Human chromosome 2 was formed by the head-to-head fusion of two ancestral chromosomes that remained separate in other primates. Sequences that once resided near the ends of the ancestral chromosomes are now interstitially located in 2q13-2q14.1. Portions of these sequences had duplicated to other locations prior to the fusion. Here we present analyses of the genomic structure and evolutionary history of >600 kb surrounding the fusion site and closely related sequences on other human chromosomes. Sequence blocks that closely flank the inverted arrays of degenerate telomere repeats marking the fusion site are duplicated at many, primarily subtelomeric, locations. In addition, large portions of a 168-kb centromere-proximal block are duplicated at 9pter, 9p11.2, and 9q13, with 98%-99% average sequence identity. A 67-kb block on the distal side of the fusion site is highly homologous to sequences at 22qter. A third ~100-kb segment is 96% identical to a region in 2q11.2. By integrating data on the extent and similarity of these paralogous blocks, including the presence of phylogenetically informative repetitive elements, with observations of their chromosomal distribution in nonhuman primates, we infer the order of the duplications that led to their current arrangement. Several of these duplicated blocks may be associated with breakpoints of inversions that occurred during primate evolution and of recurrent chromosome rearrangements in humans. 相似文献
Osteopontin (OPN) is a macrophage chemotactic and adhesion molecule that acts to promote macrophage infiltration in rat anti-glomerular basement membrane (GBM) glomerulonephritis. The present study investigated the role of interleukin-1 (IL-1) in the up-regulation of renal OPN expression in this disease model. Accelerated anti-GBM glomerulonephritis was induced in groups of six rats. Animals were treated by a constant infusion of the IL-1 receptor antagonist or saline (control) over days -1 to 14 (induction phase) or days 7 to 21 (established disease). In normal rat kidney, OPN was expressed in a few tubules (<5%) and absent from glomeruli. During the development of rat anti-GBM disease (days 7 to 21), there was substantial up-regulation of OPN mRNA and protein expression in glomeruli (>5 cells per glomerular cross-section) and tubular epithelial cells (50-75% OPN-positive). Up-regulation of OPN expression was associated with macrophage accumulation within the kidney, severe proteinuria, loss of renal function, and severe histological damage including glomerular crescentic formation and tubulointerstitial fibrosis. In contrast, IL-1 receptor antagonist treatment of either the induction phase of disease or established disease significantly reduced OPN mRNA and protein expression in glomeruli (/75-85%, P < 0.001) and tubules (/45-60%, P < 0.001). The reduction in OPN expression was associated with significant inhibition of macrophage accumulation and progressive renal injury. In vitro, the addition of IL-1 to the normal rat tubular epithelial cell line NRK52E up-regulated OPN mRNA and protein levels, an effect that was dose-dependent and inhibited by the addition of IL-1 receptor antagonist, thus demonstrating that IL-1 can act directly to up-regulate renal OPN expression. In conclusion, this study provides in vivo and in vitro evidence that IL-1 up-regulates OPN expression in experimental kidney disease and support for the argument that inhibition of OPN expression is one mechanism by which IL-1 receptor antagonist treatment suppresses macrophage-mediated renal injury. 相似文献
The missing asymptomatic COVID-19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic.
Measure
Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty-three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS-CoV-2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset.
Results
A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS-CoV-2. Different from strong and persistent N-specific antibodies, S1-specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months.
Conclusion
Our findings might have important implications for the definition of asymptomatic COVID-19 infections, diagnosis, serological survey, public health, and immunization strategies. 相似文献
DNA sequencing of the major outer membrane protein (MOMP) gene (omp1) from Chlamydia trachomatis shows that some strains have a mosaic structure suggestive of homologous recombination between two distinct omp1 genes. On the basis of this conjecture, we attempted to clone by complementation and sequence the chlamydial recA homolog from C. trachomatis serovar L2. Chlamydial genomic DNA was partially restricted with XbaI, and fragments of 2 to 4 kb were ligated into pUC19. The recombinant plasmid was electroporated into Escherichia coli HB101 (RecA-), and colonies were selected in the presence of methyl methanesulfonate (MMS). A 2.1-kb fragment of C. trachomatis DNA in pUC19 conferred relative MMS resistance to E. coli HB101. When this recombinant plasmid (pX203) was electroporated into E. coli JC14604 (RecA- lacZ), lac+ recombinants were isolated. Rabbit polyclonal antibodies produced to purified E. coli RecA were immunoreactive in an immunoblot assay with a 35-kDa antigen in RecA- strains of E. coli transformed with pX203. The 2.1-kb insert was cycle sequenced by the dideoxy chain termination method. An open reading frame of 1,056 bp encoding 352 amino acids that had 44% sequence identity with E. coli RecA was identified. The finding of a recA homolog in C. trachomatis suggests that homologous recombination may occur in this organism. The cloned C. trachomatis RecA-encoding gene will be useful for the construction of a recA mutant once a gene transfer system is developed for chlamydiae. 相似文献
To clarify mechanisms underlying cell-to-cell interactions between hemopoietic stem cells (HSCs) and stromal cells, we established a stromal cell line (FMS/PA6-P) from day-16 fetal bone marrow (BM) adherent cells using an anti-PA6 monoclonal antibody (mAb) specific for BM stromal cells. Importantly, this FMS/PA6-P cell line, showing homogenous fibroblastic morphology, is absent from hematolymphoid and endothelial lineage markers and maintains a high level of expression of PA6 molecule, recognized by the anti-PA6 mAb, for approximately 20 passages. Further, the cell line expressing a high level of PA6 molecule has a better hemopoiesis-supporting capacity in vitro than other stromal cell lines such as PA6 and MS-5. In fact, the PA6 molecule is closely related to the hemopoiesis-supporting capacity of the stromal cells because the proliferation of HSCs was suppressed to a great extent by the anti-PA6 mAb. Affinity chromatography and mass peptide fingerprinting revealed that the protein reacting with the anti-PA6 mAb is neural cell adhesion molecule (NCAM). The frequencies of long-term cobblestone area-forming cells and long-term culture-initiating cells were significantly suppressed by repression of NCAM in the FMS/PA6-P cells using NCAM small interfering RNA. Our findings clearly indicate that NCAM functions on the maintenance of HSCs. 相似文献
Jaagsiekte sheep retrovirus (JSRV) is a betaretrovirus causing ovine pulmonary adenocarcinoma, a transmissible lung tumor of sheep. A very closely related endogenous retrovirus (enJSRV) occurs as 15 to 20 copies in the genome of all sheep, and is not known to be linked to pathogenesis. We previously localized a particle release defect of the full-length endogenous-derived expression construct pCMV2enJS56A1 to the amino-terminal region of gag that incorporates the two variable regions VR1 and VR2, which harbor the main sequence differences between endogenous and exogenous JSRV in this part of gag. Here, we tested the hypothesis that either or both of these variable regions are responsible for the observed particle release defect in enJS56A1. We found that the PPPPPPPS motif of the exogenous VR1 is neither necessary nor sufficient for particle release. Furthermore, the precise substitution of VR1 and VR2 in the exogenous JSRV expression plasmid pCMV2JS 21, using their enJS56A1-derived counterparts, did not abrogate the ability of the resulting constructs to release particles. The particle release defect of enJS56A1 is therefore not determined exclusively by either VR1 or VR2. These results point to a small number of amino acids lying outside of VR1 and VR2 that may be responsible for the particle defect of enJS56A1 Gag. 相似文献
HLA-A2 subtypes (A*0201 - *0212) were determined by oligotyping in HLA-A2 positive samples from four populations (Han Chinese, Dai Chinese, Caucasoids from Germany and Turkish individuals from Kayseri)(see table).
Two different findings can be concluded from this study: 1) Significant HLA-A*02 allelic variations found in four populations. A*0207 is the predominant A*02 allele in the Dai population and absent in the German Caucasian and the Turkish population. In contrast, A*0201 is the most prevalent allele in the Caucasian, Turkish and Han Chinese group. We also found a high proportion of A*0206 and A*0207 in Han Chinese. 2) A strong association has been found between A*0207 and HLA-B46 and DR9 in the Dai minority population. This haplotype is also found in Han Chinese. Three DNA samples from Turkish and one from the Dai population are presently being sequenced because the reaction pattern was out of the expected (Supported by SFB 217) 相似文献