A Na pump with reduced stoichiometry is up-regulated by brine shrimp in extreme salinities.

Brine shrimp (Artemia) are the only animals to thrive at sodium concentrations above 4 M. Salt excretion is powered by the Na+,K+-ATPase (NKA), a heterodimeric (αß) pump that usually exports 3Na+ in exchange for 2 K+ per hydrolyzed ATP. Artemia express several NKA catalytic α-subunit subtypes. High-salinity adaptation increases abundance of α2KK, an isoform that contains two lysines (Lys308 and Lys758 in transmembrane segments TM4 and TM5, respectively) at positions where canonical NKAs have asparagines (Xenopus α1's Asn333 and Asn785). Using de novo transcriptome assembly and qPCR, we found that Artemia express two salinity-independent canonical α subunits (α1NN and α3NN), as well as two ß variants, in addition to the salinity-controlled α2KK. These ß subunits permitted heterologous expression of the α2KK pump and determination of its CryoEM structure in a closed, ion-free conformation, showing Lys758 residing within the ion-binding cavity. We used electrophysiology to characterize the function of α2KK pumps and compared it to that of Xenopus α1 (and its α2KK-mimicking single- and double-lysine substitutions). The double substitution N333K/N785K confers α2KK-like characteristics to Xenopus α1, and mutant cycle analysis reveals energetic coupling between these two residues, illustrating how α2KK's Lys308 helps to maintain high affinity for external K+ when Lys758 occupies an ion-binding site. By measuring uptake under voltage clamp of the K+-congener 86Rb+, we prove that double-lysine-substituted pumps transport 2Na+ and 1 K+ per catalytic cycle. Our results show how the two lysines contribute to generate a pump with reduced stoichiometry allowing Artemia to maintain steeper Na+ gradients in hypersaline environments.

Assessment of Renal Deterioration and Associated Risk Factors in Patients With Multiple Sclerosis.

OBJECTIVE: To evaluate predictors of renal deterioration (RD) in patients with multiple sclerosis (MS) at a tertiary referral center. METHODS: We reviewed adult patients with MS presenting for evaluation of lower urinary tract symptoms, with baseline urodynamic study (UDS) and either serum creatinine (SCr) or renal ultrasound, from a prospectively maintained database, and excluded patients with abnormal renal function. RD was defined as doubled SCr, new hydronephrosis, or renal atrophy on follow-up ultrasound. Demographic and UDS parameters were evaluated in multivariable models of RD. RESULTS: From 1999 to 2016, 660 patients were evaluated, and 355 met criteria with median follow-up of 79 months. SCr doubled in 8 patients, 4 had decline by renal ultrasound, and 1 by both (3%). Overall, 46 patients met less strict criteria of decrease in estimated glomerular filtration rate by ≥30%. Using the less rigid criterion, detrusor overactivity (DO) remained associated with RD on multivariable analysis. Eleven of 355 patients had RD by either imaging or doubled Cr, with which only history of diabetes mellitus and nephrolithiasis were associated. CONCLUSION: By strict criteria, the rate of RD in patients with neurogenic bladder due to MS was low (3%) at intermediate-term follow-up and was not associated with UDS parameters. Using more liberal criteria, DO was associated with deterioration, suggesting that study of the impact of more aggressive control of DO in this population may be warranted.

Tuning quantum measurements to control chaos.

Environment-induced decoherence has long been recognised as being of crucial importance in the study of chaos in quantum systems. In particular, the exact form and strength of the system-environment interaction play a major role in the quantum-to-classical transition of chaotic systems. In this work we focus on the effect of varying monitoring strategies, i.e. for a given decoherence model and a fixed environmental coupling, there is still freedom on how to monitor a quantum system. We show here that there is a region between the deep quantum regime and the classical limit where the choice of the monitoring parameter allows one to control the complex behaviour of the system, leading to either the emergence or suppression of chaos. Our work shows that this is a result from the interplay between quantum interference effects induced by the nonlinear dynamics and the effectiveness of the decoherence for different measurement schemes.