Dynamic approach to predict pH profiles of biologically relevant buffers

Recently, dynamic approach has been applied to determine the steady state concentrations of multiple ionic species present in complex buffers at equilibrium. Here, we have used the dynamic approach to explicitly model the pH profiles of biologically relevant phosphate buffer and universal buffer (a mixture of three tri-protic acids such as citric acid, boric acid and phosphoric acid). The results from dynamic approach are identical to that of the conventional algebraic approach, but with an added advantage that the dynamic approach, allow for the modelling of complex buffer systems relatively easy compared to that of algebraic method.     

Estimating and minimizing movement artifacts in surface electromyogram

While recording surface electromyography [sEMG], it is possible to record the electrical activities coming from the muscles and transients in the half-cell potential at the electrode–electrolyte interface due to micromovements of the electrode–skin interface. Separating the two sources of electrical activity usually fails due to the overlapping frequency characteristics of the signals. This paper aims to develop a method that detects movement artifacts and suggests a minimization technique. Towards that aim, we first estimated the frequency characteristics of movement artifacts under various static and dynamic experimental conditions. We found that the extent of the movement artifact depended on the nature of the movement and varied from person to person. Our study's highest movement artifact frequency for the stand position was 10 Hz, tiptoe 22, walk 32, run 23, jump from box 41, and jump up and down 40 Hz. Secondly, using a 40 Hz highpass filter, we cut out most of the frequencies belonging to the movement artifacts. Finally, we checked whether the latencies and amplitudes of reflex and direct muscle responses were still observed in the highpass-filtered sEMG. We showed that the 40 Hz highpass filter did not significantly alter reflex and direct muscle variables. Therefore, we recommend that researchers who use sEMG under similar conditions employ the recommended level of highpass filtering to reduce movement artifacts from their records. However, suppose different movement conditions are used. In that case, it is best to estimate the frequency characteristics of the movement artifact before applying any highpass filtering to minimize movement artifacts and their harmonics from sEMG.     

Allostery and Missense Mutations as Intermittently Linked Promising Aspects of Modern Computational Drug Discovery

Drug research and development is a multidisciplinary field with its own successes. Yet, given the complexity of the process, it also faces challenges over the long development stages and even includes those that develop once a drug is marketed, i.e. drug toxicity and drug resistance. Better success can be achieved via well designed criteria in the early drug development stages. Here, we introduce the concepts of allostery and missense mutations, and argue that incorporation of these two intermittently linked biological phenomena into the early computational drug discovery stages would help to reduce the attrition risk in later stages of the process. We discuss the individual or in concert mechanisms of actions of mutations in allostery. Design of allosteric drugs is challenging compared to orthosteric drugs, yet they have been gaining popularity in recent years as alternative systems for the therapeutic regulation of proteins with an action-at-a-distance mode and non-invasive mechanisms. We propose an easy-to-apply computational allosteric drug discovery protocol which considers the mutation effect, and detail it with three case studies focusing on (1) analysis of effect of an allosteric mutation related to isoniazid drug resistance in tuberculosis; (2) identification of a cryptic pocket in the presence of an allosteric mutation of falcipain-2 as a malarial drug target; and (3) deciphering the effects of SARS-CoV-2 evolutionary mutations on a potential allosteric modulator with changes to allosteric communication paths.     

Mathematical modelling of carbohydrate degradation by human colonic microbiota

The human colon is an anaerobic ecosystem that remains largely unexplored as a result of its limited accessibility and its complexity. Mathematical models can play a central role for a better insight into its dynamics. In this context, this paper presents the development of a mathematical model of carbohydrate degradation. Our aim was to provide an in silico approach to contribute to a better understanding of the fermentation patterns in such an ecosystem. Our mathematical model is knowledge-based, derived by writing down mass-balance equations. It incorporates physiology of the intestine, metabolic reactions and transport phenomena. The model was used to study various nutritional scenarios and to assess the role of the mucus on the system behavior. Model simulations provided an adequate qualitative representation of the human colon. Our model is complementary to experimental studies on human colonic fermentation, which, of course, is not meant to replace. It may be helpful to gain insight on questions that are still difficult to elucidate by experimentation and suggest future experiments.     

Effect of sample treatment on biomechanical properties of insect cuticle

Experimental limitations often prevent to perform biomechanical measurements on fresh arthropod cuticle samples. Hence, in many cases short- or long-term storage of samples is required. So far, it is not known whether any of the standard lab-techniques commonly used to fix or store insect cuticle samples in any way affects the biomechanical properties of the respective samples.In this paper we systematically address this question for the first time, with a focus on practical, easily accessible and common lab-methods including storage in water, ethanol, glutaraldehyde, freezing and desiccation. We performed a comprehensive and sensitive non-destructive Dynamic Mechanical Analysis (DMA) on locust hind leg tibiae using a three-point-bending setup. Our results show that from all tested treatments, freezing samples at −20 °C was the best option to maintain the original values for Young's modulus and damping properties of insect cuticle. In addition, our results indicate that the damping properties of locust hind legs might be mechanically optimized in respect to the jumping and kicking direction.     

Dynamic light-scattering studies on thermal motions of native DNAs in solution

The basic character of dynamic light-scattering properties of native DNA was investigated on two DNA samples. The degree of non-single exponentiality of photocount correlation functions. C(t), and its dependence on Kquantitatively characterized by two methods. The spectral linewidth. Γ₃, determined from C(t) exhibits a K dependence near to but significantly different from the prediction for Rouse-Zimm (RZ) chains by Dubois-Violelte and De Gennes: It is inferred from data on λ-DNA that the exponent in She K dependence of the spectral linewidth for native DNA takes a value larger than 3 in the K region corresponding to the ‘K³’ region for RZ chains. These results are in good agreement with the prediction from the dynamic theory of semiflexible chains presented by one of us (K.S.). The apparent diffusion coefficients are fairly insensitive to DNA concentration and ionic strength at large K. On the other hand, it is indicated that the stiffness of native DNA may vary with temperature even in a temperature range substantially lower than thai of melting.