[Establishment and validation of prediction models for human leukocyte antigen haplotypes and human leukocyte antigen genotypes].

Objective: To establish prediction models for human leukocyte antigen (HLA) haplotypes and HLA genotypes, and verify the prediction accuracy. Methods: The prediction models were established based on the characteristic of HLA haplotype inheritance and linkage disequilibrium (LD), as well as the invention patents and software copyrights obtained. The models include algorithm and reference databases such as HLA A-C-B-DRB1-DQB1 high-resolution haplotypes database, B-C and DRB1-DQB1 LD database, G group alleles table, and NMDP Code alleles table. The prediction algorithm involves data processing, comparison with reference data, filtering results, probability calculation and ranking, confidence degree estimation, and output of prediction results. The accuracy of the predictions was verified by comparing them with the correct results, and the relationship between prediction accuracy and the probability distribution and confidence degree of the predicted results was analyzed. Results: The HLA haplotypes and genotypes prediction models were established. The prediction algorithm included the prediction of A-C-B-DRB1-DQB1 haplotypes according to HLA-A, B, DRB1, C, DQB1 genotypes, the prediction of C and DQB1 high-resolution results according to A, B and DRB1 high-resolution results, and the prediction of A, B, DRB1, C and DQB1 high resolution results according to the A, B and DRB1 intermediate or low resolution results. Validation results of "Predicting A-C-B-DRB1-DQB1 haplotypes basing on HLA-A, B, DRB1, C, DQB1 genotypes" model: for 787 data, the accuracy was 94.0% (740/787) with 740 correct predictions, 34 incorrect predictions, and 13 instances with no predicted results. For 847 data, the accuracy was 100% (847/847). The 2 411 and 2 594 haplotype combinations predicted from 787 and 847 data were grouped according to confidence degree, the accuracy was 100% (48/48, 114/114) for a confidence degree of 1, 96.2% (303/315) and 97.8% (409/418) for a confidence degree of 2 respectively. Validation results of "Predicting A, B, DRB1 and C, DQB1 high-resolution genotypes basing on HLA-A, B, DRB1 high, intermediate, or low resolution genotypes" model: when predicting C and DQB1 high resolution genotypes basing on A, B, and DRB1 high resolution genotypes, 89.3% (1 459/1 634) of the predictions were correct. The accuracy for the top 2 predicted probability (GPP) ranking was 79.2% (1 156/1 459), and for the top 10, it was 95.0% (1 386/1 459). Furthermore, when GPP≥90% and GPP 50%-90%, the prediction accuracy was 81.3% (209/257) and 72.8% (447/614) respectively. The accuracy of predicting C and DQB1 high resolution genotypes basing on the results of A, B, and DRB1 high resolution genotypes from the China Marrow Donor Program was 87.0% (20/23). The accuracy of predicting A, B, DRB1, C, and DQB1 high resolution genotypes basing on the results of A, B, and DRB1 intermediate or low-resolution genotypes was 70.0% (7/10) and 52.5% (21/40) respectively. When predicting whether the patient is likely to have a HLA 10/10 matched donor, the accuracy of the top 2 GPP combinations with a proportion of ≥50% was 85.7% (6/7). Conclusions: When using A, B, DRB1, C, DQB1 genotypes to predict A-C-B-DRB1-DQB1 haplotype combinations, the results with a confidence degree of 1 and 2 are reliable. When predicting C and DQB1 genotypes according to A, B and DRB1 genotypes, the top 10 results ranked by GPP are reliable, and the top 2 results with GPP≥50% are more reliable.

[One case of adult-onset dystonia presenting with chronic progressive external ophthalmoplegia].

We report a case of adult-onset dystonia presenting with chronic progressive external ophthalmoplegia. The patient had ptosis in both eyes, particularly the left eye, for no obvious reason since the age of 10, which was progressively aggravated. The clinical diagnosis was chronic progressive external ophthalmoplegia. However, whole gene sequencing revealed the mitochondrial A3796G missense mutation, so the patient was clearly diagnosed as adult-onset dystonia and given treatment to reduce blood glucose and improve muscle metabolism. The A3796G mutation in the ND1 subunit of the mitochondrial complex leading to ophthalmoplegia is relatively rare, requiring a combination with genetic testing for confirmation of diagnosis.

Arbuscular mycorrhizal fungi improve the growth and disease resistance of the invasive plant Wedelia trilobata.

AIMS: Arbuscular mycorrhizal fungi (AMF) are symbiotic partners of many invasive plants, however, it is still unclear how AMF contribute to traits that are important for the successful invasion of their host and how environmental factors, such as nutrient conditions, influence this. This study was to explore the effects of Glomus versiforme (GV) and Glomus mosseae (GM) on the growth and disease resistance of the invasive plant Wedelia trilobata under different nutrient conditions. METHODS AND RESULTS: We found that GV and GM had higher root colonization rates resulting in faster W. trilobata growth under both low-N and low-P nutrient conditions compared to the normal condition. Also, the colonization of W. trilobata by GV significantly reduced the infection area of the pathogenic fungus Rhizoctonia solani under low-N conditions. CONCLUSIONS: These results demonstrated that AMF can promote the growth and pathogenic defence of W. trilobata in a nutrient-poor environment, which might contribute to their successful invasion into certain type of habitats. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we report for the first time that AMF can promote growth and disease resistance of W. trilobata under nutrient-poor environment, which contribute to a better understanding of plant invasion.

Genetic contribution of suppressor of cytokine signalling polymorphisms to the susceptibility to infection after traumatic injury.

Suppressor of cytokine signalling (SOCS) proteins are crucial negative regulators in many signalling pathways and are implicated in the pathogenesis of infectious diseases. The purpose of this study was to uncover possible associations of common polymorphisms within SOCS genes with infectious outcomes after traumatic injury. A total of 1087 trauma patients (Chongqing cohort 806 and Yunnan cohort 281) were recruited and followed-up for the development of infectious outcomes, such as sepsis and multiple organ dysfunction syndrome (MODS). Twelve selected single nucleotide polymorphisms (SNPs) were screened by pyrosequencing to determine their genotypes and associations with infectious complications. Among the 12 selected SNPs, only the cytokine-inducible Src homology (SH2) domain protein (CISH) promoter rs414171 polymorphism was found consistently to be associated statistically with the incidence of sepsis and MOD score in the two cohorts, despite analysing the SNPs independently or in combination. Further, patients with a T allele had significantly lower CISH expression and lower production of tumour necrosis factor (TNF)-α, but higher production of interleukin (IL)-10. Luciferase assay confirmed that the A→T variant in the rs414171 polymorphism inhibited the transcriptional activities of the CISH gene significantly. The CISH rs414171 polymorphism is associated significantly with susceptibility to sepsis and MODS in traumatic patients, which might prove to be a novel biomarker for indicating risk of infectious outcomes in critically injured patients.

The Paris System for urine cytology in upper tract urothelial specimens: A comparative analysis with biopsy and surgical resection.

INTRODUCTION: The Paris System (TPS) has recently been used in classification of urinary tract cytological specimens. Upper urinary tract (UUT) specimens are cytologically challenging. The utility of TPS was investigated in evaluating UUT specimens and its correlation with subsequent histological follow-up. METHOD: From 2014 to 2017, 324 cytology cases of UUT from 179 patients were retrieved. Concurrent or subsequent biopsy or resection within a 2-month period was available in 125 cases from 74 patients. RESULT: None of the cases with a cytology of low-grade urothelial neoplasm was found to have a high-grade urothelial carcinoma (HGUC) on biopsy. Among the 19 atypical urothelial cells (AUC) cytology cases, the histology is heterogeneous (seven benign, one atypia, five low-grade lesion, and six HGUC). The risk of HGUC for each cytological diagnostic category are 0% for non-diagnostic/unsatisfactory, 6% for negative for HGUC, 27.3% for AUC, 0% for low-grade urothelial neoplasm, 48% for suspicious for HGUC and 95% for positive HGUC. When we considered cytology cases with suspicious or positive for HGUC interpretations as positive, the performance of TPS in predicting high grade urothelial carcinoma on histology had values of: 78.6% sensitivity, 86% specificity, 80.5% positive predictive value and 84.5% negative predictive value. CONCLUSION: More than one-third of the UUT cytological cases were classified as AUC and approximately 1/15 as suspicious or positive for HGUC. Based on UUT cytology specimens, the risk of malignancy of each cytological diagnostic category of TPS was comparable to those reported in the literature. The use of TPS in evaluating UUT cytology specimens was specific and sensitive in identifying patients with HGUC by histology.

Comparative study of radiotherapy plus erlotinib versus chemoradiotherapy for elderly patients with esophageal cancer: a propensity score-matched analysis.

This study compared the efficiency and safety of radiotherapy plus erlotinib with concurrent chemoradiotherapy (CCRT) based on paclitaxel plus cisplatin in elderly esophageal cancer patients. The eligible patients were retrospectively enrolled at Wenzhou Medical University cancer center from January 2005 to December 2011. Propensity score matching generated a matched cohort (1:1) composed from radiotherapy plus erlotinib and CCRT groups. The efficiency and safety were compared between two groups. Multivariable analysis was used to identify significant prognostic factors. Thirty-four patients treated with radiotherapy plus erlotinib were matched with patients who received CCRT. Radiotherapy plus erlotinib group showed better treatment compliance compared with the CCRT group (91.2% vs. 67.6%, hazard ratio [HR] 0.202, 95% confidence interval [CI] 0.051-0.809; P = .016). No significant overall response rate differences were found between the two groups (88.2% vs. 79.4%, HR 0.514, 95% CI 0.135-1.952; P = .323). The 5-year overall survival (OS) rate was 23.5% vs. 19.2% for patients treated with CCRT or radiotherapy plus erlotinib (HR 1.008, 95% CI 0.574-1.768; P = .979). The 5-year progression-free survival (PFS) rate was 16.8% versus 17.1% for patients treated with CCRT or radiotherapy plus erlotinib, respectively (HR 0.978, 95% CI 0.576-1.662; P = .934). The rate of severe hematologic toxicities in the CCRT group was significantly higher than that in the radiotherapy plus erlotinib group (HR 4.306, 95% CI 1.066-17.389; P = .031). Late toxicities were similar between radiotherapy plus erlotinib group and the CCRT group. Multivariate analysis showed that T stage (HR 1.730, 95% CI 1.062-2.816; P = .028), M stage (HR 2.859, 95% CI 1.407-5.811; P = .004), and complete response (HR 2.154, 95% CI 1.190-3.901; P = .011) were independent prognostic factors associated with OS. In conclusion, the present study suggested radiotherapy plus erlotinib should be a preferable modality compared with CCRT, with similar survival outcomes but better treatment compliance and less toxicities.

CARD9 mutation linked to Corynespora cassiicola infection in a Chinese patient.

Corynespora cassiicola is a plant pathogen associated with leaf-spotting disease. The fungus has been found on diverse substrates: leaves, stems and roots of plants; nematode cysts and human skin. It rarely causes human infections. Here we report one case of subcutaneous phaeohyphomycosis caused by C. cassiicola with prominent tissue necrosis in a woman. All of her clinical features pointed towards a genetic linkage. Hence, whole-exome sequencing and Sanger sequencing were performed on this patient. One mutation of CARD9 was detected.

Production and genetic analysis of resynthesized Brassica napus from a B. rapa landrace from the Qinghai-Tibet Plateau and B. alboglabra.

This study aimed to reveal the genetic and epigenetic variations involved in a resynthesized Brassica napus (AACC) generated from a hybridization between a B. rapa (AA) landrace and B. alboglabra (CC). Amplified fragment length polymorphism (AFLP), methylation-sensitive amplified polymorphism, and the cDNA-AFLP technique were performed to detect changes between different generations at the genome, methylation, and transcription levels. We obtained 30 lines of resynthesized B. napus with a mean 1000-seed weight of over 7.50 g. All of the lines were self-compatible, probably because both parents were self-compatible. At the genome level, the S0 generation had the lowest frequency of variations (0.18%) and the S3 generation had the highest (6.07%). The main variation pattern was the elimination of amplified restriction fragments on the CC genome from the S0 to the S4 generations. At the methylation level, we found three loci that exhibited altered methylation patterns on the parental A genome; the variance rate was 1.35%. At the transcription level, we detected 43.77% reverse mutations and 37.56% deletion mutations that mainly occurred on the A and C genomes, respectively, in the S3 generation. Our results highlight the genetic variations that occur during the diploidization of resynthesized B. napus.

Association between XRCC1 polymorphisms and laryngeal cancer susceptibility in a Chinese sample population.

Laryngeal cancer is the major malignant tumor affecting the upper respiratory tract. Previous studies have reported on the association between XRCC1 genetic polymorphisms and risk of laryngeal cancer, but with conflicting results. In this study, we attempted to assess the association between XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms and risk of laryngeal cancer in a Chinese population. A total of 126 laryngeal cancer patients and 254 control subjects were recruited to this study from the Second Medical College of Jinan University between December 2013 and May 2015. The XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphic sites were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Our results revealed a significant association between the AA genotype of XRCC1 Arg280His [odds ratio (OR) = 2.51, 95% confidence interval (CI) = 1.29-4.87, P = 0.01] and an increased risk of laryngeal cancer susceptibility compared to the GG genotype. Moreover, the A allele showed a higher risk of laryngeal cancer susceptibility compared to the G allele (OR = 1.63, 95%CI = 1.19-2.50, P = 0.002). In conclusion, the results of our study suggest that the AA genotype and A allele of the XRCC1 Arg280His polymorphism are associated with an increased laryngeal cancer risk in a Chinese population.

Positive expression of insulin-like growth factor-1 receptor is associated with a positive hormone receptor status in ovarian cancer.

UNLABELLED: Summary PURPOSE: Ovarian cancer is the most deadly of all gynecologic malignancies, due in part to the diagnosis at an advanced stage caused by the deficiency of specific marks and symptoms, by the absence of reliable tests for screening, and by early detection. MATERIALS AND METHODS: Insulin-like growth factor-I (IGF-I) is known to be involved in the development and promotion of diverse examples of solid tumors including ovarian cancer. IGF-I levels in local tissue are subject to both endocrine and paracrine/autocrine regulation. RESULTS: Most patients will react initially to treatment, but almost 70% of them will have a recurrence. Consequently, new therapeutic modalities are urgently required to overcome chemoresistance observed in ovarian cancer patients. IGF-1R expression was evaluated immunohistochemically in tissue microarray blocks constructed from 1,200 ovarian cancer samples collected from three medical institutions. CONCLUSION: Evidence accumulates suggesting that the insulin/insulin growth factor (IGF) pathways could play a good therapeutic target in various cancers, including ovarian cancer.

Application of high-throughput, high-resolution and cost-effective next generation sequencing-based large-scale HLA typing in donor registry.

Next generation sequencing (NGS)-based human leukocyte antigen (HLA) typing was used for ultra large-scale genotyping of registry donors for the China Marrow Donor Program (CMDP). More than 79,000 samples were subjected to HLA genotyping at 4-digit allelic level without ambiguities for HLA-A, -B, -C, DRB1 and DQB1 loci, with throughput up to 2068 samples per lane in a HiSeq flow cell (eight lanes per run), and cost reduced by 95% compared with that of Sanger-based typing. Two percent of randomly selected samples were quality control (QC) tested at 4-digit allelic level by the CMDP QC laboratory, yielded a concordance of 99.72%. These results demonstrate that NGS is a cost effective and valuable tool for HLA typing of registry donors.

Genomewide Histone H3 Lysine 9 Acetylation Profiling in CD4+ T Cells Revealed Endoplasmic Reticulum Stress Deficiency in Patients with Acute-on-chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) displayed 'sepsis-like' immune paralysis. Little is known about the role of CD4+ T lymphocytes, the primary regulator of innate and adopted immune system, played in ACLF. Acetylation of histone H3 lysine 9 (H3K9ac), a key epigenetic modification, tightly controls gene transcription. Whether and how does H3K9ac modification regulate CD4+ T cells in ACLF remains unclear. PBMCs were isolated from patients with ACLF, immune tolerance of chronic hepatitis B (CHB-T) and immune active of chronic hepatitis B (CHB-A). Then, CD4+ T lymphocytes were purified by magnetic microbeads, and the purity was confirmed by flow cytometry. H3K9ac variations were analysed in CD4+ T cells using chromatin immunoprecipitation microarray and then confirmed by quantitative PCR. Whole-genome H3K9 acetylation analyses were conducted by bioinformatics. A total of 70 genes were differently modified in H3K9ac between CHB-A and ACLF groups, while 44 genes were differently modified in H3K9ac between CHB-T and ACLF groups. Clustering algorithm analysis showed patients with ACLF displayed 'sepsis-like' immune paralysis. Functional analysis showed endoplasmic reticulum (ER) stress, or downstream pathway-related genes, such as BIP, ATF4, PER1, CSNK1D, IRF3, BNIP1, AKT1 and UBC, were differentially modified in ACLF. We profiled H3K9 acetyl modification in CD4+ T lymphocytes from HBV-infected patients with three different immune states, that is ACLF, immune tolerance and immune active phases. ACLF displayed 'sepsis-like' immune paralysis. ER stress in CD4+ T lymphocytes attributed to ACLF. This study provides some useful clues for revealing the mechanisms underlying ACLF.

A cytokine and angiogenic factor (CAF) analysis in plasma for selection of sorafenib therapy in patients with metastatic renal cell carcinoma.

BACKGROUND: We investigated cytokines and angiogenic factors (CAFs) in patients with metastatic renal cell carcinoma (mRCC) treated in a randomized phase II clinical trial of sorafenib versus sorafenib+ interferon-α (IFN-α) that yielded no differences in progression-free survival (PFS). We aimed to link the CAF profile to PFS and select candidate predictive and prognostic markers for further study. METHODS: The concentrations of 52 plasma CAFs were measured pretreatment (n = 69), day 28, and day 56 using multiplex bead arrays and enzyme-linked immunosorbent assay. We investigated the association between baseline levels of CAFs with PFS and posttreatment changes. RESULTS: Unsupervised CAF clustering analysis revealed two distinct mRCC patient groups with elevated proangiogenic or proinflammatory mediators. A six-marker baseline CAF signature [osteopontin, vascular endothelial growth factor (VEGF), carbonic anhydrase 9, collagen IV, VEGF receptor-2, and tumor necrosis factor-related apoptosis-inducing ligand] correlated with PFS benefit (hazard ratio 0.20 versus 2.25, signature negative versus positive, respectively; P = 0.0002). While changes in angiogenic factors were frequently attenuated by the sorafenib+ IFN combination, most key immunomodulatory mediators increased. CONCLUSIONS: Using CAF profiling, we identified two mRCC patient groups, a candidate plasma signature for predicting PFS benefit, and distinct marker changes occurring with each treatment. This platform may provide valuable insights into renal cell carcinoma biology and the molecular consequences of targeted therapies.

BAP18 induces growth of non-small-cell lung carcinoma through upregulating transcriptional level of CCND1/2.

OBJECTIVE: To elucidate the biological function of BAP18 (BPTF-associated protein of 18 kDa) in non-small-cell lung carcinoma (NSCLC) and the molecular mechanism. PATIENTS AND METHODS: Relative levels of BAP18 in NSCLC tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and its influence on pathological characteristics of NSCLC patients was analyzed. Correlation between BAP18 and Ki67 levels in NSCLC was assessed by Pearson correlation test. Furthermore, Kaplan-Meier curves were depicted for revealing survival difference in NSCLC patients expressing high or low level of BAP18. Relative levels of BAP18, CCND1, CCND2 and CCND3 in A549 and H1299 cells transfected with siBAP18 were determined, as well as colony number. In addition, after knockdown of protein level of BAP18 in A549 and H1299 cells by lentivirus transfection, cell cycle progression was examined. Co-regulation of BAP18 and CCND1/2 on cell growth of NSCLC was finally detected. RESULTS: BAP18 was upregulated in NSCLC tissues, especially cases with advanced stage (III-IV) or large tumor size (>5 cm). BAP18 was closely linked to tumor size, TNM staging and lymphatic metastasis in NSCLC. Knockdown of BAP18 reduced transcriptional levels of CCND1 and CCND2 in A549 and H1299 cells. Furthermore, knockdown of BAP18 delayed transition from G1 to S phase, and weakened growth of NSCLC cells. CONCLUSIONS: BAP18 triggers the progression of NSCLC by regulating transcriptional activities of CCND1/2, which may be a potential target for the treatment and diagnosis of NSCLC.

Polymorphisms in the toll-like receptor 9 gene associated with sepsis and multiple organ dysfunction after major blunt trauma.

BACKGROUND: Toll-like receptor (TLR) 9 is the pattern recognition receptor for microbial DNA. Genetic variation within pattern recognition receptors for bacterial endotoxin and exotoxin has been shown to be associated with the risk of sepsis and organ dysfunction in critical illness. However, little is known about the clinical relevance of TLR9 gene polymorphisms in critical illness. METHODS: A total of 557 patients with major blunt trauma were included in the study. Genetic variation data for the entire TLR9 gene were obtained from the HapMap Project. The genotypes of TLR9 gene polymorphisms were determined using a pyrosequencing method. Whole peripheral blood samples obtained immediately after admission were stimulated with bacterial DNA and production of tumour necrosis factor (TNF) α was then determined. Sepsis morbidity rate and multiple organ dysfunction (MOD) scores were assessed. RESULTS: Of five single-nucleotide polymorphisms (SNPs) genotyped, four (rs187084, rs352139, rs352140 and rs352162) existed as common SNPs and were in strong linkage disequilibrium. Both rs187084 and rs352162 were significantly associated with TNF-α production by peripheral blood leucocytes in response to bacterial DNA stimulation and a higher sepsis morbidity rate in patients with major trauma. In addition, the rs352162 polymorphism was significantly associated with MOD scores, whereas rs187084 showed a trend to be associated with MOD score. CONCLUSION: TLR9 polymorphisms rs187084 and rs352162 might be used to provide relevant risk estimates for the development of sepsis and MOD in patients with major trauma.

Analysis of high-resolution HLA-A, -B, -Cw, -DRB1, and -DQB1 alleles and haplotypes in 718 Chinese marrow donors based on donor-recipient confirmatory typings.

High-resolution human leucocyte antigen (HLA)-A, -B, -Cw, -DRB1, and -DQB1 alleles and haplotype frequencies were analysed from 718 Chinese healthy donors selected from the Chinese Marrow Donor Program registry based on HLA donor-recipient confirmatory typings. A total of 28 HLA-A, 61 HLA-B, 30 HLA-Cw, 40 HLA-DRB1 and 18 HLA-DQB1 alleles were identified, and HLA-A*1101, A*2402, A*0201, B*4001, Cw*0702, Cw*0102, Cw*0304, DRB1*0901, DRB1*1501, DQB1*0301, DQB1*0303 and DQB1*0601 were found with frequencies higher than 10% in this study population. Multiple-locus haplotype analysis by the maximum-likelihood method revealed 45 A-B, 38 Cw-B, 47 B-DRB1, 29 DRB1-DQB1, 24 A-B-DRB1, 38 A-Cw-B, 23 A-Cw-B-DRB1, 33 Cw-B-DRB1-DQB1 and 22 A-Cw-B-DRB1-DQB1 haplotypes with frequencies >0.5%. The most common two-, three-, four- and five-locus haplotypes in this population were: A*0207-B*4601 (7.34%), Cw*0102-B*4601 (8.71%), B*1302-DRB1*0701 (6.19%), DRB1*0901-DQB1*0303 (14.27%), A*3001-B*1302-DRB1*0701 (5.36%), A*0207-Cw*0102-B*4601 (7.06%), A*3001-Cw*0602-B*1302-DRB1*0701 (5.36%), Cw*0602-B*1302-DRB1*0701-DQB1*0202 (6.12%) and A*3001-Cw*0602-B*1302-DRB1*0701-DQB1*0202 (5.29%). Presentation of the high-resolution alleles and haplotypes data at HLA-A, -B, -Cw, -DRB1 and -DQB1 loci will be useful for HLA matching in transplantation as well as for other medical and anthropological applications in the Chinese population.

The invasive tree staghorn sumac affects soil N2 -fixing bacterial communities in north China.

Soil N2 -fixing bacterial communities (SNB) can enhance soil N availability and the invasiveness of invaders. Some invaders display different degrees of invasion across different climate regions. Given that bacterial communities may change with different climate regions, it is important to understand soil micro-ecological mechanisms driving the successful invasion of invaders across different climate regions. This study performed cross-site comparisons to comprehensively analyse effects of the invasive tree staghorn sumac (Rhus typhina L.) on the structure of SNB. In north China, we selected three sites within two sampling regions (a warm temperate region and a cold temperate region). Staghorn sumac invasion did not significantly affect soil physicochemical properties and the diversity and richness of SNB. LEfSe analysis showed that numerous SNB taxa changed significantly during staghorn sumac invasion. This may be attributed in part to the selective effects of allelochemicals released by staghorn sumac via leaf litter and/or root exudates. Consequently, staghorn sumac invasion may alter the structure, rather than the diversity and richness, of SNB to facilitate its invasion process by establishing a favourable soil microenvironment in the invaded habitats. The number of species and richness of SNB under staghorn sumac invasion were significantly lower in the warm temperate region than in the cold temperate region. A possible reason for the increased diversity and richness of SNB under staghorn sumac invasion in the cold temperate region may be because staghorn sumac in the cold temperate region can provide more nutrients into the soil sub-ecosystem, presumably to support a higher diversity and richness of SNB via the nutritional requirements of SNB. The changed structure of SNB under staghorn sumac invasion, especially across different climate regions, may play an important role in its successful invasion across most regions of north China.

Semi-dominant mutation in the cysteine-rich receptor-like kinase gene, ALS1, conducts constitutive defence response in rice.

Plants have evolved a sophisticated two-branch defence system to prevent the growth and spread of pathogen infection. The novel Cys-rich repeat (CRR) containing receptor-like kinases, known as CRKs, were reported to mediate defence resistance in plants. For rice, there are only two reports of CRKs. A semi-dominant lesion mimic mutant als1 (apoptosis leaf and sheath 1) in rice was identified to demonstrate spontaneous lesions on the leaf blade and sheath. A map-based cloning strategy was used for fine mapping and cloning of ALS1, which was confirmed to be a typical CRK in rice. Functional studies of ALS1 were conducted, including phylogenetic analysis, expression analysis, subcellular location and blast resistance identification. Most pathogenesis-related (PR) genes and other defence-related genes were activated and up-regulated to a high degree. ALS1 was expressed mainly in the leaf blade and sheath, in which further study revealed that ALS1 was present in the vascular bundles. ALS1 was located in the cell membrane of rice protoplasts, and its mutation did not change its subcellular location. Jasmonic acid (JA) and salicylic acid (SA) accumulation were observed in als1, and enhanced blast resistance was also observed. The mutation of ALS1 caused a constitutively activated defence response in als1. The results of our study imply that ALS1 participates in a defence response resembling the common SA-, JA- and NH1-mediated defence responses in rice.

Multidisciplinary advisory teams to manage multidrug-resistant tuberculosis: the example of the French Consilium.

SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.

Scavenger receptor class B type I mediates cell entry of hepatitis C virus.

This study assessed the functional role of human scavenger receptor class B type I (SR-BI) as a putative hepatitis C virus (HCV) receptor using Chinese hamster ovary (CHO) cells transfected with human SR-BI (CHO-huSR-BI). The expression of SR-BI by primary Tupaia hepatocytes (PTHs), human hepatocarcinoma cell line (HepG2) cells, untransfected CHO cells and CHO-huSR-BI cells was analysed by Western blotting. Receptor competition assays showed that anti-SR-BI antibodies that block the binding of soluble envelope glycoprotein E2 could prevent HCV infection. Pre-incubation of CHO-huSR-BI and HepG2 cells with anti-SR-BI antibodies resulted in marked inhibition of E2 binding. After incubation with HCV RNA-positive serum from a patient with chronic HCV infection, however, HCV infection could not be detected in CHO-huSR-BI cells, but was detected in PTHs. These results demonstrate that, whilst SR-BI represents an important cell surface molecule for HCV infection, the presence of SR-BI alone is insufficient for HCV entry.