Baggeringgaard1517

When the amphibious mangrove rivulus (Kryptolebias marmoratus) leaves water for extended periods, hemoglobin-O2 binding affinity increases. We tested the hypothesis that the change in affinity was a consequence of hemoglobin isoform switching driven by exposure to environments associated with increased internal CO2 levels. We exposed K. marmoratus to either water (control, pH 8.1), air, aquatic hypercarbia (5.1 kPa CO2, pH 6.6-6.8), or aquatic acid (isocarbic control, pH 6.6-6.8), for 7 days, and measured hemoglobin-O2 affinity spectrophotometrically. We found that mangrove rivulus compensated for elevated CO2 and aquatic acid exposure by shifting hemoglobin-O2 affinity back to aquatic (control) levels when measured at an ecologically-relevant high CO2 level that would be experienced in vivo. Using proteomics, we found that the hemoglobin subunits present in the blood did not change between treatments, but air and aquatic acid exposure altered the abundance of cathodic hemoglobin subunits. We therefore conclude that hemoglobin isoform switching is not a primary strategy used by mangrove rivulus to adjust P50 under these conditions. Abundances of other RBC proteins also differed between treatment groups relative to control fish (e.g. Rhesus protein type A, band 3 anion exchanger). Overall, our data indicate that both aquatic hypercarbia and aquatic acidosis create similar changes in hemoglobin-O2 affinity as air exposure. However, the protein-level consequences differ between these groups, indicating that the red blood cell response of mangrove rivulus can be modulated depending on the environmental cue received.Pharmaceutical drugs are widespread environmental contaminants, but data about their adverse effects are still limited to a few compounds. This study analyzed the acute (96 h) and chronic (28 days) impacts of environmentally realistic levels of diazepam (acute exposure 0.001, 0.01, 0.1, 1, 10 μg/L; chronic exposure 0.1, 1, 10, 100, 1000 ng/L), in the polychaete Hediste diversicolor, by measuring behavioral and biochemical (catalase [CAT], glutathione-S-transferases [GSTs], cholinesterases [ChEs], glutathione peroxidase [GPx], lipid peroxidation [TBARS]) parameters. Acute exposure to diazepam altered behavioral traits, decreasing burrowing times and causing hyperactivity, whilst burrowing time increased and hypoactivity resulted after chronic exposure. All biomarkers were affected after the chronic exposure, with the exception of lipid peroxidation. Our data demonstrate that realistic levels of diazepam may impair behavioral and biochemical traits in polychaetes, suggesting that diazepam exposure presents a significant challenge to the environment that supports these organisms.We propose an integrated model of aqueous outflow control that employs a pump-conduit system in this article. Our model exploits accepted physiologic regulatory mechanisms such as those of the arterial, venous, and lymphatic systems. Here, we also provide a framework for developing novel diagnostic and therapeutic strategies to improve glaucoma patient care. In the model, the trabecular meshwork distends and recoils in response to continuous physiologic IOP transients like the ocular pulse, blinking, and eye movement. The elasticity of the trabecular meshwork determines cyclic volume changes in Schlemm's canal (SC). Tube-like SC inlet valves provide aqueous entry into the canal, and outlet valve leaflets at collector channels control aqueous exit from SC. Connections between the pressure-sensing trabecular meshwork and the outlet valve leaflets dynamically control flow from SC. Normal function requires regulation of the trabecular meshwork properties that determine distention and recoil. The aqueous pump-conduit provides short-term pressure control by varying stroke volume in response to pressure changes. Modulating TM constituents that regulate stroke volume provides long-term control. The aqueous outflow pump fails in glaucoma due to the loss of trabecular tissue elastance, as well as alterations in ciliary body tension. These processes lead to SC wall apposition and loss of motion. Visible evidence of pump failure includes a lack of pulsatile aqueous discharge into aqueous veins and reduced ability to reflux blood into SC. selleckchem These alterations in the functional properties are challenging to monitor clinically. Phase-sensitive OCT now permits noninvasive, quantitative measurement of pulse-dependent TM motion in humans. This proposed conceptual model and related techniques offer a novel framework for understanding mechanisms, improving management, and development of therapeutic options for glaucoma.It is well known that if the hypothesis test is left unchanged, the Type I error rate may be inflated for sample size re-estimation (SSR) designs. To address this issue, three main approaches have been proposed in the literature combination test, conditional error and conventional test with sample size increase in the allowable region (AR) only. These three seemingly different approaches are in fact connected. For each combination test, there is a corresponding conditional error function and AR. Designing adaptation rules in this AR with conventional test guarantees the Type I error rate control but at the same time always leads to smaller power comparing to the corresponding combination test (or conditional error) approach. In cases where conventional test is still preferable, step-wise type adaptation rules that do not fully reside in the AR can be alternatively considered. We believe controversies in the statistical community on the efficiency comparisons between group sequential (GS) and SSR design stem partially from the misalignment of performance metrics and conditional versus unconditional evaluations. We advocate summary metrics, such as median, variance or tail probabilities of the sample size in addition to expectation and personalizing efficiency definition for each trial sponsor. Conditional metrics by favorable, promising and unfavorable zones of the interim results provide additional insights and should always be incorporated into the decision-making process.