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Cole CG McCann OT Collins JE Oliver K Willey D Gribble SM Yang F McLaren K Rogers J Ning Z Beare DM Dunham I 《Genome biology》2008,9(5):R78-11
Background
Although the human genome sequence was declared complete in 2004, the sequence was interrupted by 341 gaps of which 308 lay in an estimated approximately 28 Mb of euchromatin. While these gaps constitute only approximately 1% of the sequence, knowledge of the full complement of human genes and regulatory elements is incomplete without their sequences.Results
We have used a combination of conventional chromosome walking (aided by the availability of end sequences) in fosmid and bacterial artificial chromosome (BAC) libraries, whole chromosome shotgun sequencing, comparative genome analysis and long PCR to finish 8 of the 11 gaps in the initial chromosome 22 sequence. In addition, we have patched four regions of the initial sequence where the original clones were found to be deleted, or contained a deletion allele of a known gene, with a further 126 kb of new sequence. Over 1.018 Mb of new sequence has been generated to extend into and close the gaps, and we have annotated 16 new or extended gene structures and one pseudogene.Conclusion
Thus, we have made significant progress to completing the sequence of the euchromatic regions of human chromosome 22 using a combination of detailed approaches. Our experience suggests that substantial work remains to close the outstanding gaps in the human genome sequence. 相似文献88.
Increase in soluble CD4 binding to and CD4-induced dissociation of gp120 from virions correlates with infectivity of human immunodeficiency virus type 1. 总被引:2,自引:20,他引:2 下载免费PDF全文
Mutations in the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins gp120 and gp41, previously shown to confer an enhanced replicative capacity and broadened host range to the ELI1 strain of HIV-1, were analyzed for their biochemical effects on envelope structure and function. The tendency of purified virions to release their extracellular gp120 component, either spontaneously or after interacting with soluble CD4 (CD4-induced shedding) was assessed. A single amino acid substitution in part of the CD4 binding site of gp120 (Gly-427 to Arg) enhanced both spontaneous and CD4-induced shedding of gp120 from virions, while a single change in the fusogenic region of gp41 (Met-7 to Val) affected only CD4-induced shedding. Although each codon change alone conferred increased growth ability, virus with both mutations exhibited the most rapid replication kinetics. In addition, when both of these mutations were present, virions had the highest tendency to shed gp120, both spontaneously and after exposure to soluble CD4. Analysis of CD4 binding to virion-associated gp120 showed that the changes in both gp120 and gp41 contributed to increased binding. These results demonstrated that the increased replicative capacity of the ELI variants in human CD4+ cell lines was associated with altered physical and functional properties of the virion envelope glycoproteins. 相似文献
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Wyatt Vander Voort Brandon Wilkinson Nicholas Bedard Nathan Hendrickson Michael Willey 《The Iowa orthopaedic journal》2022,42(1):213
BackgroundThe indications for operative treatment of scapula fractures have been debated over the past decade. Our purpose was to determine 1) the incidence and trends in the operative treatment of scapula fractures, 2) the incidence of conversion from operative fixation to total or hemi-shoulder arthroplasty (THSA) and 3) rates of associated injuries in scapula fractures. We hypothesized that the operative treatment of scapula fractures is increasing over time and that scapula fractures treated with open reduction and internal fixation (ORIF) would have increased risk for conversion to THSA.MethodsThe Humana Inc. administrative claims database was queried from 2008 to 2015. Patients with any scapular fracture, ORIF of scapula fracture, total or hemi-shoulder arthroplasty, and associated injuries were identified by ICD-9 and CPT codes. Analysis was performed for 1) all patients with a scapula fracture undergoing operative fixation (i.e. ORIF and THSA), 2) all scapular fractures treated with ORIF with subsequent conversion to ipsilateral THSA, and 3) all associated injuries.ResultsThere were 10,097 scapula fractures (28.4% glenoid, 48% female). 60% occurred in patients 65 years and older. There were 198 (1.96%) fractures (70% glenoid) treated with ORIF. There were 287 (2.84%) fractures (45% glenoid) treated with THSA (76% total shoulder). The rate of ORIF of scapular fractures did not significantly increase (RR=0.87, p=0.58). There was a significant increase in THSA as primary treatment of scapula fractures in 2015 compared to 2007 (RR=0.43, p=0.0016). Conversion from ORIF to THSA was 12.6% (25/198). Scapula fractures treated with ORIF were at significant risk for conversion to THSA (RR=4.77, p<0.0001). Associated injuries occurred in nearly 50% of scapula fractures—other fractures, lung contusion and pneumothorax/hemothorax ranking the highest, accounting for 37%, 14.5% and 8.3% of all associated injuries, respectively.ConclusionThe incidence of operative treatment of scapula fractures was 1.96% and 2.84% for ORIF and THSA, respectively. Scapular fractures previously treated with ORIF were at significant risk for conversion to THSA. Although ORIF in scapular fractures did not significantly increase over time, both THSA and overall (ORIF+THSA) operative treatment of scapula fractures increased significantly. Level of Evidence: IV 相似文献
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Comparison of Early versus Late Below Knee Amputation After Trauma With Standardized Prosthetic Care
Gabrielle Bui Joseph Buckwalter V Jason Wilken John Davison Jeffrey Palmer Don Shurr Nathan Davidson Ignacio Gracia-Fleury Michael Willey 《The Iowa orthopaedic journal》2022,42(1):89
BackgroundHigh energy, lower extremity trauma is associated with longstanding pain and functional limitations. The clinical decision to proceed with early amputation or limb salvage is often controversial. This study was designed to compare differences in complications, costs, and clinical outcomes of below knee amputation (BKA) performed early after injury or after attempted limb salvage in a hospital with standardized prosthetic care following amputation.MethodsThis is a retrospective comparative study of subjects who underwent BKA for a traumatic injury at a single level 1 trauma center and received standardized prosthetic care from a single manufacturer from 1999-2016 with minimum 2-year post-amputation follow up. Outcomes collected included demographics, surgical management, unplanned re-operations, and hospital and prosthetic cost data 2 years from time of injury.ResultsOverall, 79 subjects met criteria. Early amputation (EA) was defined by median duration between injury and amputation (6 weeks) with 41 subjects in the EA group and 38 subjects in the late amputation (LA) group. Subjects in the EA group were more likely to have open fractures, high energy mechanism, and less likely to have medical comorbidities. Post-amputation infection was common in both groups (17/41 (42%) vs 17/38 (45%), p=0.77). Subjects undergoing EA were more likely to require unplanned post-amputation revision, 22/41 (54%) versus 10/38 (27%), p=0.017. Hospital costs and prosthetics/orthotics costs from the time of injury to two years following amputation were comparable, with mean hospital EA costs $136,044 versus LA costs $125,065, p=0.38. Mean prosthetics/orthotics costs of EA subjects were $33,252 versus LA costs $37,684, p=0.59.ConclusionUnplanned post-amputation revision surgeries were more common when BKA was performed early after trauma. Otherwise, outcomes and cost were comparable when amputation was performed early versus late. Level of Evidence: IV 相似文献