Effects of experimental calcium availability,egg parameters and laying order on Great Tit Parus major eggshell pigmentation patterns

Many bird species lay eggs speckled with protoporphyrin‐based spots, however, for most of them the function of eggshell spotting is unknown. A plausible hypothesis is that protoporphyrin might have a structural function in strengthening the eggshell and is therefore deposited when calcium is scarce. In this study, we experimentally provided Great Tit Parus major females with supplemental calcium to examine its effect on the protoporphyrin‐based maculation of their eggs. In addition, we studied variation in eggshell pigmentation patterns in relation to other egg parameters and laying order. Calcium‐supplemented females laid larger eggs but shell thickness was not significantly affected by the treatment. Calcium supplementation may reduce the time and energy females devote to searching for calcium‐rich material, so that they can collect more nutrients and so lay larger eggs. Furthermore, pigment darkness was associated with egg volume and shape, which suggests that female quality and environmental food availability may also influence the shell pigmentation pattern. Within clutches, later‐laid eggs had larger and darker spots that were distributed more unevenly on the shell surface. This within‐clutch pattern could be explained by the increase in egg volume and egg shape and a decline in shell thickness with egg‐laying order, which characteristics were all related to shell‐spotting pattern. Eggs with a coronal ring had thinner shells, but pigment intensity and spot size were not related to shell thickness. Thus, our results suggest that concentrated spotting distribution may have a mechanical function, supporting the structural‐function hypothesis.     

Exploring the antimalarial potential of the methoxy-thiazinoquinone scaffold: Identification of a new lead candidate

A small library of antiplasmodial methoxy-thiazinoquinones, rationally designed on the model of the previously identified hit 1, has been prepared by a simple and inexpensive procedure. The synthetic derivatives have been subjected to in vitro pharmacological screening, including antiplasmodial and toxicity assays. These studies afforded a new lead candidate, compound 9, endowed with higher antiplasmodial potency compared to 1, a good selectivity index when tested against a panel of mammalian cells, no toxicity against RBCs, a synergistic antiplasmodial action in combination with dihydroartemisinin, and a promising inhibitory activity on stage V gametocyte growth. Computational studies provided useful insights into the structural requirements needed for the antiplasmodial activity of thiazinoquinone compounds and on their putative mechanism of action.     

Behavior of the ATP grasp domain of biotin carboxylase monomers and dimers studied using molecular dynamics simulations

The enzyme biotin carboxylase (BC) uses adenosine triphosphate (ATP) to carboxylate biotin and is involved in fatty acid synthesis. Structural evidence suggests that the B domain of BC undergoes a large hinge motion of ～45° when binding and releasing substrates. Escherichia coli BC can function as a natural homodimer and as a mutant monomer. Using molecular dynamics simulations, we evaluate the free energy profile along a closure angle of the B domain of E. coli BC for three cases: a monomer without bound Mg(2)ATP, a monomer with bound Mg(2)ATP, and a homodimer with bound Mg(2)ATP in one subunit. The simulation results show that a closed state is the most probable for the monomer with or without bound Mg(2)ATP. For the dimer with Mg(2)ATP in one of its subunits, communication between the two subunits was observed. Specifically, in the dimer, the opening of the subunit without Mg(2)ATP caused the other subunit to open, and hysteresis was observed upon reclosing it. The most stable state of the dimer is one in which the B domain of both subunits is closed; however, the open state for the B domain without Mg(2)ATP is only approximately 2k(B)T higher in free energy than the closed state. A simple diffusion model indicates that the mean times for opening and closing of the B domain in the monomer with and without Mg(2)ATP are much smaller than the overall reaction time, which is on the order of seconds.     

Adverse health consequences in COPD patients with rapid decline in FEV1 - evidence from the UPLIFT trial

Background

The rate of decline in forced expiratory volume in 1 second (FEV₁) is representative of the natural history of COPD. Sparse information exists regarding the associations between the magnitude of annualised loss of FEV₁ with other endpoints.

Methods

Retrospective analysis of UPLIFT^® trial (four-year, randomized, double-blind, placebo-controlled trial of tiotropium 18 μg daily in chronic obstructive pulmonary disease [COPD], n = 5993). Decline of FEV₁ was analysed with random co-efficient regression. Patients were categorised according to quartiles based on the rate of decline (RoD) in post-bronchodilator FEV_1. The St George''s Respiratory Questionnaire (SGRQ) total score, exacerbations and mortality were assessed within each quartile.

Results

Mean (standard error [SE]) post-bronchodilator FEV₁ increased in the first quartile (Q1) by 37 (1) mL/year. The other quartiles showed annualised declines in FEV₁ (mL/year) as follows: Q2 = 24 (1), Q3 = 59 (1) and Q4 = 125 (2). Age, gender, respiratory medication use at baseline and SGRQ did not distinguish groups. The patient subgroup with the largest RoD had less severe lung disease at baseline and contained a higher proportion of current smokers. The percentage of patients with ≥ 1 exacerbation showed a minimal difference from the lowest to the largest RoD, but exacerbation rates increased with increasing RoD. The highest proportion of patients with ≥ 1 hospitalised exacerbation was in Q4 (Q1 = 19.5% [tiotropium], 26% [control]; Q4 = 33.8% [tiotropium] and 33.1% [control]). Time to first exacerbation and hospitalised exacerbation was shorter with increasing RoD. Rate of decline in SGRQ increased in direct proportion to each quartile. The group with the largest RoD had the highest mortality.

Conclusion

Patients can be grouped into different RoD quartiles with the observation of different clinical outcomes indicating that specific (or more aggressive) approaches to management may be needed.

Trial Registration

ClinicalTrials.gov number, {"type":"clinical-trial","attrs":{"text":"NCT00144339","term_id":"NCT00144339"}}NCT00144339     

Dopamine Secretion Is Mediated by Sparse Active Zone-like Release Sites

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Characteristics of the volume- and chloride-dependent K transport in human erythrocytes homozygous for hemoglobin C

Summary In human red cells homozygous for hemoglobin C (CC), cell swelling and acid pH increase K efflux and net K loss in the presence of ouabain (0.1mm) and bumetanide. We report herein, that K influx is also dependent on cell volume in CC cells: cell swelling induces a marked increase in the maximal rate (from 6 to 18 mmol/liter cell × hr) and in the affinity for external K (from 77±16mm to 28±3mm) of K influx. When the external K concentration is varied from 0 to 140mm, K efflux from CC and normal control cells is unaffected. Thus, K/K exchange is not a major component of this K movement. K transport through the pathway of CC cells is dependent on the presence of chloride or bromide; substitution with nitrate, acetate or thiocyanate inhibits the volume- and pH-dependent K efflux. When CC cells are separated according to density, a sizable volume-dependent component of K efflux can be identified in all the fractions and is the most active in the least dense fraction. N-ethylmaleimide (NEM) markedly stimulates K efflux from CC cells in chloride but not in nitrate media, and this effect is present in all the fractions of CC cells separated according to density. The persistence of this transport system in denser CC cells suggests that not only cell age, but also the presence of the positively charged C hemoglobin is an important determinant of the activity of this system. These data also indicate that the K transport pathway of CC cells is not an electrodiffusional process and is coupled to chloride.     

Adaptive neuro-fuzzy inference system: Estimation of soil aggregates stability

In present study, the capabilities of multiple linear regression (MLR) and adaptive neuro-fuzzy inference system (ANFIS) in developing pedotransfer functions (PTFs) for estimating geometric mean diameter (GMD) and mean weight diameter (MWD), from routine soil properties and combination of routine soil properties and fractal dimension of aggregates were evaluated. For this reason 101 samples were collected form the Northwest of Iran and some their properties such as soil texture, pH, cation exchange capacity (CEC), and organic matter (OM), fractal dimension of aggregates between number-diameter (Dn), mass-diameter (Dmt), and bulk density-diameter (Dmy) were determined and used as an input variables for determining of mean weight diameter (MWD) and geometric mean diameter (GMD) by MLR and ANFIS PTFs. Results showed that the application of fractal dimension of aggregates as a predictor in two methods improved the accuracy of PTFs. As well as, results showed that ANFIS have greater potential for determination of the relationships between soil aggregate stability indices and other soil properties in compared with MLR. Therefore using of adaptive neuro-fuzzy inference system (ANFIS) in developing pedotransfer functions is recommended.     

Mean growth rate when rare is not a reliable metric for persistence of species

The coexistence of many species within ecological communities poses a long‐standing theoretical puzzle. Modern coexistence theory (MCT) and related techniques explore this phenomenon by examining the chance of a species population growing from rarity in the presence of all other species. The mean growth rate when rare, , is used in MCT as a metric that measures persistence properties (like invasibility or time to extinction) of a population. Here we critique this reliance on and show that it fails to capture the effect of temporal random abundance variations on persistence properties. The problem becomes particularly severe when an increase in the amplitude of stochastic temporal environmental variations leads to an increase in , since at the same time it enhances random abundance fluctuations and the two effects are inherently intertwined. In this case, the chance of invasion and the mean extinction time of a population may even go down as increases.