Relevant bibliographies by topics / Β-defensin

Academic literature on the topic 'Β-defensin'

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Published: 10 December 2022
Last updated: 28 January 2023

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Journal articles on the topic "Β-defensin"

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Ryan, Lisa K., Janice Rhodes, Meenakshi Bhat, and Gill Diamond. "Expression of β-Defensin Genes in Bovine Alveolar Macrophages." Infection and Immunity 66, no. 2 (February 1, 1998): 878–81. http://dx.doi.org/10.1128/iai.66.2.878-881.1998.

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ABSTRACT Bovine alveolar macrophages (BAM) were examined for the expression of β-defensins and to determine whether their expression could be upregulated by bacterial lipopolysaccharide (LPS), as observed with β-defensins expressed in bovine tracheal epithelial cells. Four β-defensins were expressed constitutively in BAM, with bovine neutrophil β-defensin (BNBD)-4 and BNBD-5 being the most predominant. This is the first evidence of β-defensin gene expression in a mature myeloid cell. LPS had no effect on β-defensin expression in BAM, even though tumor necrosis factor alpha (TNF-α) production was induced. Nonbacterial inflammatory particles had little effect on β-defensin gene expression or TNF-α production in BAM. We hypothesize that constitutively expressed β-defensins of alveolar macrophages may have a role in lung host defense.
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Tarver, Alan P., Douglas P. Clark, Gill Diamond, John P. Russell, Hediye Erdjument-Bromage, Paul Tempst, Kenneth S. Cohen, et al. "Enteric β-Defensin: Molecular Cloning and Characterization of a Gene with Inducible Intestinal Epithelial Cell Expression Associated with Cryptosporidium parvumInfection." Infection and Immunity 66, no. 3 (March 1, 1998): 1045–56. http://dx.doi.org/10.1128/iai.66.3.1045-1056.1998.

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ABSTRACT A growing body of evidence suggests that endogenous antibiotics contribute to the innate defense of mammalian mucosal surfaces. In the cow, β-defensins constitute a large family of antibiotic peptides whose members have been previously isolated from the respiratory and oral mucosa, as well as circulating phagocytic cells. A novel bovine genomic clone with sequence related to those of these α-defensins was isolated and characterized. The corresponding cDNA was isolated from a small intestinal library; its open reading frame predicts a deduced sequence of a novel β-defensin, which we designate enteric β-defensin (EBD). Northern blot analysis of a variety of bovine tissues revealed that EBD mRNA is highly expressed in the distal small intestine and colon, anatomic locations distinct from those for previously characterized β-defensins. EBD mRNA was further localized by in situ hybridization to epithelial cells of the colon and small intestinal crypts. Infection of two calves with the intestinal parasiteCryptosporidium parvum induced 5- and 10-fold increases above control levels of EBD mRNA in intestinal tissues. An anchored-PCR strategy was used to identify other β-defensin mRNAs expressed in the intestine. In addition to that of EBD, several low-abundance cDNAs which corresponded to other β-defensin mRNAs were cloned. Most of these clones encoded previously characterized β-defensins or closely related isoforms, but two encoded a previously uncharacterized prepro-β-defensin. Northern blot evidence supported that all of these other β-defensin genes are expressed at levels lower than that of the EBD gene in enteric tissue. Furthermore, some of these β-defensin mRNAs were abundant in bone marrow, suggesting that in enteric tissue their expression may be in cells of hematopoietic origin. Extracts of small intestinal mucosa obtained from healthy cows have numerous active chromatographic fractions as determined by an antibacterial assay, and one peptide was partially purified. The peptide corresponded to one of the low-abundance cDNAs. This study provides evidence of β-defensin expression in enteric tissue and that the mRNA encoding a major β-defensin of enteric tissue, EBD, is inducibly expressed in enteric epithelial cells. These findings support the proposal that β-defensins may contribute to host defense of enteric mucosa.
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Yang, D., O. Chertov, S. N. Bykovskaia, Q. Chen, M. J. Buffo, J. Shogan, M. Anderson, et al. "β-Defensins: Linking Innate and Adaptive Immunity Through Dendritic and T Cell CCR6." Science 286, no. 5439 (October 15, 1999): 525–28. http://dx.doi.org/10.1126/science.286.5439.525.

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Defensins contribute to host defense by disrupting the cytoplasmic membrane of microorganisms. This report shows that human β-defensins are also chemotactic for immature dendritic cells and memory T cells. Human β-defensin was selectively chemotactic for cells stably transfected to express human CCR6, a chemokine receptor preferentially expressed by immature dendritic cells and memory T cells. The β-defensin–induced chemotaxis was sensitive to pertussis toxin and inhibited by antibodies to CCR6. The binding of iodinated LARC, the chemokine ligand for CCR6, to CCR6-transfected cells was competitively displaced by β-defensin. Thus, β-defensins may promote adaptive immune responses by recruiting dendritic and T cells to the site of microbial invasion through interaction with CCR6.
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Meade, K. G., P. Cormican, F. Narciandi, A. Lloyd, and C. O'Farrelly. "Bovine β-defensin gene family: opportunities to improve animal health?" Physiological Genomics 46, no. 1 (January 1, 2014): 17–28. http://dx.doi.org/10.1152/physiolgenomics.00085.2013.

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Recent analysis of the bovine genome revealed an expanded suite of β-defensin genes that encode what are referred to as antimicrobial or host defense peptides (HDPs). Whereas primate genomes also encode α- and θ-defensins, the bovine genome contains only the β-defensin subfamily of HDPs. β-Defensins perform diverse functions that are critical to protection against pathogens but also in regulation of the immune response and reproduction. As the most comprehensively studied subclass of HDPs, β-defensins possess the widest taxonomic distribution, found in invertebrates as well as plants, indicating an ancient point of origin. Cross-species comparison of the genomic arrangement of β-defensin gene repertoire revealed them to vary in number among species presumably due to differences in pathogenic selective pressures but also genetic drift. β-Defensin genes exist in a single cluster in birds, but four gene clusters exist in dog, rat, mouse, and cow. In humans and chimpanzees, one of these clusters is split in two as a result of a primate-specific pericentric inversion producing five gene clusters. A cluster of β-defensin genes on bovine chromosome 13 has been recently characterized, and full genome sequencing has identified extensive gene copy number variation on chromosome 27. As a result, cattle have the most diverse repertoire of β-defensin genes so far identified, where four clusters contain at least 57 genes. This expansion of β-defensin HDPs may hold significant potential for combating infectious diseases and provides opportunities to harness their immunological and reproductive functions in commercial cattle populations.
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Patil, Amar A., Yibin Cai, Yongming Sang, Frank Blecha, and Guolong Zhang. "Cross-species analysis of the mammalian β-defensin gene family: presence of syntenic gene clusters and preferential expression in the male reproductive tract." Physiological Genomics 23, no. 1 (September 21, 2005): 5–17. http://dx.doi.org/10.1152/physiolgenomics.00104.2005.

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Mammalian β-defensins are an important family of innate host defense peptides with pleiotropic activities. As a first step to study the evolutionary relationship and biological role of the β-defensin family, we identified their complete repertoires in the human, chimpanzee, mouse, rat, and dog following systemic, genome-wide computational searches. Although most β-defensin genes are composed of two exons separated by an intron of variable length, some contain an additional one or two exons encoding an internal pro-sequence, a segment of carboxy-terminal mature sequences or untranslated regions. Alternatively, spliced isoforms have also been found with several β-defensins. Furthermore, all β-defensin genes are densely clustered in four to five syntenic chromosomal regions, with each cluster spanning <1.2 Mb across the five species. Phylogenetic analysis indicated that, although the majority of β-defensins are evolutionarily conserved across species, subgroups of gene lineages exist that are specific in certain species, implying that some β-defensins originated after divergence of these mammals from each other, while most others arose before the last common ancestor of mammals. Surprisingly, RT-PCR revealed that all but one rat β-defensin transcript are preferentially expressed in the male reproductive tract, particularly in epididymis and testis, except that Defb4, a human β-defensin-2 ortholog, is more restricted to the respiratory and upper gastrointestinal tracts. Moreover, most β-defensins expressed in the reproductive tract are developmentally regulated, with enhanced expression during sexual maturation. Existence of such a vast array of β-defensins in the male reproductive tract suggests that these genes may play a dual role in both fertility and host defense.
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Jia, Hong Peng, Jesse N. Mills, Fariba Barahmand-Pour, Darryl Nishimura, Rama K. Mallampali, Guoshun Wang, Kerry Wiles, Brian F. Tack, Charles L. Bevins, and Paul B. McCray. "Molecular Cloning and Characterization of Rat Genes Encoding Homologues of Human β-Defensins." Infection and Immunity 67, no. 9 (September 1, 1999): 4827–33. http://dx.doi.org/10.1128/iai.67.9.4827-4833.1999.

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ABSTRACT β-Defensins are cationic peptides with broad-spectrum antimicrobial activity that may play a role in mucosal defenses of several organs. They have been isolated in several species, and in humans, two β-defensins have been identified. Here, we report the identification of two genes encoding β-defensin homologues in the rat. Partial cDNAs were found by searching the expressed-sequence-tag database, and primers were designed to generate full-length mRNA coding sequences. One gene was highly similar to the human β-defensin-1 (HBD-1) gene and mouse β-defensin-1 gene at both the nucleic acid and amino acid levels and was termed rat β-defensin-1 (RBD-1). The other gene, named RBD-2, was homologous to the HBD-2 and bovine tracheal antimicrobial peptide (TAP) genes. The predicted prepropeptides were strongly cationic, were 69 and 63 residues in length for RBD-1 and RBD-2, respectively, and contained the six-cysteine motif characteristic of β-defensins. The β-defensin genes mapped closely on rat chromosome 16 and were closely linked to the α-defensins genes, suggesting that they are part of a gene cluster, similar to the organization reported for humans. Northern blot analysis showed that both RBD-1 and RBD-2 mRNA transcripts were ∼0.5 kb in length; RBD-1 mRNA was abundantly transcribed in the rat kidney, while RBD-2 was prevalent in the lung. Reverse transcription-PCR indicated that RBD-1 and RBD-2 mRNAs were distributed in a variety of other tissues. In the lung, RBD-1 mRNA expression localized to the tracheal epithelium while RBD-2 was expressed in alveolar type II cells. In conclusion, we characterized two novel β-defensin homologues in the rat. The rat may be a useful model to investigate the function and contribution of β-defensins to host defense in the lung, kidney, and other tissues.
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Bals, Robert, Mitchell J. Goldman, and James M. Wilson. "Mouse β-Defensin 1 Is a Salt-Sensitive Antimicrobial Peptide Present in Epithelia of the Lung and Urogenital Tract." Infection and Immunity 66, no. 3 (March 1, 1998): 1225–32. http://dx.doi.org/10.1128/iai.66.3.1225-1232.1998.

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ABSTRACT One component of host defense at mucosal surfaces appears to be epithelium-derived peptides with antimicrobial activity called defensins. Human β-defensin 1 (hBD-1) represents the first member of the β-defensin family isolated from humans and has been implicated in the pathogenesis of cystic fibrosis. We describe in this report the isolation and characterization of a murine homolog of hBD-1 called mouse β-defensin 1 (mBD-1). The predicted amino acid sequence shows the hallmark features of other known epithelial β-defensins, including the ordered array of six cysteine residues. Analysis of a genomic clone of mBD-1 revealed two exons separated by a 15-kb intron. By use of fluorescence in situ hybridization, the mBD-1 gene was localized at the proximal portion of chromosome 8, the site where mouse α-defensins are found. Lysates from cells transfected with the mBD-1 cDNA showed antibacterial activity against gram-positive and gram-negative bacteria. mBD-1 transcripts were found in kidney, liver, and female reproductive organ tissues. In the airways, mBD-1 is expressed diffusely throughout the epithelial cells of the large proximal airways with less expression in the small distal airways and no expression in alveolar cells. The present study demonstrates that a β-defensin potentially homologous to human β-defensin 1 is present in the respiratory system and other mucosal surfaces in mice.
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Antcheva, Nikolinka, Francesca Morgera, Luisa Creatti, Lisa Vaccari, Ulrike Pag, Sabrina Pacor, Yechiel Shai, Hans-Georg Sahl, and Alessandro Tossi. "Artificial β-defensin based on a minimal defensin template." Biochemical Journal 421, no. 3 (July 15, 2009): 435–47. http://dx.doi.org/10.1042/bj20082242.

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We have designed and chemically synthesized an artificial β-defensin based on a minimal template derived from the comparative analysis of over 80 naturally occurring sequences. This molecule has the disulfide-bridged β-sheet core structure of natural β-defensins and shows a robust salt-sensitive antimicrobial activity against bacteria and yeast, as well as a chemotactic activity against immature dendritic cells. An SAR (structure–activity relationship) study using two truncated fragments or a Cys→Ser point-mutated analogue, from which one or two of the three disulfide bridges were absent, indicated that altering the structure resulted in a different type of membrane interaction and a switch to different modes of action towards both microbial and host cells, and that covalent dimerization could favour antimicrobial activity. Comparison of the structural, aggregational and biological activities of the artificial defensin with those of three human β-defensins and their primate orthologues provided useful information on how their mode of action may relate to specific structural features.
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Morampudi, Vijay, Michel Y. Braun, and Sushila D'Souza. "Modulation of Early β-Defensin-2 Production as a Mechanism Developed by Type I Toxoplasma gondii To Evade Human Intestinal Immunity." Infection and Immunity 79, no. 5 (March 7, 2011): 2043–50. http://dx.doi.org/10.1128/iai.01086-10.

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ABSTRACTWe investigated the early innate immune responses induced in human intestinal epithelial cells (IEC) by the three definedToxoplasma gondiigenotype strains. Transcriptome analysis revealed that among differentially expressed genes, β-defensins distinguished the most IEC infected by fast- or slow-replicatingT. gondiigenotypes. Although β-defensin 1 and 3 genes were not expressed in host cells at early time points postinfection, the slow-replicating type II and III parasites induced high levels of β-defensin 2 gene expression. Notably, no β-defensin 2 gene expression occurred early after infection with the fast-replicating type I parasite. However, activation of this gene in IEC by poly(I:C) treatment prior to infection substantially decreased parasite viability, and pretreatment of parasites with synthetic β-defensin 2 significantly reduced their infectivity of IEC. These findings strongly support the modulation of early β-defensin 2 expression as a mechanism used by type IT. gondiiparasites to mediate immune evasion.
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Rinker, Sherri D., Michael P. Trombley, Xiaoping Gu, Kate R. Fortney, and Margaret E. Bauer. "Deletion ofmtrCin Haemophilus ducreyi Increases Sensitivity to Human Antimicrobial Peptides and Activates the CpxRA Regulon." Infection and Immunity 79, no. 6 (March 28, 2011): 2324–34. http://dx.doi.org/10.1128/iai.01316-10.

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ABSTRACTHaemophilus ducreyiresists killing by antimicrobial peptides encountered during human infection, including cathelicidin LL-37, α-defensins, and β-defensins. In this study, we examined the role of the proton motive force-dependent multiple transferable resistance (MTR) transporter in antimicrobial peptide resistance inH. ducreyi. We found a proton motive force-dependent effect onH. ducreyi's resistance to LL-37 and β-defensin HBD-3, but not α-defensin HNP-2. Deletion of the membrane fusion protein MtrC renderedH. ducreyimore sensitive to LL-37 and human β-defensins but had relatively little effect on α-defensin resistance. ThemtrCmutant 35000HPmtrCexhibited phenotypic changes in outer membrane protein profiles, colony morphology, and serum sensitivity, which were restored to wild type bytrans-complementation withmtrC. Similar phenotypes were reported in acpxAmutant; activation of the two-component CpxRA regulator was confirmed by showing transcriptional effects on CpxRA-regulated genes in 35000HPmtrC. AcpxRmutant had wild-type levels of antimicrobial peptide resistance; acpxAmutation had little effect on defensin resistance but led to increased sensitivity to LL-37. 35000HPmtrCwas more sensitive than thecpxAmutant to LL-37, indicating that MTR contributed to LL-37 resistance independent of the CpxRA regulon. The CpxRA regulon did not affect proton motive force-dependent antimicrobial peptide resistance; however, 35000HPmtrChad lost proton motive force-dependent peptide resistance, suggesting that the MTR transporter promotes proton motive force-dependent resistance to LL-37 and human β-defensins. This is the first report of a β-defensin resistance mechanism inH. ducreyiand shows that LL-37 resistance inH. ducreyiis multifactorial.
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Dissertations / Theses on the topic "Β-defensin"

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Selim, Erik. "Solid-phase synthesis of Avian β-Defensin 8." Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-32076.

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Differences in the expression of antimicrobial peptides in vivo have been proposed as underlying factors influencing susceptibility to infection. In this context, the role of avian b-defensins in inhibiting avian influenza infections is a study object in an ongoing collaboration with the Zoonotic Ecology and Epidemiology group at Lnu. In this report, an attempt to synthesize two variants of the peptide Anas Platyrhynchos AvBD-8, using Fmoc-based SPPS, is described. The length of AvBD-8 (43 aa) necessitated peptide synthesis in two segments to subsequently be ligated using native chemical ligation. The first component of a 19 aa segment was thus a Dbz-linker, which would allow to ligate this end with a second segment (24 aa). Halfway through the synthesis of this larger segment the batch was split into two pots, allowing the synthesis of two segments differing by one single amino acid (R for W). The composition of these segments were: Dbz-HDTSCTGGAQKCQVANNPA (Dbz-segment), SVVTRCCPIGQKCWGFARTNPPPC(boc) (W-segment), and  SVVTRCCPIGQKCRGFARTNPPPC(boc) (R-segment). Crude product yields were 284,5 mg; 67,6% (Dbz-segment), 137,6 mg; 52,3% (W-segment), and 166,3 mg; 64,2%. Preliminary mass spectrometric analysis on the crude products did not indicate the presence of the desired segments in major mass peaks. Further product purification is necessary in order to allow definite conclusions, but it appears as if the synthesis has not worked. Possible explanations are either impure or degraded reactant(-s), folding or shielding effects of the growing peptide chain at some point inhibiting synthesis, or experimental errors during one or more of the many steps involved in the synthesis.
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Abujaber, Razan. "Phenotypic consequences of β-defensin copy number variation in humans." Thesis, University of Leicester, 2016. http://hdl.handle.net/2381/38814.

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Beta defensins (DEFB) at the 8p23.1 genomic location are multifunctional secreted short peptides that have antibacterial and antiviral action in many species and possess immune cell signal activity, constituting a link between innate and adaptive immunity. In humans, the β-defensin region is known to be copy number variable (CNV) and contains seven genes repeated as a block, with a diploid copy number between 1 and 12. This thesis shall explore the structural variability of the β-defensin CNV region; compare and contrast the different methods used for calling DEFB CNVs and investigate the role of CNVs of DEFB in various diseases. One of its aims is to also develop a model system to investigate if DEFB expression levels differ with CN in response to treatment with Pneumolysin by using Normal Human Bronchial Epithelial (NHBE) cells. Results from this thesis confirm that the DEFB CNV region is 322kb in length, with a polymorphic inversion that occurs at a prevalence of 30% at the 8p23.1 genomic location that is independent of the DEFB CN. Paralogue Ratio Test (PRT) proved to be the best method of genotyping DEFB CNV especially in larger cohorts. In addition, work from this thesis also founded the basis of developing an in vitro model system to investigate whether DEFB expression levels differ with CN in response to treatment with pneumolysin by using Normal Human Bronchial Epithelial (NHBE) cells. As far as case/control and cohort studies are concerned, results from this thesis show that DEFB CN is not associated with lung function in the general population and has no effect on patients with COPD and Asthma, nor does it support previous results that present an association between HIV viral load and DEFB CN. DEFB CN was also found not to be associated with recurrent UTIs in VUR patients, nor with hypertension. Data suggested that DEFB CN might be associated with BMI but this has not been reproduced in a smaller cohort.
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Ottolini, Barbara. "Evolution of copy number variation in the rhesus macaque β-defensin region." Thesis, University of Leicester, 2014. http://hdl.handle.net/2381/28961.

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Beta defensins are multifunctional secreted short peptides rapidly evolving in mammals. They present antibacterial and antiviral action in many species and possess immune cell signal activity, constituting a link between innate and adaptive immunity. In humans the β-defensin region is known to be copy number variable (CNV) and contains seven genes repeated as a block, with a diploid copy number between 1 and 12 and an approximate repeat length of 240kb but the extent and nature of CNV in other mammals remains poorly known. The rhesus macaque (Macaca mulatta) is the most widespread non-human primate, hence constituting a good model to study adaptation and its divergence time from the human lineage (~25MYA) presents enough sequence diversity to investigate mechanisms of copy number variation and evolution. Its genome has been sequenced, although there is poor assembly quality in repeated segments such as the β-defensin region. This thesis studied the genomic architecture of the rhesus macaque β-defensin region using a variety of methods (aCGH, PCR-based methods, BAC library screening and cytogenetic approaches) with the aim of overcoming the limitations of the assembly and of determining the copy number distribution for this region. Evidences are here provided that only the region containing DEFB2L gene (orthologue to human DEFB4) is CNV, with a diploid copy number between 2 and 11, with a repeat size of 20kb, while the rest of the cluster shows no variation. This could represent a case where the same area prone to copy number variation evolved to present a different copy number unit structure in two different lineages, still converging in the same copy number distribution for the possible effect of similar functional constraints. Also, evidences of non-synonymous variations are shown for the DEFB2L gene, suggestive of the different evolutionary pattern followed by the rhesus macaque β-defensin region.
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Meisch, Jeffrey P. "Human β-defensin 3 peptide is increased and redistributed in Crohn’s ileitis." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1270735950.

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Zhang, Ke, and 张科. "Evaluation of anti-human respiratory syncytial virus effects of short interfering RNAs and β-defensin-4." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/209570.

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The human respiratory syncytial virus (hRSV) infection is a global public health burden in children aged under 2 years and immunocompromised or elderly adults. The choice for prophylaxis and therapy of hRSV infection was constrained to Palivizumab and Ribavirin. Therefore, this study aimed to develop effective anti-hRSV infection agents, such as short interfering RNA (siRNA) and β-defensin-4 (β-D-4). Since there still is no compatible animal model to evaluate antiviral effect of anti-hRSV agents, we first attempted to establish suitable animal model. A clinical isolate of hRSV (KI-RSV-W) was adapted in BALB/c mice by serial passages. Old male mice (age > 8 months) were used for establishment of hRSV infection model, because the more efficient viral infection in lungs of the old male mice than that old female mice and young mice (age < 3 weeks). After the virus was propagated in old male mice for 20 passages, a virus variant KI-RSV-P70-4 exhibited more efficient infection/replication in the mice. Its viral load was about 100-fold higher than that of wild type strain KI-RSV-W. The infection of KI-RSV-P70-4 also caused more severe histopathological changes in lung tissues. Although KI-RSV-P70-4 could not result in death of the infected mice, both viral load and pathological change in lungs may be good indicators for evaluating antiviral effect. The mouse model and adapted hRSV strain solidly laid the foundation for evaluation of anti-hRSV agents. We then designed and evaluated anti-hRSV effect of siRNAs. A total of 25 siRNAs targeting 4 viral genes (M2-1, NS2, N and F) were designed and their anti-hRSV effect was assessed in vitro. The results showed that 6 siRNAs respectively targeting M2-1, N and F genes exhibited higher anti-hRSV effect than that of the positive control, whereas those targeting NS2 gene did not show significant antiviral effect. The 50% inhibitory concentrations (IC50) of three most potent siRNAs (M2-1-361, N889 and F-1143) were 0.51, 2.14 and 0.64 nM, respectively. Antiviral activity of β-D-4 against hRSV infection was evaluated in vitro and in vivo. In vitro experiments showed supreme antiviral effect with IC50 around 3.4 μg/ml when the virus was pretreated with β-D-4, but no significant inhibitory effect was observed when the cells were pretreated with β-D-4 or β-D-4 was maintained in the culture medium after viral infection. These results indicated that the inhibitory effect of β-D-4 was associated with direct interaction with the virus itself and blocked virus entry of the cells. Furthermore, a single dose (13.6 μg) of β-D-4 intratracheal (i.t.) administration in old male mice after the viral infection resulted in about 0.7 log reduce of viral load in lung tissues, while inoculation of premixed β-D-4 and the virus caused about 3 logs decrease of viral load in lungs. These results have demonstrated that β-D-4 may be an effective anti-hRSV agent. Taken together, old male BALB/c mice might be used to establish hRSV infection model. Three siRNAs and the β-D-4 were validated as the potent anti-hRSV agents, respectively.
published_or_final_version
Microbiology
Doctoral
Doctor of Philosophy
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Telford, Erica. "Dual role of three natural molecules in regulating the expression of β-defensin-3 and pro-inflammatory mediators." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCC273.

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Les peptides antimicrobiens (PAMs) sont des effecteurs de la réponse innée produits et sécrétés par les cellules épithéliales intestinales. A l’interface entre l’épithélium et les microbes, ils représentent un élément important de la barrière muqueuse. Certains PAMs, tels que la bêta-défensine humaine 1 (BDH-1), sont exprimés de manière constitutive, tandis que d'autres PAMs, dont la BDH-2 et la BDH-3, sont induits par des signaux dérivés des microbes et de l'hôte. Les PAMs contrôlent la densité des bactéries commensales dans la lumière intestinale ainsi que la capacité invasive des agents pathogènes. En effet, les PAMs jouent un rôle majeur dans l’induction des réponses immunitaires innée et adaptative. Ainsi, outre leurs effets antimicrobiens et immunorégulateurs, les PAMs ont également une fonction angiogénique et anti-tumorale, entre autres. Il y a peu d’études sur la régulation des PAMs. Cependant, leur dérégulation a été associée à plusieurs pathologies humaines, notamment aux maladies inflammatoires chronique de l’intestin, ce qui souligne leur rôle majeur dans le maintien de l'homéostasie. Grâce à leurs effets multiples, les PAMs constituent une cible thérapeutique intéressante pour développer des solutions alternatives ou complémentaires aux antibiotiques afin de mieux faire face à l'émergence de maladies infectieuses et à la résistance aux antibiotiques. Enfin, les PAMs pourraient aider à rétablir l'homéostasie dans les maladies inflammatoires.À la suite d’un criblage d’une banque de molécules naturelles, notre équipe a identifié trois cibles prometteuses, l'andrographolide (AND), l'isoliquiritigénine (ISL) et l'oridonine (ORD), qui augmentent l'expression de BDH-3 sans induire celle de gènes pro-inflammatoires. Au cours de ce projet, nous avons étudié précisément l'effet de l'AND, de l'ISL et de l'ORD sur l'induction de l'expression de BDH-3 dans un modèle in vitro de cellules épithéliales intestinales. Ces molécules ont un effet inducteur non seulement individuellement mais également de manière synergique puisque la combinaison de ces molécules augmente fortement l’expression de BDH-3. En outre, AND, ISL et ORD ont réduit l'expression des gènes pro-inflammatoires IL-1β, IL-6, IL-8 et TNF-α lorsque celle-ci était induite par des stimuli inflammatoires endogènes ou bactériens. D’autres études menées par le groupe ont pour but de définir in vitro et ex vivo l’activité de ces composés et de déterminer leurs mécanismes d’actions en étudiant les voies intracellulaires impliquées.En conclusion, l’AND, l’ISL et l’ORD représentent des outils prometteurs pour étudier la régulation des PAMs et pourraient devenir des candidats thérapeutiques pour les pathologies nécessitant un renforcement de la barrière muqueuse tout en réduisant l'inflammation
Antimicrobial peptides (AMPs) are innate immune effectors produced and secreted by intestinal epithelial cells at the microbe-epithelium interface, where they represent an important component of the mucosal barrier. Some AMPs, such as human beta defensin (HBD)-1, are constitutively expressed, while others, including HBD-2 and HBD-3, are induced by a broad range of microbial- and host-derived signals. AMPs control the density of luminal commensal bacteria and invasive capacities of pathogens and have a role in perpetuating the innate immune response and inducing the adaptive response. Indeed, they present antimicrobial, immunoregulatory, angiogenic and anti-tumor effects, among the others. Little is known about regulation of AMP expression, but its deregulation has been associated with several human pathologies, including inflammatory bowel diseases, highlighting their crucial role in maintaining the homeostasis. Due to their multifaceted activities, AMPs represent an appealing therapeutic target for developing novel or complementary solutions to antibiotics, to face the emergence of infectious diseases in public health and the crisis of antimicrobial resistance, and to help re-establishing homeostasis in inflammatory diseases.By screening a bank of natural molecules, our team identified three promising targets, andrographolide (AND), isoliquiritigenin (ISL) and oridonin (ORD), which increase the expression of HBD-3 without inducing pro-inflammatory genes. This project thoroughly studied the effect of AND, ISL and ORD on inducing expression of HBD-3 in an in vitro model of intestinal epithelial cells. These molecules not only produced this effect when used alone, but also acted synergistically, highly inducing the expression of HBD-3 when used in combination. Moreover, AND, ISL and ORD hindered the expression of the pro-inflammatory genes IL-1β, IL-6, IL-8 and TNF-α upon stimulation of cells with endogenous or bacterial inflammatory stimuli. Further studies conducted by the group aimed at characterizing the activity of the compounds in vitro and ex vivo and unravelling their mechanisms of action by studying the intracellular pathways involved.In conclusion, AND, ISL and ORD represent useful tools to study the regulatory network controlling expression of AMPs and might develop to be candidate drugs for pathologic conditions in which strengthening the mucosal barrier, while reducing inflammation, is needed
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Steiner, Tamara Alice [Verfasser]. "Die Bedeutung des humanen β-Defensin-3 für die Infektion von humanem respiratorischem Epithel mit Moraxella catarrhalis / Tamara Alice Steiner." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2014. http://d-nb.info/1052221475/34.

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Pahl, René [Verfasser]. "Rolle von IL-1β und ADAM17 in der Regulation der β-Defensin-Antwort im Rahmen der Candida-Ösophagitis / René Pahl." Kiel : Universitätsbibliothek Kiel, 2013. http://d-nb.info/1041255527/34.

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Reynolds, Natalie Louise. "Functional studies of vertebrate β-defensins." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/27262.

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The β-defensins are a family of small, cationic antimicrobial peptides. They are conserved in a variety of species ranging from lower vertebrates to mammals and plants, and were first identified for their broad-spectrum antimicrobial activity. Since their initial discovery, this role has broadened to include a number of diverse additional functions including the chemotaxis of immune cells (immature dendritic cells, macrophages and CD4+ T cells), the determination of coat colour in dogs and seed maturation in tomatoes. The aim of this thesis is to investigate the function of vertebrate beta-defensins. I address this question by assessing how mouse β-defensin structure affects its bactericidal activity and also by carrying out β-defensin knockdown studies in zebrafish. In this work, I address the question of how β-defensin structure affects its bactericidal activity by examining the effects of sequentially removing amino acids from the N-terminal of murine Defbl4. I show that these deletions reduce bactericidal activity however the effects are much more striking in gram positive species than gram negative. Through the comparison of monomeric and dimeric species as well as analysis of peptide charge and hydrophobicity, this work indicates that a combination of primary sequence and structure is responsible for the bactericidal properties of this peptide. In addition, this thesis describes the characterisation of three β-defensin-like peptides (Defbll, Defbl2 and Defbl3) previously described in zebrafish. I utilise antimicrobial assays to determine the bactericidal properties of synthetic Defbl2 and Defbl3 against a panel of microbes and also show that Defbll is antimicrobially inactive. Furthermore, this work identifies the expression of defbl1 during zebrafish gastrulation and utilises a combination of wholemount in situ hybridisation, morpholino knockdown and rescue and microarray analysis to ascertain a novel essential role for this peptide in early development. This work is the first report of a β-defensin being involved in vertebrate development and presents a further widening of the influence of the defensin family.
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Rolfe, Mark J. "The antibacterial and chemoattractant activities of murine β-defensins." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/27300.

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Antimicrobial peptides form an important aspect of the innate immune response of mammals. They function to kill invading microorganisms and in many cases activate other aspects of the innate and adaptive immune systems. One of the largest families of antimicrobial peptides is the defensins. In vertebrates, there are three subfamilies of defensins, termed α, β and θ based on the connectivity of the six conserved cysteines. The β-defensins, which are produced mainly by epithelial tissues and keratinocytes, came to wider interest when it was proposed that their loss of function might play a role in the pathogenesis of cystic fibrosis (CF) lung disease. Previous work has suggested that the airway surface liquid (ASL) of primary cultures of human airway epithelial cells possess salt-sensitive antibacterial activity and that this is impaired in CF individuals by elevated levels of sodium chloride. Further work has also suggested that the β-defensins secreted by the airway epithelia might comprise an important component of this salt-sensitive defence system. The aim of this project was 1) to characterise the salt-sensitive antibacterial activity of members of the human and murine β-defensin subfamily, 2) to analyse their activity as chemoattractants, 3) to establish a cell culture-based system for the production of β-defensins to allow for greater analysis of their range of activities and 4) to verify the validity of novel human β-defensins identified by bioinformatics techniques. In this thesis describes the characterisation of the salt-sensitive activities of synthetic human β-defensin 2 (DEFB2), mouse β-defensin2 (Defb2), and a novel β-defensin related 1, Defrl, which lacks the first of the canonical six cysteines are described against a range of CF-related pathogens. This work has concluded that a) DEFB2, Defb2 and Defrl display, to varying degrees, salt-sensitive antibacterial activity, b) The differences observed between the activities of the peptides may represent the evolution of species-specific profiles of antibacterial activity for specific defensins. c) That the loss of in Defrl of the first canonical cysteine does not result in loss of antibacterial activity and, most interestingly, Defrl also demonstrates activity against B. cenocepacia - a pathogen normally resistant to the activity of antimicrobials. Data presented in this thesis also suggests that synthetic Defb2 and Defrl show chemotactic activity to CD4+ T-lymphocytes and to immature dendritic cells. This work concludes that, like human β-defensins 1 and 2, the murine β-defensins, Defb2 and Defrl, can act as a bridge between the innate and adaptive immune systems. In this thesis, expression pattern of five novel human β-defensins in a range of human tissues is also analysed. Evidence is presented that they are all expressed at high levels in the testis and that two of these genes are expressed at much lower levels a variety of other tissues. These data suggest that the β-defensins are an expanding, and potentially quite large, subfamily of genes, many of which are yet to be characterised in terms of their expression profile and the antimicrobial and chemotactic activities.
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Book chapters on the topic "Β-defensin"

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Bensch, K. W., U. Ballnus, P. Schulz-Knappe, M. Raida, H. J. Mägert, and W. G. Forssmann. "Isolation and structural analysis of a novel β-defensin hBD-1 from human hemofiltrate." In Peptides 1994, 50–51. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-011-1468-4_14.

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Matsuzaki, Katsumi, Miwako Komori, Masaru Fukui, Susumu Funakoshi, Nobutaka Fujii, and Koichiro Miyajima. "Effects of membrane charge and transmembrane potential on the interactions of β-sheet peptides (tachyplesin I, defensin, gramicidin S) with lipid bilayers." In Peptide Chemistry 1992, 694–96. Dordrecht: Springer Netherlands, 1993. http://dx.doi.org/10.1007/978-94-011-1474-5_197.

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Donnarumma, Giovanna, Iole Paoletti, Alessandra Fusco, Brunella Perfetto, Elisabetta Buommino, Vincenza de Gregorio, and Adone Baroni. "β-Defensins: Work in Progress." In Advances in Experimental Medicine and Biology, 59–76. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/5584_2015_5016.

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Jäger, Kristin, Fabian Garreis, Matthias Dunse, and Friedrich P. Paulsen. "Cationic Amino Acid Transporters and β-Defensins in Dry Eye Syndrome." In Research Projects in Dry Eye Syndrome, 12–15. Basel: KARGER, 2010. http://dx.doi.org/10.1159/000315015.

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Batra, Vipul, A. Kumaresan, Rakesh Kumar, and T. K. Datta. "β-Defensins: Antimicrobial Peptides at the Intersection of Immunity and Male Fertility." In Current Concepts in Bovine Reproduction, 293–317. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-19-0116-4_15.

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Choudhary, Anuj, Antul Kumar, Harmanjot Kaur, A. Balamurugan, Asish Kumar Padhy, and Sahil Mehta. "Plant Performance and Defensive Role of β-Amino Butyric Acid Under Environmental Stress." In Plant Performance Under Environmental Stress, 249–75. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-78521-5_10.

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"β-Defensin." In Encyclopedia of Signaling Molecules, 44. Cham: Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-67199-4_100007.

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Patricia Rosete Olvera, Dora, and Carlos Cabello Gutiérrez. "Multifunctional Activity of the β-Defensin-2 during Respiratory Infections." In Immune Response Activation and Immunomodulation. IntechOpen, 2019. http://dx.doi.org/10.5772/intechopen.80611.

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Harwig, Sylvia S. L., Kristine M. Swiderek, Vladimir Kokryakov, Terry D. Lee, and Robert I. Lehrer. "Primary Structure of Gallinacin-1, an Antimicrobial β-Defensin from Chicken Leukocytes." In Techniques in Protein Chemistry, 81–88. Elsevier, 1994. http://dx.doi.org/10.1016/b978-0-12-194710-1.50014-x.

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Ullah, Waheed, and Shandana Ali. "Antimicrobial Resistance in Escherichia coli." In Escherichia coli [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.101583.

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The ability of microbes to resist or neutralize the action of drugs that have been used against microbes is considered as antimicrobial resistance (AMR). AMR among different strains of Escherichia coli is considered as a major threat to public health. Drug-resistant in E. coli is found predominantly in the hospital sittings, in the community, and surrounding environment. It has adopted different defensive strategies to minimize the effects of drugs. Extended-spectrum β-lactamase (ESBL), fluoroquinolones, and carbapenemases have been considered as strong resistance strategies being present in most of resistant bacterial strains. Mobile genetic elements (MGEs) have the major contribution in the transfer of resistance genes in between or among bacterial cells. Plasmids are normally present in most of resistant strains, helping in the transfer of genetic material between bacterial cells. Transposons another MGEs, are being considered as one of the major sources of resistance transmission. Collectively, MGEs play an important role in facilitating in exchange, acquisition, and dissemination of resistance genes. Resistance in E. coli has been reported worldwide and there is variation in its resistance pattern. CTX-M ESBLs, carbapenems, colistin-resistant, and ST-131 E. coli resistant clones are considered the most dominant phenotypes. The aforesaid resistant variants are predominantly found in densely populated regions, Sub-Saharan Africa, China, and South Asian countries.
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Conference papers on the topic "Β-defensin"

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Rupp, A., DJ Romberger, L. Tang, S. Sethi, and TD LeVan. "Differential Susceptibility of NontypeableHaemophilus influenzaeStrains to the Antimicrobial Peptide, Human β-Defensin-2, in COPD Subjects." In American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a3226.

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Layton, Austin, Pierre O. Bohanes, Wu Zhang, Heinz-Josef Lenz, and Melissa J. Labonte. "Abstract 1526: Evaluation of the novel tumor suppressor gene, β-Defensin-1, in colorectal cancer cell line models." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-1526.

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Fischer, A., P. Valentin-Weigand, and S. Neumann. "Analyse des bovinen β-Defensin-4 in Serum und Milch während einer klinischen oder subklinischen Mastitis verglichen mit gesunden Milchkühen." In 28. Jahrestagung der FG „Innere Medizin und klinische Labordiagnostik“ der DVG (InnLab) – Teil 1: Vorträge. © Georg Thieme Verlag KG, 2020. http://dx.doi.org/10.1055/s-0039-3402379.

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Wang, D., X. Jing, W. Wang, and Y. Su. "Wnt/β-Catenin Mediates α-Defensins-Induced Increases in Proliferation and Collagen Synthesis of Lung Fibroblasts." In American Thoracic Society 2009 International Conference, May 15-20, 2009 • San Diego, California. American Thoracic Society, 2009. http://dx.doi.org/10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a3468.

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Costa, Kaue Santana da, João Marcos Galúcio, Clauber Henrique Costa, Rodolpho C. Braga, Élcio Leal, and Paulo Sérgio Taube. "PIPELINE COMPUTACIONAL PARA O DESENHO DE PROTEÍNAS IMUNOGÊNICAS MULTI-EPITOPO DO VÍRUS NIPAH VISANDO O DESENVOLVIMENTO DE VACINAS." In I Congresso de Engenharia de Biotecnologia. Revista Multidisciplinar de Educação e Meio Ambiente, 2021. http://dx.doi.org/10.51189/rema/1388.

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Introdução: O Nipah (NiV) é um vírus zoonótico emergente pertencente à família Paramyxoviridae que está envolvido com doenças respiratórias e neurológicas fatais em humanos. O NiV representa um desafio para a saúde pública com o risco potencial de disseminação pandemica, bem como, aplicação como agente de bioterrorismo. Metodologia: No presente estudo, usando métodos de imunoinformática e modelagem molecular, desenhou-se modelos de proteínas multi-epítopos reconhecidos pelo sistema imunológico humano usando sequências conservadas de cepas de NiV. Estes epítopos preditos foram selecionados de acordo com parâmetros físico-químicos, complementariedade e afinidade de ligação ao complexo principal de histocompatibilidade (MHC) classes I e II. Em seguida, essas cadeias polipeptídicas foram unidas usando linkers GPGPG, AAY e KK; e adjuvantes de β-defensina foram adicionados na estrutura com o propósito de aumentar a imunogenicidade. A antigenicidade, imunogenicidade, alergenicidade, bem como as propriedades físico-químicas das proteínas multi-epítopos desenhadas foram avaliadas usando algoritmos de aprendizado de máquina. Além disso, simulações de docagem molecular foram realizados entre os modelos de proteína multi-epitopo com as estruturas do toll-like humano tipo 3 (TLR3), MHC-I e -II; em seguida, os complexos foram analisados ​​por simulações de dinâmica molecular e cálculos de energia livre de ligação para explorar a estabilidade dos complexos e suas afinidades de ligação, respectivamente. Resultados: Os epítopos selecionados formaram interação estável com diferentes moléculas de HLA que cobrem mais de 98,0% da população humana em todo o mundo. Os modelos propostos mostraram-se potencialmente antigênicos e não alergênicos e demonstraram alta afinidade e seletividade contra o TLR3. Além disso, as sequências de cDNA desenhadas mostraram-se compatíveis com vetores de expressão de hospedeiros bacterianos, o que poderia facilitar sua expressão heteróloga. Conclusão: Nossas análises computacionais forneceram evidências sobre proteínas multi-epítopos biologicamente viáveis ​​para vacinas candidatas de próxima geração contra o NiV e oferecem uma visão geral da imunogenicidade das proteínas NiV que podem ser usadas parao desenho de novos modelos multiepítopos com propriedades físico-químicas otimizadas.
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