Processes controlling carbon cycling in Antarctic glacier surface ecosystems

Glacier surface ecosystems, including cryoconite holes and cryolakes, are significant contributors to regional carbon cycles. Incubation experiments to determine the net production (NEP) of organic matter in cryoconite typically have durations of 6-24 hours, and produce a wide range of results, many of which indicate that the system is net heterotrophic. We employ longer term incubations to examine the temporal variation of NEP in cryoconite from the McMurdo Dry Valleys, Antarctica to examine the effect of sediment disturbance on system production, and to understand processes controlling production over the lifetimes of glacier surface ecosystems. The shorter-term incubations have durations of one week and show net heterotrophy. The longer term incubations of approximately one year show net autotrophy, but only after a period of about 40 days (~1000 hours). The control on net organic carbon production is a combination of the rate of diffusion of dissolved inorganic carbon from heterotrophic activity within cryoconite into the water, the rate of carbonate dissolution, and the saturation of carbonate in the water (which is a result of photosynthesis in a closed system). We demonstrate that sediment on glacier surfaces has the potential to accumulate carbon over timescales of months to years

The mechanism of the reverse recovery-step, phosphate release, and actin activation of Dictyostelium myosin II.

The rate-limiting step of the myosin basal ATPase (i.e. in absence of actin) is assumed to be a post-hydrolysis swinging of the lever arm (reverse recovery step), that limits the subsequent rapid product release steps. However, direct experimental evidence for this assignment is lacking. To investigate the binding and the release of ADP and phosphate independently from the lever arm motion, two single tryptophan-containing motor domains of Dictyostelium myosin II were used. The single tryptophans of the W129+ and W501+ constructs are located at the entrance of the nucleotide binding pocket and near the lever arm, respectively. Kinetic experiments show that the rate-limiting step in the basal ATPase cycle is indeed the reverse recovery step, which is a slow equilibrium step (k(forward) = 0.05 s(-1), k(reverse) = 0.15 s(-1)) that precedes the phosphate release step. Actin directly activates the reverse recovery step, which becomes practically irreversible in the actin-bound form, triggering the power stroke. Even at low actin concentrations the power stroke occurs in the actin-attached states despite the low actin affinity of myosin in the pre-power stroke conformation

Bioabsorbable metal zinc differentially affects mitochondria in vascular endothelial and smooth muscle cells

Zinc is an essential trace element having various structural, catalytic and regulatory interactions with an estimated 3000 proteins. Zinc has drawn recent attention for its use, both as pure metal and alloyed, in arterial stents due to its biodegradability, biocompatibility, and low corrosion rates. Previous studies have demonstrated that zinc metal implants prevent the development of neointimal hyperplasia, which is a common cause of restenosis following coronary intervention. This suppression appears to be smooth muscle cell-specific, as reendothelization of the neointima is not inhibited. To better understand the basis of zinc\u27s differential effects on rat aortic smooth muscle (RASMC) versus endothelial (RAENDO) cells, we conducted a transcriptomic analysis of both cell types following one-week continuous treatment with 5 µM or 50 µM zinc. This analysis indicated that genes whose protein products regulate mitochondrial functions, including oxidative phosphorylation and fusion/fission, are differentially affected by zinc in the two cell types. To better understand this, we performed Seahorse metabolic flux assays and quantitative imaging of mitochondrial networks in both cell types. Zinc treatment differently affected energy metabolism and mitochondrial structure/function in the two cell types. For example, both basal and maximal oxygen consumption rates were increased by zinc in RASMC but not in RAENDO. Zinc treatment increased apparent mitochondrial fusion in RASMC cells but increased mitochondrial fission in RAENDO cells. These results provide some insight into the mechanisms by which zinc treatment differently affects the two cell types and this information is important for understanding the role of zinc treatment in vascular cells and improving its use in biodegradable metal implants

A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis

Abstract Introduction Our aim was to investigate the impact of early versus late initiation of renal replacement therapy (RRT) on clinical outcomes in critically ill patients with acute kidney injury (AKI). Methods Systematic review and meta-analysis were used in this study. PUBMED, EMBASE, SCOPUS, Web of Science and Cochrane Central Registry of Controlled Clinical Trials, and other sources were searched in July 2010. Eligible studies selected were cohort and randomised trials that assessed timing of initiation of RRT in critically ill adults with AKI. Results We identified 15 unique studies (2 randomised, 4 prospective cohort, 9 retrospective cohort) out of 1,494 citations. The overall methodological quality was low. Early, compared with late therapy, was associated with a significant improvement in 28-day mortality (odds ratio (OR) 0.45; 95% confidence interval (CI), 0.28 to 0.72). There was significant heterogeneity among the 15 pooled studies (I2 = 78%). In subgroup analyses, stratifying by patient population (surgical, n = 8 vs. mixed, n = 7) or study design (prospective, n = 10 vs. retrospective, n = 5), there was no impact on the overall summary estimate for mortality. Meta-regression controlling for illness severity (Acute Physiology And Chronic Health Evaluation II (APACHE II)), baseline creatinine and urea did not impact the overall summary estimate for mortality. Of studies reporting secondary outcomes, five studies (out of seven) reported greater renal recovery, seven (out of eight) studies showed decreased duration of RRT and five (out of six) studies showed decreased ICU length of stay in the early, compared with late, RRT group. Early RRT did not; however, significantly affect the odds of dialysis dependence beyond hospitalization (OR 0.62 0.34 to 1.13, I2 = 69.6%). Conclusions Earlier institution of RRT in critically ill patients with AKI may have a beneficial impact on survival. However, this conclusion is based on heterogeneous studies of variable quality and only two randomised trials. In the absence of new evidence from suitably-designed randomised trials, a definitive treatment recommendation cannot be made

Magnesium lactate in the treatment of Gitelman syndrome: patient-reported outcomes.

BACKGROUND: Gitelman syndrome (GS) is a rare recessively inherited renal tubulopathy associated with renal potassium (K) and magnesium (Mg) loss. It requires lifelong K and Mg supplementation at high doses that are at best unpalatable and at worst, intolerable. In particular, gastrointestinal side effects often limit full therapeutic usage. METHODS: We report here the analysis of a cohort of 28 adult patients with genetically proven GS who attend our specialist tubular disorders clinic, in whom we initiated the use of a modified-release Mg preparation (slow-release Mg lactate) and who were surveyed by questionnaire. RESULTS: Twenty-five patients (89%) preferred the new treatment regimen. Of these 25, 17 (68%) regarded their symptom burden as improved and seven reported no worsening. Of the 25 who were not Mg-treatment naïve, 13 (59%) patients reported fewer side effects, 7 (32%) described them as the same and only 2 (9%) considered side effects to be worse. Five were able to increase their dose without ill-effect. Overall, biochemistry improved in 91% of the 23 patients switched from therapy with other preparations who chose to continue the modified-release Mg preparation. Eleven (48%) improved both their Mg and K mean levels, 3 (13%) improved Mg levels only and in 7 cases (30%), K levels alone rose. CONCLUSIONS: Patient-reported and biochemical outcomes using modified-release Mg supplements were very favourable, and patient choice should play a large part in choosing Mg supplements with GS patients.This work was supported by the Wellcome Trust and the NIHR Cambridge Biomedical Research Centre, and contains data that were presented in abstract form at ASN Kidney week 2014.This is the final version of the article. It first appeared from Oxford University Press via https://doi.org/10.1093/ndt/gfw01

Association between recurrence of acute kidney injury and mortality in intensive care unit patients with severe sepsis

Background: Acute kidney injury (AKI) occurs in more than half critically ill patients admitted in intensive care units (ICU) and increases the mortality risk. The main cause of AKI in ICU is sepsis. AKI severity and other related variables such as recurrence of AKI episodes may influence mortality risk. While AKI recurrence after hospital discharge has been recently related to an increased risk of mortality, little is known about the rate and consequences of AKI recurrence during the ICU stay. Our hypothesis is that AKI recurrence during ICU stay in septic patients may be associated to a higher mortality risk. Methods: We prospectively enrolled all (405) adult patients admitted to the ICU of our hospital with the diagnosis of severe sepsis/septic shock for a period of 30 months. Serum creatinine was measured daily. ?In-ICU AKI recurrence? was defined as a new spontaneous rise of ?0.3 mg/dl within 48 h from the lowest serum creatinine after the previous AKI episode. Results: Excluding 5 patients who suffered the AKI after the initial admission to ICU, 331 patients out of the 400 patients (82.8%) developed at least one AKI while they remained in the ICU. Among them, 79 (19.8%) developed ?2 AKI episodes. Excluding 69 patients without AKI, in-hospital (adjusted HR = 2.48, 95% CI 1.47?4.19), 90-day (adjusted HR = 2.54, 95% CI 1.55?4.16) and end of follow-up (adjusted HR = 1.97, 95% CI 1.36?2.84) mortality rates were significantly higher in patients with recurrent AKI, independently of sex, age, mechanical ventilation necessity, APACHE score, baseline estimated glomerular filtration rate, complete recovery and KDIGO stage. Conclusions: AKI recurred in about 20% of ICU patients after a first episode of sepsis-related AKI. This recurrence increases the mortality rate independently of sepsis severity and of the KDIGO stage of the initial AKI episode. ICU physicians must be aware of the risks related to AKI recurrence while multiple episodes of AKI should be highlighted in electronic medical records and included in the variables of clinical risk scores