DEFB1 (defensin, beta 1)

Review on DEFB1 (defensin, beta 1), with data on DNA, on the protein encoded, and where the gene is implicated

Dark Matter and Higgs Sector

The inert doublet model is an extension of the Standard Model of Elementary Particles that is defined by the only addition of a second Higgs doublet without couplings to quarks or leptons. This minimal framework has been studied for many reasons. In particular, it has been suggested that the new degrees of freedom contained in this doublet can account for the Dark Matter of the Universe.Comment: 6 pages, 3 figures,To appear in the Proceedings of the sixth International Workshop on the Dark Side of the Universe (DSU2010) Leon, Guanajuato, Mexico 1-6 June 201

Characterization of early host responses in adults with dengue disease

BACKGROUND: While dengue-elicited early and transient host responses preceding defervescence could shape the disease outcome and reveal mechanisms of the disease pathogenesis, assessment of these responses are difficult as patients rarely seek healthcare during the first days of benign fever and thus data are lacking. METHODS: In this study, focusing on early recruitment, we performed whole-blood transcriptional profiling on dengue virus PCR positive patients sampled within 72 h of self-reported fever presentation (average 43 h, SD 18.6 h) and compared the signatures with autologous samples drawn at defervescence and convalescence and to control patients with fever of other etiology. RESULTS: In the early dengue fever phase, a strong activation of the innate immune response related genes were seen that was absent at defervescence (4-7 days after fever debut), while at this second sampling genes related to biosynthesis and metabolism dominated. Transcripts relating to the adaptive immune response were over-expressed in the second sampling point with sustained activation at the third sampling. On an individual gene level, significant enrichment of transcripts early in dengue disease were chemokines CCL2 (MCP-1), CCL8 (MCP-2), CXCL10 (IP-10) and CCL3 (MIP-1α), antimicrobial peptide β-defensin 1 (DEFB1), desmosome/intermediate junction component plakoglobin (JUP) and a microRNA which may negatively regulate pro-inflammatory cytokines in dengue infected peripheral blood cells, mIR-147 (NMES1). CONCLUSIONS: These data show that the early response in patients mimics those previously described in vitro, where early assessment of transcriptional responses has been easily obtained. Several of the early transcripts identified may be affected by or mediate the pathogenesis and deserve further assessment at this timepoint in correlation to severe disease

[Human defensins: prophylaxis and therapy against HIV?]

Human defensins are endogenous antimicrobial peptides with prophylactic and therapeutic potential against HIV. The ability of defensins to bind the HIV envelope could be exploited to design topic agents that block viral entry into exposed mucosa. Additionally, their capacity to inhibit viral replication, complement system activation, dendritic and memory T cells chemoattraction, together with peptide engineering could bring about new and better antiretroviral drugs. Clinical trials could be demonstrated the efficacy of defensins against HIV in clinical practice

[Human defensins: prophylaxis and therapy against HIV?]

Human defensins are endogenous antimicrobial peptides with prophylactic and therapeutic potential against HIV. The ability of defensins to bind the HIV envelope could be exploited to design topic agents that block viral entry into exposed mucosa. Additionally, their capacity to inhibit viral replication, complement system activation, dendritic and memory T cells chemoattraction, together with peptide engineering could bring about new and better antiretroviral drugs. Clinical trials could be demonstrated the efficacy of defensins against HIV in clinical practice

Prediction of Regulatory SNPs in Putative Minor Genes of the Neuro-Cardiovascular Variant in Fabry Reveals Insights into Autophagy/Apoptosis and Fibrosis

Even though a mutation in monogenic diseases leads to a “classic” manifestation, many disorders exhibit great clinical variability that could be due to modifying genes also called minor genes. Fabry disease (FD) is an X-linked inborn error resulting from the deficient or absent activity of alpha-galactosidase A (α-GAL) enzyme, that leads to deposits of globotriaosylceramide. With our proprietary software SNPclinic v.1.0, we analyzed 110 single nucleotide polymorphisms (SNPs) in the proximal promoter of 14 genes that could modify the FD phenotype FD. We found seven regulatory-SNP (rSNPs) in three genes (IL10, TGFB1 and EDN1) in five cell lines relevant to FD (Cardiac myocytes and fibroblasts, Astrocytes-cerebellar, endothelial cells and T helper cells 1-TH1). Each SNP was confirmed as a true rSNP in public eQTL databases, and additional software suggested the prediction of variants. The two proposed rSNPs in IL10, could explain components for the regulation of active B cells that influence the fibrosis process. The three predicted rSNPs in TGFB1, could act in apoptosis-autophagy regulation. The two putative rSNPs in EDN1, putatively regulate chronic inflammation. The seven rSNPs described here could act to modulate Fabry’s clinical phenotype so we propose that IL10, TGFB1 and EDN1 be considered minor genes in FD

Small grain size zirconium-based coatings deposited by magnetron sputtering at low temperatures

Leprosy is an infectious disease caused by Mycobacterium leprae. The peptide human ?-defensin 1 is an antimicrobial effector of innate epithelial immunity. A study was done on the association of three single nucleotide polymorphisms (SNPs) in the ?-defensin 1 gene (DEFB1) - 668 C/G (-44 C/G or rs1800972; in 5? UTR), 692 A/G (-20 A/G or rs11362; in 5? UTR) and A1836G (rs1800971; in 3? UTR) - with leprosy susceptibility per se and clinical leprosy variants. The SNPs were genotyped by real-time polymerase chain reaction (rt-PCR) and PCR-restriction fragment length polymorphisms. Subjects were of Mexican mestizo ethnicity from Sinaloa state, México. Analysis was done on borderline leprosy, lepromatous leprosy (L-lep) and indeterminate leprosy subgroups compared with healthy controls. Results: The genotypes associated with L-lep and no other leprosy subgroup after Bonferroni correction were those that contain 668C in a dominant model (OR = 3.06, 95% CI 1.47-6.4, p = 0.024). Estimated haplotype CGA is over-represented in L-lep (p = 0.009; OR = 2.25, 1.23-4.03). Five NF-?B1 putative binding sites (NPBSs) were identified with JASPAR software in non-coding strand spanning the 5? UTR and intron 1 of DEFB1, including one which is altered when SNP 668C is present. SNP 668C probably abrogates NF-?B-dependent DEFB1 upregulation leading to L-lep variant. " 2009.",,,,,,"10.1016/j.meegid.2009.03.006",,,"http://hdl.handle.net/20.500.12104/44594","http://www.scopus.com/inward/record.url?eid=2-s2.0-68649115023&partnerID=40&md5=2abfc02faaf4716b6f8ea5d93b41441

SNP 668C (-44) alters a NF-κB1 putative binding site in non-coding strand of human β-defensin 1 (DEFB1) and is associated with lepromatous leprosy

Leprosy is an infectious disease caused by Mycobacterium leprae. The peptide human β-defensin 1 is an antimicrobial effector of innate epithelial immunity. A study was done on the association of three single nucleotide polymorphisms (SNPs) in the β-defensin 1 gene (DEFB1) - 668 C/G (-44 C/G or rs1800972; in 5′ UTR), 692 A/G (-20 A/G or rs11362; in 5′ UTR) and A1836G (rs1800971; in 3′ UTR) - with leprosy susceptibility per se and clinical leprosy variants. The SNPs were genotyped by real-time polymerase chain reaction (rt-PCR) and PCR-restriction fragment length polymorphisms. Subjects were of Mexican mestizo ethnicity from Sinaloa state, México. Analysis was done on borderline leprosy, lepromatous leprosy (L-lep) and indeterminate leprosy subgroups compared with healthy controls. Results: The genotypes associated with L-lep and no other leprosy subgroup after Bonferroni correction were those that contain 668C in a dominant model (OR = 3.06, 95% CI 1.47-6.4, p = 0.024). Estimated haplotype CGA is over-represented in L-lep (p = 0.009; OR = 2.25, 1.23-4.03). Five NF-κB1 putative binding sites (NPBSs) were identified with JASPAR software in non-coding strand spanning the 5′ UTR and intron 1 of DEFB1, including one which is altered when SNP 668C is present. SNP 668C probably abrogates NF-κB-dependent DEFB1 upregulation leading to L-lep variant. © 2009

Association of beta-defensin 1 single nucleotide polymorphisms with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic multifactorial allergic disease with unclear etiology. The antimicrobial human beta-defensin 1 is chemotactic for dendritic cells, which are important regulators of allergic immune responses. In an attempt to identify useful markers that could predict susceptibility to AD, we investigated single nucleotide polymorphisms (SNPs) of the beta-defensin 1 gene (DEFB1) with potential functional consequences. METHODS: Four SNPs of the DEFB1 gene were genotyped either by real-time polymerase chain reaction or polymerase chain reaction-restriction fragment length polymorphisms in 59 patients with AD and 151 controls from the Mexican population. Correlation analyses were carried out between genetic, environmental and clinical variables in AD patients. RESULTS: The genotypes associated with susceptibility to AD and no other allergy were 692 GG (OR = 3.21, 95% CI 1.37-7.34) and 1654 AA (OR = 17.37, 95% CI 1.62-860.83). The allele 668 C is a risk factor for AD (OR = 2.23, 95% CI 1.22-4.01) and the allele A in site 1836 correlates with earlier age at onset (Spearman's rho = 0.232; p = 0.03). The prolonged duration of breastfeeding correlates with earlier age at onset as well as with the severity of AD. CONCLUSIONS: The DEFB1 gene is probably involved in the incidence and development of AD, but additional functional studies will be necessary to understand the biological role of these SNPs