Description and analysis of metabolic connectivity and dynamics in the human red blood cell

The human red blood cell (hRBC) metabolic network is relatively simple compared with other whole cell metabolic networks, yet too complicated to study without the aid of a computer model. Systems science techniques can be used to uncover the key dynamic features of hRBC metabolism. Herein, we have studied a full dynamic hRBC metabolic model and developed several approaches to identify metabolic pools of metabolites. In particular, we have used phase planes, temporal decomposition, and statistical analysis to show hRBC metabolism is characterized by the formation of pseudoequilibrium concentration states. Such equilibria identify metabolic "pools" or aggregates of concentration variables. We proceed to define physiologically meaningful pools, characterize them within the hRBC, and compare them with those derived from systems engineering techniques. In conclusion, systems science methods can decipher detailed information about individual enzymes and metabolites within metabolic networks and provide further understanding of complex biological networks.     

Separate modeling of cortical and trabecular bone offers little improvement in FE predictions of local structural stiffness at the proximal tibia

Abstract

Quantitative computed tomography-based finite element (QCT-FE) modeling has potential to clarify the role of altered subchondral bone stiffness in osteoarthritis. The objective of this research was to evaluate different QCT-FE modeling and thresholding approaches to identify the method which best predicted experimentally measured local subchondral structural stiffness with highest explained variance and least error. Our results showed that separate modeling of proximal tibial cortical and trabecular bone offered little improvement in QCT-FE-predicted stiffness (0% to +3% improvement in explained variance) when compared to modeling the proximal tibia as a single structure. Based on the results of this study, we do not recommend separate modeling of cortical bone and trabecular bone when developing QCT-FE models of the proximal tibia for predicting subchondral bone stiffness.     

Assessment of changes in growth traits,oxidative stress parameters,and enzymatic and non-enzymatic antioxidant defense mechanisms in Lepidium draba plant under osmotic stress induced by polyethylene glycol

Protoplasma - Lepidium draba is a weed with the medicinal properties which few researches have been done on it. In this study, some traits, related to the osmotic stress, in 14-day-old L. draba...     

Coxsackievirus A24 variant uses sialic acid-containing O-linked glycoconjugates as cellular receptors on human ocular cells

Coxsackievirus A24 variant (CVA24v) is a main causative agent of acute hemorrhagic conjunctivitis (AHC), which is a highly contagious eye infection. Previously it has been suggested that CVA24v uses sialic acid-containing glycoconjugates as attachment receptors on corneal cells, but the nature of these receptors is poorly described. Here, we set out to characterize and identify the cellular components serving as receptors for CVA24v. Binding and infection experiments using corneal cells treated with deglycosylating enzymes or metabolic inhibitors of de novo glycosylation suggested that the receptor(s) used by CVA24v are constituted by sialylated O-linked glycans that are linked to one or more cell surface proteins but not to lipids. CVA24v bound better to mouse L929 cells overexpressing human P-selectin glycoprotein ligand-1 (PSGL-1) than to mock-transfected cells, suggesting that PSGL-1 is a candidate receptor for CVA24v. Finally, binding competition experiments using a library of mono- and oligosaccharides mimicking known PSGL-1 glycans suggested that CVA24v binds to Neu5Acα2,3Gal disaccharides (Neu5Ac is N-acetylneuraminic acid). These results provide further insights into the early steps of the CVA24v life cycle.     

Implications of the noncoding RNAs in rheumatoid arthritis pathogenesis

Epigenetics refers to a set of regulatory mechanisms that affect gene expression, while the original sequence of the DNA remains unchanged. Because the advance of noncoding RNAs (ncRNAs), the role of microRNAs (miRNAs) has been gradually highlighted in the regulation of numerous cellular processes. A bulk of studies has identified that ncRNAs might be divided into several subtypes. On the one hand, investigations have disclosed the role of these molecules in normal physiological conditions of the cells. On the other hand, there is sufficient evidence that ncRNAs participate in the pathogenesis of diseases. Through this review article, we attempted to gain a comprehensive understanding of the role of ncRNAs, long ncRNAs, miRNAs, and other subtypes in pathogenesis, diagnosis, and treatment of rheumatoid arthritis (RA). Research demonstrated aberrant expression of several miRNAs in various cell and tissue types of patients with RA in comparison to the healthy individuals as well as in animal studies. Furthermore, plausible molecular mechanisms of alterations in ncRNAs expression has been discussed in causing the disease state. These alterations seem promising to be used as biomarkers in RA diagnosis. Alternately, they might be targeted by drugs to interrupt inflammation and other disease complications to treat patients with RA.     

On the Ability of Formaldehyde to Act as a Tethering Catalyst in Water

The low concentration issue is a fundamental challenge when it comes to prebiotic chemistry, as macromolecular systems need to be assembled via intermolecular reactions, and this is inherently difficult in dilute solutions. This is especially true when the reactions are challenging, and reactions that proceeded more rapidly could have dictated chemical evolution. Herein we establish that formaldehyde is capable of catalyzing, via temporary intramolecularity, a challenging reaction in water at low concentrations, thus providing an alternative to other approaches that can either lead to higher concentrations or higher effective molarities.