Chunk-level Retrieval Eval
Collection
Contextualized chunk-level (query2chunk) retrieval eval for the Citras benchmark. • 23 items • Updated
chunk_id stringlengths 3 7 | chunk stringlengths 6 791 | source_url stringclasses 147
values | title stringclasses 1
value | chunk_idx int64 0 158 | chunk_start_char int64 0 70.4k | chunk_end_char int64 38 70.8k |
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0_0 | Functional Genetic Variants in DC-SIGNR Are Associated with Mother-to-Child Transmission of HIV-1
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752805/
Boily-Larouche, Geneviève; Iscache, Anne-Laure; Zijenah, Lynn S.; Humphrey, Jean H.; Mouland, Andrew J.; Ward, Brian J.; Roger, Michel
2009-10-07
DOI:10.1371/journal.... | c0 | 0 | 0 | 356 | |
0_1 | : BACKGROUND: Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Given that the C-type lectin receptor, dendritic cell-specific ICAM-grabbing non-integrin-related (DC-SIGNR, also known as CD209L or liver/lymph node–specific ICAM-grabbing non-integrin (L-SIGN)), can interact ... | c0 | 1 | 356 | 811 | |
0_2 | METHODS AND FINDINGS: To investigate the potential role of DC-SIGNR in MTCT of HIV-1, we carried out a genetic association study of DC-SIGNR in a well-characterized cohort of 197 HIV-infected mothers and their infants recruited in Harare, Zimbabwe. | c0 | 2 | 811 | 1,060 | |
0_3 | Infants harbouring two copies of DC-SIGNR H1 and/or H3 haplotypes (H1-H1, H1-H3, H3-H3) had a 3.6-fold increased risk of in utero (IU) (P = 0.013) HIV-1 infection and a 5.7-fold increased risk of intrapartum (IP) (P = 0.025) HIV-1 infection after adjusting for a number of maternal factors. | c0 | 3 | 1,060 | 1,351 | |
0_4 | The implicated H1 and H3 haplotypes share two single nucleotide polymorphisms (SNPs) in promoter region (p-198A) and intron 2 (int2-180A) that were associated with increased risk of both IU (P = 0.045 and P = 0.003, respectively) and IP (P = 0.025, for int2-180A) HIV-1 infection. The promoter variant reduced transcrip... | c0 | 4 | 1,351 | 1,696 | |
0_5 | In homozygous H1 infants bearing both the p-198A and int2-180A mutations, we observed a 4-fold decrease in the level of placental DC-SIGNR transcripts, disproportionately affecting the expression of membrane-bound isoforms compared to infant noncarriers (P = 0.011). CONCLUSION: These results suggest that DC-SIGNR play... | c0 | 5 | 1,696 | 2,129 | |
0_6 |
Text: Without specific interventions, the rate of HIV-1 mother-tochild transmission (MTCT) is approximately 15-45% [1] . UNAIDS estimates that last year alone, more than 400,000 children were infected worldwide, mostly through MTCT and 90% of them lived in sub-Saharan Africa. In the most heavilyaffected countries, su... | c0 | 6 | 2,129 | 2,551 | |
0_7 | MTCT of HIV-1 can occur during pregnancy (in utero, IU), delivery (intrapartum, IP) or breastfeeding (postpartum, PP). High maternal viral load, low CD4 cells count, vaginal delivery, low gestational age have all been identified as independent factors associated with MTCT of HIV-1 [1] . Although antiretrovirals can re... | c0 | 7 | 2,551 | 3,015 | |
0_8 | A better understanding of the mechanisms acting at the maternal-fetal interface is crucial for the design of alternative interventions to antiretroviral therapy for transmission prevention.
Dendritic cell-specific ICAM-grabbing non-integrin-related (DC-SIGNR, also known as CD209L or liver/lymph node-specific ICAM-gra... | c0 | 8 | 3,015 | 3,485 | |
0_9 | DC-SIGNR is organized in three distinct domains, an N-terminal cytoplasmic tail, a repeat region containing seven repeat of 23 amino acids and a C-terminal domain implicated in pathogen binding. Alternative splicing of DC-SIGNR gene leads to the production of a highly diversify isoforms repertoire which includes membr... | c0 | 9 | 3,485 | 3,841 | |
0_10 | It has been proposed that interaction between DC-SIGNR and HIV-1 might enhance viral transfer to other susceptible cell types [2] but DC-SIGNR can also internalize and mediate proteasome-dependant degradation of viruses [4] that may differently affect the outcome of infection.
Given the presence of DC-SIGNR at the ma... | c0 | 10 | 3,841 | 4,270 | |
0_11 | To investigate the potential role of DC-SIGNR in MTCT of HIV-1, we carried out a genetic association study of DC-SIGNR in a well-characterized cohort of HIV-infected mothers and their infants recruited in Zimbabwe, and identified specific DC-SIGNR variants associated with increased risks of HIV transmission. We furthe... | c0 | 11 | 4,270 | 4,776 | |
0_12 |
Samples consisted of stored DNA extracts obtained from 197 mother-child pairs co-enrolled immediately postpartum in the ZVITAMBO Vitamin A supplementation trial (Harare, Zimbabwe) and followed at 6 weeks, and 3-monthly intervals up to 24 months. The ZVITAMBO project was a randomized placebocontrolled clinical trial t... | c0 | 12 | 4,776 | 5,295 | |
0_13 | The samples used in the present study were from mother-child pairs randomly assigned to the placebo group of the ZVITAMBO project. Antiretroviral prophylaxis for HIV-1-positive antenatal women was not available in the Harare public-sector during ZVITAMBO patient recruitment. The samples were consecutively drawn from t... | c0 | 13 | 5,295 | 5,816 | |
0_14 | Infants were considered to be infected if they were HIV-1 seropositive at 18 months or older and had two or more positive HIV-1-DNA polymerase chain reaction (PCR) results at earlier ages. 100 infants were considered to be uninfected as they were ELISA negative at 18 months or older and had two DNA PCR negative result... | c0 | 14 | 5,816 | 6,178 | |
0_15 | Of the 97 HIV-1-infected infants, 57 were infected IU, 11 were infected IP, and 17 were infected PP as determined by PCR analyses of blood samples collected at birth, 6 weeks, 3 and 6 months of age and according to the following definitions adapted from Bryson and colleagues [5] . Briefly, infants who were DNA PCR pos... | c0 | 15 | 6,178 | 6,654 | |
0_16 | Infants with negative PCR results at birth and 6 weeks of age but who subsequently became DNA PCR positive were considered to be infected during the PP period. In the analysis comparing the 3 different modes of MTCT, 12 HIV-1-infected infants were excluded because the PCR results were not available at 6 weeks of age. ... | c0 | 16 | 6,654 | 7,264 | |
0_17 | Haplotype reconstruction was performed using Bayesian statistical method implemented in PHASE [8] , version 2.1.1, using single nucleotide polymorphism (SNP) with a minimum allele frequency (MAF) of 2%. We applied the algorithm five times, using different randomly generated seeds, and consistent results were obtained ... | c0 | 17 | 7,264 | 7,717 | |
0_18 | These htSNPs were genotyped in the 197 infants by direct PCR sequencing analysis as we have described previously [7] . The DC-SIGNR exon 4 repeat region genotype was determined by PCR amplification followed by migration in 1.5% agarose gels [10] . DNA sequences in the promoter region were analysed with the TESS interf... | c0 | 18 | 7,717 | 8,151 | |
0_19 |
Luciferase reporter assays using pGL2-Basic vector were performed in order to investigate the functional effect of mutations on DC-SIGNR promoter activity. Genomic DNA from subjects homozygous for the promoter variants and WT was amplified from nucleotide position 2715 to 21 and cloned between the BglII and HindIII m... | c0 | 19 | 8,151 | 8,680 | |
0_20 | The firefly luciferase test reporter vector was co-transfected at a ratio of 10:1 with the constitutive expressor of Renilla luciferase, phRL-CMV (Promega, Madison, WI, USA). We cultured HeLa cells in 6 wells plates (2610 5 cells) and transfected them the following day using lipofectamine (Invitrogen) according to the... | c0 | 20 | 8,680 | 9,166 | |
0_21 | Firefly luciferase activity was normalized to Renilla luciferase activity. 0 mg, 0,5 mg or 1 mg CMV-Tat vector was transfected with LTR-Luc as a positive control in these experiments. We carried out lucierase assays in triplicate in three independent experiments. Results are expressed as mean6 standard error of the me... | c0 | 21 | 9,166 | 9,648 | |
0_22 | Tissues from 3 H1 (associated with MTCT of HIV-1) and 3 H15 (wild-type) homozygous haplotypes were used to analyse possible differences in isoform expression. Total placental RNAs were extracted by MasterPure DNA and RNA Extraction Kit (Epicentre Biotechnologies, Madison, WI, USA) according to the manufacturer. | c0 | 22 | 9,648 | 9,961 | |
0_23 | Fragments corresponding to the DC-SIGNR coding region were reversed transcribed (RT) and then amplified by nested PCR with the following primers; RT primers RR, first PCR RF and RR and second PCR RcF and RcR according to Liu and colleagues [11] . 1 mg of total RNA was reverse transcribed with Expand RT (Roche Applied ... | c0 | 23 | 9,961 | 10,412 | |
0_24 | Major PCR products from the second PCR reaction were gel extracted with the Qiagen Gel Extraction Kit (Qiagen Canada inc, Mississauga, ON, Canada) and cloned using the TOPO TA Cloning Kit for sequencing (Invitrogen). For each placenta, 15 different clones were randomly selected and amplified with M13 primers and seque... | c0 | 24 | 10,412 | 10,830 | |
0_25 | Sequences were analysed and aligned with GeneBank reference sequence NM_014257 using Lasergene software (DNA Stars, Madison, WI, USA).
Quantitative expression of DC-SIGNR isoforms 1,5 mg of placental RNA was reverse transcribed using 2.5 mM of Oligo dT 20 and Expand RT in 20 ml volume according to the manufacturer (R... | c0 | 25 | 10,830 | 11,172 | |
0_26 | 15 ng of total cDNA in a final volume of 20 ml was used to perform quantitative real-time PCR using Universal Express SYBR GreenER qPCR Supermix (Invitrogen) on a Rotor Gene Realtime Rotary Analyser (Corbett Life Science, Sydney, Australia). Samples from 2 subjects in each group were used because RNA quality of others... | c0 | 26 | 11,172 | 11,636 | |
0_27 | Membrane-bound isoforms were amplified using primers specific for exon 3, corresponding to the common trans-membrane domain of DC-SIGNR. Primers were targeted to the exon-exon junction and RNA extracts were treated with DNase (Fermantas International inc, Burlington, ON, Canada) to avoid amplification of contaminant D... | c0 | 27 | 11,636 | 12,117 | |
0_28 | All qPCR reactions had efficiencies ranging from 99% to 100%, even in the presence of 20 ng of non-specific nucleic acids, and therefore could be compared. The copy number of unknown samples was estimated by placing the measured PCR cycle number (crossing threshold) on the standard curve. To correct for differences in... | c0 | 28 | 12,117 | 12,652 | |
0_29 | The results are presented as target gene copy number per 10 5 copies of GAPDH. The ratio of membrane-bound isoforms was calculated as E3/E5. Soluble isoforms were calculated by subtracting membrane-bound from total isoforms. We carried out qPCR assays in triplicate in three independent experiments. Results are express... | c0 | 29 | 12,652 | 13,111 | |
0_30 | Differences in baseline characteristics and genotypic frequencies of haplotypes or htSNPs were compared between groups using the x 2 analysis or Fisher's exact test. Logistic regression analysis was used to estimate odds ratios (OR) for each genotype and baseline risk factors. Multiple logistic regression was used to ... | c0 | 30 | 13,111 | 13,781 | |
0_31 | Differences were considered significant at P,0.05.
Written informed consent was obtained from all mothers who participated in the study and the ZVITAMBO trial and the investigation reported in this paper were approved by The
We carried out an association study of DC-SIGNR polymorphism in 197 infants born to untreat... | c0 | 31 | 13,781 | 14,237 | |
0_32 | Of the 97 HIV-1-infected infants, 57 were infected IU, 11 were infected IP, and 17 were infected PP. Timing of infection was not determined for 12 HIV-1-infected infants. Baseline characteristics of mothers and infants are presented in Table 1 . Maternal age and CD4 cell count, child sex, mode of delivery, duration of... | c0 | 32 | 14,237 | 14,625 | |
0_33 | However, maternal viral load .29 000 copies/ml was associated with increased risk in both IU and PP with odds ratios (OR) of 3.64 (95% CI = 1.82-7.31, P = 0.0002) and 4.45 (95% CI = 1.50-13.2, P = 0.0045) for HIV-1 transmission, respectively. | c0 | 33 | 14,625 | 14,868 | |
0_34 |
Fifteen haplotype-tagged SNPs (htSNPs) corresponding to the 15 major DC-SIGNR haplotypes ( Figure 1 ) described among Zimbabweans [7] were genotyped in our study samples (Tables S2 and S3 ). H1 (31%) and H3 (11%) were the most frequent haplotypes observed (Figure 1 ). | c0 | 34 | 14,868 | 15,139 | |
0_35 | Being homozygous for the H1 haplotype was associated with increased risk of both IU (OR: 4.42, P = 0.022) and PP (OR: 7.31, P = 0.016) HIV-1 transmission ( Table 2) . | c0 | 35 | 15,139 | 15,306 | |
0_36 | Infants harbouring two copy combinations of H1 and/ or H3 haplotypes (H1-H1, H1-H3 or H3-H3) had increased risk of IU (OR: 3.42, P = 0.007) and IP (OR: 5.71, P = 0.025) but not PP (P = 0.098) HIV-1 infection compared to infant noncarriers ( Table 2 ). | c0 | 36 | 15,306 | 15,558 | |
0_37 | The latter associations remained significant after adjustment was made for the maternal viral load for both IU (OR: 3.57, 95% CI = 1.30-9.82, P = 0.013) and IP (OR: 5.71, 95% CI = 1.40-23.3, P = 0.025) HIV-1 transmission. | c0 | 37 | 15,558 | 15,780 | |
0_38 | The H1 and H3 haplotypes share a cluster of mutations (p-198A, int2-391C, int2-180A, ex4RPT, int5+7C) ( Figure 1 ). Of these, the p-198A and int2-180A variants were significantly associated with MTCT of HIV-1 (Table S2 ). | c0 | 38 | 15,780 | 16,002 | |
0_39 | In the unadjusted regression analysis, homozygous infants for the p-198A and int2-180A variants had increased risk of IU (OR: 2.07 P = 0.045, OR: 3.78, P = 0.003, respectively) and IP (OR: 2.47, P = 0.17, O.R: 5.71, P = 0.025, respectively) HIV-1 infection compared to heterozygote infants or noncarriers (Table 3 | c0 | 39 | 16,002 | 16,316 | |
0_40 | ) . When adjustment was made for maternal factors, only the association with the int2-180A variant remained significant for IU (OR: 3.83, 95% CI = 1.42-10.4, P = 0.008) and IP (O.R: 5.71, 95% CI = 1.40-23.3, P = 0.025) HIV-1 transmission. | c0 | 40 | 16,316 | 16,554 | |
0_41 | Thus, infants homozygous for DC-SIGNR variant int2-180A contained in H1 and H3 haplotypes were 4-fold to 6-fold more likely to be infected by HIV-1 during pregnancy or at delivery, respectively.
Alternative splicing of the DC-SIGNR gene in the placenta produces both membrane-bound and soluble isoform repertoires [3] ... | c0 | 41 | 16,554 | 17,009 | |
0_42 | We therefore hypothesized that the DC-SIGNR mutations associated with MTCT of HIV-1 would have an impact on both the level of DC-SIGNR expression and in the isoform repertoire produced. We investigated DC-SIGNR transcript expression in first-term placentas obtained after elective abortion. | c0 | 42 | 17,009 | 17,300 | |
0_43 |
We cloned DC-SIGNR from placental tissues by RT-PCR from 3 homozygous H1 samples containing both the DC-SIGNR p-198AA and int2-180AA variants associated with HIV-1 transmission and 3 homozygous wild-type (WT) (p-198CC, int2-180GG) samples. Fifteen clones per sample were randomly selected for sequencing. As expected, ... | c0 | 43 | 17,300 | 17,739 | |
0_44 | A total of 65 distinct transcripts were identified ( Figure S1 ), of which 3 were full-length transcripts. 64 of the sequenced clones contained a total of 69 amino acid substitutions with 3 new C termini and 2 premature stop codons. However, the diversity was mostly attributable to the entire deletion of exon 2 or exo... | c0 | 44 | 17,739 | 18,134 | |
0_45 | The deletion of exon 3 eliminates the trans-membrane domain of the protein and leads to the expression of soluble DC-SIGNR isoforms [3] . Interestingly, the abundance of membrane-bound isoforms in placental tissues of the H1 homozygotes appears to be lower than that observed in samples from WT individuals ( Figure S1 ... | c0 | 45 | 18,134 | 18,653 | |
0_46 | In fact, this intron mutation is located 180 bp downstream from exon 3 and potentially modifies splicing events (Figure 2A ). We confirmed that the variation in transcript proportions seen between the two groups was also reflected at the level of mRNA expression in the placenta. To quantify membrane-bound vs soluble i... | c0 | 46 | 18,653 | 19,128 | |
0_47 | We then amplified exon 3 (E3) which is deleted in the soluble forms and then calculated the E3:E5 ratio. We found that placental tissues from homozygous H1 infants express a significantly lower proportion of membrane-bound DC-SIGNR (18%) compared to that in WT individuals (36%) (P = 0.004) ( Figure 2B ) suggesting tha... | c0 | 47 | 19,128 | 19,566 | |
0_48 |
The DC-SIGNR int2-180A variant is always transmitted with the promoter mutation p-198A (Figure 1 ). In the unadjusted regression analysis, the p-198A variant was significantly associated with IU but not with IP and PP HIV-1 transmission (Table 3) . Computational transcription factor binding site analysis predicts Tab... | c0 | 48 | 19,566 | 20,061 | |
0_49 | The luciferase activity of the p-198A variant construct was significantly lower than that of the WT p-198C promoter construct (p-198C/A ratio = 2, P = 0.006) ( Figure 3B ) suggesting that DC-SIGNR p-198A affects promoter activity. The other promoter mutants (p-577C and p-323A) observed in the Zimbabwean population did... | c0 | 49 | 20,061 | 20,444 | |
0_50 | To determine the net impact of the DC-SIGNR p-198A mutation on DC-SIGNR expression in the placenta, we quantitated the absolute number of total and membrane-bound DC-SIGNR transcripts in the H1 homozygote and wild-type placental samples as described earlier. | c0 | 50 | 20,444 | 20,703 | |
0_51 | The total number of DC-SIGNR transcripts was determined to be 6856213 (DC-SIGNR copies6S.E.M per 10 5 GAPDH copies) in the placental samples from homozygous H1 infants and was 4-fold lower compared to that found in placentas from WT individuals (27816638, P = 0.011) ( Figure 3C ). As suggested earlier, the int2-180A m... | c0 | 51 | 20,703 | 21,117 | |
0_52 | Although, the decrease in the total number of DC-SIGNR transcripts in H1 homozygous placental samples containing both the p-198AA and int2-180AA variants affected the proportion of membrane-bound and soluble isoforms, the effect of these mutations was more pronounced on the membrane-bound isoforms with an 8-fold decre... | c0 | 52 | 21,117 | 21,550 | |
0_53 | 86181.9 vs WT = 19256495.3, P = 0.03) ( Figure 3C ). Therefore, DC-SIGNR p-198A and int2-180A mutations associated with MTCT of HIV-1 significantly decreased the level of total placental DC-SIGNR transcripts, disproportionately affecting the membrane-bound isoform production. Table 3 . | c0 | 53 | 21,550 | 21,836 | |
0_54 | Associations between infant DC-SIGNR promoter p-198 and intron 2 (int2)-180 variants and intrauterine (IU), intrapartum (IP) and postpartum (PP) mother-to-child HIV-1 transmission.
Our genetic results, supported by expression assay in placenta, suggest the involvement of DC-SIGNR in MTCT of HIV-1. Homozygosity for t... | c0 | 54 | 21,836 | 22,246 | |
0_55 | However, the association disappeared after adjustment was made for the maternal factors presumably because of the small number of H1 homozygote infants analysed in each groups. H1 and H3 were the most frequent haplotypes observed in the study population and they share a cluster of mutations (Figure 1 ). Grouping haplo... | c0 | 55 | 22,246 | 22,815 | |
0_56 | The int2-180A was associated with a 4-fold increased risk of IU and 6fold increased risk of IP after adjustment for the maternal factors. Although the p-198A variant was associated with IU transmission, the association disappeared after adjustment was made for the maternal viral load. Nevertheless, we showed that this... | c0 | 56 | 22,815 | 23,308 | |
0_57 | Since int2-180A is always transmitted with p-198A on the MTCT associated combined haplotypes H1/H3, whereas p-198A is carried on other nonassociated haplotypes (Figure 1) , we can speculate that the p-198A mutation alone may have a minor effect in vivo whereas in combination with the int2-180A variant, they both act t... | c0 | 57 | 23,308 | 23,728 | |
0_58 |
The majority of IU transmission occurs during the last trimester of pregnancy (reviewed in [12] ). Full-term placenta samples were not available for the current study and the expression assays were performed on first-term placental tissues. A previous study looking at DC-SIGNR placental isoforms repertoire in full-te... | c0 | 58 | 23,728 | 24,182 | |
0_59 | However, since levels of DC-SIGNR expression have never been compared between the different terms of pregnancy, it is not known whether DC-SIGNR expression varies during the course of pregnancy. Nevertheless, it is reasonable to assume that the inter-individual differences in both DC-SIGNR isoform repertoire and trans... | c0 | 59 | 24,182 | 24,725 | |
0_60 | However, the multiple mechanisms involved in trans infection and redundancy among C-type lectin functions make it difficult to determine the actual participation of DC-SIGNR in this mode of infection in vivo [13, 14] . The strong correlation we observed between MTCT of HIV-1 and DC-SIGNR genetic variants producing low... | c0 | 60 | 24,725 | 25,303 | |
0_61 | Chan and colleagues recently demonstrated that DC-SIGNR transfected CHO cells diminish SARS-CoV titers by enhanced capture and degradation of the virus in a proteasome-dependent manner [4] . Since endothelial cells express MHC-I and II, degraded viral antigens could then be presented to immune cells to elicit an adapt... | c0 | 61 | 25,303 | 25,795 | |
0_62 | HIV-1 gp120 binding to CCR5 receptor on endothelial cells compromises BBB integrity and enhances monocytes adhesion and transmigration across the BBB [20, 21] . It is thus possible that reduced expression of DC-SIGNR, particularly the membranebound isoforms, on placental capillary endothelial cells might favour HIV-1 ... | c0 | 62 | 25,795 | 26,298 | |
0_63 |
The int2-180A variant contained in the H1 and H3 haplotypes was associated with IP transmission suggesting that DC-SIGNR also affect transmission of HIV-1 during delivery. Little is known about the mechanisms underlying transmission of HIV-1 during delivery. Passage through the birth canal could potentially expose in... | c0 | 63 | 26,298 | 26,877 | |
0_64 | Such process called microtransfusion has been proposed in regards to the results obtain in a Malawian cohort. Kweik and colleagues found a significant association between levels of maternal DNA in umbilical cord blood and IP transmission of HIV-1 suggesting that passage of maternal infected cells through the placenta ... | c0 | 64 | 26,877 | 27,238 | |
0_65 | Thus, in a similar fashion as suggested earlier for IU transmission, the relatively lower level of DC-SIGNR in the placenta of homozygous infants harbouring the int2-180A variant could promote HIV-1 binding to CCR5 receptor on endothelial cells affecting the placental barrier integrity and facilitating the passage of ... | c0 | 65 | 27,238 | 27,718 | |
0_66 | Genetic variants in CCR5 have been shown to influence vertical transmission of HIV-1. CCR5 promoter variants resulting in higher expression of the receptor were associated with increased risk of MTCT of HIV-1 among sub-Saharan Africans [25, 26] . The 32-pb deletion polymorphism in CCR5 has be shown to protect from ver... | c0 | 66 | 27,718 | 28,142 | |
0_67 | High copy numbers of CCL3L1, a potent HIV-1 suppressive ligand for CCR5, are associated with higher chemokine production and lower risk of MTCT of HIV-1 among South African infants [29, 30] . Mannose-binding lectin (MBL) is an innate immune receptor synthesised in the liver and secreted in the bloodstream in response ... | c0 | 67 | 28,142 | 28,485 | |
0_68 | MBL promotes pathogen elimination by opsonization and phagocytosis, and reduced expression of MBL resulting from polymorphism in coding and non-coding regions has been associated with an increased risk of MTCT of HIV-1 [31, 32] .
In this study, we demonstrate for the first time, the potential functional impact of DC-... | c0 | 68 | 28,485 | 28,893 | |
0_69 | We believe that the presence of DC-SIGNR at the placental endothelial cell surface may protect infants from HIV-1 infection by capturing virus and promoting its degradation/presentation. However, in placenta containing low levels of DC-SIGNR, HIV-1 would preferentially binds CCR5 on endothelial cells resulting in a lo... | c0 | 69 | 28,893 | 29,348 | |
0_70 | This mechanism may also apply to other vertically-transmitted pathogens known to interact with DC-SIGNR such as HIV-2, hepatitis C and dengue viruses and warrant further investigation.
Associations between child DC-SIGNR exon 4 repeated region genotypes and mother-to-child HIV-1 transmission.CI, Confidence interval;... | c0 | 70 | 29,348 | 29,808 | |
0_71 | Found at: doi:10.1371/journal.pone.0007211.s003 (0.05 MB DOC) Figure S1 DC-SIGNR transcripts repertoire in placenta. Major RT-PCR products from RNA extract from 3 homozygous H1 and 3 homozygous WT placenta samples were purified, cloned and sequenced. Sequenced were analysed according to NCBI reference sequence NM_0142... | c0 | 71 | 29,808 | 30,131 | |
0_72 | CT; cytoplasmic tail, TM; trans-membrane domain; WT; wild-type Found at: doi:10.1371/journal.pone.0007211.s004 (0.11 MB DOC) Figure S2 Effect of DC-SIGNR promoter variant on transcriptional activity in luciferase reporter assay in vitro in transfected HeLa cells. Relative luciferase expression from pGL2-Basic, parenta... | c0 | 72 | 30,131 | 30,477 | |
0_73 | Expression DC-SIGNR promoter constructs, spanning p-577C variant or p-323A variant were calculated relatively to this value. Data are presented in mean values6S.E.M of three independent experiments performed in triplicate. One-way ANOVA test followed by the Dunnett test for multiple comparison was used to compare the ... | c0 | 73 | 30,477 | 30,926 | |
0_74 | 0 mg, 0,5 mg or 1 mg CMV-Tat vector was transfected with LTR-Luc as a positive control in these experiments. | c0 | 74 | 30,926 | 31,035 | |
1_0 | Role of S-Palmitoylation on IFITM5 for the Interaction with FKBP11 in Osteoblast Cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776769/
Tsukamoto, Takashi; Li, Xianglan; Morita, Hiromi; Minowa, Takashi; Aizawa, Tomoyasu; Hanagata, Nobutaka; Demura, Makoto
2013-09-18
DOI:10.1371/journal.pone.0075831 | c1 | 0 | 0 | 306 | |
1_1 |
License:cc-by
Abstract: Recently, one of the interferon-induced transmembrane (IFITM) family proteins, IFITM3, has become an important target for the activity against influenza A (H1N1) virus infection. In this protein, a post-translational modification by fatty acids covalently attached to cysteine, termed S-palmito... | c1 | 1 | 306 | 683 | |
1_2 | IFITM3 possesses three cysteine residues for the S-palmitoylation in the first transmembrane (TM1) domain and in the cytoplasmic (CP) loop. Because these cysteines are well conserved in the mammalian IFITM family proteins, the S-palmitoylation on these cysteines is significant for their functions. | c1 | 2 | 683 | 982 | |
1_3 | IFITM5 is another IFITM family protein and interacts with the FK506-binding protein 11 (FKBP11) to form a higher-order complex in osteoblast cells, which induces the expression of immunologically relevant genes. In this study, we investigated the role played by S-palmitoylation of IFITM5 in its interaction with FKBP11... | c1 | 3 | 982 | 1,383 | |
1_4 | Our investigations using an established reporter, 17-octadecynoic acid (17-ODYA), and an inhibitor for the S-palmitoylation, 2-bromopalmitic acid (2BP), revealed that IFITM5 was S-palmitoylated in addition to IFITM3. Specifically, we found that cysteine residues in the TM1 domain and in the CP loop were S-palmitoylate... | c1 | 4 | 1,383 | 1,715 | |
1_5 | Then, we revealed by immunoprecipitation and western blot analyses that the interaction of IFITM5 with FKBP11 was inhibited in the presence of 2BP. The mutant lacking the S-palmitoylation site in the TM1 domain lost the interaction with FKBP11. These results indicate that the S-palmitoylation on IFITM5 promotes the in... | c1 | 5 | 1,715 | 2,217 | |
1_6 | The experiment resulted in a morphological aberration of the bone nodule. This also indicated that the S-palmitoylation contributes to bone formation.
Text: The interferon-induced transmembrane (IFITM) protein family (also known as the Fragilis family in mice) is a part of the dispanin family [1] and is composed of d... | c1 | 6 | 2,217 | 2,691 | |
1_7 | The IFITM proteins are evolutionarily conserved in vertebrates [2] . Recent genomic research has revealed that there are 5 IFITM members in humans (IFITM1, 2, 3, 5 and 10) and 7 members in mice (IFITM1, 2, 3, 5, 6, 7, and 10). | c1 | 7 | 2,691 | 2,918 | |
1_8 | These proteins play roles in diverse biological processes, such as germ cell maturation during gastrulation (IFITM1-3) [3] [4] [5] , cell-to-cell adhesion (IFITM1) [6] [7] [8] , antiviral activity (IFITM1-3) [9] [10] [11] [12] [13] [14] [15] [16] [17] , and bone formation (IFITM5) [18] [19] [20] [21 | c1 | 8 | 2,918 | 3,219 | |
1_9 | ] [22] , although the detailed functions of IFITM6, 7, and 10 are unknown at present. In particular, IFITM3 has been a target of intensive studies on its activity against influenza A (H1N1) virus infection and internalization [9] [10] [11] [12] [13] [14] .
In 2010, Dr. Yount and co-workers reported that the antiviral ... | c1 | 9 | 3,219 | 3,612 | |
1_10 | The S-palmitoylation [23] is a post-translational modification on proteins by C 16 saturated-fatty acids (palmitic acids) covalently attached to certain cysteine residues via a thioester linkage (Figure 1-B) . | c1 | 10 | 3,612 | 3,822 | |
1_11 | The modification is reversibly catalyzed by protein acyltransferases and acylprotein thioesterases, and confers unique properties to the protein, such as membrane binding and targeting, immunoreactivity,
Amino-acid sequence alignment of IFITM5, IFITM1, IFITM2, and IFITM3 derived from mice. The conserved residues are ... | c1 | 11 | 3,822 | 4,288 | |
1_12 | The residues unique in IFITM5 are highlighted in gray. The first and the second transmembrane domains, the extracellular sequences, and the cytoplasmic loop are indicated by arrows and denoted as TM1 and TM2, EC, and the CP loop, respectively. The TM domains were predicted by SOSUI. The aspartates at the C-terminal re... | c1 | 12 | 4,288 | 4,777 | |
1_13 | The palmitoylation and depalmitoylation are catalyzed by protein acyltransferases and acylprotein thioesterases, respectively. In this study, hydroxylamine, NH 2 OH, was used to reduce the thioester linkage. C) The amino acid sequence identity (similarity) among IFITM5, IFITM1, IFITM2, and IFITM3 is summarized. doi: 1... | c1 | 13 | 4,777 | 5,162 | |
1_14 | The authors revealed that IFITM3 is S-palmitoylated on three membrane proximal cysteines, Cys71 and Cys72 in the first transmembrane (TM1) domain, and Cys105 in the CP loop (Figure 1-A) [10] . In addition, IFITM3 lacking the S-palmitoylation is not clustered in the cell membrane and significantly diminishes the antivi... | c1 | 14 | 5,162 | 5,495 | |
1_15 | Moreover, the cysteines in IFITM2, Cys70, Cys71, and Cys104 are also palmitoylated in the same manner, which affects the intracellular localization [24] . A resent study has revealed that murine IFITM1 has four cysteine residues (Cys49, Cys50, Cys83, and Cys103) for the S-palmitoylation, which is required for the anti... | c1 | 15 | 5,495 | 5,862 | |
1_16 | The other IFITM family members also possess these cysteines (Figure 1-A) , and thus the role of the Spalmitoylation on the cysteines should be significant for the functions of IFITM proteins.
Here, we focused on IFITM5, which is also known as bonerestricted IFITM-like (BRIL) protein [18] . Among the IFITM family prot... | c1 | 16 | 5,862 | 6,205 | |
1_17 | (i) Expression of IFITM5: Unlike the other IFITM family proteins, the expression of IFITM5 is not induced by interferons because the region upstream of the ifitm5 gene lacks the interferon regulatory elements [26] . Furthermore, the expression of IFITM5 is mostly restricted to osteoblast cells [18, 19, 27] , while the... | c1 | 17 | 6,205 | 6,579 | |
1_18 | Amino-acid sequence similarity: The amino acid sequence of IFITM5 is relatively dissimilar to IFITM1-3 proteins (~ 65% similarity), while IFITM1-3 proteins share ~ 85% similarity with each other (Figure 1 -C). In addition, IFITM5 has an aspartate-rich domain in the C-terminal region, which could be involved in calcium... | c1 | 18 | 6,579 | 6,928 | |
1_19 | (iii) Role of IFITM5 in bone formation: The expression of IFITM5 is associated with mineralization during the bone formation process in osteoblast cells [18] [19] [20] [21] . Previous studies have confirmed the expression of IFITM5 in bone tissues in mice, rats, humans and tammar wallabies [2] . The ifitm5-gene knocko... | c1 | 19 | 6,928 | 7,281 | |
1_20 | Moreover, the knockdown of the ifitm5 gene by small hairpin RNA induces a decrease in bone nodule formation, whereas overexpression of the gene in UMR106 cells has been shown to increase calcium uptake and bone nodule formation [18] . | c1 | 20 | 7,281 | 7,516 | |
1_21 | (iv) Role of IFITM5 for immune activity: Recent studies have revealed that IFITM5 interacts with the FK506-binding protein 11 (FKBP11) to form IFITM5-FKBP11-CD81-the prostaglandin F2 receptor negative regulator (FPRP) complex [28] . | c1 | 21 | 7,516 | 7,749 | |
1_22 | When the complex is formed, the expressions of 5 interferon-induced genes are induced, including bone marrow stromal cell antigen 2 (Bst2), interferon inducible protein 1 (Irgm), interferoninduced protein with tetratricopeptide repeats 3 (Ifit3), b(2)microglobulin (B2m), and MHC class I antigen gene. Consequently, the... | c1 | 22 | 7,749 | 8,183 | |
1_23 |
In this study, we investigated the S-palmitoylation of IFITM5 and its role in the interaction with FKBP11 in mouse osteoblast cells. Cells transfected by a plasmid DNA encoding mouse IFITM5 were grown in the presence of an established chemical reporter, 17-octadecynoic acid (17-ODYA) [29, 30] , or an inhibitor for th... | c1 | 23 | 8,183 | 8,556 | |
1_24 | The biochemical assays using these compounds revealed that the wild-type IFITM5 is S-palmitoylated. To identify the Spalmitoylation site in IFITM5, we prepared cysteine-substituted mutants, IFITM5-C86A, -C52A/C53A, and -C52A/53A/86A (Cys-less). The chemical reporter assay suggested that at least two out of three cyste... | c1 | 24 | 8,556 | 8,911 |
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