294 research outputs found
ROLE OF FUSION PROTEIN IN NEWCASTLE DISEASE VIRUS PATHOGENESIS
No full textThe fusion (F) protein of Newcastle disease virus (NDV) is a type I membrane glycoprotein that mediates the merger of the viral envelope to the host cell membrane. The F protein activation initiates a series of conformational changes in the F protein leading to membrane merge which occurs at the cell surface at neutral pH thus modulating NDV entry and spread. The present studies have given an insight to understand the role of F protein in NDV pathogenesis by using established reverse genetic techniques. The F gene of NDV has six glycosylation sites, two of which are present in heptad repeats that facilitate conformational changes during fusion process. To understand the importance of the glycosylation sites in NDV replication and virulence, each site was eliminated individually and in combination on a cDNA clone of NDV strain BC. Our results suggest that glycosylation of F protein plays a major role in virulence and some of the N-glycosylation sites are critical for fusogenicity of the F protein thus modulating NDV infectivity.
The F protein is synthesized as an inactive precursor, F0, which is only
fusogenic after cleavage into disulfide-linked F1 and F2 polypeptides by host cell proteases. The amino acid sequence surrounding the F protein cleavage site determines the virulence of NDV, since different host proteases that cleave the F protein of virulent strains are present in more tissues than those that cleave the F protein of non-virulent strains. The role of conserved glutamine residue in NDV F protein cleavage site in viral pathogenesis has been examined. This study has helped us to understand the requirement of F protein cleavage site conserved amino acids in proteolytic processing and viral infectivity.
Further in this study, the role of F protein cytoplasmic domain and conserved cysteine residues in viral pathogenesis have been explored using reverse genetics. These regions have been suggested to play important roles in F protein conformation, stability and thus affecting the fusion process and viral infectivity.
In summary, the purpose of this work is to determine the important domains and residues of the NDV F protein that facilitates fusion process and regulates viral pathogenesis and immunogenicity. An understanding of how NDV F protein fusion process are regulated may lead to the creation of more effective therapies and better vaccine against NDV and other paramyxoviruses in general
Inducing two-way shape memory effect in Nitinol-Polymer Composite
No full textTitle: Inducing Two-way Shape Memory Effect in NiTi-polymer Composite Author: Jakub Zeman Supervisor: Sneha Manjaree Samal, Ph.D., Institute of Physics of the Czech Academy of Sciences Abstract: Two-way shape memory effect (TWSME) allows material to ac- tively deform between two remembered shapes without the application of ex- ternal force. The most common stimulus is temperature change with several approaches to induce shape memory effect in the material. The approach stud- ied in this thesis utilizes Nitinol and shape memory polymer. By combining these two materials, bistable TWSME was induced in the composite. Bistable TWSME allows the material to be in both of its remembered shapes at a single temperature. The shape of the material depends on the temperature profile by which the target temperature was reached. To create the composite Nitinol foil was shape set and its surface laser lined to increase adhesion with the polymer. Out of the studied polymers, the best properties for the preparation of com- posite were exhibited by a blend of 60 % TPU and 40 % PCL by weight. The composite was then prepared by hot press and tested. Keywords: inducing two-way shape memory effect, Nitinol, shape memory polymer, composite
Immune mechanisms and potential immunological treatment in atherosclerosis
No full textOur immune system is an important and central part of the defence mechanisms of our body. It carries out various important functions such as protecting us from invading microorganisms, removing dead cells, and producing antibodies for future defence. For this, proper synchronization between the innate and adaptive immunity is required. Our innate immune system acts as the first line of defence by eliminating non-specifically various pathogens and by activating antigen-presenting cells (APCs) that inform B-cells and T-cells of the adaptive immune system. B-cells can exhibit more specific actions against pathogens by an intricately regulated production of antibodies directed against antigens expressed by the pathogens. T-cells can produce cytokines and chemokines to alarm the complete immune system recruiting immune cells such as natural killer cells, mast cells and neutrophils. The immune system can also produce antibodies against self-antigens (autoantibodies). Autoantibodies can have pathogenic effects that cause autoimmune diseases such as Systemic Lupus Erythematosis. Interestingly, it has been shown recently that autoantibodies can also have protective effects alleviating diseases such as lupus nephritis and atherosclerosis. This thesis focuses specifically on homeostatic functions of the human autoantibodies anti-phoshorylcholine (anti-PC) and anti-malondialdehyde (anti-MDA) and their prevalence in cardiovascular disease (CVD) and chronic kidney disease (CKD).1. Study I: Investigates the role of anti-PC and anti-MDA antibodies in patients undergoing hemodialysis and explores the associations with all-cause mortality in both males and females, also their relation to inflammation.2. Study II: Evaluates the potential of natural immunization in hibernating bears, tigers, and polar bears with respect to the levels of anti-PC and anti-MDA antibodies.3. Study III: Evaluates the role of antibodies against anti-PC antibodies among 60-Year-Olds with its clinical role and simulated interactions.4. Study IV: Investigates the role of anti-PC antibody levels in Covid-19 patients and also investigates the interaction of spike protein with phosphorylcholine by using an in silico approach.List of scientific papersI. Samal SK, Qureshi AR, Rahman M, Stenvinkel P and Frostegard J. Different subclasses and isotypes of antibodies against phosphorylcholine in haemodialysis patients: association with mortality. Clin exp Immunol. 2020;201:94. https://doi.org/10.1111/cei.13441 II. Samal SK, Qureshi AR, Rahman M, Stenvinkel P and Frostegard J. Antibodies against Malondialdehyde in Haemodialysis Patients and Its Association with Clinical Outcomes: Differences between Subclasses and Isotypes. J Clin Med. 2020;9:753. https://doi.org/10.3390/jcm9030753 III. Samal SK, Frobert O, Kindberg J, Stenvinkel P and Frostegard J. Potential natural immunization against atherosclerosis in hibernating bears. Sci Rep. 2021;11:12120. https://doi.org/10.1038/s41598-021-91679-1 IV. Samal SK, Panda PK, Vikström M, et al. Antibodies Against Phosphorylcholine Among 60-Year-Olds: Clinical Role and Simulated Interactions. Frontiers in Cardiovascular Medicine. 2022; 9. https://doi.org/10.3389/fcvm.2022.809007 V. Samal SK*, Busch M*, Panda KP, Kumar N, Timmermans S, Schurgers LJ, Reutelingsperger CR, Paassen PV*, Frostegård J*. Antibodies against phosphorylcholine are associated with less severe disease in COVID-19: clinical role and simulated interactions using In-silico methods. *Denotes equal author contribution. [Manuscript]</p
Vyvolání obousměrné tvarové paměti v NiTi-polymerovém kompozitu
No full textNázev práce: Vyvolání obousměrné tvarové paměti v NiTi-polymerovém kompozitu Autor: Jakub Zeman Katedra: Katedra fyziky materiálů, Matematicko-fyzikální fakulta, Uni- verzita Karlova Vedoucí bakalářské práce: Sneha Manjaree Samal, Ph.D., Fyzikální ústav Akademie věd České republiky Abstrakt: Obousměrná tvarová paměť umožňuje deformaci materiálu mezi dvěma zapamatovatelnými tvary bez působení vnějších sil, přičemž aktivaci změny tvaru se využívá nejčastěji změna teploty. Mezi řadou způsobů, jak dosáhnout obousměrné tvarové paměti, byla v této práci využita kombinace kovového materiálu Nitinol a vybraného polymeru s tvarovou pamětí. V kom- pozitním materiálu z těchto dvou složek bylo dosaženo bistabilní obousměrné tvarové paměti. Bistabilní obousměrná tvarová paměť je unikátní tím, že umožňuje existenci materiálu v obou zapamatovaných stavech při stejné teplotě. Bylo prokázáno, že rozhodujícím faktorem pro dosažení určitého tvaru je předešlý teplotní průběh kompozitního materiálu. Pro zlepšené spojení kovového Niti- nolu a polymerního materiálu byl povrch NiTi upraven laserem. Mezi několika studovanými polymery prokázal nejlepší vlastnosti polymer vyrobený ze dvou složek, a to 60...Title: Inducing Two-way Shape Memory Effect in NiTi-polymer Composite Author: Jakub Zeman Supervisor: Sneha Manjaree Samal, Ph.D., Institute of Physics of the Czech Academy of Sciences Abstract: Two-way shape memory effect (TWSME) allows material to ac- tively deform between two remembered shapes without the application of ex- ternal force. The most common stimulus is temperature change with several approaches to induce shape memory effect in the material. The approach stud- ied in this thesis utilizes Nitinol and shape memory polymer. By combining these two materials, bistable TWSME was induced in the composite. Bistable TWSME allows the material to be in both of its remembered shapes at a single temperature. The shape of the material depends on the temperature profile by which the target temperature was reached. To create the composite Nitinol foil was shape set and its surface laser lined to increase adhesion with the polymer. Out of the studied polymers, the best properties for the preparation of com- posite were exhibited by a blend of 60 % TPU and 40 % PCL by weight. The composite was then prepared by hot press and tested. Keywords: inducing two-way shape memory effect, Nitinol, shape memory polymer, composite 1Department of Physics of MaterialsKatedra fyziky materiálůMatematicko-fyzikální fakultaFaculty of Mathematics and Physic
A single amino acid change, Q114R, in the cleavage-site sequence of Newcastle disease virus fusion protein attenuates viral replication and pathogenicity
No full textA key determinant of Newcastle disease virus (NDV) virulence is the amino acid sequence at the fusion (F) protein cleavage site. The NDV F protein is synthesized as an inactive precursor, F0, and is activated by proteolytic cleavage between amino acids 116 and 117 to produce two disulfide-linked subunits, F1 and F2. The consensus sequence of the F protein cleavage site of virulent [112(R/K)-R-Q-(R/K)-R↓F-I118] and avirulent [112(G/E)-(K/R)-Q-(G/E)-R↓L-I118] strains contains a conserved glutamine residue at position 114. Recently, some NDV strains from Africa and Madagascar were isolated from healthy birds and have been reported to contain five basic residues (R-R-R-K-R↓F-I/V or R-R-R-R-R↓F-I/V) at the F protein cleavage site. In this study, we have evaluated the role of this conserved glutamine residue in the replication and pathogenicity of NDV by using the moderately pathogenic Beaudette C strain and by making Q114R, K115R and I118V mutants of the F protein in this strain. Our results showed that changing the glutamine to a basic arginine residue reduced viral replication and attenuated the pathogenicity of the virus in chickens. The pathogenicity was further reduced when the isoleucine at position 118 was substituted for valine.</jats:p
Newcastle Disease Virus Expressing Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Induces Strong Mucosal and Serum Antibody Responses in Guinea Pigs
No full textABSTRACT
Human immunodeficiency virus type 1 (HIV-1) is transmitted mainly through mucosal sites. Optimum strategies to elicit both systemic and mucosal immunity are critical for the development of vaccines against HIV-1. We therefore sought to evaluate the induction of systemic and mucosal immune responses by the use of Newcastle disease virus (NDV) as a vaccine vector. We generated a recombinant NDV, designated rLaSota/gp160, expressing the gp160 envelope (Env) protein of HIV-1 from an added gene. The gp160 protein expressed by rLaSota/gp160 virus was detected on an infected cell surface and was incorporated into the NDV virion. Biochemical studies showed that gp160 present in infected cells and in the virion formed a higher-order oligomer that retained recognition by conformationally sensitive monoclonal antibodies. Expression of gp160 did not increase the virulence of recombinant NDV (rNDV) strain LaSota. Guinea pigs were administered rLaSota/gp160 via the intranasal (i.n.) or intramuscular (i.m.) route in different prime-boost combinations. Systemic and mucosal antibody responses specific to the HIV-1 envelope protein were assessed in serum and vaginal washes, respectively. Two or three immunizations via the i.n. or i.m. route induced a more potent systemic and mucosal immune response than a single immunization by either route. Priming by the i.n. route was more immunogenic than by the i.m. route, and the same was true for the boosts. Furthermore, immunization with rLaSota/gp160 by any route or combination of routes induced a Th1-type response, as reflected by the induction of stronger antigen-specific IgG2a than IgG1 antibody responses. Additionally, i.n. immunization elicited a stronger neutralizing serum antibody response to laboratory-adapted HIV-1 strain MN.3. These data illustrate that it is feasible to use NDV as a vaccine vector to elicit potent humoral and mucosal responses to the HIV-1 envelope protein.</jats:p
Chaos in classical string dynamics in γˆ deformed AdS5×T1,1
No full textAbstractWe consider a circular string in γˆ deformed AdS5×T1,1 which is localized in the center of AdS5 and winds around the two circles of deformed T1,1. We observe chaos in the phase space of the circular string implying non-integrability of string dynamics. The chaotic behaviour in phase space is controlled by energy as well as the deforming parameter γˆ. We further show that the point like object exhibits non-chaotic behaviour. Finally we calculate the Lyapunov exponent for both extended and point like object in support of our first result
Growth of thin film containing high density ZnO nanorods with low temperature calcinated seed layer
No full text
Low‐mass young stellar population and star formation history of the cluster IC 1805 in theW4 HII region
No full textInternational audienceW4 is a giant HII region ionized by the OB stars of the cluster IC 1805. The HII region/cluster complex has been a subject of numerous investigations as it is an excellent laboratory for studying the feedback effect of massive stars on the surrounding region. However, the low‐mass stellar content of the cluster IC 1805 remains poorly studied till now. With the aim to unravel the low‐mass stellar population of the cluster, we present the results of amultiwavelength study based on deep optical data obtained with the Canada‐France‐Hawaii Telescope, infrared data from Two Micron All Sky Survey and Spitzer Space Telescope and X‐ray data from Chandra Space Telescope. The present optical data set is complete enough to detect stars down to 0.2 M‐circle dot, which is the deepest optical observation so far for the cluster. We identified 384 candidate young stellar objects (YSOs; 101 Class I/II and 283 Class III) within the cluster using various colour‐colour and colour‐magnitude diagrams. We inferred the mean age of the identified YSOs to be similar to 2.5 Myr and mass in the range 0.3‐2.5 M‐circle dot. The mass function of our YSO sample has a power‐law index of ‐1.23 +/‐ 0.23, close to the Salpeter value (‐1.35), and consistent with those of other star‐forming complexes. We explored the disc evolution of the cluster members and found that the disc‐less sources are relatively older compared to the disc bearing YSO candidates. We examined the effect of high‐mass stars on the circumstellar discs and within uncertainties, the influence of massive stars on the disc fraction seems to be insignificant. We also studied the spatial correlation of the YSOs with the distribution of gas and dust of the complex to conclude that IC 1805 would have formed in a large filamentary cloud
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