The enzymatic activity of human carbonic anhydrase II (HCAII) was studied in the presence of nanoparticles of different nature and charge. Negatively charged nanoparticles inhibit HCAII whereas no effect is seen for positively charged particles. The kinetic effects were correlated with the strength of binding of the enzyme to the particle surface as measured by ITC and adsorption assays. Moreover, conformational changes upon adsorption were observed by circular dichroism. The main initial driving force for the adsorption of HCAII to nanoparticles is of electrostatic nature whereas the hydrophobic effect is not strong enough to drive the initial binding. This is corroborated by the fact that HCAII do not adsorb on positively charged hydrophobic polystyrene nanoparticles. Furthermore, the dehydration of the particle and protein surface seems to play an important role in the inactivation of HCAII by carboxyl-modified polystyrene nanoparticles. On the other hand, the inactivation by unmodified polystyrene nanoparticles is mainly driven by intramolecular interactions established between the protein and the nanoparticle surface upon conformational changes in the protein.
Between 1962 and 1965, before Kimura postulated the neutral theory of evolution (Kimura, 1968), Zuckerkandl and Pauling published two fundamental papers on the evolutionary rate of proteins (Zuckerkandl & Pauling, 1962; Zuckerkandl & Pauling, 1965). They noticed that the genetic distance of two sequences coding for the same protein, but isolated from different species, seems to increase linearly with the divergence time of the two species. Since several proteins showed a similar behavior, Zuckerkandl and Pauling hypothesized that the rate of evolution for any given protein is constant over time. This suggestion implies the existence of a sort of molecular clock ticking faster or slower for different genes but at a more or less constant rate for any given gene among different phylogenetic lineages (see Fig. 11.1). The clock hypothesis received an enormous popularity almost immediately for several reasons. If a molecular clock exists and the rate of evolution of a gene can be calculated, then this information can easily be used for dating the unknown divergence time between two species just by comparing their DNA or protein sequences. If, on the other hand, the information about the divergence time between two species (for example, estimated from fossil data) is known, then the rate of molecular evolution of a given gene can be inferred. An additional advantage of assuming a molecular clock is that it can render phylogenetic reconstruction much easier and more accurate (see Chapter 5).
Quantitative genetics is the study of continuously varying traits which make up the majority of biological attributes of evolutionary and commercial interest. This book provides a much-needed up-to-date, in-depth yet accessible text for the field. In lucid language, the author guides readers through the main concepts of population and quantitative genetics and their applications. It is written to be approachable to even those without a strong mathematical background, including applied examples, a glossary of key terms, and problems and solutions to support students in grasping important theoretical developments and their relevance to real-world biology. An engaging, must-have textbook for advanced undergraduate and postgraduate students. Given its applied focus, it also equips researchers in genetics, genomics, evolutionary biology, animal and plant breeding, and conservation genetics with the understanding and tools for genetic improvement, comprehension of the genetic basis of human diseases, and conservation of biological resources.
Asleep SBP is the most significant BP-derived risk factor for CVD events. Furthermore, treatment-induced decrease of asleep, but not awake SBP, a novel hypertension therapeutic target requiring periodic patient evaluation by ambulatory monitoring, is associated with significantly lower risk for CVD morbidity and mortality.
Abstract Zero-dimensional nanostructures such as ZnO#ZnS QDs heterojunctures (QDHJs) are green nanoparticles and have gained a tremendous amount of attention. However, very little information is available on the effects of these heterojunctures on the transportation of drugs in blood. Herein, stilbenes were studied for their affinities for common bovine plasma proteins (CBPP) in the presence and absence of QDHJs with different diameters. The affinities of QDHJs for CBPP improved with increasing QDHJs size. QDHJs improved the affinities of resveratrol and polydatin for CBPP by 14.74% to 22.36% and 12.56% to 21.34% depending on the size of QDHJs. The number of binding sites (n) between resveratrol and polydatin for CBPP in the presence of QDHJs were 1.04 ± 0.03 and 1.06 ± 0.04, which were obviously higher than those in the absence of QDHJs (n = 0.89 and 0.92). QDHJs in blood will decrease the free concentration of stilbenes and weaken their pharmacological effects.
<b><i>Background:</i></b> Focal and segmental glomerulosclerosis (FSGS) is a clinical-pathologic condition marked by segmental and localized glomerular damages. Despite investigations, the molecular mechanisms behind FSGS development remain to be more clarified. By a comprehensive analysis of an FSGS-related array set, the aim of this study was to unravel the top pathways and molecules involved in the pathogenesis of this disorder. <b><i>Methods:</i></b> FSGS-related microarray dataset (GSE129973) from the Gene Expression Omnibus database was quality checked, analyzed, and its differentially expressed genes (DEGs) (log2 fold change &#x3e; 1) were used for the construction of a protein-protein interaction (PPI) network (STRING). The degree of centrality was considered to select the hub molecules in the network. The weighted gene co-expression network analysis (WGCNA) was utilized to construct co-expression modules. Hub molecules were selected based on module membership and gene significance values in the disease’s most correlated module. After spotting the key molecules considering both strategies, their expression pattern was checked in other FSGS microarray datasets. Gene ontology and Reactome pathway enrichment analyses were performed on the DEGs of the related module. <b><i>Results:</i></b> After quality checking, normalization, and analysis of the dataset, 5,296 significant DEGs, including 2,469 upregulated and 2,827 downregulated DEGs were identified. The WGCNA algorithm clustered the DEGs into nine independent co-expression modules. The disease most correlated module (black module) was recognized and considered for further enrichment analysis. The immune system, cell cycle, and vesicle-mediated transports were among the top enriched terms for the identified module’s DEGs. The immune system, cell cycle, and vesicle-mediated transports were among the top enriched terms for the black module’s DEGs. The key molecules (<i>BMP-2</i> and <i>COL4A1</i>) were identified as common hub molecules extracted from the two methods of PPI and the co-expressed networks. The two identified key molecules were validated in other FSGS datasets, where a similar pattern of expression was observed for both the genes. <b><i>Conclusions:</i></b> Two hub molecules (<i>BMP-2</i> and <i>COL4A</i>) and some pathways (vesicle-mediated transport) were recognized as potential players in the pathogenesis of FSGS.
The volatilisation of chromium as its acetylacetonate and subsequent atomisation in a silica tube, heated with an air-acetylene flame was used for the determination of chromium in steel. The proposed method gives a detection limit (DL) of 0.2 ng (DL =kσ/s) and the reproducibility, expressed as the relative standard deviation, is of the order of 4%. The conditions of chelate formation and the matrix effects were investigated. This method eliminates the interference effect produced by iron and acids on the chromium signal.
