Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution

Phenotypic variation is the raw material of adaptive Darwinian evolution. The phenotypic variation found in organismal development is biased towards certain phenotypes, but the molecular mechanisms behind such biases are still poorly understood. Gene regulatory networks have been proposed as one cause of constrained phenotypic variation. However, most pertinent evidence is theoretical rather than experimental. Here, we study evolutionary biases in two synthetic gene regulatory circuits expressed in Escherichia coli that produce a gene expression stripe—a pivotal pattern in embryonic development. The two parental circuits produce the same phenotype, but create it through different regulatory mechanisms. We show that mutations cause distinct novel phenotypes in the two networks and use a combination of experimental measurements, mathematical modelling and DNA sequencing to understand why mutations bring forth only some but not other novel gene expression phenotypes. Our results reveal that the regulatory mechanisms of networks restrict the possible phenotypic variation upon mutation. Consequently, seemingly equivalent networks can indeed be distinct in how they constrain the outcome of further evolution.     

Silicon increases phosphorus (P) uptake by wheat under low P acid soil conditions

Plant and Soil - Although silicon (Si) is known to improve plant growth under low phosphorus (P) conditions, the in planta mechanisms responsible for this effect are still unknown. Here, we...     

Close and distant: Contrasting the metabolism of two closely related subspecies of Scots pine under the effects of folivory and summer drought

Metabolomes, as chemical phenotypes of organisms, are likely not only shaped by the environment but also by common ancestry. If this is the case, we expect that closely related species of pines will tend to reach similar metabolomic solutions to the same environmental stressors. We examined the metabolomes of two sympatric subspecies of Pinus sylvestris in Sierra Nevada (southern Iberian Peninsula), in summer and winter and exposed to folivory by the pine processionary moth. The overall metabolomes differed between the subspecies but both tended to respond more similarly to folivory. The metabolomes of the subspecies were more dissimilar in summer than in winter, and iberica trees had higher concentrations of metabolites directly related to drought stress. Our results are consistent with the notion that certain plant metabolic responses associated with folivory have been phylogenetically conserved. The larger divergence between subspecies metabolomes in summer is likely due to the warmer and drier conditions that the northern iberica subspecies experience in Sierra Nevada. Our results provide crucial insights into how iberica populations would respond to the predicted conditions of climate change under an increased defoliation in the Mediterranean Basin.     

Docking studies suggest ligand-specific δ-opioid receptor conformations

An automated docking procedure was used to study binding of a series of δ-selective ligands to three models of the δ-opioid receptor. These models are thought to represent the three ligand-specific receptor conformations. Docking results are in agreement with point mutation studies and suggest that different ligands—agonists and antagonists—may bind to the same binding site under different receptor conformations. Docking to different receptor models (conformations) also suggests that by changing to a receptor-specific conformation, the receptor may open or close different binding sites to other ligands. Figure  Ligands 5 (green) and 6 (orange) in bindingpocket BP1 of the R1 δ-opioid receptor model     

The lignicolous fungus Trametes versicolor (L.) Lloyd (1920): a promising natural source of antiradical and AChE inhibitory agents

This study aimed to determine antiradical (DPPH^? and ^?OH) and acetylcholinesterase (AChE) inhibitory activities along with chemical composition of autochtonous fungal species Trametes versicolor (Serbia). A total of 38 phenolic compounds with notable presence of phenolic acids were identified using HPLC/MS-MS. Its water extract exhibited the highest antiradical activity against ^?OH (3.21?μg/mL), among the rest due to the presence of gallic, p-coumaric and caffeic acids. At the concentration of 100?μg/mL, the same extract displayed a profound AChE inhibitory activity (60.53%) in liquid, compared to donepezil (89.05%), a drug in clinical practice used as positive control. The flavonoids baicalein and quercetin may be responsible compounds for the AChE inhibitory activity observed. These findings have demonstrated considerable potential of T. versicolor water extract as a natural source of antioxidant(s) and/or AChE inhibitor(s) to be eventually used as drug-like compounds or food supplements in the treatment of Alzheimer’s disease.     

Correlation of cardio-ankle vascular index, ten-year risk assessment and other atherosclerosis risk factors

The aim of the study was to assess correlation of atherosclerosis severity as determined by two different methods of screening for atherosclerosis: (A) measurement of the cardio-ankle vascular index-CAVI by use of the VaseraVS-1500 vascular screening device, and (B) Framingham scale scoring. 52 subjects (28 male and 24 female) were enrolled in the study. Classification of study subjects into four quartiles based on theoretically calculated 10-year risk according to Framingham scale (medians: 1%, 3%, 4% and 15%) confirmed the risk increase to be associated with a statistically significant increase in CAVI, age and total cholesterol, and a statistically significant decrease in HDL-cholesterol (p < 0.001 all). Spearman correlation coefficients showed a statistically significant correlation of 10-year risk with CAVI (p = 0.0242; r = 0.4494). Study results suggested that simultaneous determination of CAVI and 10-year risk might prove justified. They are not contradictory, the more so, these two parameters showed a significant positive correlation. This test panel yields comprehensible, implying all the possible consequences and highly motivating information that may stimulate the person for lifestyle modification.     

Impaired cerebral vasoreactivity in type 2 diabetes mellitus

The aim of our study was to assess cerebral vasoreactivity (CVR) in type 2 diabetes mellitus (DM2) and factors which may influence on it. According to previous studies, evaluating CVR in DM2 on the similar way, the results were dubious. For the evaluation CVR we used breath holding index (BHI) and transcranial Doppler ultrasound (TCD) in 50 patients with DM2 and 50 sex- and age-matched healthy controls. We observed epidemiologic and clinic data, other vascular risk factors and laboratory parameters. We found statistically significant difference in BHI between patients with DM2 (BHI = 0.69 +/- 0.31) and age- and sex-matched healthy controls (BHI = 1.33+/-0.28) (p < 0.05 ). Because of a significant correlation between BHI and age (p < 0.001) in healthy controls we made an adjustment of BHI for age before further analyses (BHIadj). In DM2 group we found a significant correlation between BHIadj and age (p = 0.0004), fasting glycemia (p = 0.04), and albuminuria (p = 0.04) (creatinine clearance in multivariate analysis (p = 0.007)). Our study has shown that CVR is impaired in DM2 patients and that it's severity was associated with age, fasting glycemia and renal function. Functional TCD is a very good screening method for detection and monitoring of cerebral microangiopathic changes in DM2 patients.