Macromolecules and urolithiasis: parallels and paradoxes

BASEL, SWITZERLAN

Face-specific binding of prothrombin fragment 1 and human serum albumin to inorganic and urinary calcium oxalate monohydrate crystals

OBJECTIVE To compare the intracrystalline distributions of prothrombin fragment 1 (PTF1) and human serum albumin (HSA) within inorganic and urinary calcium oxalate (CaOx) monohydrate (COM) crystals and to determine whether binding of PTF1 can be explained by interactions between particular γ-carboxyglutamic (Gla) residues and atomic arrays on individual faces of the COM crystal. MATERIALS AND METHODS COM crystals were precipitated from inorganic solutions and ultrafiltered urine containing fluorescent HSA or PTF1 at different relative concentrations and examined by fluorescence microscopy. Accelrys Materials Studio and Discovery Studio were used to model the binding of PTF1 to the top, side and apical faces of the COM crystal. RESULTS PTF1 alone always adsorbed predominantly to the COM apical surfaces, while HSA bound principally to the side faces under inorganic conditions, but to the apical faces in urine. In the presence of each other, both proteins competed for adsorption to the apical faces, with attachment of PTF1 dominating over that of HSA. Modelling showed that urinary PTF1 had equal theoretical bonding potential for all three COM surfaces. CONCLUSIONS (i) Anisotropic inclusion of HSA and PTF1 into urinary and inorganic COM crystals results from their preferential binding to specific COM faces; (ii) the binding preference of HSA differs under inorganic and urinary conditions; (iii) preferential binding of PTF1 to the apical faces of COM is more complex than can be explained by interactions between Gla groups and surface atomic arrays; (iv) future studies of interactions between urinary proteins and stone mineral crystal surfaces should be performed in urine.Alison F. Cook, Phulwinder K. Grover and Rosemary L. Ryal

High calcium concentration and calcium oxalate crystals cause significant inaccuracies in the measurement of urinary osteopontin by enzyme linked immunosorbent assay

Finding a holistic and integrative – yet applied and manageable - framework for both understanding and reducing disaster risk has been at the forefront of the most challenging disaster risk research for decades. Still, the search for what some consider unachievable involves multiple challenges, from institutional or cultural site-specific obstacles to more structural complications, including social conditions of knowledge-production and competing epistemological framings. As part of the ongoing REMAKE programme (Seismic Risk in Ecuador: Mitigation, Anticipation and Knowledge of Earthquakes), contributions from the social sciences provide a contextual approach to enlighten the understanding and management of seismic disaster risk, especially in Esmeraldas after the 2016 Pedernales disaster. Analysing experience reports and feedback from REMAKE allows the authors to highlight the contribution of geosciences and social sciences to the field of risk prevention. Such analysis also emphasizes the relevance of interdisciplinary research. Further, looking more deeply at this research experience shows the importance of underlying social conditionings in producing prescriptive knowledge on disaster risk. The search for more integrative research and action frameworks cannot avoid addressing an epistemological debate on approaches and conceptual models of disaster risk. Such a level of reflexivity within the discourse of research programming and risk management is consistent with the Risk Society thesis and the primary challenges that it posits. Lessons learned from REMAKE offer some insights to nurture the very first steps towards interdisciplinary research programmes and integrative disaster prevention policies, so that a significant difference might be made in disaster risk reduction