Similarity between physicochemical properties of recombinant rat prorenin and native inactive renin.
Ontology highlight
ABSTRACT:
SUBMITTER: Hosoi M
PROVIDER: S-EPMC1150114 | biostudies-other | 1991 May
REPOSITORIES: biostudies-other
Similar Datasets
Project description:The world population has crossed seven billion and such a huge population has increased the pressure and considerably affects our ability to feed ourselves. It has now emerged as a new challenge for policy makers, food scientists and other associated people to make food available to everyone. To achieve this, underutilized crops/plants that act as good sources of starch need to be explored. Starch in its native form have certain limitations in its functional properties to be used for different applications. Therefore, it becomes important to explore certain technologies which could be used for modification of properties of starch. During the last decades gamma irradiation has emerged as an efficient processing technique for the modification of starch when compared to the other available processes. This review, aims to summarize the effects of gamma irradiation on various properties of starch such as physicochemical and rheological properties, functional characteristics, thermal behaviour etc. so as to make the starch suitable for various applications in different industries including the food industry.
| S-EPMC6400748 | biostudies-literature
Project description:How native and non-native languages are represented in the brain is one of the most important questions in neurolinguistics. Much research has found that the similarity in neural activity of native and non-native languages are influenced by factors such as age of acquisition, language proficiency, and language exposure in the non-native language. Nevertheless, it is still unclear how the similarity between native and non-native languages in orthographic transparency, a key factor that affects the cognitive and neural mechanisms of phonological access, modulates the cross-language similarity in neural activation and which brain regions show the modulatory effects of language distance in orthographic transparency. To address these questions, the present study used representational similarity analysis (RSA) to precisely estimate the neural pattern similarity between native language and two non-native languages in Uyghur-Chinese-English trilinguals, whose third language (i.e., English) was more similar to the native language (i.e., Uyghur) in orthography than to their second language (i.e., Chinese). Behavioral results revealed that subjects responded faster to words in the non-native language with more similar orthography to their native language in the word naming task. More importantly, RSA revealed greater neural pattern similarity between Uyghur and English than between Uyghur and Chinese in select brain areas for phonological processing, especially in the left hemisphere. Further analysis confirmed that those brain regions represented phonological information. These results provide direct neuroimaging evidence for the modulatory effect of language distance in orthographic transparency on cross-language pattern similarity between native and non-native languages during word reading.
| S-EPMC7856648 | biostudies-literature
Project description:Development of bio-therapeutics has exhibited exponential growth in China over the past decade. However, no biosimilar drug has been approved in China (CN) due to the lack of a national biosimilar regulatory guidance. HLX01, a rituximab biosimilar developed in China under European Medicines Agency biosimilar guidelines and requirements, was the first such drug submitted for regulatory review in China, and it is expected to receive approval there as a biosimilar product. To demonstrate the analytical similarities of HLX01, CN-rituximab (sourced in China but manufactured in Europe) and EU-rituximab (sourced and manufactured in Europe), an extensive 3-way physicochemical and functional similarity assessment using a series of orthogonal and state-of-the-art techniques was conducted, following the similarity requirement guidelines recently published by China's Center for Drug Evaluation. The results of the similarity study showed an identical protein amino acid sequence and highly similar primary structures between HLX01 and the reference product (RP) MabThera®, along with high similarities in higher order structures, potency, integrity, purity and impurity profiles, biological and immunological binding functions, as well as degradation behaviors under stress conditions. In addition, HLX01 presented slightly lower aggregates and better photostability compared with the RP. Despite slight changes in relative abundance of glycan moieties and heavy chain C-terminal lysine modification, no differences in biological activities and immunological properties were observed between the RP and HLX01. In conclusion, HLX01 is highly similar to CN- and EU-sourced RP in terms of physicochemical properties and biological activities, suggesting similar product quality, efficacy, and safety. The regulatory requirements interpreted and applied towards the HLX01 marketing application sets a precedent for analytical similarity assessment of biosimilar products in China.
| S-EPMC6512903 | biostudies-literature
Project description:Biosimilars are biological products that are highly similar to existing products approved by health authorities. Demonstration of similarity starts with the comprehensive analysis of the reference product and its proposed biosimilar at the physicochemical and functional levels. Here, we report the results of a comparative analysis of a proposed biosimilar adalimumab MSB11022 and its reference product, Humira®. Three batches of MSB11022 and up to 23 batches of Humira® were analyzed by a set of state-of-the-art orthogonal methods. Primary and higher order structure analysis included N/C-terminal modifications, molecular weight of heavy and light chains, C-terminal lysine truncation, disulfide bridges, secondary and tertiary structures, and thermal stability. Purity ranged from 98.4%-98.8% for MSB11022 batches (N = 3) and from 98.4%-99.6% for Humira® batches (N = 19). Isoform analysis showed 5 isoform clusters within the pI range of 7.94-9.14 and 100% glycan site occupancy for both MSB11022 and Humira®. Functional analysis included Fab-dependent inhibition of tumor necrosis factor (TNF)-induced cytotoxicity in L929-A9 cell line and affinity to soluble and transmembrane forms of TNF, as well as Fc-dependent binding to Fcγ and neonatal Fc receptors and C1q complement proteins. All tested physicochemical and functional parameters demonstrated high similarity of MSB11022 and Humira®, with lower variability between MSB11022 and Humira® batches compared with variability within individual batches of Humira®. Based on these results, MSB11022 is anticipated to have safety and efficacy comparable to those of Humira®.
| S-EPMC5240642 | biostudies-literature
Project description:Quantitative electroencephalography from freely moving rats is commonly used as a translational tool for predicting drug-effects in humans. We hypothesized that drug-effects may be expressed differently depending on whether the rat is in active locomotion or sitting still during recording sessions, and proposed automatic state-detection as a viable tool for estimating drug-effects free of hypo-/hyperlocomotion-induced effects. We aimed at developing a fully automatic and validated method for detecting two behavioural states: active and inactive, in one-second intervals and to use the method for evaluating ketamine, DOI, d-cycloserine, d-amphetamine, and diazepam effects specifically within each state. The developed state-detector attained high precision with more than 90% of the detected time correctly classified, and multiple differences between the two detected states were discovered. Ketamine-induced delta activity was found specifically related to locomotion. Ketamine and DOI suppressed theta and beta oscillations exclusively during inactivity. Characteristic gamma and high-frequency oscillations (HFO) enhancements of the NMDAR and 5HT2A modulators, speculated associated with locomotion, were profound and often largest during the inactive state. State-specific analyses, theoretically eliminating biases from altered occurrence of locomotion, revealed only few effects of d-amphetamine and diazepam. Overall, drug-effects were most abundant in the inactive state. In conclusion, this new validated and automatic locomotion state-detection method enables fast and reliable state-specific analysis facilitating discovery of state-dependent drug-effects and control for altered occurrence of locomotion. This may ultimately lead to better cross-species translation of electrophysiological effects of pharmacological modulations.
| S-EPMC6806018 | biostudies-literature
Project description:Membrane proteins, including G protein-coupled receptors (GPCRs), present a challenge in studying their structural properties under physiological conditions. Moreover, to better understand the activity of proteins requires examination of single molecule behaviors rather than ensemble averaged behaviors. Force-distance curve-based AFM (FD-AFM) was utilized to directly probe and localize the conformational states of a GPCR within the membrane at nanoscale resolution based on the mechanical properties of the receptor. FD-AFM was applied to rhodopsin, the light receptor and a prototypical GPCR, embedded in native rod outer segment disc membranes from photoreceptor cells of the retina in mice. Both FD-AFM and computational studies on coarse-grained models of rhodopsin revealed that the active state of the receptor has a higher Young's modulus compared to the inactive state of the receptor. Thus, the inactive and active states of rhodopsin could be differentiated based on the stiffness of the receptor. Differentiating the states based on the Young's modulus allowed for the mapping of the different states within the membrane. Quantifying the active states present in the membrane containing the constitutively active G90D rhodopsin mutant or apoprotein opsin revealed that most receptors adopt an active state. Traditionally, constitutive activity of GPCRs has been described in terms of two-state models where the receptor can achieve only a single active state. FD-AFM data are inconsistent with a two-state model but instead require models that incorporate multiple active states.
| S-EPMC6557672 | biostudies-literature
Project description:1. Rat alpha2 acute-phase macroglobulin was isolated from turpentine-injected rats by Sephadex G-200 chromatography and ion-exchange chromatography on DEAE-cellulose. This method, since it does not include (NH4)2SO4 treatment, allows the study of the physicochemical as well as the biological properties of the molecule. 2. The purity of the preparation was demonstrated by ultracentrifugation, polyacrylamide-gel electrophoresis, fused "rocket" immunoelectrophoresis as well as double immunodiffusion. 3. The rat alpha2 acute-phase macroglobulin was characterized in terms of its main physical and chemical properties. Its isoelctric point was determined by isoelectrofocusing to be 4.55; s020,w was 18.4S and E1%/1cm at 278 nm was 6.8. The mol.wt. was determined by light-scattering to be 770000. 4. The amino acid content was compared with that of rat alpha1 macroglobulin and was found very similar. The carbohydrate composition of alpha2 acute-phase macroglobulin was determined to be: hexose, 4.25%; glucosamine, 3.4%; sialic acid, 2%; fucose, 0.2%. From these results it was concluded that alpha2 acute-phase macroglobulin, although a typical acute-phase reactant, possesses the characteristic physicochemical properties of alpha macroglobulins.
| S-EPMC1164166 | biostudies-other
Project description:Human prohormone convertase PC2 was expressed in Xenopus oocytes and its properties were compared with those of the Type-2 endopeptidase of rat insulin secretory granules, previously identified as PC2 [Bennett, Bailyes, Nielson, Guest, Rutherford, Arden and Hutton (1992) J. Biol. Chem. 267, 15229-15236]. Recombinant PC2 had the same substrate specificity as the Type-2 endopeptidase, cleaving at the CA-junction (Lys64, Arg65) of human des-31,32-proinsulin to generate insulin; little activity was found toward human des-64,65-proinsulin or proinsulin itself. Recombinant PC2 was maximally active in 5-7 mM Ca2+ (K0.5 = 1.6 mM) whereas the Type-2 endopeptidase was maximally active in 0.5-1 mM Ca2+ (K0.5 = 40 microM). Both enzymes had a pH optimum of 5.0-5.5 but the Type-2 endopeptidase was active over a wider pH range. Two molecular forms of recombinant PC2 (71 kDa and 68 kDa) were found, both had an intact C-terminus but differed by the presence of the propeptide. The endogenous PC2 comprised several overlapping forms (size range 64-68 kDa), approximately two-thirds of which lacked C-terminal immunoreactivity. Part of the size difference between recombinant and endogenous PC2 was attributable to differences in N-glycosylation. The different post-translational proteolytic modifications of recombinant and endogenous PC2 did not account for the different pH and Ca2+ sensitivities shown by the enzymes. A modulating effect of carbohydrate on enzyme activity could not be excluded.
| S-EPMC1135771 | biostudies-other
Project description:The discovery of novel mechanism of action (MOA) antibacterials has been associated with the concept that antibacterial drugs occupy a differentiated region of physicochemical space compared to human-targeted drugs. With, in broad terms, antibacterials having higher molecular weight, lower logP and higher polar surface area (PSA). By analysing the physicochemical properties of about 1700 approved drugs listed in the ChEMBL database, we show, that antibacterials for whose targets are riboproteins (i.e., composed of a complex of RNA and protein) fall outside the conventional human 'drug-like' chemical space; whereas antibacterials that modulate bacterial protein targets, generally comply with the 'rule-of-five' guidelines for classical oral human drugs. Our analysis suggests a strong target-class association for antibacterials-either protein-targeted or riboprotein-targeted. There is much discussion in the literature on the failure of screening approaches to deliver novel antibacterial lead series, and linkage of this poor success rate for antibacterials with the chemical space properties of screening collections. Our analysis suggests that consideration of target-class may be an underappreciated factor in antibacterial lead discovery, and that in fact bacterial protein-targets may well have similar binding site characteristics to human protein targets, and questions the assumption that larger, more polar compounds are a key part of successful future antibacterial discovery.
| S-EPMC4537081 | biostudies-literature
Project description:Invasive species can significantly affect native species when their niches are similar. Ecological and morphological similarities between the invasive Australian palm, Archontophoenix cunninghamiana, and the native palm from the Brazilian Atlantic Forest, Euterpe edulis, suggest that they have similar environmental requirements and functional roles (i.e., the function a species performs in an ecosystem). This similarity raises concerns about how the invasive palm could impact the native species in the present and future. We used spatial (species occurrences) and ecological information (frugivory events) to characterize the environmental niche and functional role of the two palms and assess their overlap. In addition, we predicted the potential area of occurrence of each palm within the Brazilian Atlantic Forest under current and future climate conditions.We estimated the environmental conditions used by the invasive plant based on its native distribution only, and based on all areas where the species is able to establish across the globe. We found that the environmental niches of the two palm species overlap up to 39%, which corresponds to 50% of the current geographic distribution of E. edulis in the Atlantic Forest. In the areas where the two species potentially co-occur, the impact of the invasive species on the native should be influenced by the invasive species interactions with frugivores. We found that the frugivory functional role of the two palms was similar (84% overlap) which suggest that A. cunninghamiana might disrupt the seed dispersal of the native palm. However, co-occurrence between the palms may decline with future climate change, as the potentially environmental suitable area for the invasive palm is predicted to decline by 10% to 55%. Evaluating the similarity in both the environmental niche, of the native and global extent, and the functional role of native and invasive plants provides a detailed understanding of the potential impact of invasive species on native species now and in the future.
| S-EPMC7900028 | biostudies-literature