scholarly journals Viroporin activity of SARS-CoV-2 Orf3a and Envelope protein impacts viral pathogenicity

2021 ◽  
Author(s):  
Manish Sarkar ◽  
Paul Etheimer ◽  
Soham Saha
Keyword(s):  
Electrostatic Interactions ◽  
Inflammatory Responses ◽  
Water Channel ◽  
Point Of View ◽  
Alveolar Cells ◽  
E Protein ◽  
Ionic Imbalance ◽  
Cellular Compartments ◽  
Shed Light ◽  
Structural Point

COVID-19 is caused by SARS-CoV-2 which has affected nearly 220 million people worldwide and death toll close to 5 million as of present day. The approved vaccines are lifesaving yet temporary solutions to such a devastating pandemic. Viroporins are important players of the viral life cycle of SARS-Cov-2 and one of the primary determinants of its pathogenesis. We studied the two prominent viroporins of SARS-CoV-2 (i) Orf3a and (ii) Envelope (E) protein from a structural point of view. Orf3a has several hotspots of mutations which has been reported in SARS-CoV-2 with respect to SARS-CoV-1. Mutations in SARS-CoV-2 Orf3a channel forming residues enhances the formation of a prominent the inter-subunit channel, which was not present in the SARS-CoV-1 Orf3a. This enhanced structural feature can be correlated with higher channelling activity in SARS-CoV-2 than in SARS-CoV-1. On the other hand, E protein is one of the most conserved protein among the SARS-CoV proteome. We found that the water molecules form networks of electrostatic interactions with the polar residues in the E protein putative wetted condition while no water channel formation was observed in the putative dewetted condition. This aqueous medium mediates the non-selective translocation of cations thus affecting the ionic homeostasis of the host cellular compartments. This ionic imbalance leads to increased inflammatory response in the host cell. Our results shed light into the mechanism of viroporin action, which can be leveraged for the development of antiviral therapeutics. Furthermore, our results corroborate with previously published transcriptomic data from COVID-19 infected lung alveolar cells where inflammatory responses and molecular regulators directly impacted by ion channelling were upregulated. These observations overlap with transcript upregulation observed in diseases having acute lung injury, pulmonary fibrosis and Acute Respiratory Distress Syndrome (ARDS).

scholarly journals Structural study on ligand specificity of human vitamin B12 transporters

2007 ◽  
Vol 403 (3) ◽  
pp. 431-440 ◽  
Author(s):  
Jochen Wuerges ◽  
Silvano Geremia ◽  
Lucio Randaccio
Keyword(s):  
Vitamin B12 ◽  
Electrostatic Interactions ◽  
Intrinsic Factor ◽  
Point Of View ◽  
Tryptophan Residue ◽  
Ligand Specificity ◽  
Binding Assays ◽  
Terminal Domain ◽  
Affinity Constants ◽  
Structural Point

Studies comparing the binding of genuine cobalamin (vitamin B12) to that of its natural or synthetic analogues have long established increasing ligand specificity in the order haptocorrin, transcobalamin and intrinsic factor, the high-affinity binding proteins involved in cobalamin transport in mammals. In the present study, ligand specificity was investigated from a structural point of view, for which comparative models of intrinsic factor and haptocorrin are produced based on the crystal structure of the homologous transcobalamin and validated by results of published binding assays. Many interactions between cobalamin and its binding site in the interface of the two domains are conserved among the transporters. A structural comparison suggests that the determinant of specificity regarding cobalamin ligands with modified nucleotide moiety resides in the β-hairpin motif β3-turn-β4 of the smaller C-terminal domain. In haptocorrin, it provides hydrophobic contacts to the benzimidazole moiety through the apolar regions of Arg357, Trp359 and Tyr362. Together, these large side chains may compensate for the missing nucleotide upon cobinamide binding. Intrinsic factor possesses only the tryptophan residue and transcobalamin only the tyrosine residue, consistent with their low affinity for cobinamide. Relative affinity constants for other analogues are rationalized similarly by analysis of steric and electrostatic interactions with the three transporters. The structures also indicate that the C-terminal domain is the first site of cobalamin-binding since part of the β-hairpin motif is trapped between the nucleotide moiety and the N-terminal domain in the final holo-proteins.

Masonry: the brittle or plastic material?

2019 ◽  
pp. 22-28
Keyword(s):  
Plastic Material ◽  
Experimental Studies ◽  
Point Of View ◽  
Plastic Properties ◽  
Plastic Deformations ◽  
Base Materials ◽  
Stress States ◽  
Creep Deformations ◽  
Structural Point

The results of experimental studies of masonry on the action of dynamic and static (short-term and long-term) loads are presented. The possibility of plastic deformations in the masonry is analyzed for different types of force effects. The falsity of the proposed approach to the estimation of the coefficient of plasticity of masonry, taking into account the ratio of elastic and total deformations of the masonry is noted. The study of the works of Soviet scientists revealed that the masonry under the action of seismic loads refers to brittle materials in the complete absence of plastic properties in it in the process of instantaneous application of forces. For the cases of uniaxial and plane stress states of the masonry, data on the coefficient of plasticity obtained from the experiment are presented. On the basis of experimental studies the influence of the strength of the so-called base materials (brick, mortar) on the bearing capacity of the masonry, regardless of the nature of the application of forces and the type of its stress state, is noted. The analysis of works of prof. S. V. Polyakov makes it possible to draw a conclusion that at the long application of the load, characteristic for the masonry are not plastic deformations, but creep deformations. It is shown that the proposals of some authors on the need to reduce the level of adhesion of the mortar to the brick for the masonry erected in earthquake-prone regions in order to improve its plastic properties are erroneous both from the structural point of view and from the point of view of ensuring the seismic resistance of structures. It is noted that the proposal to assess the plasticity of the masonry of ceramic brick walls and large-format ceramic stone with a voidness of more than 20% is incorrect, and does not meet the work of the masonry of hollow material. On the basis of the analysis of a large number of research works it is concluded about the fragile work of masonry.

Crimes against marriage and family before Criminal Code 1968

2020 ◽  
Vol 15 (1-3) ◽  
pp. 44-59
Author(s):  
Lidia Peneva
Keyword(s):  
Criminal Code ◽  
Point Of View ◽  
Marriage And Family ◽  
Historical Method ◽  
Legal Method ◽  
The Subject ◽  
The Republic ◽  
Criminal Groups ◽  
The Moment ◽  
Structural Point

Crimes against marriage and family are a particular group of social relation­ships that the law has defended properly in view of the high public significance and value they enjoy. At the moment they are regulated in Chapter VI, Section I, of the specific part of the Penal Code the Repub­lic of Bulgaria. The subject matter of this Statement will, however, be the legisla­tive provisions concerning these criminal­ized acts in retrospect. The purpose of the study is to show by historical method and through the comparatively legal method the development of these criminal groups during the periods of various criminal laws in Bulgaria. This will also provide a basis for reflection on possible de lege ferenda proposals. This report from a structural point of view will be divided into three distinct points, marking each of the penal laws in the Republic of Bulgaria, which were in force before 1968.

scholarly journals Recuperative Amino Acids Separation through Cellulose Derivative Membranes with Microporous Polypropylene Fiber Matrix

Membranes ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 429
Author(s):  
Aurelia Cristina Nechifor ◽  
Andreia Pîrțac ◽  
Paul Constantin Albu ◽  
Alexandra Raluca Grosu ◽  
Florina Dumitru ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cellulose Acetate ◽  
Polypropylene Fiber ◽  
Point Of View ◽  
Hydroxyethyl Cellulose ◽  
Separation Performance ◽  
Thermal Gravimetric Analyzer ◽  
Microfiltration Membranes ◽  
Ft Ir ◽  
Structural Point

The separation, concentration and transport of the amino acids through membranes have been continuously developed due to the multitude of interest amino acids of interest and the sources from which they must be recovered. At the same time, the types of membranes used in the sepa-ration of the amino acids are the most diverse: liquids, ion exchangers, inorganic, polymeric or composites. This paper addresses the recuperative separation of three amino acids (alanine, phe-nylalanine, and methionine) using membranes from cellulosic derivatives in polypropylene ma-trix. The microfiltration membranes (polypropylene hollow fibers) were impregnated with solu-tions of some cellulosic derivatives: cellulose acetate, 2-hydroxyethyl-cellulose, methyl 2-hydroxyethyl-celluloseand sodium carboxymethyl-cellulose. The obtained membranes were characterized in terms of the separation performance of the amino acids considered (retention, flux, and selectivity) and from a morphological and structural point of view: scanning electron microscopy (SEM), high resolution SEM (HR-SEM), Fourier transform infrared spectroscopy (FT-IR), energy dispersive spectroscopy (EDS) and thermal gravimetric analyzer (TGA). The re-sults obtained show that phenylalanine has the highest fluxes through all four types of mem-branes, followed by methionine and alanine. Of the four kinds of membrane, the most suitable for recuperative separation of the considered amino acids are those based on cellulose acetate and methyl 2-hydroxyethyl-cellulose.

scholarly journals Growth Arrest-Specific Factor 6 (GAS6) Is Increased in COVID-19 Patients and Predicts Clinical Outcome

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 335
Author(s):  
Albert Morales ◽  
Silvia Rojo Rello ◽  
Helena Cristóbal ◽  
Aida Fiz-López ◽  
Elisa Arribas ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Growth Arrest ◽  
Emergency Admission ◽  
Human Macrophage ◽  
Specific Factor ◽  
Alveolar Cells ◽  
Lps Challenge ◽  
Tam Receptors ◽  
Relevant Role ◽  
Severity Of The Disease

Background: Growth arrest-specific factor 6 (GAS6) and the Tyro3, AXL, and MERTK (TAM) receptors counterbalance pro-inflammatory responses. AXL is a candidate receptor for SARS-CoV-2, particularly in the respiratory system, and the GAS6/AXL axis is targeted in current clinical trials against COVID-19. However, GAS6 and TAMs have not been evaluated in COVID-19 patients at emergency admission. Methods: Plasma GAS6, AXL, and MERTK were analyzed in 132 patients consecutively admitted to the emergency ward during the first peak of COVID-19. Results: GAS6 levels were higher in the SARS-CoV-2-positive patients, increasing progressively with the severity of the disease. Patients with initial GAS6 at the highest quartile had the worst outcome, with a 3-month survival of 65%, compared to a 90% survival for the rest. Soluble AXL exhibited higher plasma concentration in deceased patients, without significant differences in MERTK among SARS-CoV-2-positive groups. GAS6 mRNA was mainly expressed in alveolar cells and AXL in airway macrophages. Remarkably, THP-1 human macrophage differentiation neatly induces AXL, and its inhibition (bemcentinib) reduced cytokine production in human macrophages after LPS challenge. Conclusions: Plasma GAS6 and AXL levels reflect COVID-19 severity and could be early markers of disease prognosis, supporting a relevant role of the GAS6/AXL system in the immune response in COVID-19.

scholarly journals Crystallographic and structural characterization of heterometallic platinum compounds Part VII. Heterohepta- and heterooctanuclear clusters

2014 ◽  
Vol 13 (1) ◽  
Author(s):  
Milan Melnik ◽  
Peter Mikuš ◽  
Clive E. Holloway
Keyword(s):  
Structural Characterization ◽  
Structural Parameters ◽  
Bond Distance ◽  
Point Of View ◽  
Platinum Compounds ◽  
Metal Atoms ◽  
Platinum Clusters ◽  
Structural Point

AbstractThis review classifies and analyzes over fifty heterohepta- and heterooctanuclear platinum clusters. There are eight types of metal combinations in heteroheptanuclear: Pt6M, Pt5M2, Pt4M3, Pt3M4, Pt2M5, PtM6, Pt3Hg2Ru2 and Pt2Os3Fe2. The seven metal atoms are in a wide variety of arrangements, with the most common being one in which the central M atom (mostly M(I)) is sandwiched by two M3 triangles. Another arrangement often found is an octahedron of M6 atoms asymmetrically capped by an M atom. The shortest Pt-M bond distances (non-transition and transition) are 2.326(1) Å (M = Ga) and 2.537(6) Å (M = Fe). The shortest Pt-Pt bond distance is 2.576(2) Å.In heterooctanuclear platinum clusters there are eight types of metal combinations: Pt6M2, Pt4M4, Pt3Ru5, Pt2M6, PtM7, Pt2W4Ni2, PtAu6Hg and PtAu5Hg2. From a structural point of view, the clusters are complex with bicapped octahedrons of eight metal atoms prevailing. The shortest Pt-M bond distances (non-transition and transition) are 2.651(3) Å (M = Hg) and 2.624(1) Å (M = Os). The shortest Pt-Pt bond distance is 2.622(1) Å. These values are somewhat longer than those in the heteroheptanuclear clusters. Several relationships between the structural parameters were found, and are discussed and compared with the smaller heterometallic platinum clusters

The phenomenon of migration of nociogenic structures in the human sensor-algic system (results of clinical and neurophysiological studies and morphological experiments)

2020 ◽  
pp. 16-24
Author(s):  
Maksim Vladimirovich Shpagin ◽  
Mikhail Valerievich Kolesnikov ◽  
Olga Yurievna Khutorskaya ◽  
Dmitriy Evgenievich Timoshkin ◽  
Artem Andreevich Belikin ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Pain Syndrome ◽  
Point Of View ◽  
Chronic Pain Syndrome ◽  
Integrative Therapy ◽  
Neurophysiological Studies ◽  
Positive Results ◽  
Structural Point ◽  
Chronicity Of Pain

From the informational and structural point of view, the chronicity of pain is associated with the migration of nociogenic zones. The phenomenon of migration is based on the mechanisms of neuroplasticity, compensatory-restorative processes in the nervous system. On the basis of the phenomenon of migration of the nociogenic zone, a system of regional integrative therapy of chronic pain syndrome has been developed. Recommendations on the advisability of invasive shutdown of the nociogenic zone using invasive pharmacotherapy or surgical denervation have been proposed. In the course of studying the characteristics of chronic pain, depending on the duration of the disease, a direct proportional correlation was revealed between the increase in the components of pain and the duration of the pain syndrome, which can be explained by the increase in the number of nociogenic structures that form the complexity and stability of the pain syndrome. Thus, the necessity of neurodestructive interventions increases for attaining positive results. An important area of therapy is the inclusion of psychotherapy, pharmacotherapy and neuromodulation into the system of regional-integrative influence.

scholarly journals Design & Weight Optimization of a Wheel Rim for Sport Utility Vehicle.

2018 ◽  
Vol 172 ◽  
pp. 03006
Author(s):  
Harish Panjagala ◽  
Balakrishna M ◽  
Shasikant Kushnoore ◽  
E L N Rohit Madhukar
Keyword(s):  
Structural Analysis ◽  
Point Of View ◽  
Weight Optimization ◽  
Strength Assessment ◽  
Suitable Material ◽  
The Road ◽  
Wheel Rim ◽  
Standard Values ◽  
Design Weight ◽  
Structural Point

Automobile have various parts which are important for good running of the vehicle. The most important safety components from a structural point of view are the road wheels. They are required to be lighter and more fascinating to the buyer all the time. This implies that it's important to perform a lot of accurate strength assessment on wheel styles. The wheel rim plays a major role in vehicle dynamics. This paper deals with the design and model of different wheel rims based on weight optimization and also structural analysis has been carried out. It has been compared with standard values by varying two different materials. In addition, from the obtained outputs of simulations and the weight optimization, we suggested Aluminium alloys as most suitable material for SUV. Model is created by using SOLIDWORKS software 2015 and structural analysis &; weight optimization is done by using ANSYS WORKBENCH 16.0.

scholarly journals Survey on energetic short rotation forestry systems – Possibilities of spatial development and job creation

2010 ◽  
pp. 7-11
Author(s):  
József Antal ◽  
Gábor Grasseli
Keyword(s):  
Rural Areas ◽  
Structural Characteristics ◽  
Job Creation ◽  
Product Line ◽  
Point Of View ◽  
The European Union ◽  
Short Rotation ◽  
Support Policy ◽  
Education Profession ◽  
Structural Point

Both the European and the Hungarian rural areas suffer multi dimensional problems. Beside infrastructural under development the most important difficulty is employment. Unemployment is significant in the rural areas, while other structural characteristics like education, profession, work circumstances and seasonality worsen this unfavourable situation. It can be stated that the challenge with the highest priority in rural and spatialdevelopment is to create jobs and to strengthen local employment. The authors examine the job generating possibilities of energetic biomass of agricultural origin in a structural point of view. The aim is to develop spatial biomass product line models that permanently support the raise of employment by utilizing the possibilities of the European Union support policy and the popularity of this branch.

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