ABSTRACT
Inner-shell electrons naturally sense the electric field close to the nucleus, which can reach extreme values beyond 1015 V cm-1 for the innermost electrons1. Especially in few-electron, highly charged ions, the interaction with the electromagnetic fields can be accurately calculated within quantum electrodynamics (QED), rendering these ions good candidates to test the validity of QED in strong fields. Consequently, their Lamb shifts were intensively studied in the past several decades2,3. Another approach is the measurement of gyromagnetic factors (g factors) in highly charged ions4-7. However, so far, either experimental accuracy or small field strength in low-Z ions5,6 limited the stringency of these QED tests. Here we report on our high-precision, high-field test of QED in hydrogen-like 118Sn49+. The highly charged ions were produced with the Heidelberg electron beam ion trap (EBIT)8 and injected into the ALPHATRAP Penning-trap setup9, in which the bound-electron g factor was measured with a precision of 0.5 parts per billion (ppb). For comparison, we present state-of-the-art theory calculations, which together test the underlying QED to about 0.012%, yielding a stringent test in the strong-field regime. With this measurement, we challenge the best tests by means of the Lamb shift and, with anticipated advances in the g-factor theory, surpass them by more than an order of magnitude.
ABSTRACT
We report a detailed study on the magnetic behaviors and magnetocaloric (MC) effect of a single crystal of lithium samarium tetraphosphate, LiSm(PO3)4. The analyses of temperature-dependent magnetization data have revealed magnetic ordering established with decreasing temperature below T p, where T p is the minimum of a dM/dT vs. T curve and varies as a linear function of the applied field H. The Curie temperature has been extrapolated from T p(H) data, as H â 0, to be about 0.51 K. The establishment of magnetic-ordering causes a substantial change in the heat capacity C p. Above T p, the crystal exhibits paramagnetic behavior. Using the Curie-Weiss (CW) law and Arrott plots, we have found the crystal to have a CW temperature θ CW ≈ -36 K, and short-range magnetic order associated with a coexistence of antiferromagnetic and ferromagnetic interactions ascribed to the couplings of magnetic dipoles and octupoles at the Γ7 and Γ8 states. An assessment of the MC effect has shown increases in value of the absolute magnetic-entropy change (|ΔS m|) and adiabatic-temperature change (ΔT ad) when lowering the temperature to 2 K, and increasing the magnetic-field H magnitude. Around 2 K, the maximum value of |ΔS m| is about 3.6 J kg-1 K-1 for the field H = 50 kOe, and ΔT ad is about 5.8 K for H = 20 kOe, with the relative cooling power (RCP) of â¼82.5 J kg-1. In spite of a low MC effect in comparison to Li(Gd,Tb,Ho)(PO3)4, the absence of magnetic hysteresis reflects that LiSm(PO3)4 is also a candidate for low-temperature MC applications below 25 K.
ABSTRACT
We present the measurements of individual bound electron g factors of ^{20}Ne^{9+} and ^{22}Ne^{9+} on the relative level of 0.1 parts per billion. The comparison with theory represents the most stringent test of bound-state QED in strong electric fields. A dedicated mass measurement results in m(^{20}Ne)=19.992 440 168 77(9) u, which improves the current literature value by a factor of 18, disagrees by 4 standard deviations, and represents the most precisely measured mass value in atomic mass units. Together, these measurements yield an electron mass on the relative level of 0.1 ppb with m_{e}=5.485 799 090 99(59)×10^{-4} u as well as a factor of seven improved m(^{22}Ne)=21.991 385 098 2(26) u.
ABSTRACT
Objective: To analyze the effects and mechanisms of three commonly used epidural coverings, gelatin sponge, bovine Achilles tendon extract collagen and polyester urethane fiber, in preventing epidural scar adhesions after laminectomy in rats. Methods: Forty-eight adult Wistar rats were excised from L2 to L5 lamina to establish laminectomy models, and were divided into four groups with random number table according to different covering materials (12 rats in each group): blank group (group A), gelatin sponge group (absorbable, group B), polyester urethane fiber group (non-absorbable, group C) and bovine Achilles tendon extract collagen group (absorbable, group D). At 4 and 12 weeks postoperatively, the spinal tissues of the operated area were taken for gross observation (Rydell scar adhesion rating criteria) and histological observation (Nussbaum criteria); and the expression of three scar proliferation-related cytokines, basic fibroblast growth factor (bFGF), growth transforming factor ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF), were measured in the peridural tissues. The differences between the indices in each group were analyzed and compared. Results: All 48 rats survived, and gross and histological findings at 4 and 12 weeks showed no dural adhesions in the gelatin sponge and bovine Achilles tendon extract collagen groups, adhesions in the polyester urethane fiber group, and heavy adhesions and spinal cord compression in the blank control group. There were significant differences in the Rydell grade and Nussbaum histological score between the absorbable material group and the non-absorbable group (both P<0.05). Western protein blotting at 4 and 12 weeks confirmed that the expression levels of three cytokines, including bFGF, TGF-ß1, and VEGF, were lower in the absorbable material group than those in the non-absorbable group (all P<0.01). Immunofluorescence tests at 12 weeks confirmed that the expression of bFGF, TGF-ß1 and VEGF were all lower in the gelatin sponge group (9.81±0.81, 12.42±2.35, 8.63±1.76) and the bovine Achilles tendon extract collagen group (12.70±2.02, 8.23±1.03, 10.19±2.67) than those in the polyester urethane fiber group (33.94±2.03, 30.29±2.76, 25.79±1.21) (all P<0.01). Conclusions: Bovine achilles tendon extract collagen and gelatin sponge can effectively reduce the hyperplasia of scar and dural adhesions after spinal surgery.
Subject(s)
Cicatrix , Vascular Endothelial Growth Factor A , Animals , Cattle , Cicatrix/pathology , Cicatrix/prevention & control , Collagen/metabolism , Gelatin , Hyperplasia , Laminectomy , Polyesters , Rats , Rats, Wistar , Tissue Adhesions/pathology , Tissue Adhesions/prevention & control , Transforming Growth Factor beta1/metabolism , UrethaneABSTRACT
Salmonella is a crucial food-borne pathogen causing food poisoning, leading to severe public health events. Here, we developed a technique by integrating recombinase polymerase amplification with CRISPR-LbCas12a and employing two targets with engineered crRNA for detection of Salmonella (RPA-LbCas12a-TTECDS). Our findings revealed that this novel method rapidly detects trace Salmonella in food through fluorescence intensity and provides a template for other food-borne pathogen detection methods. Further, crRNA was optimized to increase detection sensitivity. Double targets were used to enhance the detection accuracy, reaching the level of qPCR, which was superior to fluorescent RPA. The RPA-LbCas12a-TTECDS system specifically detected Salmonella levels as low as 50 CFU per ml at 37°C in 1 h. In summary, a simple, rapid, sensitive and high accuracy detection technique based on CRISPR-Cas12a was created for Salmonella detection without complicated equipment.
Subject(s)
CRISPR-Cas Systems , Recombinases , Nucleic Acid Amplification Techniques/methods , Real-Time Polymerase Chain Reaction , Recombinases/genetics , Salmonella/geneticsABSTRACT
Objective: To investigate the effect of programmed death receptor (PD)-1 antibody therapy in patients with hepatitis B-associated liver cancer. Methods: Data of 29 chronically infected HBV patients with liver cancer who received PD-1 antibody combined with tyrosine kinase inhibitor in the Department of Infectious Diseases of the Fifth Medical Center of PLA General Hospital from March 2020 to January 2021 were selected. At the same time, all of the above-mentioned hepatitis B virus (HBV) patients were treated with nucleos(t)ide analogues. Patients clinical diagnostic data, laboratory test results, tumor response and the incidence of adverse reactions were collected retrospectively to understand the overall safety, therapeutic anti-tumor effect, HBV changes condition and the correlation between HBV changes and anti-tumor PD-1 antibody efficacy, high viral load treatment condition, and HBV reactivation safety issues. Statistical analysis was performed by non-parametric rank sum test. Results: Therapeutic anti-tumor effect and safety profile were good in patients. The complete remission rate was reached 27.6%. Adverse reactions were mostly mild, and the incidence of serious adverse reactions was low. After 12 weeks of follow-up, HBV DNA and hepatitis B surface antigen (HBsAg) was quantitatively decreased (P < 0.05). HBV DNA and HBsAg were decreased more significantly in patients with progressive disease (PD), stable disease (SD) and partial response (PR) (P < 0.05). Five patients with HBV DNA ≥ 10(4) IU/ml had responded well to the tumor treatment without serious adverse reactions. One patient had a slight increase in HBV DNA and alanine aminotransferase, while there was no HBV reactivation and correlated liver damage. Conclusion: Patients with HBV-associated liver cancer who received combined therapy have good anti-tumor efficacy and safety profile. PD-1 treatment has a certain effect on HBV. Compared with non-responders, patients with tumor response have better antiviral treatment efficacy. The safety of treatment in patients with high viral load is manageable, and there are no safety issues related to HBV reactivation.
Subject(s)
Hepatitis B , Liver Neoplasms , Antiviral Agents/therapeutic use , DNA, Viral , Hepatitis B/complications , Hepatitis B/drug therapy , Hepatitis B Surface Antigens , Hepatitis B virus/genetics , Humans , Liver Neoplasms/drug therapy , Receptors, Death Domain , Retrospective Studies , Virus ActivationABSTRACT
We have measured the ground-state g factor of boronlike argon ^{40}Ar^{13+} with a fractional uncertainty of 1.4×10^{-9} with a single ion in the newly developed Alphatrap double Penning-trap setup. The value of g=0.663 648 455 32(93) obtained here is in agreement with our theoretical prediction of 0.663 648 12(58). The latter is obtained accounting for quantum electrodynamics, electron correlation, and nuclear effects within the state-of-the-art theoretical methods. Our experimental result distinguishes between existing predictions that are in disagreement, and lays the foundations for an independent determination of the fine-structure constant.
ABSTRACT
Objective: o investigate the features of pathogenic bacteria for community-acquired bloodstream infection due to Gram-negative bacilli in patients with liver cirrhosis and optimal therapeutic strategy. Methods: A retrospective analysis was performed for the clinical data of patients with liver cirrhosis who were admitted to 302 Hospital of PLA due to community-acquired bloodstream infection from January 2010 to December 2015, and a statistical analysis was performed for their clinical features, pathogenic bacteria, and results of drug sensitivity test. The Pearson chi-square test was used for comparison of rates, and the Wilcoxon rank sum test was used for comparison of ranked data. Results: A total of 240 patients (including 178 male patients) with liver cirrhosis caused by various reasons were enrolled, with a mean age of 51.7 ± 11.1 years, an overall clinical remission rate of 80.42%, and an ineffective/mortality rate of 19.58%. The patients who used sensitive antibiotics within 12 hours after the onset of community-acquired bloodstream infection achieved a significantly higher improvement rate than those who used such drugs at more than 12 hours after onset (88.2% vs 58.1%, P < 0.001). The improvement rate achieved by the application of sensitive antibiotics at more than 12 hours after onset decreased with the increase in the Child-Pugh grade (P < 0.05). A total of 245 strains of Gram-negative bacilli were isolated, among which the six most common ones were 135 strains of Escherichia coli (55.1%), 62 strains of Klebsiella pneumoniae (25.3%), 16 strains of Aeromonas (6.5%), 4 strains of non-typhoidal Salmonella (1.6%), 3 strains of Enterobacter cloacae (1.2%), and 2 strains of Acinetobacter baumannii (0.8%). These Gram-negative bacilli had the highest sensitivity to meropenem (98.5%), followed by imipenem (97.9%), amikacin (97.5%), piperacillin/tazobactam (94.7%), cefmetazole (93.7%), and cefoperazone/sulbactam (93%). Different bacteria had different sensitivities to antibiotics. Conclusion: Once community-acquired bloodstream infection occurs in patients with liver cirrhosis, highly sensitive antibiotics should be used as early as possible. Cefoperazone/sulbactam, piperacillin/tazobactam, imipenem, and meropenem can be used as first-line empirical antibiotics, and drug combination should be considered when necessary.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteremia/microbiology , Community-Acquired Infections/microbiology , Drug Resistance, Bacterial , Liver Cirrhosis/complications , Microbial Sensitivity Tests , Adult , Child , Cross Infection , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
At the end of 2013, China reported a countrywide outbreak of measles. From January to May 2014, we investigated the clinical and immunological features of the cases of the outbreak admitted to our hospital. In this study, all 112 inpatients with clinically diagnosed measles were recruited from the 302 Military Hospital of China. The virus was isolated from throat swabs from these patients, and cytokine profiles were examined. By detecting the measles virus of 30 of the 112 patients, we found that this measles outbreak was of the H1 genotype, which is the major strain in China. The rates of complications, specifically pneumonia and liver injury, differed significantly in patients aged 18 years: pneumonia was more common in children, while liver injury was more common in adults. Pneumonia was a significant independent risk factor affecting measles duration. Compared to healthy subjects, measles patients had fewer CD4+IL-17+, CD4+IFN-γ +, and CD8+IFN-γ + cells in both the acute and recovery phases. In contrast, measles patients in the acute phase had more CD8+IL-22+ cells than those in recovery or healthy subjects. We recommend that future studies focus on the age-related distribution of pneumonia and liver injury as measles-related complications as well as the association between immunological markers and measles prognosis.
Subject(s)
Disease Outbreaks , Measles virus/physiology , Measles/epidemiology , Adolescent , Adult , Aged , Beijing/epidemiology , Child , Child, Preschool , Female , Genotype , Hospitalization/statistics & numerical data , Humans , Infant , Male , Measles/immunology , Measles/virology , Measles virus/genetics , Middle Aged , Pneumonia/epidemiology , Prospective Studies , Risk Factors , Young AdultABSTRACT
In order to reduce the time required to identify a match for unrelated donor hematopoietic stem cell transplantation, a one-step DNA sequencing strategy was employed at the time of recruitment. The impact of this strategy on human leukocyte antigen (HLA) typing resolution and the effect of current registry requirements on resolution and coding of assignments were evaluated. Sanger-based DNA sequencing was used to obtain diploid exons 2 and 3 HLA-A, -B and -C assignments of 2747 unrelated African American and 1822 European American volunteers at recruitment. The results demonstrate the high resolution of the approach and challenge several aspects of the current registry typing strategy. Of the 46% of African American and 74% of European American individuals whose HLA typing resulted in alternative genotypes, the majority (≥93%) was predicted to have only a single 'common' genotype among the alternatives. The common practice of adding secondary assays to resolve alternative genotype assignments that include more than two antigen groups was also evaluated. While the percentage of assignments with greater than two antigen groups reached as high as 21% (HLA-A in European Americans), only 1.8% of individuals at most carried two common genotypes encompassing three antigen groups. The assignment of (National Marrow Donor Program) NMDP-designated allele codes to the one-pass results reduced the resolution substantially and introduced genotypes that were not included in the laboratory's assignments. We suggest the alternative strategy of using the exons 2-3 diploid nucleotide sequence as the assignment submitted to the registry with the added benefit of immortalizing the assignment in time regardless of the introduction of novel alleles. To keep pace with current donor selection criteria and with the increasing number of new alleles, it is time to rethink our recruitment typing strategies.
Subject(s)
Hematopoietic Stem Cells/cytology , Histocompatibility Testing/methods , Patient Selection , Sequence Analysis, DNA/methods , Tissue Donors , Alleles , Base Sequence , Diploidy , Gene Frequency/genetics , Genotype , Hematopoietic Stem Cells/metabolism , HumansABSTRACT
HLA-A, -B, -C, -DRB1, -DQB1 assignments were obtained for 374 pairs of African American mothers and their umbilical cord blood units (CBU) by DNA sequencing. An algorithm developed by the National Marrow Donor Program was used to assign 1122 haplotypes by segregation. Seventy percent of the haplotypes carried assignments at all five loci. In the remainder, alleles at various loci, most often DQB1 in 48% of the haplotypes with a missing assignment, could not be assigned due to sharing of both alleles by mother and CBU. There were 652 haplotypes carrying a unique combination of alleles at the five loci; the majority (74%) were singletons. Novel Bâ¼C and DRB1~DQB1 associations were observed. The results show the genetic diversity in this population and provide validation for a publically available tool for pedigree analysis. Our observations underscore the need for procurement of increased numbers of units in the national cord blood inventory in order to identify matching donors for all patients requiring hematopoietic stem cell transplantation.
Subject(s)
Black or African American , Fetal Blood/immunology , Genetic Variation , HLA Antigens/genetics , Haplotypes , Algorithms , Alleles , Humans , MothersABSTRACT
BACKGROUND: Patients with prostate cancer tend to die from bone metastases. Until now, no evidence has shown that Paget's disease of bone (PDB) affects the progression of bone metastasis or overall survival of patients with prostate cancer. METHODS: We searched our patient database for men who had presented with prostate cancer and PDB between June 1993 and March 2009, and identified best-matched control patients according to stage, grade, age, date of diagnosis, treatment, and race. RESULTS: Among 1346 consecutive patients with prostate cancer diagnosed before 2008, 15 were confirmed to have comorbid PDB. Twenty-six more were identified from the institutional billing search. Including the 41 best-matched controls, our total study population was 82 patients. In the Kaplan-Meier analysis, we estimated median times from diagnosis of prostate cancer to bone metastasis to be 21.5 years for those with PDB and 9.4 years for those without PDB (P=0.044). Median overall survival times were 11.8 and 9.2 years for the two groups, respectively (P=0.008). CONCLUSION: For the first time, we have obtained evidence that patients with prostate cancer and PDB have delayed time to bone metastases and improved overall survival than do patients with prostate cancer alone.
Subject(s)
Bone Neoplasms/secondary , Osteitis Deformans/complications , Prostatic Neoplasms/complications , Aged , Case-Control Studies , Humans , Male , Middle Aged , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Time FactorsABSTRACT
AIMS: To investigate the protective role of nitric oxide (NO) induced by ischemic preconditioning (IP) on cold ischemic-reperfusion (IR) injury of rat liver grafts. METHODS: One hundred twenty-eight male Sprague Dawley rats used for orthotopic liver transplantation were randomly divided into four groups (n = 32): administering heparin before ischemic reperfusion (control group); IP with 10-minute ischemia and 10-minute reperfusion before IR (IP group); adenosine before IR (Ade group); and L-NAME (NG-nitro-L-arginine methyl ester) + IP before IR (NAME group). Half of each group were used to investigate 1-week recipient survival rate, and another to obtain blood and hepatic tissue samples after 2-hour reperfusion. RESULTS: One-week survival bile production, serum NO, and antioxidase activity were higher but serum alanine aminotransferase, tumor necrosis factor-α, and superoxide levels in hepatic tissue were lower in the IP group and Ade group versus the control group or NAME group. Liver sinusoidal endothelial cells in the IP and Ade groups showed less injury than the other groups. CONCLUSION: NO induced by IP can improve 1-week survival and rat liver function as well as protect liver sinusoidal endothelial cells.
Subject(s)
Cold Ischemia/adverse effects , Ischemic Preconditioning/methods , Liver Transplantation/adverse effects , Liver/surgery , Nitric Oxide/blood , Reperfusion Injury/prevention & control , Adenosine/administration & dosage , Alanine Transaminase/blood , Animals , Anticoagulants/administration & dosage , Apoptosis , Bile/metabolism , Disease Models, Animal , Endothelial Cells/metabolism , Endothelial Cells/pathology , Enzyme Inhibitors/administration & dosage , Heparin/administration & dosage , Liver/blood supply , Liver/metabolism , Liver/pathology , Male , NG-Nitroarginine Methyl Ester/administration & dosage , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Rats , Rats, Sprague-Dawley , Reperfusion Injury/etiology , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Superoxide Dismutase/metabolism , Superoxides/metabolism , Time Factors , Tumor Necrosis Factor-alpha/bloodABSTRACT
AIMS: Bioremediation of highly arsenic (As)-contaminated soil is difficult because As is very toxic for plants and micro-organisms. The aim of this study was to investigate soil arsenic removal effects using poplar in combination with the inoculation of a plant growth-promoting rhizobacterium (PGPR). METHODS AND RESULTS: A rhizobacterium D14 was isolated and identified within Agrobacterium radiobacter. This strain was highly resistant to arsenic and produced indole acetic acid and siderophore. Greenhouse pot bioremediation experiments were performed for 5 months using poplar (Populus deltoides LH05-17) grown on As-amended soils, inoculated with strain D14. The results showed that P. deltoides was an efficient arsenic accumulator; however, high As concentrations (150 and 300 mg kg(-1)) inhibited its growth. With the bacterial inoculation, in the 300 mg kg(-1) As-amended soils, 54% As in the soil was removed, which was higher than the uninoculated treatments (43%), and As concentrations in roots, stems and leaves were significantly increased by 229, 113 and 291%, respectively. In addition, the As translocation ratio [(stems + leaves)/roots = 0·8] was significantly higher than the uninoculated treatments (0·5). About 45% As was translocated from roots to the above-ground tissues. The plant height and dry weight of roots, stems and leaves were all enhanced; the contents of chlorophyll and soluble sugar, and the activities of superoxide dismutase and catalase were all increased; and the content of a toxic compound malondialdehyde was decreased. CONCLUSIONS: The results indicated that the inoculation of strain D14 could contribute to the increase in the As tolerance of P. deltoides, promotion of the growth, increase in the uptake efficiency and enhancement of As translocation. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of P. deltoides in combination with the inoculation of strain D14 provides a potential application for efficient soil arsenic bioremediation.
Subject(s)
Agrobacterium/growth & development , Arsenic/isolation & purification , Populus/metabolism , Soil Microbiology , Soil Pollutants/isolation & purification , Agrobacterium/drug effects , Agrobacterium/genetics , Biodegradation, Environmental , DNA, Bacterial/genetics , Phylogeny , Plant Leaves/growth & development , Plant Leaves/metabolism , Plant Leaves/microbiology , Plant Roots/growth & development , Plant Roots/metabolism , Plant Roots/microbiology , Plant Stems/growth & development , Plant Stems/metabolism , Plant Stems/microbiology , Populus/growth & development , Populus/microbiology , RNA, Ribosomal, 16S/genetics , Soil/chemistryABSTRACT
Many activities within a cell must be intimately coordinated with its metabolic state. Understanding these connections to metabolism is critical to deciphering the regulation of a variety of cellular processes. However, despite intensive research in these areas, the precise mechanisms by which a cell monitors its metabolic state remain controversial and poorly understood. Herein, we discuss the thesis that intracellular levels of the metabolite acetyl-CoA represent a critical gauge of cellular metabolic state, which is cleverly monitored by the cell through dynamic acetylation modifications to direct a variety of outputs connected to energy metabolism, cell growth, and survival.
Subject(s)
Acetyl Coenzyme A/metabolism , Cells/metabolism , Acetylation , Animals , Gene Expression Regulation, Developmental , Histones/metabolism , Humans , Mammals/metabolismABSTRACT
AIM: The aim of this study was to determine whether Astragaloside IV (AST-IV) inhibited the transcriptional activity of nuclear factor-κB (NF-κB), attenuating liver transplant ischemia-reperfusion injury (IRI). METHODS: Sprague Dawley (SD) rats were randomly divided into 2 groups: donors given AST-IV (1.5 mL; 100 µg/mL, intravenous [IV]) 1 hour before surgery (n = 32), versus controls treated with 1.5 mL physiological saline (n = 32). Orthotropic liver transplantation was performed according to the Kamada technique. Eight animals in each group were followed for seven days after surgery to assess survival. The remaining hosts in each group were divided into 3 subgroups (n = 8) to be examined at 3, 6, and 24 hours after portal vein reperfusion. We analyzed levels of alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α, and NF-κB transcriptional activity and performed a morphological study of liver tissues, NF-κB, and glucocorticoid receptor (GR) expression in Kupffer cells (KCs). RESULTS: Pretreatment with AST-IV significantly improved survival rates and liver function, attenuating liver parenchymal cell damage by down-regulating TNF-α levels and NF-κB expressions, inhibiting NF-κB transcriptional activity, up-regulating GR expression. CONCLUSION: AST-IV attenuated hepatic IRI by inhibiting NF-κB transcriptional activity. The mechanism may relate to up-regulation of GR expression.
Subject(s)
Liver Transplantation , Reperfusion Injury/prevention & control , Saponins/therapeutic use , Triterpenes/therapeutic use , Animals , Base Sequence , Blotting, Western , DNA Primers , Immunohistochemistry , Liver Transplantation/adverse effects , Male , Mice , Microscopy, Confocal , NF-kappa B/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Glucocorticoid/metabolism , Survival Rate , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Seventy-eight novel human leukocyte antigen (HLA) class I and class II alleles are described: 19 HLA-A alleles, 30 HLA-C alleles, 21 HLA-B alleles, 7 HLA-DRB1 alleles and 1 HLA-DPB1 allele. Eight (â¼10%) of the novel alleles were found in more than one individual and may be more common in the population. Sixty-two (â¼80%) of the 78 novel alleles are single nucleotide substitution variants when compared with their most homologous allele. Twelve of these single nucleotide variants are silent substitutions and one creates a null allele (C*08:26N). One of the novel HLA-C alleles, C*03:58, is a hybrid that likely resulted from an intra-locus recombination. The remaining novel alleles differ from their most similar allele by two to seven nucleotide substitutions. Four of the novel HLA-C alleles encode amino acid changes at codons 41, 42, 55 or 200 which have not previously been reported to be polymorphic. Some of the new alleles encode novel codons and unique amino acid changes at polymorphic positions in the HLA-A (codons 55 and 120), HLA-C (codons 151, 153 and 176), HLA-B (codons 31 and 84) and HLA-DRB1 (codon 47) loci.
Subject(s)
Alleles , Histocompatibility Antigens Class II/genetics , Histocompatibility Antigens Class I/genetics , Histocompatibility Testing , Registries , HumansABSTRACT
Mexicans are the most common minority population of the United States. From a sample of 553 bone marrow donor registrants of self-described Mexican ancestry, human leukocyte antigen (HLA) loci A, C, B and DRB1 were typed by high resolution sequence based typing (SBT) methods. A total of 47, 34, 76 and 46 distinct alleles at A, C, B and DRB1 respectively were identified, including 3 new alleles. The four-locus haplotype frequency distribution was extremely skewed with only 53.9% of 1106 chromosomes present with more than one estimated copy. Haplotypes of Native American origin were identified. These data form an initial basis for determining the requirements for an adequate donor pool for stem cell transplantation in this population.
Subject(s)
HLA-A Antigens/genetics , Mexican Americans/genetics , Gene Frequency , Haplotypes , Histocompatibility Testing , HumansABSTRACT
Sequence-based typing was used to identify human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 alleles from 558 consecutively recruited US volunteers with Eastern European ancestry for an unrelated hematopoietic stem cell registry. Four of 31 HLA-A alleles, 29 HLA-C alleles, 59 HLA-B alleles, and 42 HLA-DRB1 alleles identified (A*0325, B*440204, Cw*0332, and *0732N) are novel. The HLA-A*02010101g allele was observed at a frequency of 0.28. Two-, three-, and four-locus haplotypes were estimated using the expectation-maximization algorithm. The highest frequency extended haplotypes (A*010101g-Cw*070101g-B*0801g-DRB1*0301 and A*03010101g-Cw*0702-B*0702-DRB1*1501) were observed at frequencies of 0.04 and 0.03, respectively. Linkage disequilibrium values (Dij') of the constituent two-locus haplotypes were highly significant for both extended haplotypes (P values were less than 8 x 10(-10)) but were consistently higher for the more frequent haplotype. Balancing selection was inferred to be acting on all the four loci, with the strongest evidence of balancing selection observed for the HLA-C locus. Comparisons of the A-C-B haplotypes and DRB1 frequencies in this population with those for African, European, and western Asian populations showed high degrees of identity with Czech, Polish, and Slovenian populations and significant differences from the general European American population.
Subject(s)
Gene Frequency/genetics , HLA Antigens/genetics , Haplotypes/genetics , White People/genetics , Alleles , Europe/ethnology , Europe, Eastern/ethnology , Genetic Variation , HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-C Antigens/genetics , HLA-DR Antigens/genetics , HLA-DRB1 Chains , HumansABSTRACT
Sequence-based typing was used to identify human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 alleles from 564 consecutively recruited African American volunteers for an unrelated hematopoietic stem cell registry. The number of known alleles identified at each locus was 42 for HLA-A, HLA-B 67, HLA-C 33, and HLA-DRB1 44. Six novel alleles (A*260104, A*7411, Cw*0813, Cw*1608, Cw*1704, and DRB1*130502) not observed in the initial sequence-specific oligonucleotide probe testing were characterized. The action of balancing selection, shaping more 'even' than expected allele frequency distributions, was inferred for all four loci and significantly so for the HLA-A and DRB1 loci. Two-, three-, and four-locus haplotypes were estimated using the expectation maximization algorithm. Comparisons with other populations from Africa and Europe suggest that the degree of European admixture in the African American population described here is lower than that in other African American populations previously reported, although HLA-A:B haplotype frequencies similar to those in previous studies of African American individuals were also noted.