S-Thiolation Targets Albumin in Heart Failure

Human serum albumin (HSA) is associated with several physiological functions, such as maintaining oncotic pressure and microvascular integrity, among others. It also represents the major and predominant antioxidant in plasma due to the presence of the Cys34 sulfhydryl group. In this study, we assessed qualitative and quantitative changes in HSA in patients with heart failure (HF) and their relationship with the severity of the disease. We detected by means of mass spectrometry a global decrease of the HSA content in the plasma of HF patients in respect to control subjects, a significant increase of thio-HSA with a concomitant decrease in the reduced form of albumin. Cysteine and, at a lesser extent, homocysteine represent the most abundant thiol bound to HSA. A strong inverse correlation was also observed between cysteine-HSA and peak VO2/kg, an index of oxygen consumption associated with HF severity. Moreover, in HL-1 cardiomyocytes incubated with H2O2, we showed a significant decrease of cell viability in cells treated with thio-HSA in respect to restored native-HSA. In conclusion, we found for the first time that S-thiolation of albumin is increased in the plasma of HF patients and induced changes in the structure and antioxidant function of HSA, likely contributing to HF progression

The patchwork governance of ecologically available water: A case study in the Upper Missouri Headwaters, Montana, United States

Institutional authority and responsibility for allocating water to ecosystems (“ecologically available water” [EAW]) is spread across local, state, and federal agencies, which operate under a range of statutes, mandates, and planning processes. We use a case study of the Upper Missouri Headwaters Basin in southwestern Montana, United States, to illustrate this fragmented institutional landscape. Our goals are to (a) describe the patchwork of agencies and institutional actors whose intersecting authorities and actions influence the EAW in the study basin; (b) describe the range of governance mechanisms these agencies use, including laws, policies, administrative programs, and planning processes; and (c) assess the extent to which the collective governance regime creates gaps in responsibility. We find the water governance regime includes a range of nested mechanisms that in various ways facilitate or hinder the governance of EAW. We conclude the current multilevel governance regime leaves certain aspects of EAW unaddressed and does not adequately account for the interconnections between water in different parts of the ecosystem, creating integrative gaps. We suggest that more intentional and robust coordination could provide a means to address these gaps