Does developmental acclimatization reduce the susceptibility to predation in newt larvae?

Many organisms respond to the heterogeneity of abiotic environmental conditions by plastic modifications of their phenotypes (acclimation or acclimatization). Despite considerable research efforts in this area, the beneficial (adaptive) effect of acclimation or acclimatization is still debated. We examined whether the development of newt larvae (Ichthyosaura alpestris) under different natural light and thermal conditions subsequently altered their susceptibility to predation in sun‐exposed versus shaded tanks in nature. During predation trials in various light and temperature conditions, newt larvae that developed in sun‐exposed warmer tanks consistently suffered from higher predation by dragonfly nymphs (Aeshna cyanea) compared to larvae from shaded or colder tanks. We conclude that higher sun exposure during embryonic and larval development negatively affects antipredator performance even in sun‐exposed tanks: this result is inconsistent with the beneficial acclimation hypothesis. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, ●● , ●●–●●.     

A study of wall shear stress in 12 aneurysms with respect to different viscosity models and flow conditions

Recent computational fluid dynamics (CFD) studies relate abnormal blood flow to rupture of cerebral aneurysms. However, it is still debated how to model blood flow with sufficient accuracy. Common assumptions made include Newtonian behaviour of blood, traction free outlet boundary conditions and inlet boundary conditions based on available literature. These assumptions are often required since the available patient specific data is usually restricted to the geometry of the aneurysm and the surrounding vasculature. However, the consequences of these assumptions have so far been inadequately addressed.     

Effects of small interfering RNA-mediated hepatic glucagon receptor inhibition on lipid metabolism in db/db mice

Hepatic glucose overproduction is a major characteristic of type 2 diabetes. Because glucagon is a key regulator for glucose homeostasis, antagonizing the glucagon receptor (GCGR) is a possible therapeutic strategy for the treatment of diabetes mellitus. To study the effect of hepatic GCGR inhibition on the regulation of lipid metabolism, we generated siRNA-mediated GCGR knockdown (si-GCGR) in the db/db mouse. The hepatic knockdown of GCGR markedly reduced plasma glucose levels; however, total plasma cholesterol was increased. The detailed lipid analysis showed an increase in the LDL fraction, and no change in VLDL HDL fractions. Further studies showed that the increase in LDL was the result of over-expression of hepatic lipogenic genes and elevated de novo lipid synthesis. Inhibition of hepatic glucagon signaling via siRNA-mediated GCGR knockdown had an effect on both glucose and lipid metabolism in db/db mice.     

Substituted imidazopyridazines are potent and selective inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1)

A series of imidazopyridazines which are potent inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) was identified from a high-throughput screen against the isolated enzyme. Subsequent exploration of the SAR and optimisation has yielded leading members which show promising in vitro anti-parasite activity along with good in vitro ADME and selectivity against human kinases. Initial in vivo testing has revealed good oral bioavailability in a mouse PK study and modest in vivo efficacy in a Plasmodium berghei mouse model of malaria.     

Energetic Pathway Sampling in a Protein Interaction Domain

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The development and characterization of a competitive ELISA for measuring active ADAMTS-4 in a bovine cartilage ex vivo model

ADAMTS-4 (aggrecanase1) is believed to play an important role in the degradation of aggrecan during the progression of joint diseases. ADAMTS-4 is synthesized as a latent pro-enzyme that requires the removal of the pro-domain, exposing the N-terminal neoepitope, to achieve activity. We developed a monoclonal antibody against this neoepitope of active ADAMTS-4. Furthermore, we established and characterized a competitive ELISA for measuring active ADAMTS-4 form applying the specific antibody. We used this assay to profile the presence of active ADAMTS-4 and its aggrecan degradation product (NITEGE³⁷³) in a bovine cartilage ex vivo model. We found that after stimulation with catabolic factors, the cartilage initially released high levels of aggrecanase-derived aggrecan fragments into supernatant but subsequently decreased to background levels. The level of active ADAMTS-4 released into the supernatant and retained in the cartilage matrix increased continuously throughout the 21 days of the study. The activity of ADAMTS-4 on the last day of catabolic stimulation was verified in vitro by adding deglycosylated or native aggrecan to the conditioned medium. Samples of human cartilage affected by varying degrees of osteoarthritis stained strongly for active ADAMTS-4 where surface fibrillation and clustered chondrocytes were observed. This assay could be an effective tool for studying ADAMTS-4 activity and for screening drugs regulating ADAMTS-4 activation. Moreover, it could be a potential biomarker for degenerative joint disease.     

Advanced electron paramagnetic resonance on the catalytic iron–sulfur cluster bound to the CCG domain of heterodisulfide reductase and succinate: quinone reductase

Heterodisulfide reductase (Hdr) is a key enzyme in the energy metabolism of methanogenic archaea. The enzyme catalyzes the reversible reduction of the heterodisulfide (CoM-S-S-CoB) to the thiol coenzymes M (CoM-SH) and B (CoB-SH). Cleavage of CoM-S-S-CoB at an unusual FeS cluster reveals unique substrate chemistry. The cluster is fixed by cysteines of two cysteine-rich CCG domain sequence motifs (CX_31–39CCX_35–36CXXC) of subunit HdrB of the Methanothermobacter marburgensis HdrABC complex. We report on Q-band (34 GHz) ⁵⁷Fe electron-nuclear double resonance (ENDOR) spectroscopic measurements on the oxidized form of the cluster found in HdrABC and in two other CCG-domain-containing proteins, recombinant HdrB of Hdr from M. marburgensis and recombinant SdhE of succinate: quinone reductase from Sulfolobus solfataricus P2. The spectra at 34 GHz show clearly improved resolution arising from the absence of proton resonances and polarization effects. Systematic spectral simulations of 34 GHz data combined with previous 9 GHz data allowed the unambiguous assignment of four ⁵⁷Fe hyperfine couplings to the cluster in all three proteins. ¹³C Mims ENDOR spectra of labelled CoM-SH were consistent with the attachment of the substrate to the cluster in HdrABC, whereas in the other two proteins no substrate is present. ⁵⁷Fe resonances in all three systems revealed unusually large ⁵⁷Fe ENDOR hyperfine splitting as compared to known systems. The results infer that the cluster’s unique magnetic properties arise from the CCG binding motif.     

The effect of high pH on structural lipids in diatoms

We tested the hypothesis that increased pH reduces the amount of structural lipids. To do this, we used three different diatoms (Phaeodactylum tricornutum CCAP strain, P. tricornutum TV strain and Amphiprora sp). We tested the effect of rapid increase from pH?7.5 to 10 by adding NaOH. The total lipid content was reduced by 13, 36 and 47 % in the P. tricornutum CCAP strain, TV strain and Amphiprora sp., respectively, 1 h after increasing the pH. The P. tricornutum CCAP strain was used for further testing the effect of pH on the lipid content during active growth. This strain was cultivated at pH?7.5 and 10, and the pH was regulated by the CO₂ inflow. The growth rate was similar (0.3 day^?1) in both pH treatments, but the lipid content in the pH?10 treatment was on average 28 % lower than in the pH?7.5 treatment. Our data support the hypothesis that structural lipids are reduced when pH increases to high levels. The results suggest that regulating the pH during algae cultivation could be used to refine the lipid composition in the harvested algal biomass.     

Individualized closed-loop control of propofol anesthesia: A preliminary study

This paper proposes an individualized approach to closed-loop control of depth of hypnosis during propofol anesthesia. The novelty of the paper lies in the individualization of the controller at the end of the induction phase of anesthesia, based on a patient model identified from the dose–response relationship during induction of anesthesia. The proposed approach is shown to be superior to administration of propofol based on population-based infusion schemes tailored to individual patients. This approach has the potential to outperform fully adaptive approaches in regards to controller robustness against measurement variability due to surgical stimulation. To streamline controller synthesis, two output filters were introduced (inverting the Hill dose–response model and the linear time-invariant sensor model), which yield a close-to-linear representation of the system dynamics when used with a compartmental patient model. These filters are especially useful during the induction phase of anesthesia in which a nonlinear dose–response relationship complicates the design of an appropriate controller. The proposed approach was evaluated in simulation on pharmacokinetic and pharmacodynamic models of 44 patients identified from real clinical data. A model of the NeuroSense, a hypnotic depth monitor based on wavelet analysis of EEG, was also included. This monitor is similar to the well-known BIS, but has linear time-invariant dynamics and does not introduce a delay. The proposed scheme was compared with a population-based controller, i.e. a controller only utilizing models based on demographic covariates for its tuning. On average, the proposed approach offered 25% improvement in disturbance attenuation, measured as the integrated absolute error following a step disturbance. The corresponding standard deviation from the reference was also decreased by 25%. Results are discussed and possible directions of future work are proposed.     

Risk of Inflammatory Bowel Disease According to Self-Rated Health,Pregnancy Course,and Pregnancy Complications: A Study within the Danish National Birth Cohort

Background

Poor self-rated health (SRH) has been connected to immunological changes, and pregnancy complications have been suggested in the etiology of autoimmune diseases including inflammatory bowel disease (IBD). We evaluated the impact of self-rated pre-pregnancy health and pregnancy course, hyperemesis, gestational hypertension, and preeclampsia on risk of IBD.

Methods

Information was collected by questionnaires from The Danish National Birth Cohort (enrolment 1996–2002) at 16^th and 30^th week of pregnancy and 6 months postpartum. A total of 55,699 women were followed from childbirth until development of IBD (using validated National Hospital Discharge Register diagnoses), emigration, death, or end of follow-up, 31^st of October, 2011. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusting for age and evaluating pre-pregnancy BMI, parity, alcohol and tobacco consumption, and socio-occupational status as potential confounders.

Results

Risk of IBD increased with decreasing level of self-rated pre-pregnancy health (p = 0.002) and was elevated in women with poor self-rated pregnancy course (HR, 1.61, 95% CI 1.22–2.12). Associations persisted for more than 5 years postpartum. Hyperemesis and preeclampsia were not significantly associated with risk of IBD.

Conclusions

This is the first prospective observational study to suggest that poor self-rated health – in general and in relation to pregnancy – is associated with increased risk of IBD even in the long term though results needs further confirmation. Symptoms of specific pregnancy complications were, on the other hand, not significantly associated with risk of IBD.