Association Rate Constants of Ras-Effector Interactions Are Evolutionarily Conserved

Evolutionary conservation of protein interaction properties has been shown to be a valuable indication for functional importance. Here we use homology interface modeling of 10 Ras-effector complexes by selecting ortholog proteins from 12 organisms representing the major eukaryotic branches, except plants. We find that with increasing divergence time the sequence similarity decreases with respect to the human protein, but the affinities and association rate constants are conserved as predicted by the protein design algorithm, FoldX. In parallel we have done computer simulations on a minimal network based on Ras-effector interactions, and our results indicate that in the absence of negative feedback, changes in kinetics that result in similar binding constants have strong consequences on network behavior. This, together with the previous results, suggests an important biological role, not only for equilibrium binding constants but also for kinetics in signaling processes involving Ras-effector interactions. Our findings are important to take into consideration in system biology approaches and simulations of biological networks

Effective Stimuli for Constructing Reliable Neuron Models

The rich dynamical nature of neurons poses major conceptual and technical challenges for unraveling their nonlinear membrane properties. Traditionally, various current waveforms have been injected at the soma to probe neuron dynamics, but the rationale for selecting specific stimuli has never been rigorously justified. The present experimental and theoretical study proposes a novel framework, inspired by learning theory, for objectively selecting the stimuli that best unravel the neuron's dynamics. The efficacy of stimuli is assessed in terms of their ability to constrain the parameter space of biophysically detailed conductance-based models that faithfully replicate the neuron's dynamics as attested by their ability to generalize well to the neuron's response to novel experimental stimuli. We used this framework to evaluate a variety of stimuli in different types of cortical neurons, ages and animals. Despite their simplicity, a set of stimuli consisting of step and ramp current pulses outperforms synaptic-like noisy stimuli in revealing the dynamics of these neurons. The general framework that we propose paves a new way for defining, evaluating and standardizing effective electrical probing of neurons and will thus lay the foundation for a much deeper understanding of the electrical nature of these highly sophisticated and non-linear devices and of the neuronal networks that they compose

Engineering of cyclodextrin glucanotransferases and the impact for biotechnological applications

Cyclodextrin glucanotransferases (CGTases) are industrially important enzymes that produce cyclic α-(1,4)-linked oligosaccharides (cyclodextrins) from starch. Cyclodextrin glucanotransferases are also applied as catalysts in the synthesis of glycosylated molecules and can act as antistaling agents in the baking industry. To improve the performance of CGTases in these various applications, protein engineers are screening for CGTase variants with higher product yields, improved CD size specificity, etc. In this review, we focus on the strategies employed in obtaining CGTases with new or enhanced enzymatic capabilities by searching for new enzymes and improving existing enzymatic activities via protein engineering

Regional anesthesia or patient-controlled analgesia and compartment syndrome in orthopedic surgical procedures: a systematic review

Elizabeth BS Driscoll,1 Ana Hosseinzadeh Maleki,2 Leila Jahromi,3 Brittany Nelson Hermecz,4 Lauren E Nelson,5 Imelda L Vetter,6 Spencer Evenhuis,2 Lee Ann Riesenberg2 1Department of Anesthesiology, University of Tennessee, Knoxville, TN, 2Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL, 3Department of Biology, Georgia State University, Atlanta, GA, 4Department of Diagnostic Radiology, University of Alabama at Birmingham School of Medicine, Birmingham, 5University of South Alabama College of Medicine, Mobile, 6School of Health Professions, Lister Hill Library, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: A systematic review of the literature on the use of regional anesthesia (RA) and patient-controlled analgesia (PCA) was conducted in patients who require orthopedic extremity procedures to determine whether either analgesic technique contributes to a delayed diagnosis of compartment syndrome (CS). A total of 34 relevant articles (28 case reports and six research articles) were identified. Of all case report articles published after 2009, the majority (75%) concluded that RA does not put the patient at an increased risk of a delayed diagnosis of CS. Of these, only two relevant prospective research studies focusing on RA or PCA and their relationship to CS were identified. Neither study resulted in any cases of CS. However, both had relatively small sample sizes. Given the lack of evidence identified in this systematic review, prospective studies or large-scale retrospective data reviews are needed to more strongly advocate the use of one modality of analgesia over the other in this patient population. Keywords: compartment syndrome, patient-controlled analgesia, regional anesthesia, peripheral nerve bloc