Stability and rigidity/flexibility—Two sides of the same coin?

Protein molecules require both flexibility and rigidity for functioning. The fast and accurate prediction of protein rigidity/flexibility is one of the important problems in protein science. We have determined flexible regions for four homologous pairs from thermophilic and mesophilic organisms by two methods: the fast FoldUnfold which uses amino acid sequence and the time consuming MDFirst which uses three-dimensional structures. We demonstrate that both methods allow determining flexible regions in protein structure. For three of the four thermophile–mesophile pairs of proteins, FoldUnfold predicts practically the same flexible regions which have been found by the MD/First method. As expected, molecular dynamics simulations show that thermophilic proteins are more rigid in comparison to their mesophilic homologues. Analysis of rigid clusters and their decomposition provides new insights into protein stability. It has been found that the local networks of salt bridges and hydrogen bonds in thermophiles render their structure more stable with respect to fluctuations of individual contacts. Such network includes salt bridge triads Agr-Glu-Lys and Arg-Glu-Arg, or salt bridges (such as Arg-Glu) connected with hydrogen bonds. This ionic network connects alpha helices and rigidifies the structure. Mesophiles can be characterized by stand alone salt bridges and hydrogen bonds or small ionic clusters. Such difference in the network of salt bridges results in different flexibility of homologous proteins. Combining both approaches allows characterizing structural features in atomic detail that determine the rigidity/flexibility of a protein structure. This article is a part of a Special Issue entitled: The emerging dynamic view of proteins: Protein plasticity in allostery, evolution and self-assembly.     

A review of thermoregulation and physiological performance in reptiles: what is the role of phenotypic flexibility?

Biological functions are dependent on the temperature of the organism. Animals may respond to fluctuation in the thermal environment by regulating their body temperature and by modifying physiological and biochemical rates. Phenotypic flexibility (reversible phenotypic plasticity, acclimation, or acclimatisation) in rate functions occurs in all major taxonomic groups and may be considered as an ancestral condition. Within the Reptilia, representatives from all major groups show phenotypic flexibility in response to long-term or chronic changes in the thermal environment. Acclimation or acclimatisation in reptiles are most commonly assessed by measuring whole animal responses such as oxygen consumption, but whole animal responses are comprised of variation in individual traits such as enzyme activities, hormone expression, and cardiovascular functions. The challenge now lies in connecting the changes in the components to the functioning of the whole animal and its fitness. Experimental designs in research on reptilian thermal physiology should incorporate the capacity for reversible phenotypic plasticity as a null-hypothesis, because the significance of differential body temperature–performance relationships (thermal reaction norms) between individuals, populations, or species cannot be assessed without testing that null-hypothesis.     

Structural flexibility of small GTPases. Can it explain their functional versatility?

Multiple interactions with many different partners are responsible for the amazing functional versatility of proteins, especially those participating in cellular regulation. The structural properties that could facilitate multiple interactions are examined for small GTPases. The role of cellular constraints, compartmentation and scaffolds on protein-protein interactions is considered.     

Subjectivity and flexibility in invasion terminology: too much of a good thing?

Invasions biologists have frequently debated whether the definition of invasive should include ecological and economic impacts. More recent criticisms posit that objective definitions are impossible in any absolute sense, while subjectivity is desirable for its flexibility and motivational qualities. We argue that such criticisms underestimate the extent of subjectivity already present in invasion biology. Ecological questions may be methodological if they relate directly to other ecological theories and models, or motivational if they focus on issues important to society as a whole. Motivational questions are important for engaging scientists, improving public understanding of science, and often have applied benefits. In contrast, methodological questions are constrained by established scientific theories, and are therefore more efficient for the development of scientific knowledge. Contrary to recent critiques, we suggest that greater objectivity is both achievable and desirable for the discipline of invasion biology and ecology generally.     

Does there exist an intrinsic relationship between the flexibility and self-assembly of pepfactants?

Short peptide surfactants (pepfactants) bearing the amphiphilic molecular architecture of hydrophobic and hydrophilic moieties are attractive for a wide range of biological and medical applications. Understanding of structural basis and molecular mechanism underlying the self-assembling behaviour of pepfactants is fundamentally important for rationally designing surfactant-like peptides to function as diverse biomaterials. To date, however, the relationship between the physicochemical properties and self-assembly of pepfactants still remains largely unexplored. In this study, we attempt to elucidate the role of structural flexibility and dynamics in peptide self-assembly. Two fast and reliable quantitative structure–property relationship predictors are carefully developed with the sophisticated genetic algorithm/partial least squares method; the predictors are then applied to estimate molecular flexibility and self-assembling ability for 10,000 randomly generated surfactant-like peptides. As a result, a significant negative correlation between the flexibility and self-assembly is observed, which can be fitted fairly well using an exponential curve. Furthermore, atomistic molecular dynamics simulations also reveal a noticeable difference of flexibility profile between strong and weak self-assembling peptides. All these come together to suggest that the self-assembling behaviour of pepfactants is highly dependent on their structural flexibility.     

Has general practitioner computing made a difference to patient care? A systematic review of published reports.

OBJECTIVE--To review findings from studies of the influence of desktop computers on primary care consultations. DESIGN--Systematic review of world reports from 1984 to 1994. SETTING--The computerised catalogues of Medline, BIDS, and GPlit were searched, as well as conference proceedings, books, bibliographies, and references in books and journal articles. SUBJECTS--30 papers met the inclusion criteria and were included for detailed review. INTERVENTIONS--A validated scheme for assessing methodological adequacy was used to score each paper. MAIN OUTCOME MEASURES--Papers were rated on sample formation, baseline differences, unit of allocation, outcome measures, and follow up. Differences in outcomes were also recorded. RESULTS--Four of the six papers dealing with the consultation process showed that consultations took longer. Doctor initiated and "medical" content of consultations increased at the expense of a reduction in patient initiated and "social" content. Each of the 21 studies which looked at clinician performance showed an improvement when a computer was used (from 8% to 50%, with better results for single preventive measures). Only one of the three studies looking at patient outcomes showed an improvement (diastolic blood pressure control 5 mm Hg better after one year, with fewer doctor-patient consultations). CONCLUSIONS--Using a computer in the consultation may help improve clinician performance but may increase the length of the consultation. More studies are needed to assess the effects on patient outcomes of using a computer in consultations.     

Where is the difference between the genomes of humans and annelids?

The first systematic investigation of an annelid genome has revealed that the genes of the marine worm Platynereis dumerilii are more closely related to those of vertebrates than to those of insects or nematodes. For hundreds of millions of years vertebrates have preserved exon-intron structures descended from their last common ancestor with the annelids.     

Is death-feigning adaptive? Heritable variation in fitness difference of death-feigning behaviour.

The adaptation of death-feigning (thanatosis), a subject that has been overlooked in evolutionary biology, was inferred in a model prey-and-predator system. We studied phenotypic variation among individuals, fitness differences, and the inheritance of death-feigning behaviour in the red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). Two-way artificial selections for the duration of death-feigning, over 10 generations, showed a clear direct response in the trait and a correlated response in the frequency of death-feigning, thus indicating variation and inheritance of death-feigning behaviour. A comparison of the two selected strains with divergent frequencies of death-feigning showed a significant difference in the fitness for survival when a model predator, a female Adanson jumper spider, Hasarius adansoni Audouin (Araneomophae: Salticidae), was presented to the beetles. The frequency of predation was lower among beetles from strains selected for long-duration than among those for short-duration death-feigning. The results indicate the possibility of the evolution of death-feigning under natural selection.     

Men and sin: what's the difference?

A conserved signalling cascade--termed the mitotic-exit network in budding yeast and the septation-initiation network in fission yeast--controls key events during exit from mitosis and cytokinesis. Although the components of these signalling networks are highly conserved between the two yeasts, the outputs seem quite different. How, then, do these two pathways function, and how are they regulated?     

Interleukin-10 ?592C/A, ?819C/T and ?1082A/G Polymorphisms with Risk of Type 2 Diabetes Mellitus: A HuGE Review and Meta-analysis

Background

Several studies have been conducted in recent years to evaluate the risk of type 2 diabetes mellitus (T2DM) and polymorphisms of interleukin (IL)-10. However, the results remain conflicting rather than conclusive. This meta-analysis aimed to summarize the current evidence from case-control studies that evaluated this association.

Methods

We carried out a search in Medline, EMBASE, and the Chinese National Knowledge Infrastructure (CNKI) database for relevant studies. Data were extracted using a standardized form and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of the association.

Results

10 studies were included in our meta-analysis and systemic review. Our meta-analysis indicated that IL-10 −1082A/G polymorphism was associated with the risk of T2DM (GA vs. AA: OR = 1.21, 95% CI = 1.03–1.14; GA/GG vs. AA: OR = 1.22, 95% CI = 1.05–1.41), whereas there was no association between IL-10 −592C/A (CC/CA vs. AA: OR = 1.07, 95% CI = 0.59–1.93) or -819C/T (CC/CT vs. TT: OR = 0.93, 95% CI = 0.49–1.75) polymorphism and T2DM risk was found in our study.

Conclusions

This meta-analysis provides strong evidence that IL-10 −1082A/G polymorphism associated with risk of T2DM. However, no association of the IL-10 −592C/A or −819C/T polymorphism with T2DM risk was found. Additional well-designed large studies were required for the validation of our results.