value of the Hubble constant $H_0$, significantly contributing to the tension reported between CMB based and direct measurements of $H_0$. On the other hand, we find that the appearance of the so-called low $\ell$ anomaly, a well-known tension between the high- and low-resolution CMB anisotropy amplitude, is not significantly affected by the details of large-angle polarization, or by the particular high-$\ell$ dataset employed.Comment: 19 pages, 4 figures, 3 table

Donor-to-recipient gender match in liver transplantation. A systematic review and meta-analysis

AIM To perform a systematic review and meta-analysis on donor-to-recipient gender mismatch as a risk factor for post-transplant graft loss. METHODS A systematic literature search was performed using PubMed, Cochrane Library database and EMBASE. The primary outcome was graft loss after liver transplantation. Odds ratios and 95% confidence intervals were calculated to compare the pooled data between groups with different donor-to-recipient gender matches. Three analyses were done considering (1) gender mismatches (F-M and M-F) vs matches (M-M and F-F); (2) Female-to-Male mismatch vs other matches; and (3) Male-to-Female mismatch vs other matches. RESULTS A total of 7 articles were analysed. Gender mismatch (M-F and F-M) was associated with a significant increase of graft loss respect to match (M-M and F-F) (OR: 1.30; 95%CI: 1.13-1.50; P < 0.001). When F-M mismatch was specifically investigated, it confirmed its detrimental role in terms of graft survival (OR: 1.83; 95%CI: 1.20-2.80; P = 0.005). M-F mismatch failed to present a significant role (OR: 1.09; 95%CI: 0.73-1.62; P = 0.68). CONCLUSION Gender mismatch is a risk factor for poor graft survival after liver transplantation. Female-to-male mismatch represents the worst combination. More studies are needed with the intent to better clarify the reasons for these results

Organic bioelectronics probing conformational changes in surface confined proteins

The study of proteins confined on a surface has attracted a great deal of attention due to its relevance in the development of bio-systems for laboratory and clinical settings. In this respect, organic bio-electronic platforms can be used as tools to achieve a deeper understanding of the processes involving protein interfaces. In this work, biotin-binding proteins have been integrated in two different organic thin-film transistor (TFT) configurations to separately address the changes occurring in the protein-ligand complex morphology and dipole moment. This has been achieved by decoupling the output current change upon binding, taken as the transducing signal, into its component figures of merit. In particular, the threshold voltage is related to the protein dipole moment, while the field-effect mobility is associated with conformational changes occurring in the proteins of the layer when ligand binding occurs. Molecular Dynamics simulations on the whole avidin tetramer in presence and absence of ligands were carried out, to evaluate how the tight interactions with the ligand affect the protein dipole moment and the conformation of the loops surrounding the binding pocket. These simulations allow assembling a rather complete picture of the studied interaction processes and support the interpretation of the experimental results

Quality assessment and community detection methods for anonymized mobility data in the Italian Covid context

We discuss how to assess the reliability of partial, anonymized mobility data and compare two different methods to identify spatial communities based on movements: Greedy Modularity Clustering (GMC) and the novel Critical Variable Selection (CVS). These capture different aspects of mobility: direct population fluxes (GMC) and the probability for individuals to move between two nodes (CVS). As a test case, we consider movements of Italians before and during the SARS-Cov2 pandemic, using Facebook users’ data and publicly available information from the Italian National Institute of Statistics (Istat) to construct daily mobility networks at the interprovincial level. Using the Perron-Frobenius (PF) theorem, we show how the mean stochastic network has a stationary population density state comparable with data from Istat, and how this ceases to be the case if even a moderate amount of pruning is applied to the network. We then identify the first two national lockdowns through temporal clustering of the mobility networks, define two representative graphs for the lockdown and non-lockdown conditions and perform optimal spatial community identification on both graphs using the GMC and CVS approaches. Despite the fundamental differences in the methods, the variation of information (VI) between them assesses that they return similar partitions of the Italian provincial networks in both situations. The information provided can be used to inform policy, for example, to define an optimal scale for lockdown measures. Our approach is general and can be applied to other countries or geographical scales

THz-assisted microscopy of silica matrix for biological materials encapsulation: a theoretical and experimental study

In this study, we use THz-assisted atom probe tomography (APT) to analyse silica matrices used to encapsulate biomolecules. This technique provides the chemical composition and 3D structure without significantly heating the biosample, which is crucial for studying soft organic molecules such as proteins. Our results show that THz pulses and a positive static field trigger controlled evaporation of silica matrices, enabling 4D imaging with chemical sensitivity comparable to UV laser-assisted APT. To support the interpretation of these experimental results, we devise a computational model based on time-dependent density functional theory to describe the interaction between silica matrices and THz radiation. This model captures the nonlinear dynamics driven by THz-pulses and the interplay between the THz source and the static electric field in real time. This interdisciplinary approach expands the capabilities of APT and holds promise for other THz-based analyses offering new insights into material dynamics in complex biological environments

Visually evoked phase synchronization changes of alpha rhythm in migraine: Correlations with clinical features

Objective: This study aimed to compute phase synchronization of the alpha band from a multichannel electroencephalogram (EEG) recorded under repetitive flash stimulation from migraine patients without aura. This allowed examination of ongoing EEG activity during visual stimulation in the pain-free phase of migraine. Methods: Flash stimuli at frequencies of 3, 6, 9, 12, 15, 18, 21, 24, and 27 Hz were delivered to 15 migraine patients without aura and 15 controls, with the EEG recorded from 18 scalp electrodes, referred to the linked earlobes. The EEG signals were filtered in the alpha (7.5� 13 Hz) band. For all stimulus frequencies that we evaluated, the phase synchronization index was based on the Hilbert transformation. Results: Phase synchronization separated the patients and controls for the 9, 24 and 27 Hz stimulus frequencies; hyper phase synchronization was observed in patients, whereas healthy subjects were characterized by a reduced phase synchronization. These differences were found in all regions of the scalp. Conclusions: During migraine, the brain synchronizes to the idling rhythm of the visual areas under certain photic stimulations; in normal subjects however, brain regions involved in the processing of sensory information demonstrate desynchronized activity. Hypersynchronization of the alpha rhythm may suggest a state of cortical hypoexcitability during the interictal phase of migraine. Significance: The employment of non-linear EEG analysis may identify subtle functional changes in the migraine brain. D 2005 Elsevier B.V. All rights reserved