Description of non-specific DNA-protein interaction and facilitated diffusion with a dynamical model

We propose a dynamical model for non-specific DNA-protein interaction, which is based on the 'bead-spring' model previously developed by other groups, and investigate its properties using Brownian Dynamics simulations. We show that the model successfully reproduces some of the observed properties of real systems and predictions of kinetic models. For example, sampling of the DNA sequence by the protein proceeds via a succession of 3d motion in the solvent, 1d sliding along the sequence, short hops between neighboring sites, and intersegmental transfers. Moreover, facilitated diffusion takes place in a certain range of values of the protein effective charge, that is, the combination of 1d sliding and 3d motion leads to faster DNA sampling than pure 3d motion. At last, the number of base pairs visited during a sliding event is comparable to the values deduced from single-molecule experiments. We also point out and discuss some discrepancies between the predictions of this model and some recent experimental results as well as some hypotheses and predictions of kinetic models

Analysis of red chalk drawings from the workshop of Giovanni Battista Piranesi using fiber optics reflectance spectroscopy

The viability of fiber optics reflectance spectroscopy (FORS) for the differentiation of red chalk drawing media was investigated, focusing on the group of drawings from the workshop of Giovanni Battista Piranesi (1720–1778) at the Staatliche Kunsthalle Karlsruhe, Germany. The evaluation of spectra was supported by principal component analysis (PCA). The method was tested on mock-up drawings made with recently acquired natural and synthetic red chalks of known origin. It was possible to sort these mock-up drawings according to chalk type and application technique. The compositional differences of these reference chalks were confirmed by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Subsequent FORS analysis of selected original drawings revealed the existence of several closely grouped clusters, implying similarities on the basis of the underlying spectral features among the historical red chalks used in Rome. These similarities distinguished the historical drawings from the red chalk mock-up drawings, except for the drawings made with red chalk samples from the area near the town of Theley, Germany, which were shown to bear close similarities to those in the cluster of historical samples

ABC Transport Is Inactivated by the PTS(Ntr) under Potassium Limitation in Rhizobium leguminosarum 3841.

PTS(Ntr) is a regulatory phosphotransferase system in many bacteria. Mutation of the PTS(Ntr) enzymes causes pleiotropic growth phenotypes, dry colony morphology and a posttranslational inactivation of ABC transporters in Rhizobium leguminosarum 3841. The PTS(Ntr) proteins EI(Ntr) and 2 copies of EIIA(Ntr) have been described previously. Here we identify the intermediate phosphocarrier protein NPr and show its phosphorylation by EI(Ntr) in vitro. Furthermore we demonstrate that phosphorylation of EI(Ntr) and NPr is required for ABC transport activation and that the N-terminal GAF domain of EI(Ntr) is not required for autophosphorylation. Previous studies have shown that non-phosphorylated EIIA(Ntr) is able to modulate the transcriptional activation of the high affinity potassium transporter KdpABC. In R. leguminosarum 3841 kdpABC expression strictly depends on EIIA(Ntr). Here we demonstrate that under strong potassium limitation ABC transport is inactivated, presumably by non-phosphorylated EIIA(Ntr). This is to our knowledge the first report where PTS(Ntr) dictates an essential cellular function. This is achieved by the inverse regulation of two important ATP dependent transporter classes

Alvise Gritti

Biographical note on the 16th c. Venetian Alvise Gritt

Activation of oligodendroglial Fyn kinase enhances translation of mRNAs transported in hnRNP A2–dependent RNA granules

Central nervous system myelination requires the synthesis of large amounts of myelin basic protein (MBP) at the axon–glia contact site. MBP messenger RNA (mRNA) is transported in RNA granules to oligodendroglial processes in a translationally silenced state. This process is regulated by the trans-acting factor heterogeneous nuclear ribonucleoprotein (hnRNP) A2 binding to the cis-acting A2 response element (A2RE). Release of this repression of MBP mRNA translation is thus essential for myelination. Mice deficient in the Src family tyrosine kinase Fyn are hypomyelinated and contain reduced levels of MBP. Here, we identify hnRNP A2 as a target of activated Fyn in oligodendrocytes. We show that active Fyn phosphorylates hnRNP A2 and stimulates translation of an MBP A2RE–containing reporter construct. Neuronal adhesion molecule L1 binding to oligodendrocytes results in Fyn activation, which leads to an increase in hnRNP A2 phosphorylation. These results suggest that Fyn kinase activation results in the localized translation of MBP mRNA at sites of axon–glia contact and myelin deposition

Risk factors and outcomes of unrecognised endobronchial intubation in major trauma patients

Background Emergency tracheal intubation during major trauma resuscitation may be associated with unrecognised endobronchial intubation. The risk factors and outcomes associated with this issue have not previously been fully defined. Methods We retrospectively analysed adult patients admitted directly from the scene to the ED of a single level 1 trauma centre, who received either prehospital or ED tracheal intubation prior to initial whole-body CT from January 2008 to December 2019. Our objectives were to describe tube-to- carina distances (TCDs) via CT and to assess the risk factors and outcomes (mortality, length of intensive care unit stay and mechanical ventilation) of patients with endobronchial intubation (TCD <0 cm) using a multivariable model. Results We included 616 patients and discovered 26 (4.2%) cases of endobronchial intubation identified on CT. Factors associated with an increased risk of endobronchial intubations were short body height (OR per 1 cm increase 0.89; 95% CI 0.84 to 0.94; p≤0.001), a high body mass index (OR 1.14; 95% CI 1.04 to 1.25; p=0.005) and ED intubation (OR 3.62; 95% CI 1.39 to 8.90; p=0.006). Eight of 26 cases underwent tube thoracostomy, four of whom had no evidence of underlying chest injury on CT. There was no statistically significant difference in mortality or length of stay although the absolute number of endobronchial intubations was small. Conclusions Short body height and high body mass index were associated with endobronchial intubation. Before considering tube thoracostomy in intubated major trauma patients suspected of pneumothorax, the possibility of unrecognised endobronchial intubation should be considered

Attrition of X Chromosome Inactivation in Aged Hematopoietic Stem Cells

During X chromosome inactivation (XCI), the inactive X chromosome (Xi) is recruited to the nuclear lamina at the nuclear periphery. Beside X chromosome reactivation resulting in a highly penetrant aging-like hematopoietic malignancy, little is known about XCI in aged hematopoietic stem cells (HSCs). Here, we demonstrate that LaminA/C defines a distinct repressive nuclear compartment for XCI in young HSCs, and its reduction in aged HSCs correlates with an impairment in the overall control of XCI. Integrated omics analyses reveal higher variation in gene expression, global hypomethylation, and significantly increased chromatin accessibility on the X chromosome (Chr X) in aged HSCs. In summary, our data support the role of LaminA/C in the establishment of a special repressive compartment for XCI in HSCs, which is impaired upon aging