scholarly journals MORPHOLOGICAL ANALYSIS OF HEPATITIS B VIRUS WITH ESCAPE MUTATIONS IN S-gene G145R AND S143L

2017 ◽  
Vol 62 (3) ◽  
pp. 119-128
Author(s):  
M. V. Konopleva ◽  
M. V. Sokolova ◽  
N. V. Shevlyagina ◽  
A. I. Bazhenov ◽  
A. A. Fel’Dsherova ◽  
...  
Keyword(s):  
Structural Changes ◽  
Wild Strain ◽  
Escape Mutation ◽  
Wild Type ◽  
S Gene ◽  
Morphological Heterogeneity ◽  
Morphological Organization ◽  
Recombinant Hbsag ◽  
The Impact ◽  
Subviral Particles

Background. In terms of serological properties and immunization, the wild type of HBsAg HBV and its G145R mutant behave as different antigens. This testifies to serious structural changes, which presumably could have a significant impact on the morphogenesis of virions and subviral particles. Nevertheless, morphological and ultrastructural investigations of HBV with G145R mutation have not been carried yet. Objectives. Research of structural and morphological organization of HBV in the presence of the G145R escape mutation. Methods. Studies of sera, purified viruses and recombinant HBsAg were carried out by transmission electron microscopy by the method of negative staining and indirect reaction of immunelabeling using monoclonal antibodies of different specificity. Specimens of wild type HBV and HBV with S143L mutation obtained in an identical manner were used as the control. Results. The presence of typical virus particles of HBV was shown in the specimens of wild strain and HBV with S143L mutation. Specimens of HBV with G145R mutation were characterized by expressed morphological heterogeneity. In the initial serum and in the specimen of purified virus containing G145R mutant, large oval particles 60-70 nm and up to 200 nm in size, respectively, were found. The presence of antigen structures of HBV in all heterogeneous forms was confirmed. It was shown that forming of subviral particles in the process of expression of the recombinant HBsAg with G145R mutation depends on conditions of expression and purification of the protein. They can vary from well-formed circular and oval particles to practically unstructured fine-grained masses. Conclusion. Direct data on the impact of G145R escape-mutation in S-gene, in contrast to S143L mutation, on the morphogenesis of virions and subviral particles of HBV were obtained.

P219L substitution in human D-amino acid oxidase impacts the ligand binding and catalytic efficiency

2020 ◽  
Vol 168 (5) ◽  
pp. 557-567
Author(s):  
Wanitcha Rachadech ◽  
Yusuke Kato ◽  
Rabab M Abou El-Magd ◽  
Yuji Shishido ◽  
Soo Hyeon Kim ◽  
...  
Keyword(s):  
Amino Acid ◽  
Conformational Changes ◽  
Active Site ◽  
Structural Changes ◽  
Catalytic Efficiency ◽  
Acid Oxidase ◽  
Wild Type ◽  
Amino Acid Oxidase ◽  
Adenine Ring ◽  
The Impact

Abstract Human D-amino acid oxidase (DAO) is a flavoenzyme that is implicated in neurodegenerative diseases. We investigated the impact of replacement of proline with leucine at Position 219 (P219L) in the active site lid of human DAO on the structural and enzymatic properties, because porcine DAO contains leucine at the corresponding position. The turnover numbers (kcat) of P219L were unchanged, but its Km values decreased compared with wild-type, leading to an increase in the catalytic efficiency (kcat/Km). Moreover, benzoate inhibits P219L with lower Ki value (0.7–0.9 µM) compared with wild-type (1.2–2.0 µM). Crystal structure of P219L in complex with flavin adenine dinucleotide (FAD) and benzoate at 2.25 Å resolution displayed conformational changes of the active site and lid. The distances between the H-bond-forming atoms of arginine 283 and benzoate and the relative position between the aromatic rings of tyrosine 224 and benzoate were changed in the P219L complex. Taken together, the P219L substitution leads to an increase in the catalytic efficiency and binding affinity for substrates/inhibitors due to these structural changes. Furthermore, an acetic acid was located near the adenine ring of FAD in the P219L complex. This study provides new insights into the structure–function relationship of human DAO.

scholarly journals Bioinformatics analysis of SARS-CoV-2 RBD mutant variants and insights into antibody and ACE2 receptor binding

2021 ◽  
Author(s):  
Prashant Ranjan ◽  
Neha   ◽  
Chandra Devi ◽  
Parimal Das
Keyword(s):  
Binding Affinity ◽  
Receptor Binding ◽  
Double Mutant ◽  
Structural Changes ◽  
Protective Efficacy ◽  
Spike Protein ◽  
Wild Type ◽  
Current Vaccine ◽  
New Variant ◽  
The Impact

Prevailing COVID-19 vaccines are based on the spike protein of earlier SARS-CoV-2 strain that emerged in Wuhan, China. Continuously evolving nature of SARS-CoV-2 resulting emergence of new variant/s raise the risk of immune absconds. Several RBD (receptor-binding domain) variants have been reported to affect the vaccine efficacy considerably. In the present study, we performed in silico structural analysis of spike protein of double mutant (L452R & E484Q), a new variant of SARS-CoV-2 recently reported in India along with K417G variants and earlier reported RBD variants and found structural changes in RBD region after comparing with the wild type. Comparison of the binding affinity of the double mutant and earlier reported RBD variant for ACE2 (angiotensin 2 altered enzymes) receptor and CR3022 antibody with the wild-type strain revealed the lowest binding affinity of the double mutant for CR3022 among all other variants. These findings suggest that the newly emerged double mutant could significantly reduce the impact of the current vaccine which threatens the protective efficacy of current vaccine therapy.

scholarly journals A COMPARATIVE CHARACTERISTIC OF ANTIGENIC PROPERTIES OF RECOMBINANT AND NATIVE HBS-ANTIGENS WITH G145R MUTATION AND EVALUATION OF THEIR IMMUNOGENICITY

2017 ◽  
Vol 62 (4) ◽  
pp. 179-186
Author(s):  
M. V. Konopleva ◽  
V. N. Borisova ◽  
M. V. Sokolova ◽  
A. A. Feldsherova ◽  
M. A. Krymskij ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Hepatitis B Vaccine ◽  
Comparative Characteristic ◽  
Escape Mutation ◽  
Wild Type ◽  
Mutant Type ◽  
Type Antigen ◽  
Antigenic Properties ◽  
Recombinant Hbsag ◽  
Immunogenic Properties

Background: One of the important reasons for spreading of hepatitis B virus (HBV) under conditions of vaccine pressure is emergence of escape mutations. Prevalent G145R mutation in S-gene leads to the most expressed changes of serological properties of HBV. Consequently, HBsAg is modified so thoroughly that it cannot be recognized by the majority of anti-HBs. Mutant G145R also differs from a wild type HBsAg by its immunogenic properties. At present, the relevance of enhancement of hepatitis B vaccine in view of mutant virus variants has been recognized. Objectives: a comparative study of antigenic and immunogenic properties of native and recombinant G145R mutants and an estimation of possibility for developing antigenic component of hepatitis B vaccine with G145R mutation in HBsAg. Methods: antigenic properties of recombinant HBsAg with G145R mutation were compared with each other and with native mutants by serological fingerprinting method. Then, BALB/c mice and sheep were immunized with selected recombinant antigen under different protocols. Titers of antibodies specific to wild type or mutant G145R type of HBsAg in sera of immunized animals were measured. Results: it was found that not all the recombinant HBsAg variants with G145R substitution have the same antigenic properties as native HBsAg with similar mutation. Recombinant HBsAg selected according to the principle of antigenic similarity possesses immunogenicity in mice and sheep causing the production of antibodies reacting with native wild and mutant type HBsAg. It was shown that mutant antigen is less immunogenic, requires larger doses and more time for the development of immune response; however, it is capable of causing an antibody level comparable with wild type antigen. Conclusion: preliminary selection of recombinant HBsAg containing G145R mutation with antigenic and immunogenic properties similar to the native analogue creates the basis for development of a specific component of hepatitis B vaccine with escape mutation G145R in HBsAg.

Subtle Impact of Akt1 and Akt3 on Exploratory Behavior in Gene Targeted Mice

2015 ◽  
Vol 223 (3) ◽  
pp. 173-180 ◽  
Author(s):  
Christina Leibrock ◽  
Michael Hierlmeier ◽  
Undine E. Lang ◽  
Florian Lang
Keyword(s):  
Forced Swimming Test ◽  
Open Field Test ◽  
Wild Type ◽  
Average Speed ◽  
Closed Area ◽  
Light Area ◽  
Swimming Test ◽  
The Impact ◽  
Center Area ◽  
Dark Transition

Abstract. The present study explored the impact of Akt1 and Akt3 on behavior. Akt1 (akt1-/-) and Akt3 (akt3-/-) knockout mice were compared to wild type (wt) mice. The akt1-/- mice, akt3-/- mice, and wt mice were similar in most parameters of the open-field test. However, the distance traveled in the center area was slightly but significantly less in akt3-/- mice than in wt mice. In the light/dark transition test akt1-/- mice had significantly lower values than wt mice and akt3-/- mice for distance traveled, number of rearings, rearing time in the light area, as well as time spent and distance traveled in the entrance area. They were significantly different from akt3-/- mice in the distance traveled, visits, number of rearings, rearing time in the light area, as well as time spent, distance traveled, number of rearings, and rearing time in the entrance area. In the O-maze the time spent, and the visits to open arms, as well as the number of protected and unprotected headdips were significantly less in akt1-/- mice than in wt mice, whereas the time spent in closed arms was significantly more in akt1-/- mice than in wt mice. Protected and unprotected headdips were significantly less in akt3-/- mice than in wt mice. In closed area, akt3-/- mice traveled a significantly larger distance at larger average speed than akt1-/- mice. No differences were observed between akt1-/- mice, akt3-/- mice and wt-type mice in the time of floating during the forced swimming test. In conclusion, akt1-/- mice and less so akt3-/ mice display subtle changes in behavior.

International trade: Research of the reasons for the fall

2019 ◽  
pp. 79-91 ◽  
Author(s):  
V. S. Nazarov ◽  
S. S. Lazaryan ◽  
I. V. Nikonov ◽  
A. I. Votinov
Keyword(s):  
Growth Rate ◽  
International Trade ◽  
Exchange Rate ◽  
Global Economy ◽  
Structural Changes ◽  
Global Value Chains ◽  
Value Chains ◽  
Negative Contribution ◽  
Basic Commodity ◽  
The Impact

The article assesses the impact of various factors on the growth rate of international trade. Many experts interpreted the cross-border flows of goods decline against the backdrop of a growing global economy as an alarming sign that indicates a slowdown in the processes of globalization. To determine the reasons for the dynamics of international trade, the decompositions of its growth rate were carried out and allowed to single out the effect of the dollar exchange rate, the commodities prices and global value chains on the change in the volume of trade. As a result, it was discovered that the most part of the dynamics of international trade is due to fluctuations in the exchange rate of the dollar and prices for basic commodity groups. The negative contribution of trade within global value chains in 2014 was also revealed. During the investigated period (2000—2014), such a picture was observed only in the crisis periods, which may indicate the beginning of structural changes in the world trade.

THE IMPACT OF UKRAINE'S EXCISE DUTY POLICY ON THE TRANSFORMATION PROCESSES OF THE TOBACCO MARKET

2020 ◽  
Vol 2020 (10) ◽  
pp. 19-33
Author(s):  
Nadiia NOVYTSKA ◽  
◽  
Inna KHLIEBNIKOVA ◽  
Keyword(s):  
Structural Changes ◽  
Tax Avoidance ◽  
Transformation Process ◽  
State Regulation ◽  
Tobacco Products ◽  
Excise Duty ◽  
Increasing Demand ◽  
High Level ◽  
The Impact ◽  
Transformation Processes

The market of tobacco products in Ukraine is one of the most dynamic and competitive. It develops under the influence of certain factors that cause structural changes, therefore, the aim of the article is to conduct a comprehensive analysis of transformation processes in the market of tobacco and their alternatives in Ukraine and identify the factors that cause them. The high level of tax burden and the proliferation of alternative products with a potentially lower risk to human health, including heating tobacco products and e-cigarettes, are key factors in the market’s transformation process. Their presence leads to an increase in illicit turnover of tobacco products, which accounts for 6.37% of the market, and the gradual replacement of cigarettes with alternative products, which account for 12.95%. The presence on the market of products that are not taxed or taxed at lower rates is one of the reasons for the reduction of excise duty revenues. According to the results of 2019, the planned indicators of revenues were not met by 23.5%. Other reasons for non-fulfillment of excise duty revenues include: declining dynamics of the tobacco products market; reduction in the number of smokers; reorientation of «cheap whites» cigarette flows from Ukraine to neighboring countries; tax avoidance. Prospects for further research are identified, namely the need to develop measures for state regulation and optimization of excise duty taxation of tobacco products and their alternatives, taking into account the risks to public health and increasing demand of illegal products.

Effekt of blood flow shutdown on the vein damage when exposed to HIFU

2017 ◽  
pp. 46-50
Author(s):  
Н.Н. Петрищев ◽  
Д.Ю. Семенов ◽  
А.Ю. Цибин ◽  
Г.Ю. Юкина ◽  
А.Е. Беркович ◽  
...  
Keyword(s):  
Blood Flow ◽  
Structural Changes ◽  
Focused Ultrasound ◽  
Vena Cava ◽  
Posterior Wall ◽  
High Intensity Focused Ultrasound ◽  
Vein Wall ◽  
Ultrasound Exposure ◽  
Isolated Segment ◽  
The Impact

The purpose. In the study we investigated the impact of the partial blood flow shutdown on structural changes in the rabbit vena cava posterior wall after exposure to high-intensity focused ultrasound (HIFU). Methods. Ultrasound Exposure: frequency of 1.65 MHz, the ultrasound intensity in the focus of 13.6 kW/cm, the area of the focal spot 1 mm, continuous ultrasound, exposure for 3 seconds. Results. Immediately after HIFU exposure all layers of the vein wall showed characteristic signs of thermal damage. A week after exposure structural changes in the intima, media and adventitia was minimal in the part of vessel with preserved blood flow, and after 4 weeks the changes were not revealed. A week after HIFU exposure partial endothelium destruction, destruction of myocytes, disorganization and consolidation of collagen fibers of the adventitia were observed in an isolated segment of the vessel, and in 4 weeks endothelium restored and signs of damage in media and adventitia persisted, but were less obvious than in a week after exposure. Conclusion. The shutdown of blood flow after exposure to HIFU promotes persistent changes in the vein wall. Vein compression appears to be necessary for the obliteration of the vessel, when using HIFU-technology.

scholarly journals KUALITAS AIR SUNGAI DI KAWASAN WISATA PANTAI PETITENGET, KEROBOKAN KABUPATEN BADUNG BALI

2018 ◽  
Vol 12 (2) ◽  
pp. 226
Author(s):  
Wayan Budiarsa Suyasa ◽  
Sri Kunti Pancadewi G. A ◽  
Iryanti E. Suprihatin ◽  
Dwi Adi Suastuti G. A.
Keyword(s):  
Water Quality ◽  
Structural Changes ◽  
Pollution Index ◽  
Basic Structure ◽  
Physical Damage ◽  
E Coli ◽  
Pollutant Source ◽  
Quality Category ◽  
Index Value ◽  
The Impact

In order to maintain the environmental carrying capacity of coastal tourism, this research was conducted to determine the condition of river water environmental pollution in the Petitenget beach area and pollutant source activities. Determination of water quality is carried out by analyzing the water quality taken at several sampling points in the four rivers that lead to the Petitenget beach. Determined the pollution index value (IP) of the physical chemical and biological pollution parameters. The results showed that the four rivers that flow into the Petitenget Beach area had been contaminated with indications of pH, BOD, COD, ammonia, Coliform and E. coli which exceeded water quality category III class quality (PerGub Bali No 16 Year 2016). The four rivers are included in the criteria of severe contamination. The four rivers have experienced physical damage or structural changes that have very high discharge fluctuations both in quantity and quality. Slimy basic structure, smelly and slum aesthetic waters. While the indication of the impact of pollution is waste water which is directly discharged into the river from hotels, restaurants, homestays, commercial centers and settlements.

Statistical Approaches to Structural Change in Regional Interindustry Models

1986 ◽  
Vol 18 (9) ◽  
pp. 1189-1207
Author(s):  
B Ó Huallacháin
Keyword(s):  
Structural Change ◽  
Structural Changes ◽  
Washington State ◽  
Multivariate Statistical Analyses ◽  
Input Output ◽  
Multivariate Statistical ◽  
State Data ◽  
System A ◽  
Statistical Approaches ◽  
The Impact

The conventional approach to assessing structural change in regional input – output tables is to measure the impact of coefficient change on the estimation of outputs and multipliers. The methods developed and tested in this paper focus exclusively on the coefficients. Univariate and multivariate statistical analyses can be used to identify and measure various types of changes ranging from coefficient instability to changes in interindustry relationships as a system. A distinction is made between structural changes in input relationships and those in output relationships. The methods are tested by using Washington State data for the years 1963 and 1967. The results are compared with previous analyses of change in these data.

scholarly journals Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells

2021 ◽  
Vol 22 (2) ◽  
pp. 772
Author(s):  
Javier Conde ◽  
Marlene Schwarzfischer ◽  
Egle Katkeviciute ◽  
Janine Häfliger ◽  
Anna Niechcial ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Titanium Dioxide ◽  
Genetic Risk ◽  
Intestinal Inflammation ◽  
Sodium Sulphate ◽  
Food Additive ◽  
Wild Type ◽  
Dextran Sodium Sulphate ◽  
Risk Gene ◽  
The Impact

Environmental and genetic factors have been demonstrated to contribute to the development of inflammatory bowel disease (IBD). Recent studies suggested that the food additive; titanium dioxide (TiO2) might play a causative role in the disease. Therefore, in the present study we aimed to explore the interaction between the food additive TiO2 and the well-characterized IBD risk gene protein tyrosine phosphatase non-receptor type 2 (Ptpn2) and their role in the development of intestinal inflammation. Dextran sodium sulphate (DSS)-induced acute colitis was performed in mice lacking the expression of Ptpn2 in myeloid cells (Ptpn2LysMCre) or their wild type littermates (Ptpn2fl/fl) and exposed to the microparticle TiO2. The impact of Ptpn2 on TiO2 signalling pathways and TiO2-induced IL-1β and IL-10 levels were studied using bone marrow-derived macrophages (BMDMs). Ptpn2LysMCre exposed to TiO2 exhibited more severe intestinal inflammation than their wild type counterparts. This effect was likely due to the impact of TiO2 on the differentiation of intestinal macrophages, suppressing the number of anti-inflammatory macrophages in Ptpn2 deficient mice. Moreover, we also found that TiO2 was able to induce the secretion of IL-1β via mitogen-activated proteins kinases (MAPKs) and to repress the expression of IL-10 in bone marrow-derived macrophages via MAPK-independent pathways. This is the first evidence of the cooperation between the genetic risk factor Ptpn2 and the environmental factor TiO2 in the regulation of intestinal inflammation. The results presented here suggest that the ingestion of certain industrial compounds should be taken into account, especially in individuals with increased genetic risk

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