Typograf — artysta czy rzemieślnik?

Not an author, not an editor, nor even a proofreader – yet, this person can change/influence the final shape of a text. It’s a typographer, whose main responsibility is the technical preperation of the text for the publication.  One can only speculate as to the specifics of this vocation: is he an artist who, along with an author, shapes the text, or is he merely a craftsman?  This article offers the description of this profession based on opinions of typography experts.To nie autor, nie redaktor, ani nie korektor — a również ma duży wpływ na kształt tekstu. O kim mowa? O typografie. Czy to rzemieślnik, którego zadaniem jest jedynie techniczne przygotowanie tekstu do publikacji? Czy może też artysta, który wraz z autorem uczestniczy w kształtowaniu dzieła? W artykule przedstawiono oba aspekty pracy typografa, próbując opisać naturę tego zawodu na podstawie opinii autorytetów w dziedzinie typografii

Czytacz w Bibliotece — dla seniorów i nie tylko Rozmowa z Moniką Mieczkowską i Anną Klimczak, koordynatorkami projektu Czytacz

Redaktorki Biuletynu EBIb przeprowadziły wywiad na temat projektu bibliotecznego zatytułowanego CZYTACZ, a dotyczącego seniorów

Inhibition of protein translocation at the endoplasmic reticulum promotes activation of the unfolded protein response

Selective small-molecule inhibitors represent powerful tools for the dissection of complex biological processes. ESI (eeyarestatin I) is a novel modulator of ER (endoplasmic reticulum) function. In the present study, we show that in addition to acutely inhibiting ERAD (ER-associated degradation), ESI causes production of mislocalized polypeptides that are ubiquitinated and degraded. Unexpectedly, our results suggest that these non-translocated polypeptides promote activation of the UPR (unfolded protein response), and indeed we can recapitulate UPR activation with an alternative and quite distinct inhibitor of ER translocation. These results suggest that the accumulation of non-translocated proteins in the cytosol may represent a novel mechanism that contributes to UPR activation

Does the partial molar volume of a solute reflect the free energy of hydrophobic solvation?

Halogenated heterocyclic ligands are widely used as the potent and frequently selective inhibitors of protein kinases. However, the exact contribution of the hydrophobic solvation of a free ligand is rarely accounted for the balance of interactions contributing to the free energy of ligand binding. Herein, we propose a new experimental method based on volumetric data to estimate the hydrophobicity of a ligand. We have tested this approach for a series of ten variously halogenated benzotriazoles, the binding affinity of which to the target protein kinase CK2 was assessed with the use of thermal shift assay. According to the hierarchical clustering procedure, the excess volume, defined as the difference between the experimentally determined partial molar volume and the calculated in silico molecular volume, was found to be distant from any commonly used hydrophobicity descriptors of the ligand. The excess volume, however, properly predicts solute binding affinity. On the way, we have proved that the binding of halogenated benzotriazoles to the protein kinase CK2 is driven mostly by hydrophobic interaction

First results of time series analysis of the permanent GNSS observations at Polish EPN stations using GipsyX software

The aim of this work is to explore, for the first time in Poland, the possibility of determining Earth’s crust movements from permanent observations at selected permanent stations using the GipsyX software for a period of 8 years (2011-2018) in the ITRF2014 reference frame. The data used in this work are from 15 Aktywna Sieć Geodezyjna (ASG)-EUPOS stations from 2011 to 2018, which are also European Permanent Network (EPN) stations. The stations Borowa Góra, Borowiec, Józefosław, Lamkówko, and Wroclaw are also International Global Navigation Satellite Systems (GNSS) Service (IGS) stations. Daily data, rinex files, for these stations have been made available for this work by the Main Office of Surveying and Cartography. The calculations were made using the GipsyX software in the ITRF14 reference frame. The tests performed have shown that daily solutions from 8-yearlong time series give secular trends with an accuracy of 0.01 mm/yr. Our results suggest that there are small differences in horizontal and vertical velocities and in the accuracy estimated between our and EPN solutions. At some stations, for example, Łódź, the differences are much larger. The impact of additional GNSS observations on the accuracy of determination of horizontal and vertical movements of the Earth's crust shows a submillimeter accuracy in computed coordinates of stations even at a relatively small time interval. It means that multiGNSS Precise Point Positioning (PPP) processing can be used in the future for the estimation of geodynamic processes

Competition between electrostatic interactions and halogen bonding in the protein–ligand system: structural and thermodynamic studies of 5,6-dibromobenzotriazole-hCK2αα complexes

CK2 is a member of the CMGC group of eukaryotic protein kinases and a cancer drug target. It can be efficiently inhibited by halogenated benzotriazoles and benzimidazoles. Depending on the scaffold, substitution pattern, and pH, these compounds are either neutral or anionic. Their binding poses are dictated by a hydrophobic effect (desolvation) and a tug of war between a salt bridge/hydrogen bond (to K68) and halogen bonding (to E114 and V116 backbone oxygens). Here, we test the idea that binding poses might be controllable by pH for ligands with near-neutral pK$_a$, using the conditionally anionic 5,6-DBBt and constitutively anionic TBBt as our models. We characterize the binding by low-volume Differential Scanning Fluorimetry (nanoDSF), Isothermal Calorimetry (ITC), Hydrogen/Deuterium eXchange (HDX), and X-ray crystallography (MX). The data indicate that the ligand pose away from the hinge dominates for the entire tested pH range (5.5–8.5). The insensitivity of the binding mode to pH is attributed to the perturbation of ligand pK$_a$ upon binding that keeps it anionic in the ligand binding pocket at all tested pH values. However, a minor population of the ligand, detectable only by HDX, shifts towards the hinge in acidic conditions. Our findings demonstrate that electrostatic (ionic) interactions predominate over halogen bonding

ROBO3s: a novel ROBO3 short isoform promoting breast cancer aggressiveness.

Basal-like breast cancer (BLBC) is a highly aggressive breast cancer subtype frequently associated with poor prognosis. Due to the scarcity of targeted treatment options, conventional cytotoxic chemotherapies frequently remain the standard of care. Unfortunately, their efficacy is limited as BLBC malignancies rapidly develop resistant phenotypes. Using transcriptomic and proteomic approaches in human and murine BLBC cells, we aimed to elucidate the molecular mechanisms underlying the acquisition of aggressive and chemotherapy-resistant phenotypes in these mammary tumors. Specifically, we identified and characterized a novel short isoform of Roundabout Guidance Receptor 3 (ROBO3s), upregulated in BLBC in response to chemotherapy and encoding for a protein variant lacking the transmembrane domain. We established an important role for the ROBO3s isoform, mediating cancer stem cell properties by stimulating the Hippo-YAP signaling pathway, and thus driving resistance of BLBC cells to cytotoxic drugs. By uncovering the conservation of ROBO3s expression across multiple cancer types, as well as its association with reduced BLBC-patient survival, we emphasize its potential as a prognostic marker and identify a novel attractive target for anti-cancer drug development