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Sample records for group-a xp cell

  1. Xp11 Translocation Renal Cell Carcinoma: Unusual Variant Masquerading as Upper Tract Urothelial Cell Carcinoma

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    Arash Akhavein

    2014-05-01

    Full Text Available Xp11 translocation renal cell carcinoma (TRCC is a rare subtype of renal cell carcinoma characterized by chromosomal translocations involving the TFE3 gene located at the Xp11.2 locus. Initial cases were more common in children, but cases in older adults have begun to accrue and suggest a relatively more aggressive course. We report a case of Xp11 TRCC in a 63-year-old female patient with initial presentation mimicking upper urinary tract urothelial cell carcinoma, with biopsy proving TRCC. She underwent a radical nephrectomy and paracaval lymph node dissection and is followed up with the intent to initiate vascular endothelial growth factor–targeted therapy in case of recurrence.

  2. Xp11 translocation renal cell carcinoma (RCC): extended immunohistochemical profile emphasizing novel RCC markers.

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    Argani, Pedram; Hicks, Jessica; De Marzo, Angelo M; Albadine, Roula; Illei, Peter B; Ladanyi, Marc; Reuter, Victor E; Netto, George J

    2010-09-01

    Xp11 translocation renal cell carcinoma (RCC) harbor various TFE3 gene fusions, and are known to underexpress epithelial immunohistochemical (IHC) markers such as cytokeratin and EMA relative to usual adult type RCC; however, their profile in reference to other IHC markers that are differentially expressed in other subtypes of RCC has not been systematically assessed. Few therapeutic targets have been identified in these aggressive cancers. We created 2 tissue microarrays (TMA) containing five 1.4-mm cores from each of 21 Xp11 translocation RCC (all confirmed by TFE3 IHC, 6 further confirmed by genetics), 7 clear cell RCC (CCRCC), and 6 papillary RCC (PRCC). These TMA were labeled for a panel of IHC markers. In contrast to earlier published data, Xp11 translocation RCC frequently expressed renal transcription factors PAX8 (16/21 cases) and PAX2 (14/21 cases), whereas only 1 of 21 cases focally expressed MiTF and only 5 of 21 overexpressed p21. Although experimental data suggest otherwise, Xp11 translocation RCC did not express WT-1 (0/21 cases). Although 24% of Xp11 translocation RCC expressed HIF-1alpha (like CCRCC), unlike CCRCC CA IX expression was characteristically only focal (mean 6% cell labeling) in Xp11 translocation RCC. Other markers preferentially expressed in CCRCC or PRCC, such as HIG-2, claudin 7, and EpCAM, yielded inconsistent results in Xp11 translocation RCC. Xp11 translocation RCC infrequently expressed Ksp-cadherin (3/21 cases) and c-kit (0/21 cases), markers frequently expressed in chromophobe RCC. Using an H-score that is the product of intensity and percentage labeling, Xp11 translocation RCC expressed higher levels of phosphorylated S6, a measure of mTOR pathway activation (mean H score=88), than did CCRCC (mean H score=54) or PRCC (mean H score=44). In conclusion, in contrast to prior reports, Xp11 translocation RCC usually express PAX2 and PAX8 but do not usually express MiTF. Although they may express HIF-1alpha, they only focally

  3. Xp11 translocation renal cell carcinoma morphologically mimicking clear cell-papillary renal cell carcinoma in an adult patient: report of a case expanding the morphologic spectrum of Xp11 translocation renal cell carcinomas.

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    Parihar, Asmita; Tickoo, Satish K; Kumar, Sunil; Arora, Vinod Kumar

    2015-05-01

    Xp11 translocation renal cell carcinoma (RCC) is a relatively rare tumor mainly affecting children and adolescents. It shows significant morphological overlap with the 2 most common adult renal tumors, which are the clear cell (conventional) RCC and papillary RCC. We describe case of a young adult female who presented with right flank pain and abdominal mass. Radiological investigations showed features suggestive of renal cell carcinoma in the right kidney. Histopathological findings while suggestive of Xp11 carcinoma, showed significant overlap with the recently described entity clear cell papillary RCC. TFE3 immunohistochemistry confirmed the tumor to be Xp11 translocation RCC. The patient had an aggressive course with lymph node metastasis. In this report, we discuss differential diagnosis and the diagnostic challenges of Xp11 translocation RCC in adults.

  4. Protein Degradation in a TX-TL Cell-free Expression System Using ClpXP Protease

    Science.gov (United States)

    2014-07-14

    1! Protein degradation in a TX-TL cell-free expression system using ClpXP protease AUTHORS: Zachary Z. Sun1, Jongmin Kim1, Vipul Singhal2...COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Protein Degradation in a TX-TL Cell-free Expression System Using ClpXP Protease 5a...equipment and expertise or demand lower reaction throughput. We explored the possibility of supplementing TX-TL with ClpXP, an AAA+ protease

  5. Biological characteristics of pediatric renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.

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    Song, Hong Cheng; Sun, Ning; Zhang, Wei Ping; He, LeJian; Fu, Libing; Huang, ChengRu

    2014-04-01

    To investigate the clinical features of pediatric Xp11.2 translocation renal cell carcinoma (RCC). A retrospective review of 22 cases over 35 years. Xp11.2 translocation RCCs were identified in 13 boys and 9 girls with a median age of 10.5 years (range: 2.5-16 years). RCC presented with hematuria in 17, abdominal mass in 1, abdominal masses with hematuria in 2, abdominal pain with hematuria in 1, and as an incidental finding in 1 patient. Ten patients were classified stage I, 10 were stage III, and two were stage IV. Of the 10 patients with stage I RCCs, 3 patients with tumor measuring less than 7 cm had nephron-sparing surgery (NSS) and 17 patients underwent simple nephrectomy. A 15-cm tumor was incompletely removed in one patient and another patient with a 25-cm × 18-cm × 15-cm tumor had gross residual. Of the 15 patients followed up between 6 months and 35 years, 13 were still living and 2 had died after surgery. Xp11.2 translocation RCC is the predominant form of pediatric RCC, associated with advanced stage at presentation. Nephrectomy is the usual treatment for RCC but NSS is an option for patients with tumors measuring<7 cm. Patients with N+M0 maintained a favorable prognosis following surgery alone. © 2014.

  6. Renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion: imaging findings in 21 patients

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    Chen, Xiao; Zhou, Hao; Duan, Na; Liu, Yongkang; Wang, Zhongqiu [Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Radiology, Nanjing (China); Zhu, Qingqiang [Medical School of Yangzhou University, Department of Medical Imaging, Subei People' s Hospital, Yangzhou (China); Li, Baoxin [Gulou Hospital, Department of Radiology, Nanjing (China); Cui, Wenjing [Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Radiology, Nanjing (China); Nanjing University Medical School, Department of Radiology, Jinling Hospital, Nanjing (China); Kundra, Vikas [The University of Texas, M.D. Anderson Cancer Center, Department of Radiology, Houston, TX (United States)

    2017-02-15

    To characterize imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE gene fusion. Twenty-one patients with Xp11.2/TFE RCC were retrospectively evaluated. Tumour location, size, density, cystic or solid appearance, calcification, capsule sign, enhancement pattern and metastases were assessed. Fourteen women and seven men were identified with 12 being 25 years old or younger. Tumours were solitary and cystic-solid (76.2 %) masses with a capsule (76.2 %); 90.5 % were located in the medulla. Calcifications and lymph node metastases were each observed in 24 %. On unenhanced CT, tumour attenuation was greater than in normal renal parenchyma (85.7 %). Tumour enhancement was less than in normal renal cortex on all enhanced phases, greater than in normal renal medulla on cortical and medullary phases, but less than in normal renal medulla on delayed phase. On MR, the tumours were isointense on T1WI, heterogeneously hypointense on T2WI and slightly hyperintense on diffusion-weighted imaging. Xp11.2/TFE RCC usually occurs in young women. It is a cystic-solid, hyperdense mass with a capsule. It arises from the renal medulla with enhancement less than in the cortex but greater than in the medulla in all phases except the delayed phase, when it is lower than in the medulla. (orig.)

  7. Xeroderma pigmentosum group A correcting protein from Calf Thymus.

    NARCIS (Netherlands)

    A.P.M. Eker (André); W. Vermeulen (Wim); N. Miura; K. Tanaka (Kiyoji); N.G.J. Jaspers (Nicolaas); J.H.J. Hoeijmakers (Jan); D. Bootsma (Dirk)

    1992-01-01

    textabstractA proteinous factor was purified from calf thymus and HeLa cells, which specifically corrects the excision repair defect of xeroderma pigmentosum complementation group A (XP-A) cells. Recovery of UV-induced unscheduled DNA synthesis after microinjection of XP-A cells was used as a quanti

  8. A rare case of TFE-related pigmented renal tumor with overlapping features between melanotic Xp11 translocation renal cancer and Xp11 renal cell carcinoma with melanotic features.

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    Cardili, Leonardo; Wrublevsky Pereira, Gregório; Viana, Cristiano Ribeiro

    2017-02-16

    In recent years, an increasing number of TFE3 rearrangement-associated tumors with melanotic features have been reported as primary neoplasm in different anatomical sites, including the kidney. Melanotic Xp11 translocation renal cancer (MXTRC) and Xp11 renal cell carcinoma with melanotic features (XRCCM) have been proposed to be main categories for pigmented lesions in the microophthalmia-associated transcription factor (MiTF/TFE3) family of renal tumors that may show variable degrees of melanocytic differentiation. Herein we report a rare case of TFE3-related pigmented renal tumor showing unusual immunoexpression of cytokeratins (AE1/AE3) and renal cell carcinoma markers (RCC, CD10). Cathepsin-K and Vimentin were diffusely positive whereas melanocytic markers (HMB-45 and Melan-A) displayed weak and patchy expression. We found no labelling for PAX-8, muscle markers (desmin, smooth muscle actin, muscle-specific actin and caldesmon) and S-100. TFE3 fusion was confirmed by break-apart fluorescence in situ hybridization (FISH). This case corroborates previous evidence for overlap in the TFE3-associated cancer family and illustrates that it may not be possible to set a clear cutoff between epithelial (XRCCM) and mesenchymal (MXTRC) subgroups.

  9. Identification of a yeast artificial chromosome that spans the human papillary renal cell carcinoma-associated t(X;1) breakpoint in Xp11.2

    NARCIS (Netherlands)

    Suijkerbuijk, R F; Meloni, A M; Sinke, R J; de Leeuw, B; Wilbrink, M; Janssen, H A; Geraghty, M T; Monaco, A P; Sandberg, A A; Geurts van Kessel, A

    1993-01-01

    Recently, a specific chromosome abnormality, t(X;1)(p11;q21), was described for a subgroup of human papillary renal cell carcinomas. The translocation breakpoint in Xp11 is located in the same region as that in t(X;18)(p11;q11)-positive synovial sarcoma. We used fluorescence in situ hybridization (F

  10. Xp11.2 translocation in children with renal cell carcinoma%儿童Xp11.2易位/TFE3基因融合相关肾细胞癌

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    宋宏程; 孙宁; 张潍平; 何乐健; 伏利兵; 黄澄如

    2014-01-01

    目的 研究儿童Xp11.2易位/TFE3基因融合相关肾细胞癌的生物特性,提高对该病的认识.方法 回顾性分析1973年1月至2013年6月收治的33例儿童肾细胞癌的临床病理资料,其中24例确诊为Xp11.2易位/TFE3基因融合相关肾细胞癌,总结其临床表现、分期、病理分型、治疗及随访结果.结果 本组24例中,男13例,女11例;年龄2.5~16岁,平均10.2岁;左侧肾细胞癌13例,右侧11例.无痛肉眼血尿19例(1例为外伤后血尿),血尿+腹部包块2例,腹部包块1例,血尿+腹痛1例,行B型超声检查偶然发现1例.24例患儿中,4例肿瘤直径<7.0 cm,行保留肾单位的肿瘤剜除术;1例因肿瘤直径15.0 cm包绕腹主动脉和下腔静脉,仅行肿瘤大部分切除;1例肿瘤巨大,直径25.0 cm,术中有肉眼残留.余18例患儿均行瘤肾切除术.肿瘤直径2.5~25.0 cm,平均7.2cm.Ⅰ期11例,Ⅲ期11例,Ⅳ期2例.17例获随访,随访时间6个月~35年,平均12年,死亡2例,无瘤存活15例.结论 Xp11.2易位相关肾癌是儿童肾细胞癌的主要病理类型,缺乏特异性的临床表现和影像学特点,易发生局部淋巴结转移,分期高,但在儿童表现为生物活性惰性.手术切除是主要的治疗方法,肿瘤直径小于7.0cm可行保留肾单位的肿瘤剜除术.%Objeetive To explore the unique biological,histological and clinical features of Xp11.2 translocation in pediatric renal cell carcinoma (RCC).Methods Retrospective reviews and biological analyses were performed for 24 Xp11.2 translocation RCC cases at Beijing Children's Hospital from January 1973 to June 2013.Results There were 13 boys and 11 girls with a median age of 10.2 (2.5-16) years.Hematuria occurred in 19 cases,including post-trauma hematuria (n =1),abdominal mass with hematuria (n =2),abdominal mass (n =1),abdominal pain with hematuria (n =1) and incidental finding (n =1).According to TNM staging system,there were stage Ⅰ (n =11),stage Ⅲ (n=11) and stage Ⅳ (n=2

  11. Temsirolimus in the treatment of renal cell carcinoma associated with Xp11.2 translocation/TFE gene fusion proteins: a case report and review of literature

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    James Brown

    2009-12-01

    Full Text Available Xp11.2 translocation renal cell carcinomas (TRCCs are a rare family of tumors newly recognized by the World Health Organization (WHO in 2004. These tumors result in the fusion of partner genes to the TFE3 gene located on Xp11.2. They are most common in the pediatric population, but have been recently implicated in adult renal cell carcinoma (RCC presenting at an early age. TFE3-mediated direct transcriptional upregulation of the Met tyrosine kinase receptor triggers dramatic activation of downstream signaling pathways including the protein kinase B (Akt/phosphatidylinositol-3 kinase (PI3K and mammalian target of rapamycin (mTOR pathways. Temsirolimus is an inhibitor of mammalian target of rapamycin (mTOR kinase, a component of intracellular signaling pathways involved in the growth and proliferation of malignant cells. Here we present a case of a 22-year old female who has been treated with temsirolimus for her Xp11.2/TFE3 gene fusion RCC.

  12. DNA replication arrest in XP variant cells after UV exposure is diverted into an Mre11-dependent recombination pathway by the kinase inhibitor wortmannin

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    Limoli, C.L.; Laposa, R.; Cleaver, J.E

    2002-12-29

    Ultraviolet (UV) irradiation produces DNA photoproducts that are blocks to DNA replication by normal replicative polymerases. A specialized, damage-specific, distributive polymerase, Pol H or Pol h, that is the product of the hRad30A gene, is required for replication past these photoproducts. This polymerase is absent from XP variant (XP-V) cells that must employ other mechanisms to negotiate blocks to DNA replication. These mechanisms include the use of alternative polymerases or recombination between sister chromatids. Replication forks arrested by UV damage in virus transformed XP-V cells degrade into DNA double strand breaks that are sites for recombination, but in normal cells arrested forks may be protected from degradation by p53 protein. These breaks are sites for binding a protein complex, hMre11/hRad50/Nbs1, that colocalizes with H2AX and PCNA, and can be visualized as immunofluorescent foci. The protein complexes need phosphorylation to activate their DNA binding capacity. Incubation of UV irradiated XP-V cells with the irreversible kinase inhibitor wortmannin, however, increased the yield of Mre11 focus-positive cells. One interpretation of this observation is that two classes of kinases are involved after UV irradiation. One would be a wortmannin-resistant kinase that phosphorylates the Mre11 complex. The other would be a wortmannin-sensitive kinase that phosphorylates and activates the p53/large T in SV40 transformed XP-V cells. The sensitive class corresponds to the PI3-kinases of ATM, ATR, and DNA-PK, but the resistant class remains to be identified. Alternatively, the elevated yield of Mre11 foci positive cells following wortmannin treatment may reflect an overall perturbation to the signaling cascades regulated by wortmannin-sensitive PI3 related kinases. In this scenario, wortmannin could compromise damage inducible-signaling pathways that maintain the stability of stalled forks, resulting in a further destabilization of stalled forks that then

  13. Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusion: A Rare Case Report with Review of the Literature

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    Puneet Ahluwalia

    2013-01-01

    Full Text Available Introduction. The recently recognized renal cell carcinomas associated with Xp11.2 translocations are rare tumors predominantly reported in children. Chromosome Xp11.2 translocation results in gene fusion related to transcription factor E3 (TFE3 that plays an important role in proliferation and survival. Case Report. Herein, we present two cases of a TFE3 translocation-associated RCC in young female adults, one detected incidentally and the other one presenting with gross hematuria. Tumor is characterized by immunohistochemistry and a literature review with optimal treatment regimen is presented. Discussion. Xp11.2 translocation RCCs in adult patients are associated with advanced stages, large tumors, and extracapsular disease and usually have an aggressive clinical course. Conclusion. In TFE3 RCC, the genetic background may not only contribute to tumorigenesis, but also determine the response to chemotherapy and targeted therapy. Therefore it is necessary to diagnose this tumor entity accurately. Because of the small number of TFE3 gene fusion-related renal tumors described in the literature, the exact biologic behavior and impact of current treatment modalities remain to be uncertain.

  14. Vascular endothelial growth factor (VEGF)-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma

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    Choueiri, Toni K.; Lim, Zita Dubauskas; Hirsch, Michelle S.; Tamboli, Pheroze; Jonasch, Eric; McDermott, David F.; Cin, Paola Dal; Corn, Paul; Vaishampayan, Ulka; Heng, Daniel Y.C.; Tannir, Nizar M.

    2015-01-01

    Introduction Adult “translocation” renal cell carcinoma (RCC), bearing TFE3 gene fusions at Xp11.2, is a recently recognized unique entity for which prognosis and therapy remain poorly understood. We investigated the effect of vascular-endothelial growth factor (VEGF)-targeted therapy in this distinct subtype of RCC. Patients and Methods We conducted a retrospective review to describe the clinical characteristics and outcome of adult patients with metastatic Xp11.2 RCC, who had strong TFE-3 nuclear immunostaining, and received anti-VEGF therapy. Tumor response to anti-VEGF therapy was evaluated by RECIST. Kaplan-Meier methods were used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Results Fifteen patients were identified of which 10, 3, and 2 received sunitinib, sorafenib and monoclonal anti-VEGF antibodies, respectively. The median follow-up was 19.1 months, the median age of the patients was 41 years, and the female:male ratio was 4:1. Initial histologic description included clear cell (n=8), papillary (n=1) or mixed clear cell/papillary RCC (n=6). Five patients had prior systemic therapy. Five patients had FISH analysis and all demonstrated a translocation involving chromosome Xp11.2. When treated with VEGF-targeted therapy, 3 patients had a partial response, 7 patients had stable disease and 5 patients had progressive disease. The median PFS and OS of the entire cohort were 7.1 months and 14.3 months respectively. Conclusion Adult-onset translocation-associated metastatic RCC is an aggressive disease that affects a younger population of patients with a female predominance. VEGF-targeted agents demonstrated some efficacy in this small retrospective series. PMID:20665500

  15. Bioconversion of Pinoresinol Diglucoside and Pinoresinol from Substrates in the Phenylpropanoid Pathway by Resting Cells of Phomopsis sp.XP-8.

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    Yan Zhang

    Full Text Available Pinoresinol diglucoside (PDG and pinoresinol (Pin are normally produced by plant cells via the phenylpropanoid pathway. This study reveals the existence of a related pathway in Phomopsis sp. XP-8, a PDG-producing fungal strain isolated from the bark of the Tu-chung tree (Eucommiaulmoides Oliv.. After addition of 0.15 g/L glucose to Phomopsis sp. XP-8, PDG and Pin formed when phenylalanine, tyrosine, leucine, cinnamic acid, and p-coumaric acid were used as the substrates respectively. No PDG formed in the absence of glucose, but Pin was detected after addition of all these substrates except leucine. In all systems in the presence of glucose, production of PDG and/or Pin and the accumulation of phenylalanine, cinnamic acid, or p-coumaric acid correlated directly with added substrate in a time- and substrate concentration- dependent manner. After analysis of products produced after addition of each substrate, the mass flow sequence for PDG and Pin biosynthesis was defined as: glucose to phenylalanine, phenylalanine to cinnamic acid, then to p-coumaric acid, and finally to Pin or PDG. During the bioconversion, the activities of four key enzymes in the phenylpropanoid pathway were also determined and correlated with accumulation of their corresponding products. PDG production by Phomopsis sp. exhibits greater efficiency and cost effectiveness than the currently-used plant-based system and will pave the way for large scale production of PDG and/or Pin for medical applications.

  16. Bioconversion of Pinoresinol Diglucoside and Pinoresinol from Substrates in the Phenylpropanoid Pathway by Resting Cells of Phomopsis sp.XP-8.

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    Zhang, Yan; Shi, Junling; Liu, Laping; Gao, Zhenhong; Che, Jinxin; Shao, Dongyan; Liu, Yanlin

    2015-01-01

    Pinoresinol diglucoside (PDG) and pinoresinol (Pin) are normally produced by plant cells via the phenylpropanoid pathway. This study reveals the existence of a related pathway in Phomopsis sp. XP-8, a PDG-producing fungal strain isolated from the bark of the Tu-chung tree (Eucommiaulmoides Oliv.). After addition of 0.15 g/L glucose to Phomopsis sp. XP-8, PDG and Pin formed when phenylalanine, tyrosine, leucine, cinnamic acid, and p-coumaric acid were used as the substrates respectively. No PDG formed in the absence of glucose, but Pin was detected after addition of all these substrates except leucine. In all systems in the presence of glucose, production of PDG and/or Pin and the accumulation of phenylalanine, cinnamic acid, or p-coumaric acid correlated directly with added substrate in a time- and substrate concentration- dependent manner. After analysis of products produced after addition of each substrate, the mass flow sequence for PDG and Pin biosynthesis was defined as: glucose to phenylalanine, phenylalanine to cinnamic acid, then to p-coumaric acid, and finally to Pin or PDG. During the bioconversion, the activities of four key enzymes in the phenylpropanoid pathway were also determined and correlated with accumulation of their corresponding products. PDG production by Phomopsis sp. exhibits greater efficiency and cost effectiveness than the currently-used plant-based system and will pave the way for large scale production of PDG and/or Pin for medical applications.

  17. Xp11.2 translocation renal cell carcinoma occurring during pregnancy with a novel translocation involving chromosome 19: a case report with review of the literature

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    Surti Urvashi

    2009-05-01

    Full Text Available Abstract The recently recognized renal cell carcinomas (RCCs associated with Xp11.2 translocations (TFE3 transcription factor gene fusions are rare tumors predominantly reported in children. They comprise at least one-third of pediatric RCCs and only few adult cases have been reported. Here, we present a case of Xp11.2 translocation RCC in 26-year-old pregnant female. Her routine antenatal ultrasonography accidentally found a complex cystic right renal mass. Further radiologic studies revealed unilocular cyst with multiple mural nodules at inferior pole of right kidney, which was suspicious for RCC. She underwent right radical nephrectomy at 15 weeks gestation. Macroscopically, the cystic tumor was well encapsulated with multiple friable mural nodules on its inner surface. Microscopically, the tumor consisted of clear and eosinophilic/oncocytic voluminous cells arranged in papillary, trabecular, and nested/alveolar patterns. Occasional hyaline nodules and numerous psammoma bodies were present. Immunohistochemically, the tumor showed strong nuclear positivity for TFE3. Epithelial membrane antigen, CD10, and E-cadherin were strongly positive. Cytokeratin AE1/AE3, cytokeratin CAM-5.2, calveolin, and parvalbumin were moderately positive. Cytokeratin 7, renal cell carcinoma antigen, and colloidal iron were focally weakly positive. BerEP4 and carbonic anhydrase IX were negative. Cytogenetically, the tumor harbored a novel variant translocation involving chromosomes X and 19, t(X;19(p11.2;q13.1. Interphase FISH analysis performed on cultured and uncultured tumor cells using a dual-color break-apart DNA probe within the BCL3 gene on 19q13.3 was negative for the BCL3 gene rearrangement. She received no adjuvant therapy, delivered a normal term baby five months later, and is alive without evidence of disease 27 months after diagnosis and surgery. Unlike most recently reported Xp11.2 translocation RCCs in adult patients with aggressive clinical course

  18. DISTINCT XP11.2 BREAKPOINTS IN 2 RENAL-CELL CARCINOMAS EXHIBITING X-AUTOSOME TRANSLOCATIONS

    NARCIS (Netherlands)

    DIJKHUIZEN, T; VANDENBERG, E; WETERMAN, M; VANKESSEL, AG; STORKEL, S; FOLKERS, RP; BRAAM, A; DEJONG, B

    1995-01-01

    Several human renal cell carcinomas with X;autosome translocations have been reported in recent years. The t(X; I)(p11.2;q21) appears to be a specific primary anomaly, suggesting that tumors with this translocation form a distinct subgroup of RCC. Here we report two new cases, one with a t(X;10)(p11

  19. Report of 6 cases of Xp11.2 translocation renal cell carcinoma and literature review%Xp11.2易位/TFE3基因融合相关性肾癌六例报告并文献复习

    Institute of Scientific and Technical Information of China (English)

    东洁; 陈博; 李汉忠; 纪志刚; 徐维锋

    2016-01-01

    目的 探讨Xp1 1.2易位/TFE3基因融合相关性肾癌患者的临床病理特点.方法 对2011年1月至2015年12月收治的肾癌患者进行筛选,共发现6例Xp11.2易位/TFE3基因融合相关性肾癌患者.男2例,女4例.年龄16 ~73岁,平均39岁.肿瘤直径1.9 ~19.0 cm,平均9.6 cm.其中3例常规查体发现,1例因严重贫血(Hb 66g/L)、1例因肉眼血尿、1例因腰部不适就诊.就诊时2例分别有局部淋巴结和肾盂受侵,1例有远处转移(肺转移).CT检查示肾脏软组织密度/低密度占位,增强扫描呈明显强化或不均匀强化,均考虑恶性可能.6例均接受手术治疗,其中行根治性肾切除术5例,肾部分切除术1例.结果 6例术后行病理检查,镜下观察肿瘤组织透明细胞大多排列成乳头状、巢团样结构,伴砂粒体形成.免疫组化染色检查TFE均阳性,AE1/AE3、RCC、Vimentin、CD10、EMA、P504等呈不同程度阳性表现.术后病理诊断均为Xp11.2易位/TFE3基因融合相关性肾癌.术后2例接受白细胞介素-2治疗,2例接受靶向药物治疗(舒尼替尼),1例接受局部放疗.随访9 ~56个月,平均37个月.1例术后22个月死于肿瘤多发转移;1例术后12个月出现肺部转移,接受靶向药物治疗后,肿瘤无明显进展;余患者一般情况尚可.结论 Xp11.2易位/TFE3基因融合相关性肾癌好发于儿童和青少年,CT动脉期强化略低于肾透明细胞癌,组织学特点及免疫组化染色检测TFE3阳性表达是诊断该病的重要手段,必要时可行基因检测以明确诊断.手术是首选的治疗选择.已有转移的患者预后较差,需要辅以靶向药物治疗.%Objective To explore the clinical and pathological characters of Xp1 1.2 translocation renal cell carcinoma.Method We screened patients of renal cell carcinoma of PUMCH between Jan.2011 and Dec.2015,6 patients with Xp11.2 translocation renal cell carcinoma were found.There were 2 males and 4 females,with average age of 39 (ranging

  20. Bayesian Network Based XP Process Modelling

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    Mohamed Abouelela

    2010-07-01

    Full Text Available A Bayesian Network based mathematical model has been used for modelling Extreme Programmingsoftware development process. The model is capable of predicting the expected finish time and theexpected defect rate for each XP release. Therefore, it can be used to determine the success/failure of anyXP Project. The model takes into account the effect of three XP practices, namely: Pair Programming,Test Driven Development and Onsite Customer practices. The model’s predictions were validated againsttwo case studies. Results show the precision of our model especially in predicting the project finish time.

  1. Loss of blood group A in acute leukemia. Morphologic and biochemical studies of red cells.

    Science.gov (United States)

    Atkinson, J B; Tanley, P C; Wallas, C H

    1987-01-01

    A patient with blood type A had acute myelomonocytic leukemia; his red cells (RBCs) typed as O and his serum had anti-B. RBC membranes were isolated from the patient as well as from controls with group A and O red cells. The membranes were incubated with uridine diphosphate (UDP)-N-acetyl-D-14C galactosamine in plasma from the patient and controls with group A and O red cells. RBC membranes from the patient behaved normally in that they incorporated the terminal carbohydrate responsible for blood group A activity. Scanning electron microscopy showed that the patient's RBCs had striking morphologic changes, with marked crenation and numerous knisocytes and dacryocytes. It was concluded that loss of the A antigen in this patient was not due to an abnormality of the enzyme required to convert H substance to A substance. It was postulated that weakening of the A antigen in some patients with leukemia may be related to a steric modification associated with abnormal red cell morphology.

  2. Time characteristics of PROFIBUS on Windows XP

    NARCIS (Netherlands)

    Huang, Yang

    2005-01-01

    This project is aiming to investigate the use of the PROFIBUS as a fieldbus for control purposes, and to determine the time characteristics of PROFIBUS data transmission between two PCs. The actual experiments are performed with PC¿s running Windows XP, which is a non-realtime OS. The experiments ar

  3. Novel Hybrid Model: Integrating Scrum and XP

    Directory of Open Access Journals (Sweden)

    Zaigham Mushtaq

    2012-06-01

    Full Text Available Scrum does not provide any direction about how to engineer a software product. The project team has to adopt suitable agile process model for the engineering of software. XP process model is mainly focused on engineering practices rather than management practices. The design of XP process makes it suitable for simple and small size projects and not appropriate for medium and large projects. A fine integration of management and engineering practices is desperately required to build quality product to make it valuable for customers. In this research a novel framework hybrid model is proposed to achieve this integration. The proposed hybrid model is actually an express version of Scrum model. It possesses features of engineering practices that are necessary to develop quality software as per customer requirements and company objectives. A case study is conducted to validate the proposal of hybrid model. The results of the case study reveal that proposed model is an improved version of XP and Scrum model.

  4. Structure and Barr body formation of an Xp + chromosome with two inactivation centers.

    Science.gov (United States)

    Daly, R F; Patau, K; Therman, E; Sarto, G E

    1977-01-01

    A patients with seizures, Von Willebrand disease, and symptoms of Turner syndrome was a chromosomal mosaic. In blood culture (1974), 56% of the cells were 45, X 33% 46, XXp+ and 11% 47,XXp + Xp +; in the skin, no cells with 47 chromosomes were found. Presumably the Xp + chromosome arose through a break in the Q-banded dark region next to the centromere on Xp to which an Xq had been attached. The abnormal X was late-labeling and formed a larger than normal Barr body. Of the chromatin-positive fibroblasts, 18.2% showed bipartite Barr bodies, which agrees with the hypothesis that the X inactivation center lies on the proximal part of the Xq. On the basis of the structure and behavior of the bipartite bodies in the present patient, as compared to those formed by other chromosomes with two presumed inactivation centers, we propose that the dark region next to the centromere of Xp remains active in the inactive X. In cells with 45,X and 46,XY, this region has the same relative size, whereas it is significantly shorter in the active X of three females, including the present patient, with one abnormal X. We propose that this region on the active X reveals different states of activity, as reflected in its length, depending on how many other X chromosomes are in the cell. Images Fig. 1 Fig. 2 Fig. 3 PMID:299980

  5. Schizophrenia susceptibility gene locus at Xp22.3.

    Science.gov (United States)

    Milunsky, J; Huang, X L; Wyandt, H E; Milunsky, A

    1999-06-01

    Multiple genetic loci have been implicated in the search for schizophrenia susceptibility genes, none having been proven as causal. Genetic heterogeneity is probable in the polygenic etiology of schizophrenia. We report on two unrelated Caucasian women with paranoid schizophrenia (meeting Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria) who have an Xp22.3 overlapping deletion characterized by fluorescence in situ hybridization (FISH). Patient 1 was previously reported by us (Wyandt HE, Bugeau-Michaud L, Skare JC, Milunsky A. Partial duplication of Xp: a case report and review of previously reported cases. Amer J Med Genet 1991: 40: 280-283) to have a de novo partial duplication of Xp. At that time, she was a 24-year-old woman with short stature, irregular menses, other abnormalities suggestive of Turner syndrome, and paranoid schizophrenia. Recently, FISH analysis demonstrated that she has an inverted duplication (X)(p22.1p11.2) and a microscopic deletion (X)(p22.2p22.3) between DXS1233 and DXS7108 spanning approximately 16-18 cM. Patient 2 is a 14-year-old girl with short stature, learning disabilities, and paranoid schizophrenia. High-resolution chromosome analysis revealed a de novo deletion involving Xp22. FISH analysis showed that the deletion (X)(p22.2p22.3) spanned 10-12 cM between AFMB290XG5 and DXS1060. Given that deletions of Xp22 are not common events, the occurrence of two unrelated schizophrenia patients with an overlapping deletion of this region would be extraordinarily rare. Hence, the deletion within Xp22.3 almost certainly contains a gene involved in the pathogenesis of paranoid schizophrenia.

  6. An $xp$ model on $AdS_2$ spacetime

    OpenAIRE

    2012-01-01

    In this paper we formulate the $xp$ model on the AdS$_2$ spacetime. We find that the spectrum of the Hamiltonian has positive and negative eigenvalues, whose absolute values are given by a harmonic oscillator spectrum, which in turn coincides with that of a massive Dirac fermion in AdS$_2$. We extend this result to generic $xp$ models which are shown to be equivalent to a massive Dirac fermion on spacetimes whose metric depend of the $xp$ Hamiltonian. Finally, we construct the generators of t...

  7. MR Imaging Findings in Xp21.2 Duplication Syndrome

    Science.gov (United States)

    Whitehead, Matthew T; Helman, Guy; Gropman, Andrea L

    2016-01-01

    Xp21.2 duplication syndrome is a rare genetic disorder of undetermined prevalence and clinical relevance. As the use of chromosomal microarray has become first line for the work-up of childhood developmental delay, more gene deletions and duplications have been recognized. To the best of our knowledge, the imaging findings of Xp21.2 duplication syndrome have not been reported. We report a case of a 33 month-old male referred for developmental delay that was found to have an Xp21.2 duplication containing IL1RAPL1 and multiple midline brain malformations.

  8. Windows XP Power Hound Teach Yourself New Tricks

    CERN Document Server

    Gralla, Preston

    2009-01-01

    Windows XP power-users troll the web, documentation, and friends for useful tips and tricks--a keyboard shortcut here, an undocumented double-click there to eliminate annoyances, save time, and take control of their Windows XP. There's an easier way. This insightful and amusing book is packed with hundreds of power tips, cool tricks, and workarounds in one organized, easy-to-use resource--for everything from the desktop to Office programs to the registry.

  9. Altered cell-mediated immunity to group A haemolytic streptococcal antigens in chronic plaque psoriasis.

    Science.gov (United States)

    Baker, B S; Powles, A V; Malkani, A K; Lewis, H; Valdimarsson, H; Fry, L

    1991-07-01

    The proliferative lymphocyte response to sonicated group A, beta-haemolytic streptococci (Strep-A) was measured by thymidine incorporation in 78 patients with psoriasis (guttate, chronic plaque or both). Lymphocytes from 72 of these patients were also cultured with streptokinase/streptodornase (SK/SD), and 20 of the patients with chronic plaque psoriasis were further tested with PPD, Candida albicans and sonicated Streptococcus mutans, a bacterial type not associated clinically with psoriasis. The median stimulation index (SI) of the psoriasis group to the Strep-A preparation was significantly higher than that of a group of 27 non-psoriatic individuals (P less than 0.05). Within this group, only the patients with chronic plaque psoriasis (n = 42) showed a significantly increased proliferative response compared to the non-psoriatic controls (median SI = 123.8 and 31.9, respectively, P less than 0.01). Although the lymphocyte response of the chronic plaque group to SK/SD was also markedly higher than that of the control group, this difference did not reach statistical significance. In addition, these patients did not show significantly increased responses to any of the other antigens tested, including S. mutans. No correlation was observed between the degree of proliferation to Strep-A and disease extent or activity. Similarly, ASO titres, which were raised in 11 out of 23 guttate and three out of nine chronic plaque psoriasis patients tested, did not correlate with the proliferative responses observed.

  10. Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A

    Science.gov (United States)

    Zhang, Xiaoling; Shang, Xun; Guo, Fukun; Murphy, Kim; Kirby, Michelle; Kelly, Patrick; Reeves, Lilith; Smith, Franklin O.; Williams, David A.

    2008-01-01

    Previous studies showed that Fanconi anemia (FA) murine stem cells have defective reconstitution after bone marrow (BM) transplantation. The mechanism underlying this defect is not known. Here, we report defective homing of FA patient BM progenitors transplanted into mouse models. Using cells from patients carrying mutations in FA complementation group A (FA-A), we show that when transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) recipient mice, FA-A BM cells exhibited impaired homing activity. FA-A cells also showed defects in both cell-cell and cell-matrix adhesion. Complementation of FA-A deficiency by reexpression of FANCA readily restored adhesion of FA-A cells. A significant decrease in the activity of the Rho GTPase Cdc42 was found associated with these defective functions in patient-derived cells, and expression of a constitutively active Cdc42 mutant was able to rescue the adhesion defect of FA-A cells. These results provide the first evidence that FA proteins influence human BM progenitor homing and adhesion via the small GTPase Cdc42-regulated signaling pathway. PMID:18565850

  11. Xp54, the Xenopus homologue of human RNA helicase p54, is an integral component of stored mRNP particles in oocytes.

    Science.gov (United States)

    Ladomery, M; Wade, E; Sommerville, J

    1997-01-01

    In investigating the composition of stored (maternal) mRNP particles in Xenopus oocytes, attention has focussed primarily on the phosphoproteins pp60/56, which are Y-box proteins involved in a general packaging of mRNA. We now identify a third, abundant, integral component of stored mRNP particles, Xp54, which belongs to the family of DEAD-box RNA helicases. Xp54 was first detected by its ability to photocrosslink ATP. Subsequent sequence analysis identifies Xp54 as a member of a helicase subfamily which includes: human p54, encoded at a chromosomal breakpoint in the B-cell lymphoma cell line, RC-K8; Drosophila ME31B, encoded by a maternally-expressed gene, and Saccharomyces pombe Ste13, cloned by complementation of the sterility mutant ste13. Expression studies reveal that the gene encoding Xp54 is transcribed maximally at early oogenesis: no transcripts are detected in adult tissues, other than ovary. Using a monospecific antibody raised against native Xp54, its presence in mRNP particles is confirmed by immunoblotting fractions bound to oligo(dT)-cellulose and separated by rate sedimentation and buoyant density. On isolating Xp54 from mRNP particles, it is shown to possess an ATP-dependent RNA helicase activity. Possible functions of Xp54 are discussed in relation to the assembly and utilization of mRNP particles. PMID:9023105

  12. xpMODEL: A Novel Model for ASIP Architecture

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    With greater flexibility and less cost, there is a trend that application specific instruction set processor (ASIP) will become the alternative implementation style to application of specific integrated circuit (ASIC). Architecture model is a key component in ASIP design flow. A novel ASIP model, xpMODEL, was presented. Its key features include: explicit specification of the memory subsystem allowing novel memory organizations and hierarchies; the introduction of meta-operator and instruction behavior extended finite state machine providing xpMODEL with ability to model execution sequencing, inherent parallelism, data/control/structural hazards, and out-oforder execution mode in ASIP. A comparison with other ASIP models shows the superiority of xpMODEL.

  13. Streptolysin S Promotes Programmed Cell Death and Enhances Inflammatory Signaling in Epithelial Keratinocytes during Group A Streptococcus Infection.

    Science.gov (United States)

    Flaherty, Rebecca A; Puricelli, Jessica M; Higashi, Dustin L; Park, Claudia J; Lee, Shaun W

    2015-10-01

    Streptococcus pyogenes, or group A Streptococcus (GAS), is a pathogen that causes a multitude of human diseases from pharyngitis to severe infections such as toxic shock syndrome and necrotizing fasciitis. One of the primary virulence factors produced by GAS is the peptide toxin streptolysin S (SLS). In addition to its well-recognized role as a cytolysin, recent evidence has indicated that SLS may influence host cell signaling pathways at sublytic concentrations during infection. We employed an antibody array-based approach to comprehensively identify global host cell changes in human epithelial keratinocytes in response to the SLS toxin. We identified key SLS-dependent host responses, including the initiation of specific programmed cell death and inflammatory cascades with concomitant downregulation of Akt-mediated cytoprotection. Significant signaling responses identified by our array analysis were confirmed using biochemical and protein identification methods. To further demonstrate that the observed SLS-dependent host signaling changes were mediated primarily by the secreted toxin, we designed a Transwell infection system in which direct bacterial attachment to host cells was prevented, while secreted factors were allowed access to host cells. The results using this approach were consistent with our direct infection studies and reveal that SLS is a bacterial toxin that does not require bacterial attachment to host cells for activity. In light of these findings, we propose that the production of SLS by GAS during skin infection promotes invasive outcomes by triggering programmed cell death and inflammatory cascades in host cells to breach the keratinocyte barrier for dissemination into deeper tissues. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. A Adaptive XP-based approach to Agile Development

    CERN Document Server

    Liao, Gang; Luo, Lian

    2012-01-01

    Software design is gradually becoming open, distributed, pervasive, and connected. It is a sad statistical fact that software projects are scientifically fragile and tend to fail more than other engineering fields. Agile development is a philosophy. And agile methods are processes that support the agile philosophy. XP places a strong emphasis on technical practices in addition to the more common teamwork and structural practices. In this paper, we elaborate how XP practices can be used to thinking, collaborating, releasing, planning, developing. And the state that make your team and organization more successful.

  15. A Dirac type xp-Model and the Riemann Zeros

    CERN Document Server

    Gupta, Kumar S; de Queiroz, Amilcar R

    2012-01-01

    We propose a Dirac like modification of the xp-model to a $x \\slashed{p}$ model on a semi-infinite cylinder. This model is inspired on recent work by Sierra et al. on the xp-model on the half-line. Our model realizes the Berry-Keating conjecture on the Riemann zeros. We indicate the connection of our model to that of gapped graphene with a supercritical Coulomb charge, which might provide a physical system for the study of the zeros of the Riemann Zeta function.

  16. Recovery from ultraviolet light-induced depression of ribosomal RNA synthesis in normal human, xeroderma pigmentosum and cockayne syndrome cells

    Energy Technology Data Exchange (ETDEWEB)

    Ayaki, Hitoshi; Hara, Ryujiro; Ikenaga, Mituo [Kyoto Univ. (Japan). Radiation Biology Center

    1996-06-01

    The rate of ribosomal RNA (rRNA) synthesis was analyzed at different times after ultraviolet light (UV) irradiation in normal human, xeroderma pigmentosum (XP) and Cockayne syndrome (CS) cells. In normal cells, the rate of rRNA synthesis, as measured by the incorporation of {sup 3}H-uridine into 18S and 28S rRNAs, decreased immediately after UV irradiation to about half of that of unirradiated cells, and then recovered significantly at 24h after UV. However, the rate of synthesis continued to decrease during post-UV incubation in XP cells belonging to groups A, D, E, F and G, as well as in CS cells of groups A and B. In contrast, group C XP cells showed a slight recovery at 24h after UV, suggesting that they have the capacity to repair UV lesions in rRNA genes. (author)

  17. A Red Blood Cell Membrane-Camouflaged Nanoparticle Counteracts Streptolysin O-Mediated Virulence Phenotypes of Invasive Group A Streptococcus

    Directory of Open Access Journals (Sweden)

    Tamara Escajadillo

    2017-07-01

    Full Text Available Group A Streptococcus (GAS, an important human-specific Gram-positive bacterial pathogen, is associated with a broad spectrum of disease, ranging from mild superficial infections such as pharyngitis and impetigo, to serious invasive infections including necrotizing fasciitis and streptococcal toxic shock syndrome. The GAS pore-forming streptolysin O (SLO is a well characterized virulence factor produced by nearly all GAS clinical isolates. High level expression of SLO is epidemiologically linked to intercontinental dissemination of hypervirulent clonotypes and poor clinical outcomes. SLO can trigger macrophage and neutrophil cell death and/or the inactivation of immune cell functions, and promotes tissue injury and bacterial survival in animal models of infection. In the present work, we describe how the pharmacological presentation of red blood cell (RBC derived biomimetic nanoparticles (“nanosponges” can sequester SLO and block the ability of GAS to damage host cells, thereby preserving innate immune function and increasing bacterial clearance in vitro and in vivo. Nanosponge administration protected human neutrophils, macrophages, and keratinocytes against SLO-mediated cytotoxicity. This therapeutic intervention prevented SLO-induced macrophage apoptosis and increased neutrophil extracellular trap formation, allowing increased GAS killing by the respective phagocytic cell types. In a murine model of GAS necrotizing skin infection, local administration of the biomimetic nanosponges was associated with decreased lesion size and reduced bacterial colony-forming unit recovery. Utilization of a toxin decoy and capture platform that inactivates the secreted SLO before it contacts the host cell membrane, presents a novel virulence factor targeted strategy that could be a powerful adjunctive therapy in severe GAS infections where morbidity and mortality are high despite antibiotic treatment.

  18. Antimicrobial and anti-virulence activity of capsaicin against erythromycin-resistant, cell-invasive Group A streptococci

    Directory of Open Access Journals (Sweden)

    Emanuela eMarini

    2015-11-01

    Full Text Available Capsaicin (8-methyl-N-vanillyl-6-nonenamide is the active component of Capsicum plants (chilli peppers, which are grown as food and for medicinal purposes since ancient times, and is responsible for the pungency of their fruit. Besides its multiple pharmacological and physiological properties (pain relief, cancer prevention, and beneficial cardiovascular, and gastrointestinal effects capsaicin has recently attracted considerable attention because of its antimicrobial and anti-virulence activity. This is the first study of its in vitro antibacterial and anti-virulence activity against Streptococcus pyogenes [Group A streptococci (GAS], a major human pathogen. The test strains were previously characterized, erythromycin-susceptible (n=5 and erythromycin-resistant (n=27, cell-invasive pharyngeal isolates. The MICs of capsaicin were 64-128 μg/mL (the most common MIC was 128 µg/mL. The action of capsaicin was bactericidal, as suggested by MBC values that were equal or close to the MICs, and by early detection of dead cells in the live/dead assay. No capsaicin-resistant mutants were obtained in single-step resistance selection studies. Interestingly, growth in presence of sublethal capsaicin concentrations induced an increase in biofilm production (p ≤ 0.05 and in the number of bacteria adhering to A549 monolayers, and a reduction in cell-invasiveness and haemolytic activity (both p ≤ 0.05. Cell invasiveness fell so dramatically that a highly invasive strain became non-invasive. The dose-response relationship, characterized by opposite effects of low and high capsaicin doses, suggests a hormetic response. The present study documents that capsaicin has promising bactericidal activity against erythromycin-resistant, cell-invasive pharyngeal GAS isolates. The fact that sublethal concentrations inhibited cell invasion and reduced haemolytic activity, two important virulence traits of GAS, is also interesting, considering that cell

  19. Ga-rich GaxIn1-xP solar cells on Si with 1.95 eV bandgap for ideal III-V/Si photovoltaics

    Science.gov (United States)

    Ratcliff, Christopher; Grassman, T. J.; Carlin, J. A.; Chmielewski, D. J.; Ringel, S. A.

    2014-03-01

    Theoretical models for III-V compound multijunction solar cells show that solar cells with bandgaps of 1.95-2.3 eV are needed to create ideal optical partitioning of the solar spectrum for device architectures containing three, four and more junctions. For III-V solar cells integrated with an active Si sub-cell, GaInP alloys in the Ga-rich regime are ideal since direct bandgaps of up to ~ 2.25 eV are achieved at lattice constants that can be integrated with appropriate GaAsP, SiGe and Si materials, with efficiencies of almost 50% being predicted using practical solar cell models under concentrated sunlight. Here we report on Ga-rich, lattice-mismatched Ga0.57In0.43P sub-cell prototypes with a bandgap of 1.95 eV grown on tensile step-graded metamorphic GaAsyP1-y buffers on GaAs substrates. The goal is to create a high bandgap top cell for integration with Si-based III-V/Si triple-junction devices. Excellent carrier collection efficiency was measured via internal quantum efficiency measurements and with their design being targeted for multijunction implementation (i.e. they are too thin for single junction cells), initial cell results are encouraging. The first generation of identical 1.95 eV cells on Si were fabricated as well, with efficiencies for these large bandgap, thin single junction cells ranging from 7% on Si to 11% on GaAs without antireflection coatings, systematically tracking the change in defect density as a function of growth substrate.

  20. Microinjection of Micrococcus luteus UV-endonuclease restores UV-induced unscheduled DNA synthesis in cells of 9 xeroderma pigmentosum complementation groups.

    NARCIS (Netherlands)

    A.J.R. de Jonge; W. Vermeulen (Wim); W. Keijzer; J.H.J. Hoeijmakers (Jan); D. Bootsma (Dirk)

    1985-01-01

    textabstractThe UV-induced unscheduled DNA synthesis (UDS) in cultured cells of excision-deficient xeroderma pigmentosum (XP) complementation groups A through I was assayed after injection of Micrococcus luteus UV-endonuclease using glass microneedles. In all complementation groups a restoration of

  1. Vitamin D and the human antimicrobial peptide LL-37 enhance group a streptococcus resistance to killing by human cells.

    Science.gov (United States)

    Love, John F; Tran-Winkler, Hien J; Wessels, Michael R

    2012-10-23

    The CsrRS two-component regulatory system of group A Streptococcus (GAS; Streptococcus pyogenes) responds to subinhibitory concentrations of the human antimicrobial peptide LL-37. LL-37 signaling through CsrRS results in upregulation of genes that direct synthesis of virulence factors, including the hyaluronic acid capsule and streptolysin O (SLO). Here, we demonstrate that a consequence of this response is augmented GAS resistance to killing by human oropharyngeal keratinocytes, neutrophils, and macrophages. LL-37-induced upregulation of SLO and hyaluronic acid capsule significantly reduced internalization of GAS by keratinocytes and phagocytic killing by neutrophils and macrophages. Because vitamin D induces LL-37 production by macrophages, we tested its effect on macrophage killing of GAS. In contrast to the reported enhancement of macrophage function in relation to other pathogens, treatment of macrophages with 1α,25-dihydroxy-vitamin D3 paradoxically reduced the ability of macrophages to control GAS infection. These observations demonstrate that LL-37 signals through CsrRS to induce a virulence phenotype in GAS characterized by heightened resistance to ingestion and killing by both epithelial cells and phagocytes. By inducing LL-37 production in macrophages, vitamin D may contribute to this paradoxical exacerbation of GAS infection. IMPORTANCE It remains poorly understood why group A Streptococcus (GAS) causes asymptomatic colonization or localized throat inflammation in most individuals but rarely progresses to invasive infection. The human antimicrobial peptide LL-37, which is produced as part of the innate immune response to GAS infection, signals through the GAS CsrRS two-component regulatory system to upregulate expression of multiple virulence factors. This study reports that two CsrRS-regulated GAS virulence factors-streptolysin O and the hyaluronic acid capsule-are critical in LL-37-induced resistance of GAS to killing by human throat epithelial cells

  2. Reduced dislocation density in GaxIn1-xP compositionally graded buffer layers through engineered glide plane switch

    Science.gov (United States)

    Schulte, K. L.; France, R. M.; McMahon, W. E.; Norman, A. G.; Guthrey, H. L.; Geisz, J. F.

    2017-04-01

    In this work we develop control over dislocation glide dynamics in GaxIn1-xP compositionally graded buffer layers (CGBs) through control of CuPt ordering on the group-III sublattice. The ordered structure is metastable in the bulk, so any glissile dislocation that disrupts the ordered pattern will release stored energy, and experience an increased glide force. Here we show how this connection between atomic ordering and dislocation glide force can be exploited to control the threading dislocation density (TDD) in GaxIn1-xP CGBs. When ordered GaxIn1-xP is graded from the GaAs lattice constant to InP, the order parameter η decreases as x decreases, and dislocation glide switches from one set of glide planes to the other. This glide plane switch (GPS) is accompanied by the nucleation of dislocations on the new glide plane, which typically leads to increased TDD. We develop control of the GPS position within a GaxIn1-xP CGB through manipulation of deposition temperature, surfactant concentration, and strain-grading rate. We demonstrate a two-stage GaxIn1-xP CGB from GaAs to InP with sufficiently low TDD for high performance devices, such as the 4-junction inverted metamorphic multi-junction solar cell, achieved through careful control the GPS position. Experimental results are analyzed within the context of a model that considers the force balance on dislocations on the two competing glide planes as a function of the degree of ordering.

  3. Reduced Dislocation Density in GaxIn1-xP Compositionally Graded Buffer Layers through Engineered Glide Plane Switch

    Energy Technology Data Exchange (ETDEWEB)

    Schulte, Kevin L.; France, Ryan M.; McMahon, William E.; Norman, Andrew G.; Guthrey, Harvey L.; Geisz, John F.

    2016-11-17

    In this work we develop control over dislocation glide dynamics in GaxIn1-xP compositionally graded buffer layers (CGBs) through control of CuPt ordering on the group-III sublattice. The ordered structure is metastable in the bulk, so any glissile dislocation that disrupts the ordered pattern will release stored energy, and experience an increased glide force. Here we show how this connection between atomic ordering and dislocation glide force can be exploited to control the threading dislocation density (TDD) in GaxIn1-xP CGBs. When ordered GaxIn1-xP is graded from the GaAs lattice constant to InP, the order parameter ..eta.. decreases as x decreases, and dislocation glide switches from one set of glide planes to the other. This glide plane switch (GPS) is accompanied by the nucleation of dislocations on the new glide plane, which typically leads to increased TDD. We develop control of the GPS position within a GaxIn1-xP CGB through manipulation of deposition temperature, surfactant concentration, and strain-grading rate. We demonstrate a two-stage GaxIn1-xP CGB from GaAs to InP with sufficiently low TDD for high performance devices, such as the 4-junction inverted metamorphic multi-junction solar cell, achieved through careful control the GPS position. Experimental results are analyzed within the context of a model that considers the force balance on dislocations on the two competing glide planes as a function of the degree of ordering.

  4. Mislocalization of XPF-ERCC1 nuclease contributes to reduced DNA repair in XP-F patients.

    Directory of Open Access Journals (Sweden)

    Anwaar Ahmad

    2010-03-01

    Full Text Available Xeroderma pigmentosum (XP is caused by defects in the nucleotide excision repair (NER pathway. NER removes helix-distorting DNA lesions, such as UV-induced photodimers, from the genome. Patients suffering from XP exhibit exquisite sun sensitivity, high incidence of skin cancer, and in some cases neurodegeneration. The severity of XP varies tremendously depending upon which NER gene is mutated and how severely the mutation affects DNA repair capacity. XPF-ERCC1 is a structure-specific endonuclease essential for incising the damaged strand of DNA in NER. Missense mutations in XPF can result not only in XP, but also XPF-ERCC1 (XFE progeroid syndrome, a disease of accelerated aging. In an attempt to determine how mutations in XPF can lead to such diverse symptoms, the effects of a progeria-causing mutation (XPF(R153P were compared to an XP-causing mutation (XPF(R799W in vitro and in vivo. Recombinant XPF harboring either mutation was purified in a complex with ERCC1 and tested for its ability to incise a stem-loop structure in vitro. Both mutant complexes nicked the substrate indicating that neither mutation obviates catalytic activity of the nuclease. Surprisingly, differential immunostaining and fractionation of cells from an XFE progeroid patient revealed that XPF-ERCC1 is abundant in the cytoplasm. This was confirmed by fluorescent detection of XPF(R153P-YFP expressed in Xpf mutant cells. In addition, microinjection of XPF(R153P-ERCC1 into the nucleus of XPF-deficient human cells restored nucleotide excision repair of UV-induced DNA damage. Intriguingly, in all XPF mutant cell lines examined, XPF-ERCC1 was detected in the cytoplasm of a fraction of cells. This demonstrates that at least part of the DNA repair defect and symptoms associated with mutations in XPF are due to mislocalization of XPF-ERCC1 into the cytoplasm of cells, likely due to protein misfolding. Analysis of these patient cells therefore reveals a novel mechanism to potentially

  5. An $xp$ model on $AdS_2$ spacetime

    CERN Document Server

    Molina-Vilaplana, Javier

    2013-01-01

    In this paper we formulate the $xp$ model on the AdS$_2$ spacetime. We find that the spectrum of the Hamiltonian has positive and negative eigenvalues, equal in magnitude, given by a harmonic oscillator with a zero point energy parameterized by the AdS radius, measured in units of a fundamental length of the model. We also construct the generators of the isometry group SO(2,1) of the AdS$_2$ spacetime, and discuss the relation with conformal quantum mechanics.

  6. XP13512治疗RLS效果良好

    Institute of Scientific and Technical Information of China (English)

    于淼(摘)

    2006-01-01

    Xenoport公司最近提出,该公司的加巴喷丁(gabapentin)前药XP13512(Ⅰ)尽管在600mg剂量时没有效果,但是增加至1200mg时则对腿不宁综合征(RLS,属于很少有治疗选择的运动神经元疾病)产生显著的疗效。(Ⅰ)的Ⅲ期临床试验预计在2006年上半年开始实施。

  7. Cytoplasmic localization of a functionally active Fanconi anemia group A green fluorescent protein chimera in human 293 cells

    NARCIS (Netherlands)

    Kruyt, FAE; Waisfisz, Q; Dijkmans, LM; Hermsen, M.A.; Youssoufian, H; Arwert, F; Joenje, H

    1997-01-01

    Hypersensitivity to cross-linking agents and predisposition to malignancy are characteristic of the genetically heterogeneous inherited bone marrow failure syndrome, Fanconi anemia (FA). The protein encoded by the recently cloned FA complementation group A gene, FAA, has been expected to localize in

  8. Provide a Mechanism for Enhancing Architecture in Agile Methods XP

    Directory of Open Access Journals (Sweden)

    Sajjad Behzady

    2013-11-01

    Full Text Available Agile software development is an approach to software that focuses on lightweight processes and adaptability to change. The best-known agile methodology is called Extreme Programming. It suggests twelve practices that include iterative development practices, automated unit testing, and pair programming. One challenge of XP agile method in software development is this method's underestimation over software quality attribution; these attributes are of main indices of software architecture. In this study, a method is represented for responding this challenge on the bases of probability theory. In this method, firstly, the rating matrix is structured on the bases of quality attributions an architecture solutions. Each element of this matrix shows a rating for every solution and the ratings will be initialized through analytic hierarchy process (AHP. Via quality weight implement on above matrix the rating vector is created whose each element represents the rate of each solution in reaching those quality attributes in rating matrix. Because rating vector follows normal probable distribution, its elements' rating probable density is mostly gathered around the mean. In this study, the probable density of architecture will be defined, the appropriateness of a solution in comparison to other solutions will be evaluatedor and the respond to XP challenge will be done easily in order to reach architecture solutions in the frame of rating vector.A complex of data are gathered and the results are compared in an experimental method in order to investigate the represented method of this paper.

  9. Dissociation of CAK from core TFIIH reveals a functional link between XP-G/CS and the TFIIH disassembly state.

    Directory of Open Access Journals (Sweden)

    Hany H Arab

    Full Text Available Transcription factor II H (TFIIH is comprised of core TFIIH and Cdk-activating kinase (CAK complexes. Here, we investigated the molecular and cellular manifestation of the TFIIH compositional changes by XPG truncation mutations. We showed that both core TFIIH and CAK are rapidly recruited to damage sites in repair-proficient cells. Chromatin immunoprecipitation against TFIIH and CAK components revealed a physical engagement of CAK in nucleotide excision repair (NER. While XPD recruitment to DNA damage was normal, CAK was not recruited in severe XP-G and XP-G/CS cells, indicating that the associations of CAK and XPD to core TFIIH are differentially affected. A CAK inhibition approach showed that CAK activity is not required for assembling pre-incision machinery in vivo or for removing genomic photolesions. Instead, CAK is involved in Ser5-phosphorylation and UV-induced degradation of RNA polymerase II. The CAK inhibition impaired transcription from undamaged and UV-damaged reporter, and partially decreased transcription of p53-dependent genes. The overall results demonstrated that a XP-G/CS mutations affect the disassembly state of TFIIH resulting in the dissociation of CAK, but not XPD from core TFIIH, and b CAK activity is not essential for global genomic repair but involved in general transcription and damage-induced RNA polymerase II degradation.

  10. High mobility group A1 protein expression reduces the sensitivity of colon and thyroid cancer cells to antineoplastic drugs.

    Science.gov (United States)

    D'Angelo, Daniela; Mussnich, Paula; Rosa, Roberta; Bianco, Roberto; Tortora, Giampaolo; Fusco, Alfredo

    2014-11-20

    Development of resistance to conventional drugs and novel biological agents often impair long-term chemotherapy. HMGA gene overexpression is often associated with antineoplastic drug resistance and reduced survival. Inhibition of HMGA expression in thyroid cancer cells reduces levels of ATM protein, the main cellular sensor of DNA damage, and enhances cellular sensitivity to DNA-damaging agents. HMGA1 overexpression promotes chemoresistance to gemcitabine in pancreatic adenocarcinoma cells through an Akt-dependent mechanism. To elucidate the role of HMGA1 proteins in chemoresistance we analyzed resistance to conventional drugs and targeted therapies of human colon carcinoma cells (GEO) that are sensitive to the epidermal growth factor receptor inhibitor cetuximab, and express minimal levels of HMGA1 and cetuximab-resistant (GEO CR) cells expressing high HMGA1 protein levels. GEO CR cells were less sensitive than GEO cells to cetuximab and 5-fluorouracil. GEO CR cells silenced for HMGA1 expression were more susceptible than empty vector-transfected cells to the drugs' cytotoxicity. Similar results were obtained with anaplastic thyroid carcinoma cells expressing or not HMGA1 proteins, treated with doxorubicin or the HDAC inhibitor LBH589. Finally, HMGA1 overexpression promoted the DNA-damage response and stimulated Akt phosphorylation and prosurvival signaling. Our findings suggest that the blockage of HMGA1 expression is a promising approach to enhance cancer cell chemosensitivity, since it could increase the sensitivity of cancer cells to antineoplastic drugs by inhibiting the survival signal and DNA damage repair pathways.

  11. The RNA-binding protein Xp54nrb isolated from a Ca²+-dependent screen is expressed in neural structures during Xenopus laevis development.

    Science.gov (United States)

    Neant, Isabelle; Deisig, Nina; Scerbo, Pierluigi; Leclerc, Catherine; Moreau, Marc

    2011-01-01

    In amphibian embryos, calcium (Ca(2+)) signalling is a necessary and sufficient event to induce neural fate. Transient elevations of [Ca(2+)]i are recorded in neural tissue precursor cells in whole embryos during gastrulation. Using a subtractive cDNA library between control ectoderm (animal caps) and ectoderm induced toward a neural fate by Ca(2+) release, we have isolated several Ca(2+)-induced target genes. Among the isolated genes, Xp54nrb encodes a protein which exhibits the RRM domains characteristic of RNA binding proteins, and is implicated in pre-mRNA splicing steps. Here we show that the Xp54nrb transcripts are expressed throughout early developmental stages, specifically in the neural and sensorial territories and that Xp54nrb could be involved in anterior neural patterning.

  12. Enabling to Apply XP Process in Distributed Development Environments with Tool Support

    Directory of Open Access Journals (Sweden)

    Ali Akbar Ansari

    2012-07-01

    Full Text Available The evaluation both in academic and industrial areas of the XP methodology has shown very good results if applied to small/medium co-localized working groups. In this paper, we described an approach that overcomes the XP constraint of collocation by introducing a process-support environment (called M.P.D.X.P that helps software development teams and solves the problems which arise when XP is carried out by distributed teams.

  13. The total number of Leydig and Sertoli cells in the testes of men across various age groups - a stereological study.

    Science.gov (United States)

    Petersen, Peter M; Seierøe, Karina; Pakkenberg, Bente

    2015-02-01

    The aim of this study was to estimate the total number of Sertoli and Leydig cells in testes from male subjects across the human lifespan, using an optimized stereological method for cell-counting. In comparison with many other organs, estimation of the total cell numbers in the testes is particularly sensitive to methodological problems. Therefore, using the optical fractionator technique and a sampling design specifically optimized for human testes, we estimated the total number of Sertoli and Leydig cells in the testes from 26 post mortem male subjects ranging in age from 16 to 80 years. The mean unilateral total number of Sertoli cells was 407 × 10(6) [range: 86 × 10(6) to 665 × 10(6) , coefficient of variation (CV) = 0.33], and the mean unilateral total number of Leydig cells was 99 × 10(6) (range: 47 × 10(6) to 245 × 10(6) , CV = 0.48). There was a significant decline in the number of Sertoli cells with age; no such decline was found for Leydig cells. Quantitative stereological analysis of post mortem tissue may help understand the influence of age or disease on the number of human testicular cells.

  14. Novel polyfucosylated N-linked glycopeptides with blood group A, H, X and Y determinants from human small intestinal epithelial cells

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Finne, J.; Breimer, M.E.; Hansson, G.C.; Karlsson, K.-A.; Leffler, H.; Halbeek, H. van

    1989-01-01

    A novel type of N-linked glycopeptides representing a major part of the glycans in human small intestinal epithelial cells from blood group A and O individuals were isolated by gel filtrations and affinity chromatography on concanavalin A-Sepharose and Bandeiraea simplicifolia lectin I-Sepharose. Su

  15. MATRIX EQUATION AXB = E WITH PX = sXP CONSTRAINT

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The matrix equation AXB = E with the constraint PX = sXP is considered, where P is a given Hermitian matrix satisfying P2 = I and s = ±1. By an eigenvalue decomposition of P, the constrained problem can be equivalently transformed to a well-known unconstrained problem of matrix equation whose coefficient matrices contain the corresponding eigenvector, and hence the constrained problem can be solved in terms of the eigenvectors of P. A simple and eigenvector-free formula of the general solutions to the constrained problem by generalized inverses of the coefficient matrices A and B is presented.Moreover, a similar problem of the matrix equation with generalized constraint is discussed.

  16. The total number of Leydig and Sertoli cells in the testes of men across various age groups - a stereological study

    DEFF Research Database (Denmark)

    Petersen, Peter M; Seierøe, Karina; Pakkenberg, Bente

    2015-01-01

    The aim of this study was to estimate the total number of Sertoli and Leydig cells in testes from male subjects across the human lifespan, using an optimized stereological method for cell-counting. In comparison with many other organs, estimation of the total cell numbers in the testes...... is particularly sensitive to methodological problems. Therefore, using the optical fractionator technique and a sampling design specifically optimized for human testes, we estimated the total number of Sertoli and Leydig cells in the testes from 26 post mortem male subjects ranging in age from 16 to 80 years....... The mean unilateral total number of Sertoli cells was 407 × 10(6) [range: 86 × 10(6) to 665 × 10(6) , coefficient of variation (CV) = 0.33], and the mean unilateral total number of Leydig cells was 99 × 10(6) (range: 47 × 10(6) to 245 × 10(6) , CV = 0.48). There was a significant decline in the number...

  17. Application of Office XP Smart Tag technology in ERP%Office XP Smart Tag技术在ERP中的应用

    Institute of Scientific and Technical Information of China (English)

    耿雪霏; 郑大宇

    2005-01-01

    介绍了Office XP Smart Tag 技术,并针对ERP软件中数据调用的问题,阐述了用于Office文档中Smart Tag技术在ERP中的开发方法,以Tonsoft公司的ERP软件为实例,讨论了Office XP Smart Tag技术在ERP中的应用,同时给出了应用结果.

  18. Fibroblast Growth Factor 2 Regulates High Mobility Group A2 Expression in Human Bone Marrow-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Kalomoiris, Stefanos; Cicchetto, Andrew C; Lakatos, Kinga; Nolta, Jan A; Fierro, Fernando A

    2016-09-01

    Mesenchymal stem cells (MSCs) are an excellent source for numerous cellular therapies due to their simple isolation, low immunogenicity, multipotent differentiation potential and regenerative secretion profile. However, over-expanded MSCs show decreased therapeutic efficacy. This shortcoming may be circumvented by identifying methods that promote self-renewal of MSCs in culture. HMGA2 is a DNA-binding protein that regulates self-renewal in multiple types of stem cells through chromatin remodeling, but its impact on human bone marrow-derived MSCs is not known. Using an isolation method to obtain pure MSCs within 9 days in culture, we show that expression of HMGA2 quickly decreases during early expansion of MSCs, while let-7 microRNAs (which repress HMGA2) are simultaneously increased. Remarkably, we demonstrate that FGF-2, a growth factor commonly used to promote self-renewal in MSCs, rapidly induces HMGA2 expression in a time- and concentration-dependent manner. The signaling pathway involves FGF-2 receptor 1 (FGFR1) and ERK1/2, but acts independent from let-7. By silencing HMGA2 using shRNAs, we demonstrate that HMGA2 is necessary for MSC proliferation. However, we also show that over-expression of HMGA2 does not increase cell proliferation, but rather abrogates the mitogenic effect of FGF-2, possibly through inhibition of FGFR1. In addition, using different methods to assess in vitro differentiation, we show that modulation of HMGA2 inhibits adipogenesis, but does not affect osteogenesis of MSCs. Altogether, our results show that HMGA2 expression is associated with highly proliferating MSCs, is tightly regulated by FGF-2, and is involved in both proliferation and adipogenesis of MSCs. J. Cell. Biochem. 117: 2128-2137, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Strain-Dependent Recognition of a Unique Degradation Motif by ClpXP in Streptococcus mutans

    Science.gov (United States)

    Jana, Biswanath; Tao, Liang

    2016-01-01

    ABSTRACT Streptococcus mutans, a dental pathogen, has a remarkable ability to cope with environmental stresses. Under stress conditions, cytoplasmic proteases play a major role in controlling the stability of regulatory proteins and preventing accumulation of damaged and misfolded proteins. ClpXP, a well-conserved cytoplasmic proteolytic system, is crucial in maintaining cellular homeostasis in bacteria. ClpX is primarily responsible for recognition of substrates and subsequent translocation of unfolded substrates into the ClpP proteolytic compartment for degradation. In Escherichia coli, ClpX recognizes distinct motifs present at the C-terminal end of target proteins. However, recognition sequences for ClpXP in other bacteria, including S. mutans, are not known. In this study, using two-dimensional (2D) polyacrylamide gel electrophoresis (PAGE) analysis, we have identified several putative substrates for S. mutans ClpXP. SsbA, which encodes a small DNA binding protein, is one such substrate that is degraded by ClpXP. By sequential deletions, we found that the last 3 C-terminal amino acids, LPF, are sufficient for ClpXP-mediated degradation. Addition of LPF at the C-terminal end of green fluorescent protein (GFP) rendered the protein completely degradable by ClpXP. Alterations of this tripeptide motif impeded ClpXP-mediated degradation. However, recognition of LPF by ClpXP is highly specific to some S. mutans strains (UA159, UA130, and N3209) since not all S. mutans strains recognize the motif. We speculate that an adaptor protein is involved in either substrate recognition or substrate degradation by ClpXP. Nevertheless, this is the first report of a unique recognition sequence for ClpXP in streptococci. IMPORTANCE Regulated proteolysis in bacteria is an important biological process that maintains protein homeostasis. ClpXP, an intracellular proteolytic complex, is the primary protease that is responsible for protein turnover. While the substrates for ClpXP

  20. Computer Security: Bye, Bye, Windows XP security... Welcome infections!

    CERN Multimedia

    Computer Security Team

    2014-01-01

    Rest in peace, Windows XP. Since your birth on 25 October 2001, you have struggled hard to survive this harsh Internet world. You fell prey to “Melissa”, “Sasser” and “Conficker”, and brought CERN its last large-scale infection with “Blaster” in 2004.    After being upgraded to “SP2”, you discovered software development lifecycles, regular “Patch Tuesdays” and a local firewall that rejected everything by default. In the end, you outlived your weird brother “Vista” and survived as the ugly duckling cousin to the beautiful Mr. Mac. But all your ups and downs are over now. On 8 April 2014, you were given your very last security updates. These life-sustaining measures will be stopped now. Game over. From now on, you are a zombie: presumed dead, but still kept running by your master/owner/user. They might not even understand that you now pose a risk ...

  1. End of support for Windows 2000, Office 2000 and Office XP at CERN

    CERN Document Server

    2006-01-01

    With the approval of the Desktop forum, support for Windows 2000, Office 2000 and Office XP at CERN will cease at the end of December this year. As a consequence, security patches will no longer be provided for Windows 2000 / Office 2000 / Office XP, and central services to reinstall Windows 2000 / Office 2000 / Office XP will not be available. After this date, only Windows XP and Office 2003 will be supported. Users still running Windows 2000 will be notified by e-mail and are recommended to install Windows XP / Office 2003 (as described at http://cern.ch/Win/Help/?kbid=100001). Users of Office XP will be automatically upgraded to Office 2003 as of January 2007. In the meantime, they can proactively upgrade to Office 2003 by removing 'MS Office XP' and selecting the 'MS Office 2003 SP2' package on CMF's 'Add/Remove CMF Packages' web page. Users who absolutely need to keep Windows 2000 or other obsolete software will need to maintain their systems themselves. For help during the migration, please contac...

  2. Molecular genetic analysis of 16 XP-C patients from Germany : environmental factors predominately contribute to phenotype variations

    NARCIS (Netherlands)

    Schaefer, Annika; Hofmann, Lars; Gratchev, Alexei; Laspe, Petra; Schubert, Steffen; Schuerer, Anke; Ohlenbusch, Andreas; Tzvetkov, Mladen; Hallermann, Christian; Reichrath, Joerg; Schoen, Michael P.; Emmert, Steffen

    Patients belonging to xeroderma pigmentosum (XP) complementation group C comprise one-third of all XP patients. Only four major reports compiled larger groups of XP-C patients from southern Europe (12 pts), North America (16 pts) and Africa (14 and 56 pts) as well as their genetic background (46 XPC

  3. Xp38gamma/SAPK3 promotes meiotic G(2)/M transition in Xenopus oocytes and activates Cdc25C

    DEFF Research Database (Denmark)

    Perdiguero, Eusebio; Pillaire, Marie-Jeanne; Bodart, Jean-Francois

    2003-01-01

    by anthrax lethal factor, a protease that inactivates MAPK kinases. We also show that Xp38gamma can activate the phosphatase XCdc25C, and we identified Ser205 of XCdc25C as a major phosphorylation site for Xp38gamma. Our results indicate that phosphorylation of XCdc25C by Xp38gamma/SAPK3 is important...

  4. Copy number gain at Xp22.31 includes complex duplication rearrangements and recurrent triplications.

    Science.gov (United States)

    Liu, Pengfei; Erez, Ayelet; Nagamani, Sandesh C Sreenath; Bi, Weimin; Carvalho, Claudia M B; Simmons, Alexandra D; Wiszniewska, Joanna; Fang, Ping; Eng, Patricia A; Cooper, M Lance; Sutton, V Reid; Roeder, Elizabeth R; Bodensteiner, John B; Delgado, Mauricio R; Prakash, Siddharth K; Belmont, John W; Stankiewicz, Pawel; Berg, Jonathan S; Shinawi, Marwan; Patel, Ankita; Cheung, Sau Wai; Lupski, James R

    2011-05-15

    Genomic instability is a feature of the human Xp22.31 region wherein deletions are associated with X-linked ichthyosis, mental retardation and attention deficit hyperactivity disorder. A putative homologous recombination hotspot motif is enriched in low copy repeats that mediate recurrent deletion at this locus. To date, few efforts have focused on copy number gain at Xp22.31. However, clinical testing revealed a high incidence of duplication of Xp22.31 in subjects ascertained and referred with neurobehavioral phenotypes. We systematically studied 61 unrelated subjects with rearrangements revealing gain in copy number, using multiple molecular assays. We detected not only the anticipated recurrent and simple nonrecurrent duplications, but also unexpectedly identified recurrent triplications and other complex rearrangements. Breakpoint analyses enabled us to surmise the mechanisms for many of these rearrangements. The clinical significance of the recurrent duplications and triplications were assessed using different approaches. We cannot find any evidence to support pathogenicity of the Xp22.31 duplication. However, our data suggest that the Xp22.31 duplication may serve as a risk factor for abnormal phenotypes. Our findings highlight the need for more robust Xp22.31 triplication detection in that such further gain may be more penetrant than the duplications. Our findings reveal the distribution of different mechanisms for genomic duplication rearrangements at a given locus, and provide insights into aspects of strand exchange events between paralogous sequences in the human genome.

  5. An altered redox balance and increased genetic instability characterize primary fibroblasts derived from xeroderma pigmentosum group A patients

    Energy Technology Data Exchange (ETDEWEB)

    Parlanti, Eleonora [Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Pietraforte, Donatella; Iorio, Egidio; Visentin, Sergio; De Nuccio, Chiara [Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Zijno, Andrea; D’Errico, Mariarosaria; Simonelli, Valeria [Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Sanchez, Massimo [Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Fattibene, Paola [Department of Technology and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Falchi, Mario [National AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy); Dogliotti, Eugenia, E-mail: dogliotti@iss.it [Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome (Italy)

    2015-12-15

    Highlights: • Increased levels and different types of intracellular radical species as well as an altered glutathione redox state characterize XP-A human cells when compared to normal. • A more glycolytic metabolism and higher ATP levels are associated with alteration of mitochondrial morphology and response to mitochondrial toxicants when XPA is defective. • XP-A human cells show increased spontaneous micronuclei frequency, a hallmark of cancer risk. - Abstract: Xeroderma pigmentosum (XP)-A patients are characterized by increased solar skin carcinogenesis and present also neurodegeneration. XPA deficiency is associated with defective nucleotide excision repair (NER) and increased basal levels of oxidatively induced DNA damage. In this study we search for the origin of increased levels of oxidatively generated DNA lesions in XP-A cell genome and then address the question of whether increased oxidative stress might drive genetic instability. We show that XP-A human primary fibroblasts present increased levels and different types of intracellular reactive oxygen species (ROS) as compared to normal fibroblasts, with O{sub 2−}· and H{sub 2}O{sub 2} being the major reactive species. Moreover, XP-A cells are characterized by decreased reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios as compared to normal fibroblasts. The significant increase of ROS levels and the alteration of the glutathione redox state following silencing of XPA confirmed the causal relationship between a functional XPA and the control of redox balance. Proton nuclear magnetic resonance ({sup 1}H NMR) analysis of the metabolic profile revealed a more glycolytic metabolism and higher ATP levels in XP-A than in normal primary fibroblasts. This perturbation of bioenergetics is associated with different morphology and response of mitochondria to targeted toxicants. In line with cancer susceptibility, XP-A primary fibroblasts showed increased spontaneous micronuclei (MN) frequency, a

  6. ENVIRONMENTAL TECHNOLOGY VERIFICATION REPORT: EVALUATION OF THE XP-SWMM STORMWATER WASTEWATER MANAGEMENT MODEL, VERSION 8.2, 2000, FROM XP SOFTWARE, INC.

    Science.gov (United States)

    XP-SWMM is a commercial software package used throughout the United States and around the world for simulation of storm, sanitary and combined sewer systems. It was designed based on the EPA Storm Water Management Model (EPA SWMM), but has enhancements and additional algorithms f...

  7. A Turner syndrome neurocognitive phenotype maps to Xp22.3

    Directory of Open Access Journals (Sweden)

    Elder Frederick F

    2007-05-01

    Full Text Available Abstract Background Turner syndrome (TS is associated with a neurocognitive phenotype that includes selective nonverbal deficits, e.g., impaired visual-spatial abilities. We previously reported evidence that this phenotype results from haploinsufficiency of one or more genes on distal Xp. This inference was based on genotype/phenotype comparisons of individual girls and women with partial Xp deletions, with the neurocognitive phenotype considered a dichotomous trait. We sought to confirm our findings in a large cohort (n = 47 of adult women with partial deletions of Xp or Xq, enriched for subjects with distal Xp deletions. Methods Subjects were recruited from North American genetics and endocrinology clinics. Phenotype assessment included measures of stature, ovarian function, and detailed neurocognitive testing. The neurocognitive phenotype was measured as a quantitative trait, the Turner Syndrome Cognitive Summary (TSCS score, derived from discriminant function analysis. Genetic analysis included karyotyping, X inactivation studies, fluorescent in situ hybridization, microsatellite marker genotyping, and array comparative genomic hybridization. Results We report statistical evidence that deletion of Xp22.3, an interval containing 31 annotated genes, is sufficient to cause the neurocognitive phenotype described by the TSCS score. Two other cardinal TS features, ovarian failure and short stature, as well as X chromosome inactivation pattern and subject's age, were unrelated to the TSCS score. Conclusion Detailed mapping suggests that haploinsufficiency of one or more genes in Xp22.3, the distal 8.3 megabases (Mb of the X chromosome, is responsible for a TS neurocognitive phenotype. This interval includes the 2.6 Mb Xp-Yp pseudoautosomal region (PAR1. Haploinsufficiency of the short stature gene SHOX in PAR1 probably does not cause this TS neurocognitive phenotype. Two genes proximal to PAR1 within the 8.3 Mb critical region, STS and NLGN4X, are

  8. Anti-Adhesive Activities of Flavan-3-ols and Proanthocyanidins in the Interaction of Group A-Streptococci and Human Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Aneta Janecki

    2010-10-01

    Full Text Available Bacterial adhesion to epithelial cells is a key step in infections, allowing subsequent colonization, invasion and internalization of pathogens into tissues. Anti-adhesive agents are therefore potential prophylactic tools against bacterial infections. The range of anti-adhesive compounds is largely confined to carbohydrate analogues. Tannins are generously recognized as potent antimicrobials, but little data exist on their anti-adherence potency. Using a model for mucosal pathogenesis with labeled group A-streptococci (GAS and human laryngeal HEp-2 cells, a series of flavan-3-ols (epicatechin, epigallocatechin, epigallocatechin-3-O-gallate and highly purified and chemically characterized proanthocyanidin samples including procyanidins based on epicatechin, catechin or ‘mixed’ constituent flavanyl units, prodelphinidins made up of (epigallocatechin monomeric unts as well as oligomers possessing A-type units in their molecules was evaluated for anti-adhesive effects. Reduced microbial adherence was observed exclusively for prodelphinidins, suggesting that pyrogallol-type elements, i.e., (epigallocatechin units are important structural features. This is the first report on structure-activity relationships regarding the anti-adhesive potency of proanthocyanidins. In addition, the structures of the first chemically defined proanthocyanidins from Pelargonium sidoides are disclosed.

  9. Functional analysis of the group A streptococcal luxS/AI-2 system in metabolism, adaptation to stress and interaction with host cells

    Directory of Open Access Journals (Sweden)

    Zinkl Daniela

    2008-10-01

    Full Text Available Abstract Background The luxS/AI-2 signaling pathway has been reported to interfere with important physiological and pathogenic functions in a variety of bacteria. In the present study, we investigated the functional role of the streptococcal luxS/AI-2 system in metabolism and diverse aspects of pathogenicity including the adaptation of the organism to stress conditions using two serotypes of Streptococcus pyogenes, M1 and M19. Results Exposing wild-type and isogenic luxS-deficient strains to sulfur-limited media suggested a limited role for luxS in streptococcal activated methyl cycle metabolism. Interestingly, loss of luxS led to an increased acid tolerance in both serotypes. Accordingly, luxS expression and AI-2 production were reduced at lower pH, thus linking the luxS/AI-2 system to stress adaptation in S. pyogenes. luxS expression and AI-2 production also decreased when cells were grown in RPMI medium supplemented with 10% serum, considered to be a host environment-mimicking medium. Furthermore, interaction analysis with epithelial cells and macrophages showed a clear advantage of the luxS-deficient mutants to be internalized and survive intracellularly in the host cells compared to the wild-type parents. In addition, our data revealed that luxS influences the expression of two virulence-associated factors, the fasX regulatory RNA and the virulence gene sibA (psp. Conclusion Here, we suggest that the group A streptococcal luxS/AI-2 system is not only involved in the regulation of virulence factor expression but in addition low level of luxS expression seems to provide an advantage for bacterial survival in conditions that can be encountered during infections.

  10. Index of CD34+ Cells and Mononuclear Cells in the Bone Marrow of Spinal Cord Injury Patients of Different Age Groups: A Comparative Analysis

    Directory of Open Access Journals (Sweden)

    Vidyasagar Devaprasad Dedeepiya

    2012-01-01

    Full Text Available Introduction. Recent evidence of safety and efficacy of Bone Marrow Mononuclear Cells (BMMNC in spinal cord injury makes the Bone Marrow (BM CD34+ percentage and the BMMNC count gain significance. The indices of BM that change with body mass index and aging in general population have been reported but seldom in Spinal Cord Injury (SCI victims, whose parameters of relevance differ from general population. Herein, we report the indices of BMMNC in SCI victims. Materials and Methods. BMMNCs of 332 SCI patients were isolated under GMP protocols. Cell count by Trypan blue method and CD34+ cells by flow cytometry were documented and analysed across ages and gender. Results. The average BMMNC per ml in the age groups 0–20, 21–40, 41–60, and 61–80 years were 4.71, 4.03, 3.67, and 3.02 million and the CD34+ were 1.05%, 1.04%, 0.94%, and 0.93% respectively. The decline in CD34+ was sharp between 20–40 and 40–60 age groups. Females of reproductive age group had lesser CD34+. Conclusion. The BMMNC and CD34+ percentages decline with aging in SCI victims. Their lower values in females during reproductive age should be analysed for relevance to hormonal influence. This study offers reference values of BMMNC and CD34+ of SCI victims for successful clinical application.

  11. The Hamiltonian H = xp and Classification of osp(1|2) Representations

    Science.gov (United States)

    Regniers, G.; Van der Jeugt, J.

    2010-06-01

    The quantization of the simple one-dimensional Hamiltonian H = xp is of interest for its mathematical properties rather than for its physical relevance. In fact, the Berry-Keating conjecture speculates that a proper quantization of H = xp could yield a relation with the Riemann hypothesis. Motivated by this, we study the so-called Wigner quantization of H = xp, which relates the problem to representations of the Lie superalgebra osp(1|2). In order to know how the relevant operators act in representation spaces of osp(1|2), we study all unitary, irreducible *-representations of this Lie superalgebra. Such a classification has already been made by J.W.B. Hughes, but we reexamine this classification using elementary arguments.

  12. X-linked ocular albinism and sensorineural deafness: Linkage to Xp22. 3

    Energy Technology Data Exchange (ETDEWEB)

    Winship, I.M.; Babaya, M.; Ramesar, R.S. (Univ. of Cape Town Medical School (South Africa))

    1993-11-01

    X-linked ocular albinism with late-onset sensorineural deafness (OASD) is an autonomous disorder that poses significant clinical problems, causing affected individuals to be blind and deaf by early middle age. Classical X-linked ocular albinism (without deafness; OA1) has recently been linked to markers in the Xp22.2-Xp22.3 region of the human genome. In the present report, a large South African family with OASD was investigated at the molecular level and tight linkage was found to the DXS452 locus at Xp22.3 using 25 informative meioses, with a maximum lod score of 7.1 at a recombination fraction of 0.00. These findings suggest that OA1 and OASD are allelic variants or that they may be due to contiguous gene defects. 12 refs., 1 fig.

  13. Mapping The Best Practices of XP and Project Management: Well defined approach for Project Manager

    CERN Document Server

    Javed, Muhammad; Hussain, Shahid; Ahmad, Shakeel

    2010-01-01

    Software engineering is one of the most recent additions in various disciplines of system engineering. It has emerged as a key obedience of system engineering in a quick succession of time. Various Software Engineering approaches are followed in order to produce comprehensive software solutions of affordable cost with reasonable delivery timeframe with less uncertainty. All these objectives are only satisfied when project's status is properly monitored and controlled; eXtreme Programming (XP) uses the best practices of AGILE methodology and helps in development of small size software very sharply. In this paper, authors proposed that via XP, high quality software with less uncertainty and under estimated cost can be developed due to proper monitoring and controlling of project. Moreover, authors give guidelines that how activities of project management can be embedded into development life cycle of XP to enhance the quality of software products and reduce the uncertainty.

  14. GeoXp : An R Package for Exploratory Spatial Data Analysis

    Directory of Open Access Journals (Sweden)

    Thibault Laurent

    2012-04-01

    Full Text Available We present GeoXp, an R package implementing interactive graphics for exploratory spatial data analysis. We use a data set concerning public schools of the French MidiPyrenees region to illustrate the use of these exploratory techniques based on the coupling between a statistical graph and a map. Besides elementary plots like boxplots,histograms or simple scatterplots, GeoXp also couples maps with Moran scatterplots, variogram clouds, Lorenz curves and other graphical tools. In order to make the most of the multidimensionality of the data, GeoXp includes dimension reduction techniques such as principal components analysis and cluster analysis whose results are also linked to the map.

  15. Windows XP Media Center Edition(XP MCE)2005把录下来的电视文件存放在什么地方?

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    在缺省情况下,XP MCE 2005把所有录下来的节目都放在系统盘的。Documents and Settings\All Users\Documents\Recorded TV”文件夹下。录制的节目储存为DVR—MS格式,它是一种基于digital video recording(DVR)技术的Microsoft格式。

  16. Evaluation of the automated ADVIA centaur® XP syphilis assay for serological testing.

    Science.gov (United States)

    Saw, Sharon; Zhao, Huiqin; Tan, Phyllis; Saw, Betty; Sethi, Sunil

    2017-05-01

    We evaluated the performance of the ADVIA Centaur XP Syphilis assay (Siemens Healthcare Diagnostics, Tarrytown, NY, USA) using samples previously tested on the ARCHITECT i4000SR system (Abbott Diagnostics, Lake Forest, IL, USA) and confirmed by the Treponema pallidum particle agglutination assay (TPPA) (SERODIA-TPPA, Fujirebio Diagnostics Inc., Malvern, PA, USA). Clinical patient information was included to aid resolution of discordant samples where available. Precision, interference, and cross-reactivity were also assessed. Relative to patient clinical status, the sensitivity of both the ADVIA Centaur XP and the ARCHITECT assays was 100% (95% CI, 93.9-100), and the specificity of the ADVIA Centaur XP assay was 95.5% (95% CI, 90.4-98.3), which was slightly higher than that of the ARCHITECT assay at 93.9% (95% CI, 88.4-97.3). Overall agreement relative to patient clinical status was 96.9% (95% CI, 93.3-98.8) for the ADVIA Centaur XP assay and 95.8% (95% CI, 91.9-98.2) for the ARCHITECT assay. Overall agreement between the two automated assays was 96.9% (95% CI, 93.3-98.8). ADVIA Centaur XP assay precision was <5% at all index values tested. No significant interference was observed for lipemia or hemolysis; a small effect was seen with some samples for bilirubin. The assay exhibited no significant cross-reactivity with a number of potential interfering factors. The ADVIA Centaur XP Syphilis assay can be considered a sensitive and accurate assay for identification of treponemal antibodies in screening populations as well as patients presenting with suspicion of syphilitic infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Simulación de proyectos de Software desarrollados con XP: Subsistema de desarrollo de tareas

    OpenAIRE

    Kasiak, Tamara; Godoy, Diego Alberto

    2012-01-01

    Administrar Proyectos de Software siguiendo Programación Extrema (XP) implica implementar, de forma conjunta y al extremo, prácticas ya conocidas en el ámbito del Desarrollo de Software, lo que torna a esta actividad aún más compleja. Como una manera de tratar esta complejidad, es que se ha construido un Modelo Dinámico de Simulación (siguiendo los lineamientos de la Dinámica de Sistemas), que agrupa las variables involucradas en un proyecto llevado a cabo con XP, que permite analizar el e...

  18. Programación extrema y calidad : Estudio de compatibilidad XP – CMM

    OpenAIRE

    Bertone, Rodolfo Alfredo; Pasini, Ariel C.; Ramón, Hugo Dionisio

    2005-01-01

    La Programación Extrema (XP) es una práctica de Ingeniería de Software que permite el desarrollo de aplicaciones desde una perspectiva diferente a lo que plantean la mayoría de las metodologías clásicas respecto de la construcción del software. Por su concepción XP puede ser visto como una forma un tanto caótica de trabajo donde se pone énfasis en resolver el problema del presente sin planificar hacia el futuro mediato. Desde esta perspectiva un enfoque de calidad podría verse como una exp...

  19. A YAC contig spanning the nevoid basal cell carcinoma syndrome, Fanconi anaemia group C, and xeroderma pigmentosum group A loci on chromosome 9q

    Energy Technology Data Exchange (ETDEWEB)

    Morris, D.J.; Reis, A. [Freie Universtiaet, Berlin (Germany)

    1994-09-01

    Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is an autosomal dominant disorder, characterized primarily by multiple basal cell carcinomas, epithelium-lined jaw cysts, and palmar and plantar pits, as well as various other features. Loss of heterozygosity studies and linkage analysis have mapped the NBCCS gene to chromosome 9q and suggested that it is a tumor suppressor. The apparent sensitivity of NBCCS patients to UV and X-irradiation raises the possibility of hypersensitivity to DNA-damaging reagents or defective DNA repair being etiological in the disorder. The recent mapping of the Fanconi anaemia group C (FACC) and xeroderma pigmentosum complementing group A (XPAC) genes to the same region on 9q has led us to begin the molecular dissection of the 9q22-q31 region. PCR analysis of the presence or absence of 10 microsatellite markers and exons 3 and 4 of the XPAC and FACC genes, respectively, allowed us to order 12 YACs into an overlapping contig and to order the markers as follows: D9S151/D9S12P1-D9S12P2-D9S197-D9S196-D9S280-FACC-D9S287/XPAC-D9S180-D9S6-D9S176. Sizing of the YACs has provided an initial estimate of the size of the NBCCS candidate region between D9S12 and D9S180 to be less than 1.65 Mb. 45 refs., 1 fig., 1 tab.

  20. The XP spaceplane: A near term multi-purpose suborbital RLV

    Science.gov (United States)

    Lauer, Charles J.

    2007-06-01

    This paper will describe the history, technology and design features of the XP spaceplane being developed by Rocketplane Ltd. in Oklahoma. The XP is a four seat fighter-sized spaceplane that uses turbojets for takeoff and landing and a liquid oxygen/kerosene rocket engine for main propulsion during its ascent to a 100 km apogee suborbital space flight. The XP is intended to serve a variety of markets including suborbital tourist flights, intermediate duration microgravity research, remote sensing, astronomy, and microsatellite launch missions. Changes in vehicle configuration and flight profile for serving each of these markets will be described. The prototype XP will have its rollout ceremony at the end of 2007 and will begin test flights in early 2008. Commercial space flight operations are expected to begin in fall 2008 with tourist flights and microgravity research flights being the early customer base. The spaceplane's flight systems, safety systems, and operating procedures will be reviewed. In addition, key elements of the Rocketplane business and financial model will be discussed.

  1. Recurrent deletion of ZNF630 at Xp11.23 is not associated with mental retardation

    DEFF Research Database (Denmark)

    Lugtenberg, Dorien; Zangrande-Vieira, Luiz; Kirchhoff, Maria

    2010-01-01

    ZNF630 is a member of the primate-specific Xp11 zinc finger gene cluster that consists of six closely related genes, of which ZNF41, ZNF81, and ZNF674 have been shown to be involved in mental retardation. This suggests that mutations of ZNF630 might influence cognitive function. Here, we detected...

  2. Location interval at Xp22.3 for X-linked chondrodysplasia punctata

    Energy Technology Data Exchange (ETDEWEB)

    Sheffield, L.; Hutchison, W.; Holloway, A. [Murdoch Institute for Research into Birth Defects, Paris (France)] [and others

    1994-09-01

    The literature shows that there is a gene for chondropdysplasia punctata (CDP) located at Xp22.3 from the study of chromosomal rearrangements involving Xp. It is also suspected that there are genes for short stature and mental retardation nearby. Petit has described a family of brachytelephalangic CDP that was due to a submicroscopic interstitial deletion of Xp22.3. Symmetrical (mild) CDP seems to be identical to brachytelephalangic CDP clinically, has variable features of short stature and mental retardation, and has a preponderance of affected males. We describe results using DNA probes from Xp22.3 in 10 patients with radiologically proven symmetrical CDP. Other known genes in this region have a high proportion of deletions as we screened our patients for deletions in DXYS20, MIC2, PABX, DXYS159X, DXS283, DXS285, J502(PCR), DXS31, DXS43 (listed distally to proximally). No deletions were found. We have also studied a fetus with proven CDP who has a X,Y translocation (46,V,t(X;Y)(p22.3;q12)mat). This patient was deleted for all distal probes up to J502(PCR). It is not yet known where the breakpoint lies but it may be just proximal to the CDP gene. The results of the 10 symmetrical CDPs and the X;Y translocation fetus are presented with further definition of the X chromosomal breakpoint in the translocation.

  3. SR450 and Superhawk XP applications of Bacillus thuringiensis israelensis de Barjac against Culex quinquefasciatus Say

    Science.gov (United States)

    Sprayer comparisons and larval morality assays were conducted following SR450 backpack mist blower and Superhawk XP thermal fogger applications of Vectobac® WDG Bacillus thuringiensis israelensis (Bti) de Barjac against Culex quinquefasciatus Say. Bacillus thuringiensis israelensis was applied at m...

  4. Effect of p–d hybridization, structural distortion and cation electronegativity on electronic properties of ZnSnX{sub 2} (X=P, As, Sb) chalcopyrite semiconductors

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, S. [National Institute of Technology, Rourkela 769008, Odisha (India); Ganguli, B., E-mail: biplabg@nitrkl.ac.in [National Institute of Technology, Rourkela 769008, Odisha (India)

    2013-04-15

    Significant effects of p–d hybridization, structural distortion and cation-electro-negativity are found on band gap in ZnSnX{sub 2} (X=P, As, Sb). Our study suggests these compounds to be direct band gap semiconductors with band gaps of 1.23, 0.68 and 0.19 eV respectively. Lattice constants, tetragonal distortion (η), anion displacement, bond lengths and bulk moduli are calculated by Density Functional Theory based on Tight binding Linear Muffin-Tin orbital method. Our result of structural properties is in good agreement with the available experimental and other theoretical results. Calculated band gaps also agree well with the experimental works within LDA limitation. Unlike other semiconductors in the group II–IV–V{sub 2}, there is a reduction in the band gap of 0.22, 0.20 and 0.24 eV respectively in ZnSnX{sub 2} (X=P, As, Sb) due to p–d hybridization. Structural distortion decreases band gap by 0.20, 0.12 and 0.10 eV respectively. We find that cation electronegativity effect is responsible for increasing the band gap relative to their binary analogs GaInP{sub 2}, InGaAs{sub 2} and GaInSb{sub 2} respectively and increment are 0.13, 0.04 and 0.13 eV respectively. - Graphical abstract: One unit cell of ZnSnX{sub 2} (X=P, As, Sb) chalcopyrite semiconductor. Semiconductors ZnSnX{sub 2} (X=P, As, Sb) are found to be direct band gap semiconductors with band gaps 1.23, 0.68 and 0.19 eV respectively. The quantitative estimate of effects of p–d hybridization, structural distortion and cation electronegativity shows band gaps change significantly due to these effects. Highlights: ► ZnSnX{sub 2} (X=P, As, Sb) are direct band gap semiconductors. ► These have band gaps of 1.23 eV, 0.68 eV and 0.19 eV respectively. ► The band gap reduction due to p–d hybridization is 13.41%, 18.51% and 40% respectively. ► Band gap reduction due to structural distortion is 12.12%, 11.11% and 16.66% respectively. ► Band gap increases 8.38%, 3.70% and 21.31% respectively

  5. Xp54 and related (DDX6-like) RNA helicases: roles in messenger RNP assembly, translation regulation and RNA degradation

    Science.gov (United States)

    Weston, Andrew; Sommerville, John

    2006-01-01

    The DEAD-box RNA helicase Xp54 is an integral component of the messenger ribonucleoprotein (mRNP) particles of Xenopus oocytes. In oocytes, several abundant proteins bind pre-mRNA transcripts to modulate nuclear export, RNA stability and translational fate. Of these, Xp54, the mRNA-masking protein FRGY2 and its activating protein kinase CK2α, bind to nascent transcripts on chromosome loops, whereas an Xp54-associated factor, RapA/B, binds to the mRNP complex in the cytoplasm. Over-expression, mutation and knockdown experiments indicate that Xp54 functions to change the conformation of mRNP complexes, displacing one subset of proteins to accommodate another. The sequence of Xp54 is highly conserved in a wide spectrum of organisms. Like Xp54, Drosophila Me31B and Caenorhabditis CGH-1 are required for proper meiotic development, apparently by regulating the translational activation of stored mRNPs and also for sorting certain mRNPs into germplasm-containing structures. Studies on yeast Dhh1 and mammalian rck/p54 have revealed a key role for these helicases in mRNA degradation and in earlier remodelling of mRNP for entry into translation, storage or decay pathways. The versatility of Xp54 and related helicases in modulating the metabolism of mRNAs at all stages of their lifetimes marks them out as key regulators of post-transcriptional gene expression. PMID:16769775

  6. Molecular analysis of genes on Xp controlling Turner syndrome and premature ovarian failure (POF).

    Science.gov (United States)

    Zinn, A R; Ross, J L

    2001-06-01

    Monosomy X has been known to be the chromosomal basis of Turner syndrome (TS) for more than four decades. A large body of cytogenetic data indicates that most TS features are due to reduced dosage of genes on the short arm of the X chromosome (Xp). Phenotype mapping studies using molecular cytogenetic and genetic techniques are beginning to localize the Xp genes that are important for various TS features, and a comprehensive catalog of candidate genes is becoming available through the Human Genome Project and related research. It is now possible to assess the contributions of individual genes to the TS phenotype by mutational analysis of karyotypically normal persons with specific TS features. This strategy has succeeded in identifying a gene involved in short stature and is being applied to premature ovarian failure and other TS phenotypes.

  7. New Photonis XP20D0 photomultiplier for fast timing in nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Moszynski, M. [Soltan Institute for Nuclear Studies, PL 05-400 Swierk-Otwock (Poland)]. E-mail: marek@ipj.gov.pl; Gierlik, M. [Soltan Institute for Nuclear Studies, PL 05-400 Swierk-Otwock (Poland); Kapusta, M. [Soltan Institute for Nuclear Studies, PL 05-400 Swierk-Otwock (Poland); Nassalski, A. [Soltan Institute for Nuclear Studies, PL 05-400 Swierk-Otwock (Poland); Szczesniak, T. [Soltan Institute for Nuclear Studies, PL 05-400 Swierk-Otwock (Poland); Fontaine, Ch. [Photonis. Av. Roger Roncier, B.P. 520, F 19106 Brive La Gaillarde Cedex (France); Lavoute, P. [Photonis. Av. Roger Roncier, B.P. 520, F 19106 Brive La Gaillarde Cedex (France)

    2006-11-01

    Growing interest in the time-of-flight positron emission tomography (TOF PET) prompts the study of a new Photonis XP20D0 photomultiplier, equipped with a screening grid at the anode, in application to a fast timing with LSO and LaBr{sub 3} crystals. The high time resolution of 200{+-}4 and 210{+-}4 ps was obtained for 511 keV annihilation quanta using LaBr{sub 3} and LSO crystals in the coincidence experiment with a small BaF{sub 2} crystal, respectively. It reflects an importance of the grid and high quantum efficiency of the XP20D0. A high-time resolution observed in the present experiments makes good prospects for a development of TOF PET.

  8. 不支持虚拟技术的本本也玩XP Mode!

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    虽然Windows7通过XP Mode模式实现了最大化兼容性,但问题在于,不少处理器并不支持VT虚化功能(RMD处理器全都支持)。更可恶的是,很多本本不知出于什么原因,即便处理器本身支持,也通过BIOS屏蔽掉了。

  9. N-Terminal peptidic boronic acids selectively inhibit human ClpXP.

    Science.gov (United States)

    Knott, Kenneth; Fishovitz, Jennifer; Thorpe, Steven B; Lee, Irene; Santos, Webster L

    2010-08-07

    The synthesis and development of N-terminal peptidic boronic acids as protease inhibitors is reported. N-Terminal peptidic boronic acids interrogate the S' sites of the target protein for selectivity and provide a new strategy that complements the currently known peptidic alpha-amino boronic acids (C-terminal boronic acids). After screening a series of N-terminal peptidic boronic acids, the first selective inhibitor of human ClpXP, an ATP-dependent serine protease present in the mitochondrial matrix, was discovered. This should facilitate the understanding of the physiological function of this protease.

  10. 研华UNO系列升级主Windows XP SP2

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    研华科技日前宣布,其嵌入式无风扇工业级嵌入式控制器优诺UNO系列的操作系统已全面升级至Windows XP Embedded SP2。这一系列产品的设计以EWF及HORM等多项工业级专属功能为主:它同时也内建.NET Framework 1.1、并支持9种主要语系。

  11. Detection of explosive atmospheres using the software AtmosXp V 2.0

    Directory of Open Access Journals (Sweden)

    Carlos Mauricio Álvarez Álvarez

    2014-01-01

    Full Text Available Las condiciones de atmósferas explosivas y acumulación de gases dentro de las minas subterráneas de carbón requieren un anális is detallado y el desarrollo de modelos y mecanismos que permitan su detección. Para tal fin se ha desarrollado el software Atmos Xp V2.0 que incluye el diagrama de Coward para el análisis de estas mez clas explosivas.

  12. Different patterns of evolution in the centromeric and telomeric regions of group A and B haplotypes of the human killer cell Ig-like receptor locus.

    Directory of Open Access Journals (Sweden)

    Chul-Woo Pyo

    Full Text Available The fast evolving human KIR gene family encodes variable lymphocyte receptors specific for polymorphic HLA class I determinants. Nucleotide sequences for 24 representative human KIR haplotypes were determined. With three previously defined haplotypes, this gave a set of 12 group A and 15 group B haplotypes for assessment of KIR variation. The seven gene-content haplotypes are all combinations of four centromeric and two telomeric motifs. 2DL5, 2DS5 and 2DS3 can be present in centromeric and telomeric locations. With one exception, haplotypes having identical gene content differed in their combinations of KIR alleles. Sequence diversity varied between haplotype groups and between centromeric and telomeric halves of the KIR locus. The most variable A haplotype genes are in the telomeric half, whereas the most variable genes characterizing B haplotypes are in the centromeric half. Of the highly polymorphic genes, only the 3DL3 framework gene exhibits a similar diversity when carried by A and B haplotypes. Phylogenetic analysis and divergence time estimates, point to the centromeric gene-content motifs that distinguish A and B haplotypes having emerged ~6 million years ago, contemporaneously with the separation of human and chimpanzee ancestors. In contrast, the telomeric motifs that distinguish A and B haplotypes emerged more recently, ~1.7 million years ago, before the emergence of Homo sapiens. Thus the centromeric and telomeric motifs that typify A and B haplotypes have likely been present throughout human evolution. The results suggest the common ancestor of A and B haplotypes combined a B-like centromeric region with an A-like telomeric region.

  13. Genomic amplification of Fanconi anemia complementation group A (FancA) in head and neck squamous cell carcinoma (HNSCC): Cellular mechanisms of radioresistance and clinical relevance.

    Science.gov (United States)

    Hess, Julia; Unger, Kristian; Orth, Michael; Schötz, Ulrike; Schüttrumpf, Lars; Zangen, Verena; Gimenez-Aznar, Igor; Michna, Agata; Schneider, Ludmila; Stamp, Ramona; Selmansberger, Martin; Braselmann, Herbert; Hieber, Ludwig; Drexler, Guido A; Kuger, Sebastian; Klein, Diana; Jendrossek, Verena; Friedl, Anna A; Belka, Claus; Zitzelsberger, Horst; Lauber, Kirsten

    2017-02-01

    Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance. Silencing of FancA expression in HNSCC cell lines with genomic gains on 16q23-24 resulted in significantly impaired clonogenic survival upon irradiation. Conversely, overexpression of FancA in immortalized keratinocytes conferred increased survival accompanied by improved DNA repair, reduced accumulation of chromosomal translocations, but no hyperactivation of the FA/BRCA-pathway. Downregulation of interferon signaling as identified by microarray analyses, enforced irradiation-induced senescence, and elevated production of the senescence-associated secretory phenotype (SASP) appeared to be candidate mechanisms contributing to FancA-mediated radioresistance. Data of the TCGA HNSCC cohort confirmed the association of gains on 16q24.3 with FancA overexpression and impaired overall survival. Importantly, transcriptomic alterations similar to those observed upon FancA overexpression in vitro strengthened the clinical relevance. Overall, FancA amplification and overexpression appear to be crucial for radiotherapeutic failure in HNSCC.

  14. Windows XP ends its life at CERN – register for Windows 7 training!

    CERN Multimedia

    Michał Kwiatek (IT-OIS)

    2012-01-01

    Windows XP has been around for over 10 years and it is now time to move on. At CERN, general support for Windows XP will end in December 2012, and before this date users are requested to schedule a migration to the next version of Windows – Windows 7.   Windows 7 is already well established at CERN – it is used by a large majority of users. In fact, there was a considerable user demand even before its official release in October 2009 and its adoption has been smooth. Users praise Windows 7 for its improved stability and a clear advantage on laptops is a much more efficient implementation of offline files. The migration to Windows 7 involves a reinstallation of the operating system. Files stored in user home folders on DFS will be immediately available after the reinstallation. Applications will be upgraded to more recent versions and in certain cases, an application may even be replaced by another application providing the same functionality. Microsoft Office suite is a good ...

  15. Comparative study of PP0275C hybrid photodetector and XP2020Q photomultiplier in scintillation detection

    Energy Technology Data Exchange (ETDEWEB)

    Moszynski, Marek [Soltan Institute for Nuclear Studies, PL 05-400 Swierk-Otwock (Poland); Klamra, Wlodzimierz [Royal Institute of Technology, AlbaNova, S-106 91 Stockholm (Sweden); Wolski, Dariusz [Soltan Institute for Nuclear Studies, PL 05-400 Swierk-Otwock (Poland); Czarnacki, Wieslaw [Soltan Institute for Nuclear Studies, PL 05-400 Swierk-Otwock (Poland); Kapusta, Maciej [Soltan Institute for Nuclear Studies, PL 05-400 Swierk-Otwock (Poland); Balcerzyk, Marcin [Soltan Institute for Nuclear Studies, PL 05-400 Swierk-Otwock (Poland)

    2006-05-15

    The properties of a hybrid photodetector (HPD), type PP0275C, produced by Delft Electronic Products B.V., for scintillation detection and spectrometry were studied and compared to a standard XP2020Q photomultiplier. The study was performed for several scintillators, such as NaI(Tl), CsI(Tl) and LSO(Ce) of different dimensions. The excellent capability of the HPD to resolve single photoelectron events was fully confirmed. However, the study of the HPD with the scintillators showed a dramatically reduced number of photoelectrons and a further deterioration of energy resolution, depending on the size (diameter or length) of the crystals. For a 10 mm diameter NaI(Tl) a number of 5000{+-}250 photoelectrons/MeV was measured, which corresponds to about 56% of that observed with the XP2020Q with comparable quantum efficiency. An energy resolution of 9.2% for 662 keV {gamma}-rays from a {sup 137}Cs source as measured with the HPD light readout indicated on a serious degradation, larger than that arising from the statistics of photoelectrons. In conclusion, the study showed that this HPD is optimized for single photon detection but its application to scintillation detection is very limited.

  16. An approach to SOA development methodology: SOUP comparison with RUP and XP

    Directory of Open Access Journals (Sweden)

    Sandra Svanidzaitė

    2014-08-01

    Full Text Available Service oriented architecture (SOA is an architecture for distributed applications composed of distributed services with weak coupling that are designed to meet business requirements. One of the research priorities in the field of SOA is creating such software design and development methodology (SDDM that takes into account all principles of this architecture and allows for effective and efficient application development. A lot of investigation has been carried out to find out whether can one of popular SDDM, such as agile methodologies or RUP suits, be adapted for SOA or there is a need to create some new SOA-oriented SDDM. This paper compares one of SOA-oriented SDDM – SOUP – with RUP and XP methodologies. The aim is to find out whether the SOUP methodology is already mature enough to assure successful development of SOA applications. This aim is accomplished by comparing activities, artifacts of SOUP and RUP and emphasizing which XP practices are used in SOUP.DOI: http://dx.doi.org/10.15181/csat.v2i1.77 

  17. SR450 And Superhawk XP Applications Of Bacillus thuringiensis israelensis Against Culex quinquefasciatus.

    Science.gov (United States)

    Dunford, James C; Stoops, Craig A; Estep, Alden S; Britch, Seth C; Richardson, Alec G; Walker, Todd W; Farooq, Muhammad; Hoel, David F; Platt, Raymond R; Smith, Vincent L; Wirtz, Robert A; Kerce, Jerry D

    2014-09-01

    Sprayer comparisons and larval morality assays were conducted following SR450 backpack mist blower and Superhawk XP thermal fogger applications of Vectobac® WDG Bacillus thuringiensis israelensis (Bti) against Culex quinquefasciatus. Bacillus thuringiensis israelensis was applied at maximum label rate in a 232.26-m(2) field plot located in north-central Florida with containers placed at 2 heights (ground level and 1.52 m above ground) on stakes positioned 3.04, 6.09, 9.14, 12.19, and 15.24 m from the spray line. Results indicated that there was no significant (P > 0.05) difference in 24- and 48-h larval mortality between the 2 sprayers or between the 2 heights. There was significant difference (P 70% larval mortality 3.04-9.14 m from the spray line, and <60% mortality at 12.19 and 15.24 m. The data suggest that the SR450 and Superhawk XP may be comparable sprayers for use with Bti to control mosquito larvae.

  18. Xp22. 3 deletions in isolated familial Kallmann's syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hardelin, J.P.; Levilliers, J.; Legouis, R.; Petit, C. (Institut Pasteur, Paris (France)); Young, J.; Pholsena, M.; Schaison, G. (Centre Hospitalier de Bicetre, Le Kremlin-Bicetre (France)); Kirk, J.; Bouloux, P. (Royal Free Hospital, London (United Kingdom))

    1993-04-01

    Several familial cases of Kallmann's syndrome (KS) have been reported, among which the X-chromosome-linked mode of inheritance is the most frequent. The gene responsible for the X-linked KS has been localized to the terminal part of the X-chromosome short arm (Xp22.3 region), immediately proximal to the steroid sulfatase gene responsible for X-linked ichthyosis. Large deletions of this region have been previously shown in patients affected with both X-linked ichthyosis and KS. The authors report here the search for Xp22.3 deletions in 20 unrelated males affected with isolated X-linked KS. Only 2 deletions were found using Southern blot analysis, indicating that large deletions are uncommon in patients affected with KS alone. Both deletions were shown to include the entire KAL gene responsible for X-linked KS. The patients carrying these deletions exhibit additional clinical anomalies, which are discussed: unilateral renal aplasia, unilateral absence of vas deferens, mirror movements, and sensory neural hearing loss. 47 refs., 2 figs., 1 tab.

  19. 化工厂中JX-300XP DCS的系统维护%Maintenance of JX-300XP DCS System in Chemical Plant

    Institute of Scientific and Technical Information of China (English)

    李留格

    2012-01-01

    文章对化工厂中JX-300XP系统的常规维护工作进行分析,主要介绍系统的维护方法、规范及标准、系统的预防维护方法和技能、故障维护内容和方法。提出"系统维护,重在预防"的预防性维护的管理思想。找出工作中的漏洞,提高维修能力。%The paper analyzed the routine maintenance work of the JX-300XP system in chemical plant,introduces the system's maintenance methods,norms and standards,system's preventive maintenance methods and skills,system's fault maintenance content and method.Ofers the management thought prevent is very important in system maintenance.Find out the loopholes in the work,and improve the service ability.

  20. Does the human X contain a third evolutionary block? Origin of genes on human Xp11 and Xq28.

    Science.gov (United States)

    Delbridge, Margaret L; Patel, Hardip R; Waters, Paul D; McMillan, Daniel A; Marshall Graves, Jennifer A

    2009-08-01

    Comparative gene mapping of human X-borne genes in marsupials defined an ancient conserved region and a recently added region of the eutherian X, and the separate evolutionary origins of these regions was confirmed by their locations on chicken chromosomes 4p and 1q, respectively. However, two groups of genes, from the pericentric region of the short arm of the human X (at Xp11) and a large group of genes from human Xq28, were thought to be part of a third evolutionary block, being located in a single region in fish, but mapping to chicken chromosomes other than 4p and 1q. We tested this hypothesis by comparative mapping of genes in these regions. Our gene mapping results show that human Xp11 genes are located on the marsupial X chromosome and platypus chromosome 6, indicating that the Xp11 region was part of original therian X chromosome. We investigated the evolutionary origin of genes from human Xp11 and Xq28, finding that chicken paralogs of human Xp11 and Xq28 genes had been misidentified as orthologs, and their true orthologs are represented in the chicken EST database, but not in the current chicken genome assembly. This completely undermines the evidence supporting a separate evolutionary origin for this region of the human X chromosome, and we conclude, instead, that it was part of the ancient autosome, which became the conserved region of the therian X chromosome 166 million years ago.

  1. 基于Windows XP Embedded的LKJ2000仿真系统设计与实现%Design and implementation of LKJ2000 Simulation System based on Windows XP Embedded

    Institute of Scientific and Technical Information of China (English)

    李凤华; 钱雪军

    2013-01-01

    介绍一种基于Windows XP Embedded嵌入式系统的LKJ2000列车运行控制记录装置仿真的实现方法.对仿真系统的硬件环境进行分析,定制Windows XP Embedded (XPE)作为LKJ2000仿真系统的软件环境,在此基础上实现LKJ2000仿真系统.

  2. SUPCON’S JX-300XP control system%中控JX-300XP控制系统

    Institute of Scientific and Technical Information of China (English)

    史延鹏

    2016-01-01

    JX-300XP system was configured according to the requirement of a specialty paper project in Mudanjiang Hengfeng Paper. In this article, the composition and the technical characteristics of JX-300XP DCS control system were introduced, the working condition and applying characteristics of the controller and I/O module were brielfy described, the routine maintenance was elaborated.%JX-300XP系统是根据牡丹江恒丰纸业特种纸项目的要求而配置的。本文介绍了JX-300XP DCS控制系统的组成以及系统的技术特点,简单说明控制器及I/O卡件的工作状态及应用特点,阐述了日常维护的方法。

  3. Windows XP Service Pack2提前规划——磨刀不误砍柴功

    Institute of Scientific and Technical Information of China (English)

    MarkMinasi; 彭爱华

    2004-01-01

    在我上期的文章《Windows XP Service Pack2发布倒计时:强制安全防护》和《初识WindOWS防火墙》里,讨论了windows XP SP2——尤其是该Service Pack版本默认启用Windows防火墙(以前叫ICF)。现在微软把SP2的发布时间延迟到今年8月,我就有更多的时间给大家作Windows防火墙特征的概述。

  4. Development of a GeXP-multiplex PCR assay for the simultaneous detection and differentiation of six cattle viruses

    Science.gov (United States)

    Xie, Zhixun; Xie, Zhiqin; Deng, Xianwen; Xie, Liji; Huang, Li; Luo, Sisi; Huang, Jiaoling; Zhang, Yanfang; Zeng, Tingting; Wang, Sheng; Liu, Jiabo; Pang, Yaoshan

    2017-01-01

    Foot-and-mouth disease virus (FMDV), Bluetongue virus (BTV), Vesicular stomatitis Virus (VSV), Bovine viral diarrheal (BVDV), Bovine rotavirus (BRV), and Bovine herpesvirus 1 (IBRV) are common cattle infectious viruses that cause a great economic loss every year in many parts of the world. A rapid and high-throughput GenomeLab Gene Expression Profiler (GeXP) analyzer-based multiplex PCR assay was developed for the simultaneous detection and differentiation of these six cattle viruses. Six pairs of chimeric primers consisting of both the gene-specific primer and a universal primer were designed and used for amplification. Then capillary electrophoresis was used to separate the fluorescent labeled PCR products according to the amplicons size. The specificity of GeXP-multiplex PCR assay was examined with samples of the single template and mixed template of six viruses. The sensitivity was evaluated using the GeXP-multiplex PCR assay on serial 10-fold dilutions of ssRNAs obtained via in vitro transcription. To further evaluate the reliability, 305 clinical samples were tested by the GeXP-multiplex PCR assay. The results showed that the corresponding virus specific fragments of genes were amplified. The detection limit of the GeXP-multiplex PCR assay was 100 copies/μL in a mixed sample of ssRNAs containing target genes of six different cattle viruses, whereas the detection limit for the Gexp-mono PCR assay for a single target gene was 10 copies/μL. In detection of viruses in 305 clinical samples, the results of GeXP were consistent with simplex real-time PCR. Analysis of positive samples by sequencing demonstrated that the GeXP-multiplex PCR assay had no false positive samples of nonspecific amplification. In conclusion, this GeXP-multiplex PCR assay is a high throughput, specific, sensitive, rapid and simple method for the detection and differentiation of six cattle viruses. It is an effective tool that can be applied for the rapid differential diagnosis of clinical

  5. Evidence for an asthma risk locus on chromosome Xp: a replication linkage study

    DEFF Research Database (Denmark)

    Brasch-Andersen, C; Møller, M U; Haagerup, A;

    2008-01-01

    BACKGROUND: Asthma is a complex genetic disorder characterized by chronic inflammation in the airways. Identification of genetic risk factors for asthma has been complicated due to genetic heterogeneity and influence from environmental risk factors. Despite the fact that multiple genetic linkage...... studies have been carried out the results are still conflicting and call for replication experiments. A Danish genome-wide scan has prior reported evidence for candidate regions for asthma susceptibility genes on chromosomes 1p, 5q, 6p, 12q and Xp. Linkage to chromosome 12q was later confirmed in the same...... replication sample as used in the present study. The aim of the study was to replicate linkage to candidate regions for asthma in an independent Danish sample. METHODS: We performed a replication study investigating linkage to candidate regions for asthma on chromosomes 1p36.31-p36.21, 5q15-q23.2, 6p24.3-p22...

  6. 让Windows XP SP2和OWA 2003和平共处

    Institute of Scientific and Technical Information of China (English)

    JackieLiu

    2005-01-01

    当您在企业中部署了Windows XP SP2(以下简称SP2)后,有没有听到那些正在使用Outlook Web Access(OWA)2003客户端的用户的抱怨声?因为SP2默认对IE增强了重要的安全特性,使他们发现在使用OWA 2003时总会出现问题,让我们来看一下到底都发生了什么吧。当然,最终解决掉这些让用户产生抱怨的问题才是您所期望的,也是您必须完成的任务。

  7. ERP System Evaluation on Sofi XP Based Accounting Module in Software House Industry

    Directory of Open Access Journals (Sweden)

    Shinta Mardallena

    2015-12-01

    Full Text Available Accounting module is an important module for a company business process. The roles are in the form of parameter calculation of profits, losses and financial performance based on transaction, which basically is a real-time reporting system. The amount of company needs on accounting indicates that the accounting is one of the resources which support the establishment of a company. Thus, the company constantly improves the accounting performance, especially in handling of receivables, debts, and cash transactions. Evaluations which were performed at SOFI XP-based ERP system aims to provide a solution to a problem that was discovered during the analysis of the system needs. This evaluation was done in two stages: by collecting data and analyzing the system that running in the company. By doing this evaluation, the documentation of system performance and the solution for problems that were found in the company can be generated.

  8. ERP System Evaluation on SOFI XP Based Accounting Module in Software House Industry

    Directory of Open Access Journals (Sweden)

    Shinta Mardallena

    2015-09-01

    Full Text Available Accounting module is an important module for a company business process. The roles are in the form of parameter calculation of profits, losses and financial performance based on transaction, which basically is a real-time reporting system. The amount of company needs on accounting indicates that the accounting is one of the resources which support the establishment of a company. Thus, the company constantly improves the accounting performance, especially in handling of receivables, debts, and cash transactions. Evaluations which were performed at SOFI XP-based ERP system aims to provide a solution to a problem that was discovered during the analysis of the system needs. This evaluation was done in two stages: by collecting data and analyzing the system that running in the company. By doing this evaluation, the documentation of system performance and the solution for problems that were found in the company can be generated.

  9. H2XP:OH2 Complexes: Hydrogen vs. Pnicogen Bonds

    Directory of Open Access Journals (Sweden)

    Ibon Alkorta

    2016-02-01

    Full Text Available A search of the Cambridge Structural Database (CSD was carried out for phosphine-water and arsine-water complexes in which water is either the proton donor in hydrogen-bonded complexes, or the electron-pair donor in pnicogen-bonded complexes. The range of experimental P-O distances in the phosphine complexes is consistent with the results of ab initio MP2/aug’-cc-pVTZ calculations carried out on complexes H2XP:OH2, for X = NC, F, Cl, CN, OH, CCH, H, and CH3. Only hydrogen-bonded complexes are found on the H2(CH3P:HOH and H3P:HOH potential surfaces, while only pnicogen-bonded complexes exist on H2(NCP:OH2, H2FP:OH2, H2(CNP:OH2, and H2(OHP:OH2 surfaces. Both hydrogen-bonded and pnicogen-bonded complexes are found on the H2ClP:OH2 and H2(CCHP:OH2 surfaces, with the pnicogen-bonded complexes more stable than the corresponding hydrogen-bonded complexes. The more electronegative substituents prefer to form pnicogen-bonded complexes, while the more electropositive substituents form hydrogen-bonded complexes. The H2XP:OH2 complexes are characterized in terms of their structures, binding energies, charge-transfer energies, and spin-spin coupling constants 2hJ(O-P, 1hJ(H-P, and 1J(O-H across hydrogen bonds, and 1pJ(P-O across pnicogen bonds.

  10. Mechanical vibrations emitted by Husqvarna 357XP power saw with resonance exhaust system

    Directory of Open Access Journals (Sweden)

    Roman Wojtkowiak

    2012-09-01

    Full Text Available The paper presents a concept, known for many years and commonly applied in the automotive industry, to improve engine performance of the chain saw (higher maximum power rating and more advantageous torque parameters. The analyses were conducted on a Husqvarna 357XP power saw, equipped with a modified resonance exhaust system with variable dimensions. The system was designed at the Department of Forest Technology (Poznań University of Life Sciences to the already existing power unit, with specific timing gear, size, shape and angle of cylinder ducts. The aim of the study was to assess mechanical vibrations, recorded at the handles of a Husqvarna 357XP chain saw, at three operation regimes of its engine. Analyses were conducted on the same chain saw equipped with an original vibration damper and a modified resonance system in its three variants and it may be stated that the introduction of design changes in the exhaust system has a significant effect on an increase in the power and torque of the tested chain saw. On the basis of recorded results it may be stated that the acceleration of vibrations both on the rear and front handles of the chain saw significantly differs in case of the application of the modified exhaust system in comparison to the original vibration damper. The application of the resonance system in the chain saw exhaust system leads to increased mechanical vibrations produced by the machine. However, it needs to be observed that the volume of the admissible standard is exceeded both for the chainsaw with the original damper and that with the used exhaust system. Vibrations of the chain saw with a resonance damper on the front handle are higher than those of the chain saw with the original damper on average by 28%, while on the rear handle it is by 27%. We need to stress the significantly higher difference when applying in the chain saw modified damper variants 1 and 3 in comparison with the original design.

  11. Identifying candidate genes for X-linked hypophosphatemic rickets (HYP) in the critical region X(p22.1-p22.2)

    Energy Technology Data Exchange (ETDEWEB)

    Holm, L.A.; Freedner, N.L.; Maizoub, J.A. [Harvard Medical School, Boston, MA (United States)] [and others

    1994-09-01

    X-linked hypophosphatemic rickets (HYP) is the most common inherited form of rickets, characterized by a proximal renal tubular phosphate leak leading to phosphate-wasting and abnormal 1.25-dihydroxyvitamin D metabolism. The primary defect is unknown, and the candidate gene approach has thus far been unsuccessful in identifying the gene. The HYP locus has been mapped to X(p22.1-p22.2) and more recently to a 500,000 base pair region spanned by two YACs, E01138 and A0472. In an effort to identify the HYP gene in the 500 kb region, we are taking the direct selection approach. Since the tissue expressing the HYP gene is unknown, we are using cDNA libraries from a number of tissues for direct selection, including kidney, liver, thyroid, brain, spinal cord, total fetus, bone, and an osteosarcoma cell line. The tissue cDNA is hybridized to the YACs A0472 and EO1138 (obtained courtesy of Fiona Francis, Imperial Cancer Research Fund, London) in the presence of quenchers, which block repeated and ribosomal sequences on the YACs. A selected library is created from the tissues cDNAs that hybridize to the YACs. The selected cDNA library is first screened to eliminate inserts containing repeated and ribosomal sequences. The presence of the inserts on the YAC and on X(p22.1-p22.2) is then verified using mapping panels. Candidate cDNAs that make it through this analysis are sequenced. Our first attempts at making selected libraries resulted in a number of contaminants. Three separate libraries are currently under construction, using the following combinations of tissue cDNA libraries: (1) kidney, liver, and thyroid; (2) brain, spinal cord, and total fetus; and (3) bone and an osteosarcoma cell line. We will discuss transcripts obtained from these libraries.

  12. Ion-implantation-induced amorphization of InxGa1-xP alloys as functions of stoichiometry and temperature

    Science.gov (United States)

    Hussain, Z. S.; Wendler, E.; Wesch, W.; Schnohr, C. S.; Ridgway, M. C.

    2016-05-01

    Rutherford Backscattering Spectrometry/Channeling and Extended X-ray Absorption Fine Structure measurements have been combined to investigate the amorphization of InxGa1-xP alloys at 15 and 300 K for selected stoichiometries representative of the entire stoichiometric range. The amorphization kinetics differs considerably for the two temperatures: at 15 K, the amorphization kinetics of InxGa1-xP is intermediate between the two binary extremes while at 300 K, InxGa1-xP is more easily amorphized than both InP and GaP. Direct impact and stimulated amorphization both contribute to the amorphization process at 15 K. Dynamic annealing via thermally induced Frenkel pair recombination reduces the influence of direct impact amorphization at 300 K such that the stimulated amorphization is dominant. At this temperature, stimulated amorphization in ternary InxGa1-xP alloys is supported by the structural disorder inherent from the bimodal bond length distribution.

  13. Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer.

    NARCIS (Netherlands)

    Gudmundsson, J.; Sulem, P.; Rafnar, T.; Bergthorsson, J.T.; Manolescu, A.; Gudbjartsson, D.; Agnarsson, B.A.; Sigurdsson, A.; Benediktsdottir, K.R.; Blondal, T.; Jakobsdottir, M.; Stacey, S.N.; Kostic, J.; Kristinsson, K.T.; Birgisdottir, B.; Ghosh, S.; Magnusdottir, D.N.; Thorlacius, S.; Thorleifsson, G.; Zheng, S.L.; Sun, J.; Chang, B.L.; Elmore, J.B.; Breyer, J.P.; McReynolds, K.M.; Bradley, K.M.; Yaspan, B.L.; Wiklund, F.; Stattin, P.; Lindstrom, S.; Adami, H.O.; McDonnell, S.K.; Schaid, D.J.; Cunningham, J.M.; Wang, L.; Cerhan, J.R.; Sauver, J.L. St; Isaacs, S.D.; Wiley, K.E.; Partin, A.W.; Walsh, P.C.; Polo, S.; Ruiz-Echarri, M.; Navarrete, S.; Fuertes, F.; Saez, B.; Godino, J.; Weijerman, P.C.; Swinkels, D.W.; Aben, K.K.H.; Witjes, J.A.M.; Suarez, B.K.; Helfand, B.T.; Frigge, M.L.; Kristjansson, K.; Ober, C.; Jonsson, E.; Einarsson, G.V.; Xu, J.; Gronberg, H.; Smith, J.R.; Thibodeau, S.N.; Isaacs, W.B.; Catalona, W.J.; Mayordomo, J.I.; Kiemeney, L.A.L.M.; Barkardottir, R.B.; Gulcher, J.R.; Thorsteinsdottir, U.; Kong, A.; Stefansson, K.

    2008-01-01

    We conducted a genome-wide SNP association study on prostate cancer on over 23,000 Icelanders, followed by a replication study including over 15,500 individuals from Europe and the United States. Two newly identified variants were shown to be associated with prostate cancer: rs5945572 on Xp11.22 and

  14. Positional Cloning in Xp22 : towards the isolation of the gene involved in X-linked retinoschisis

    NARCIS (Netherlands)

    Vosse, Esther van de

    1998-01-01

    The study was aimed at the positional cloning of disease genes in Xp22.1-p22.2. To this end a YAC contig covering this region was constructed. To identify candidate genes for the diseases localised in this region exon trapping was applied. Several novel transcripts were isolated from the region, of

  15. Highly Dynamic Interactions Maintain Kinetic Stability of the ClpXP Protease During the ATP-Fueled Mechanical Cycle.

    Science.gov (United States)

    Amor, Alvaro J; Schmitz, Karl R; Sello, Jason K; Baker, Tania A; Sauer, Robert T

    2016-06-17

    The ClpXP protease assembles in a reaction in which an ATP-bound ring hexamer of ClpX binds to one or both heptameric rings of the ClpP peptidase. Contacts between ClpX IGF-loops and clefts on a ClpP ring stabilize the complex. How ClpXP stability is maintained during the ATP-hydrolysis cycle that powers mechanical unfolding and translocation of protein substrates is poorly understood. Here, we use a real-time kinetic assay to monitor the effects of nucleotides on the assembly and disassembly of ClpXP. When ATP is present, complexes containing single-chain ClpX assemble via an intermediate and remain intact until transferred into buffers containing ADP or no nucleotides. ATP binding to high-affinity subunits of the ClpX hexamer prevents rapid dissociation, but additional subunits must be occupied to promote assembly. Small-molecule acyldepsipeptides, which compete with the IGF loops of ClpX for ClpP-cleft binding, cause exceptionally rapid dissociation of otherwise stable ClpXP complexes, suggesting that the IGF-loop interactions with ClpP must be highly dynamic. Our results indicate that the ClpX hexamer spends almost no time in an ATP-free state during the ATPase cycle, allowing highly processive degradation of protein substrates.

  16. Characterization of HZC XP1805 photomultiplier tube for LHAASO-WCDA with a high dynamic range base

    Science.gov (United States)

    Zhao, X.; Tang, Z.; Li, C.; Li, X.; Zha, W.; Chen, H.; Zhang, Y.; Shao, M.; Sun, Y.; Zhou, Y.

    2016-10-01

    The Water Cherenkov Detector Array (WCDA) for the Large High Altitude Air Shower Observatory (LHAASO) will employ 3000 large-sized hemisphere photomultiplier tubes (PMTs) to collect the Cherenkov light produced by shower particles crossing water. The PMTs require not only good single photoelectron (SPE) resolution and small transit time spread (TTS), but also good linearity up to 4000 photoelectrons. XP1805 PMT produced by Hainan Zhanchuang Photonics Technology Co., Ltd (HZC), China, with a production line imported from Photonis (France) is a good candidate for LHAASO-WCDA readout. In this paper, the design of a high dynamic range base for XP1805 is presented. The SPE responses and non-linearity of XP1805 with the high dynamic range base are measured. These results show that HZC XP1805 with the designed base is well qualified for LHAASO-WCDA, with peak-to-valley ratio greater than 2, TTS around 3 ns, dynamic range (non-linearity within 5%) over 1500 and 5300 photoelectrons for anode and the 6th dynode output, respectively, at PMT gain of 3 × 106 with the inciting light pulse width of 6.4 ns.

  17. Analysis of diffractive pd to Xd and pp to Xp interactions and test of the finite-mass sum rule

    CERN Document Server

    Akimov, Y; Golovanov, L B; Goulianos, K; Gross, D; Malamud, E; Melissinos, A C; Mukhin, S; Nitz, D; Olsen, S; Sticker, H; Tsarev, V A; Yamada, R; Zimmerman, P

    1976-01-01

    The first moment finite mass sum rule is tested by utilising cross- sections for pp to Xp extracted from recent Fermilab data on pd to Xd and also comparing with CERN ISR data. The dependences on M/sub x//sup 2/, t and s are also discussed. (11 refs).

  18. Invasive Group A Streptococcal Infection

    Centers for Disease Control (CDC) Podcasts

    2011-06-13

    In this podcast, CDC's Dr. Chris Van Beneden discusses the dangers of group A strep infections.  Created: 6/13/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 6/13/2011.

  19. Improved Risk Stratification in Pediatric Septic Shock Using Both Protein and mRNA Biomarkers. PERSEVERE-XP.

    Science.gov (United States)

    Wong, Hector R; Cvijanovich, Natalie Z; Anas, Nick; Allen, Geoffrey L; Thomas, Neal J; Bigham, Michael T; Weiss, Scott L; Fitzgerald, Julie C; Checchia, Paul A; Meyer, Keith; Quasney, Michael; Hall, Mark; Gedeit, Rainer; Freishtat, Robert J; Nowak, Jeffrey; Raj, Shekhar S; Gertz, Shira; Grunwell, Jocelyn R; Lindsell, Christopher J

    2017-08-15

    We previously derived and validated the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to estimate baseline mortality risk in children with septic shock. The PERSEVERE biomarkers are serum proteins selected from among the proteins directly related to 80 mortality risk assessment genes. The initial approach to selecting the PERSEVERE biomarkers left 68 genes unconsidered. To determine if the 68 previously unconsidered genes can improve upon the performance of PERSEVERE and to provide biological information regarding the pathophysiology of septic shock. We reduced the number of variables by determining the biological linkage of the 68 previously unconsidered genes. The genes identified through variable reduction were combined with the PERSEVERE-based mortality probability to derive a risk stratification model for 28-day mortality using classification and regression tree methodology (n = 307). The derived tree, PERSEVERE-XP, was then tested in a separate cohort (n = 77). Variable reduction revealed a network consisting of 18 mortality risk assessment genes related to tumor protein 53 (TP53). In the derivation cohort, PERSEVERE-XP had an area under the receiver operating characteristic curve (AUC) of 0.90 (95% confidence interval, 0.85-0.95) for differentiating between survivors and nonsurvivors. In the test cohort, the AUC was 0.96 (95% confidence interval, 0.91-1.0). The AUC of PERSEVERE-XP was superior to that of PERSEVERE. PERSEVERE-XP combines protein and mRNA biomarkers to provide mortality risk stratification with possible clinical utility. PERSEVERE-XP significantly improves on PERSEVERE and suggests a role for TP53-related cellular division, repair, and metabolism in the pathophysiology of septic shock.

  20. A child with xeroderma pigmentosum for excision of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sridevi M Mulimani

    2013-01-01

    Full Text Available Xeroderma pigmentosum (XP is characterized by hypersensitivity to sunlight, ocular involvement, and progressive neurological complications. These manifestations are due to a cellular hypersensitivity to ultraviolet radiation leading to a defect in repair of DNA by the process of nucleotide excision repair. Basal cell carcinoma which is rare in children can occur with XP. Though the XP induced changes are predominately dermatologic, pose several challenges in anaesthetic management. Hence, we are reporting a 9-year-old child with XP scheduled for excision of basal cell carcinoma under general anaesthesia.

  1. Researches Regarding the Estrus Induction to Wean Sows, During the Summer Season, Using the Hormonal Products Maprelin XP10 and P.G. 600

    Directory of Open Access Journals (Sweden)

    Ramona Untaru

    2010-05-01

    Full Text Available The researches were made with the goal to induce estrus to the wean sows, during the summer season. To the pluriparous sows we administrate 2 ml Maprelin XP 10 at 24 hours after weaning to the experimental group. Control group didn’t receive any hormonal product. Primiparous sows were split in two groups: to one group we administrate 0.5 ml Maprelin XP 10 at 24 hours after weaning; to the other group we administrate 5 ml P.G. 600 in the weaning day. Weaning to estrus interval was 5.33±0.21 days for 2 ml Maprelin XP group, 5.16±0.24 days for control group, 6.32±0.39 days for 0.5 ml Maprelin XP and 5.18±0.35 days for P.G. 600 group. Proportion in estrus after weaning was 98.01% for 2 ml Maprelin XP group, 96.28% for control group, 89.56% for 0.5 ml Maprelin XP and 91.22% for P.G. 600 group. Fecundity at 28 days after the A.I. was 91.71% for 2 ml Maprelin XP group, 92.26% for control group, 83.41% for 0.5 ml Maprelin XP and 86.61% for P.G. 600 group. Farrowing rate was 86.00% for 2 ml Maprelin XP group, 85.11% for control group, 76.68% for 0.5 ml Maprelin XP and 78.66% for P.G. 600 group.

  2. XP1菌株强化湿地植物脱氮及其对根际微生物的影响%Enhanced Denitrification with Wetland Plants by Strain XP1 and Its Effect on Rhizosphere Microorganisms

    Institute of Scientific and Technical Information of China (English)

    侯庆杰; 裴海燕; 胡文容

    2011-01-01

    A denitrifying bacterial strain named XP1 with good denitrification properties was isolated from the constructed wetland of Nansi Lake. To study the enhanced denitrification of XP1 in the rhizosphere soils of three plants (Arundo donax, Phragmites australis and Typha) , the bacterium strain XP1 was inoculated into the rhizosphere soil of the three plants. The change of XP1 in the rhizosphere soil microorganism of the three plants in the course of enhanced denitrification was investigated by polymerase chain reaction and denaturing gradient gel electrophoresis ( PCR-DGGE) . The results showed that without the enhanced denitrification for simulated wetlands, the order of nitrogen removal capacity in the three plant wetlands was Arundo donax > Phragmites australis > Typha under the same conditions. The quantitative order of the dominant microorganisms around the three plants was Arundo donax > Phragmites australis > Typha, although there was no obvious difference in the variety of microorganisms in the rhizosphere soil of the three plants. The ratio of indigenous strain XP1 in the rhizosphere soils of the three plants was 1. 5= 1. 3:1. Compared to the control group, the enhanced denitrification of the three plants were increased from 14% , 56% , 56% to more than98% , respectively, which meant the XP1 had a significant enhancement in denitrification. When ρ(TN) of the wetland was less than that of the Class Ⅲ criterion in the Environmental Quality Standards for Surface Water of China (ρ(TN) s≤ 1 mg/L), the diversity and quantities of the microorganisms in the three plants' rhizosphere soils decreased, though there was no marked change in the microbial community structure. For strain XP1, the quantities in the rhizosphere soils of the three plants decreased by up to 40% , 53% and 67% , respectively.%利用从南四湖人工湿地中分离的一株具有良好脱氮作用的反硝化细菌XP1,分别接种于湿地植物芦竹、芦苇和香蒲的根际土壤,考察菌株XP

  3. Flood Improvement and LID Modeling of Rice University in Houston, Texas Using XP-SWMM

    Science.gov (United States)

    Juan, A.; Bedient, P. B.

    2013-12-01

    In recent years, Low Impact Development (LID) has emerged as an alternative to traditional urban development strategies. However, unlike most conventional methodologies, LID is designed to manage storm runoff as close as possible to its point of origin. This feat is accomplished through the use of distributed technologies such as green roofs, bio-swales, and rain gardens, with the end goal of reducing the adverse impacts of urbanization on natural resources by maintaining pre-development hydrologic conditions. In this study, hypothetical LID scenarios throughout Rice University in Houston, Texas were simulated with the hydrologic/hydraulic software package XP-SWMM. Comparisons were made between the base scenario (existing conditions) and the various LID scenarios with several design storms. The rainfall simulated were all less than 6 in., due to LID typically being known to have limited impacts in inundation reduction during large storms, especially in the Texas Gulf Coast region. Preliminary results indicated that the LID applications were able to reduce peak flows as well as total storm runoff volume by as much as 20%. These results show that LID has the potential to replace, or to be used in conjunction with, conventional storm water management practices in Houston.

  4. Comparisons of Accurate Electronic, Transport, and Bulk Properties of XP (X = B, Al, Ga, In)

    Science.gov (United States)

    Malozovsky, Yuriy; Ejembi, John; Saliev, Azizjon; Franklin, Lashounda; Bagayoko, Diola

    We present comparisons of results from ab-initio,self-consistent local density approximation (LDA) calculations of accurate, electronic and related properties of zinc blende XP (X =B, Al, Ga, In) phosphides. We implemented the linear combination of atomic orbitals following the Bagayoko, Zhao, and Williams (BZW) method as enhanced by Ekuma and Franklin (BZW-EF). Consequently, our results have the full physical content of DFT and agree very well with corresponding experimental ones [AIP Advances, 4, 127104 (2014)]. Our calculated, indirect band gap of 2.02 eV for BP, 2.56 eV for AlP, and of 2.29 eV for GaP, from Γ to X-point, are in excellent agreement with experimental values. Our calculated direct band gap of 1.43 eV, at Γ, for InP is also in an excellent agreement with experimental value. We discuss calculated electron and hole effective masses, total (DOS) and partial (pDOS) densities of states, and the bulk modulus of these phosphides. Acknowledgments: NSF and the Louisiana Board of Regents, LASiGMA [Award Nos. EPS- 1003897, NSF (2010-15)-RII-SUBR] and NSF HRD-1002541, DOE - National, Nuclear Security Administration (NNSA) (Award Nos. DE-NA0001861 and DE- NA0002630), LaSPACE, and LONI-SUBR.

  5. Odour Pollution Measurement from Refuse Derive Fuel Operations Using Odour Concentration Meter (OCM XP-329

    Directory of Open Access Journals (Sweden)

    Zaini Sakawi

    2013-04-01

    Full Text Available Odour perception is subjective and difficult to be accurately measured between individuals. Hence many studies on odour issues are more commonly pertain to its intensity, concentration, types, standards, measurement methods, law and impacts on physical and human environments. Nevertheless, odour analysis can be conducted empirically or based on human sensorial. Among major sources of odour pollution are animal rearing, oil palm and rubber mills, dumpsites, industries and sewage treatments. This study attempted to measure odour pollution generated by Refuse Derived Fuel (RDF operation. The analysis was conducted at different times of day (morning, evening and night and weather conditions (normal days and after rains. 10 sampling stations were selected for observations using the Odour Concentration Meter Siri XP-329 III.The results indicated that there existed different level of odour concentrations on normal days and after rains due to the influence of meteorological environment. Distance factors also influenced the odour concentrations, whereby gradually, the stations further from RDF operation recorded higher odour concentrations

  6. Single photon scans of various multianode PMTs and XP85012 MCP

    Energy Technology Data Exchange (ETDEWEB)

    Pauly, Christian [Bergische Universitaet Wuppertal (Germany); Collaboration: CBM-Collaboration

    2014-07-01

    Spatially resolved single Cherenkov photon detection is an essential requirement in building a Ring Imaging Cherenkov Detector (RICH). We have set up a test stand to conduct single photon XY-scans in order to test and qualify different sensor devices for the CBM-RICH detector which is currently being designed as part of the future Compressed Baryonic Matter (CBM) experiment at FAIR. Combining a pulsed laser source and step-motor XY-table with a self-triggered multi-channel acquisition system based on the nXYter readout ASIC allows to measure many different characteristic features of the sensor devices. Quantities like spatial resolved detection efficiency, spatial resolution, single photon response, channel-to-channel gain uniformity, after-pulsing, cross-talk, dark noise and active area can all be deduced from a single data set and thus allow for a comprehensive comparison of the evaluated sensors. For the CBM RICH, we currently foresee the Hamamatsu H8500 2'' or R11265 1'' MAPMTs as baseline solution, alternatively we also consider using Photonis XP85012 MCPs. We present a detailed comparison of these sensor devices, including first measurements of the new H12700 MAPMT from Hamamatsu.

  7. Recurrent deletion of ZNF630 at Xp11.23 is not associated with mental retardation.

    Science.gov (United States)

    Lugtenberg, Dorien; Zangrande-Vieira, Luiz; Kirchhoff, Maria; Whibley, Annabel C; Oudakker, Astrid R; Kjaergaard, Susanne; Vianna-Morgante, Angela M; Kleefstra, Tjitske; Ruiter, Mariken; Jehee, Fernanda S; Ullmann, Reinhard; Schwartz, Charles E; Stratton, Michael; Raymond, F Lucy; Veltman, Joris A; Vrijenhoek, Terry; Pfundt, Rolph; Schuurs-Hoeijmakers, Janneke H M; Hehir-Kwa, Jayne Y; Froyen, Guy; Chelly, Jamel; Ropers, Hans Hilger; Moraine, Claude; Gècz, Jozef; Knijnenburg, Jeroen; Kant, Sarina G; Hamel, Ben C J; Rosenberg, Carla; van Bokhoven, Hans; de Brouwer, Arjan P M

    2010-03-01

    ZNF630 is a member of the primate-specific Xp11 zinc finger gene cluster that consists of six closely related genes, of which ZNF41, ZNF81, and ZNF674 have been shown to be involved in mental retardation. This suggests that mutations of ZNF630 might influence cognitive function. Here, we detected 12 ZNF630 deletions in a total of 1,562 male patients with mental retardation from Brazil, USA, Australia, and Europe. The breakpoints were analyzed in 10 families, and in all cases they were located within two segmental duplications that share more than 99% sequence identity, indicating that the deletions resulted from non-allelic homologous recombination. In 2,121 healthy male controls, 10 ZNF630 deletions were identified. In total, there was a 1.6-fold higher frequency of this deletion in males with mental retardation as compared to controls, but this increase was not statistically significant (P-value = 0.174). Conversely, a 1.9-fold lower frequency of ZNF630 duplications was observed in patients, which was not significant either (P-value = 0.163). These data do not show that ZNF630 deletions or duplications are associated with mental retardation.

  8. Nano-compression of carbon micro-balloons on a xp-nanoindenter

    Energy Technology Data Exchange (ETDEWEB)

    Gouadec, G.; Carlisle, K. (Kipp B.); Chawla, Krishan Kumar,; Koopman, M. (Mark); Gladysz, G. M. (Gary M.)

    2002-01-01

    Microballoons are thin hollow spheres that are bonded together with resins to form 'syntactic foam'. These foams exhibit very high specific compressive strength. Mechanical properties of the microballoons are integral to the mechanical properties of the syntactic foams and will also be useful in modeling of the system. This paper will present nano-compression results obtained for individual carbon microballoons (CMBs) tested between 5 and 50 mN on a XP nano-indentation device (MTS) customized with a special cylindrical tip. Details of the procedure will also be presented. CMBs ranging in diameter from 5 to 80 pm were randomly chosen for testing, which allowed for a statistical analysis (140 tests). Less than 25% of the CMBs were found to be nearly perfect spheres (from comparison between the 'horizontal' diameter measured with a microscope and the 'vertical' compressed diameter). CMBs smaller than 10 pm and greater than 50 pm were markedly ellipsoidal and about one third of the CMBs exhibited 'sequential' cracking, revealing the existence of flaws. SEM and optical microscopy of the foams revealed these flaws as either voids in the wall thickness or compartments in some CMBs. Conventional Berkovich nano-indentation was performed on segments of CMB walls after nanocompresseion and yielded a value of approximately 31 GPa for Young's modulus. The measured thickness was between 0.3 and 2.2 pm, showing no correlation with the diameter of the pristine CMBs.

  9. Compound haplotypes at Xp11.23 and human population growth in Eurasia.

    Science.gov (United States)

    Alonso, S; Armour, J A L

    2004-09-01

    To investigate patterns of diversity and the evolutionary history of Eurasians, we have sequenced a 2.8 kb region at Xp11.23 in a sample of African and Eurasian chromosomes. This region is in a long intron of CLCN5 and is immediately flanked by a highly variable minisatellite, DXS255, and a human-specific Ta0 LINE. Compared to Africans, Eurasians showed a marked reduction in sequence diversity. The main Euro-Asiatic haplotype seems to be the ancestral haplotype for the whole sample. Coalescent simulations, including recombination and exponential growth, indicate a median length of strong linkage disequilibrium, up to approximately 9 kb for this area. The Ka/Ks ratio between the coding sequence of human CLCN5 and its mouse orthologue is much less than 1. This implies that the region sequenced is unlikely to be under the strong influence of positive selective processes on CLCN5, mutations in which have been associated with disorders such as Dent's disease. In contrast, a scenario based on a population bottleneck and exponential growth seems a more likely explanation for the reduced diversity observed in Eurasians. Coalescent analysis and linked minisatellite diversity (which reaches a gene diversity value greater than 98% in Eurasians) suggest an estimated age of origin of the Euro-Asiatic diversity compatible with a recent out-of-Africa model for colonization of Eurasia by modern Homo sapiens.

  10. Performance of Oak Seedlings Grown under Different Oust® XP Regimes

    Directory of Open Access Journals (Sweden)

    Andrew Self

    2014-06-01

    Full Text Available Herbaceous weed control (HWC is prescribed for growing season control of vegetative competition in hardwood afforestation attempts on former agricultural areas. Without HWC, planted seedlings often exhibit poor growth and survival. While currently employed HWC methods are proven, there is a substantial void in research comparing HWC treatments spanning multiple years. A total of 4,320 bare-root seedlings of three oak species were planted on three Mississippi sites. All sites were of comparable soils and received above average precipitation for the majority of the three-year study. Eight combinations of HWC and mechanical site preparation were utilized at each site, with 480 seedlings planted in each of the nine blocks, and a total of 1,440 seedlings per species planted across all sites. Treatments were installed on 3.1 m centers, with mechanical treatments as follows: control, subsoiling, bedding, and combination plowing. HWC treatments included one and two-year applications of Oust® XP. Treatments were applied over seedlings post-planting in 1.5 m bands, at a rate of 140.1 g product/hectare. Excepting one species, HWC dependent height or groundline diameter differences were not detected among mechanical treatments, species, HWC regime, or combinations thereof. No survival differences were observed among site preparation treatments or species. However, analysis detected a growing season/HWC treatment interaction for seedling survival.

  11. DNA repair in human cells: from genetic complementation to isolation of genes.

    NARCIS (Netherlands)

    D. Bootsma (Dirk); A. Westerveld (Andries); J.H.J. Hoeijmakers (Jan)

    1988-01-01

    textabstractThe genetic disease xeroderma pigmentosum (XP) demonstrates the association between defective repair of DNA lesions and cancer. Complementation analysis performed on XP cell strains and on repair deficient rodent cell lines has revealed that at least nine and possibly more than 13 genes

  12. DNA repair in human cells: from genetic complementation to isolation of genes.

    NARCIS (Netherlands)

    D. Bootsma (Dirk); A. Westerveld (Andries); J.H.J. Hoeijmakers (Jan)

    1988-01-01

    textabstractThe genetic disease xeroderma pigmentosum (XP) demonstrates the association between defective repair of DNA lesions and cancer. Complementation analysis performed on XP cell strains and on repair deficient rodent cell lines has revealed that at least nine and possibly more than 13 genes

  13. Double Xp11.22 deletion including SHROOM4 and CLCN5 associated with severe psychomotor retardation and Dent disease.

    Science.gov (United States)

    Armanet, Narjes; Metay, Corinne; Brisset, Sophie; Deschenes, Georges; Pineau, Dominique; Petit, François M; Di Rocco, Federico; Goossens, Michel; Tachdjian, Gérard; Labrune, Philippe; Tosca, Lucie

    2015-01-01

    Here we report the clinical and molecular characterization of two Xp11.22 deletions including SHROOM4 and CLCN5 genes. These deletions appeared in the same X chromosome of the same patient. The patient is a six-year-old boy who presented hydrocephalus, severe psychomotor and growth retardation, facial dysmorphism and renal proximal tubulopathy associated with low-molecular-weight proteinuria, hypercalciuria, hyperaminoaciduria, hypophosphatemia and hyperuricemia. Standard and high resolution karyotypes showed a 46,XY formula. Array-CGH revealed two consecutive cryptic deletions in the region Xp11.22, measuring respectively 148 Kb and 2.6 Mb. The two deletions were inherited from the asymptomatic mother. Array-CGH allowed us to determine candidate genes in the deleted region. The disruption and partial loss of CLCN5 confirmed the diagnostic of Dent disease for this patient. Moreover, the previously described involvement of SHROOM4 in neuronal development is discussed.

  14. The structural, electronic and optical properties of In{sub x}Ga{sub 1-x}P alloys

    Energy Technology Data Exchange (ETDEWEB)

    Othman, M., E-mail: mazin@gazi.edu.t [Gazi University, Department of Physics, Teknikokullar, 06500 Ankara (Turkey); Kasap, E. [Gazi University, Department of Physics, Teknikokullar, 06500 Ankara (Turkey); Korozlu, N. [Erzincan University, Department of Physics, Basbaglar, 24100 Erzincan (Turkey)

    2010-05-15

    The structural, electronic energy band structure and linear optical properties In{sub x}Ga{sub 1-x}P alloys are investigated by an ab initio pseudopotential method using density functional theory in the local density approximation (LDA) and a scissors approximation. For these alloys lattice parameters, bulk modulus, band gap energy and density of state (DOS) are calculated. Electronic band structure shows that In{sub x}Ga{sub 1-x}P alloys are direct band gap and the optical band gap decrease from 2.10 to 1.41 eV with increase in In concentrations. The linear energy dependent dielectric functions and some optical properties such as energy loss function, absorption and refractive index are calculated. Our results agree well with the available data in the literature.

  15. A new nonsyndromic X-linked sensorineural hearing impairment linked to Xp21.2

    Energy Technology Data Exchange (ETDEWEB)

    Lalwani, A.K.; Brister, J.R.; Fex, J.; Grundfast, K.M.; Pikus, A.T.; Ploplis, B.; San Agustin, T.; Skarka, H.; Wilcox, E.R. [National Institutes of Health, Bethesda, MD (United States)

    1994-10-01

    X-linked deafness is a rare cause of hereditary hearing impairment. We have identified a family with X-linked dominant sensorineural hearing impairment, characterized by incomplete penetrance and variable expressivity in carrier females, that is linked to the Xp21.2, which contains the Duchenne muscular dystrophy (DMD) locus. The auditory impairment in affected males was congenital, bilateral, profound, sensorineural, affecting all frequencies, and without evidence of radiographic abnormality of the temporal bone. Adult carrier females manifested bilateral, mild-to-moderate high-frequency sensorineural hearing impairment of delayed onset during adulthood. Eighteen commercially available polymorphic markers from the X chromosome, generating a 10-15-cM map, were initially used for identification of a candidate region. DXS997, located within the DMD gene, generated a two-point LOD score of 2.91 at {theta} = 0, with every carrier mother heterozygous at this locus. Recombination events at DXS992 (located within the DMD locus, 3{prime} to exon 50 of the dystrophin gene) and at DXS1068 (5{prime} to the brain promoter of the dystrophin gene) were observed. No recombination events were noted with the following markers within the DMD locus: 5{prime}DYS II, intron 44, DXS997, and intron 50. There was no clinical evidence of Duchenne or Becker muscular dystrophy in any family member. It is likely that this family represents a new locus on the X chromosome, which when mutated results in nonsyndromic sensorineural hearing loss and is distinct from the heterogeneous group of X-linked hearing losses that have been previously described. 57 refs., 6 figs., 1 tab.

  16. Ablation of XP-V gene causes adipose tissue senescence and metabolic abnormalities.

    Science.gov (United States)

    Chen, Yih-Wen; Harris, Robert A; Hatahet, Zafer; Chou, Kai-ming

    2015-08-18

    Obesity and the metabolic syndrome have evolved to be major health issues throughout the world. Whether loss of genome integrity contributes to this epidemic is an open question. DNA polymerase η (pol η), encoded by the xeroderma pigmentosum (XP-V) gene, plays an essential role in preventing cutaneous cancer caused by UV radiation-induced DNA damage. Herein, we demonstrate that pol η deficiency in mice (pol η(-/-)) causes obesity with visceral fat accumulation, hepatic steatosis, hyperleptinemia, hyperinsulinemia, and glucose intolerance. In comparison to WT mice, adipose tissue from pol η(-/-) mice exhibits increased DNA damage and a greater DNA damage response, indicated by up-regulation and/or phosphorylation of ataxia telangiectasia mutated (ATM), phosphorylated H2AX (γH2AX), and poly[ADP-ribose] polymerase 1 (PARP-1). Concomitantly, increased cellular senescence in the adipose tissue from pol η(-/-) mice was observed and measured by up-regulation of senescence markers, including p53, p16(Ink4a), p21, senescence-associated (SA) β-gal activity, and SA secretion of proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) as early as 4 wk of age. Treatment of pol η(-/-) mice with a p53 inhibitor, pifithrin-α, reduced adipocyte senescence and attenuated the metabolic abnormalities. Furthermore, elevation of adipocyte DNA damage with a high-fat diet or sodium arsenite exacerbated adipocyte senescence and metabolic abnormalities in pol η(-/-) mice. In contrast, reduction of adipose DNA damage with N-acetylcysteine or metformin ameliorated cellular senescence and metabolic abnormalities. These studies indicate that elevated DNA damage is a root cause of adipocyte senescence, which plays a determining role in the development of obesity and insulin resistance.

  17. Role of the pseudoautosomal region in sex-chromosome pairing during male meiosis: Meiotic studies in a man with a deletion of distal Xp

    Energy Technology Data Exchange (ETDEWEB)

    Mohandas, T.K.; Passage, M.B.; Yen, P.H.; Speed, R.M.; Chandley, A.C.; Shapiro, L.J. (Univ. of California, San Francisco, CA (United States))

    1992-09-01

    Meiotic studies were undertaken in a 24-year-old male patient with short stature, chondrodysplasia punctata, ichthyosis, steroid sulfatase deficiency, and mild mental retardation with an inherited cytologically visible deletion of distal Xp. Molecular investigations showed that the pseudoautosomal region as well as the steroid sulfatase gene were deleted, but telomeric sequences were present at the pter on the deleted X chromosome. A complete failure of sex-chromosome pairing was observed in the primary spermatocytes of the patient. Telomeric approaches between the sex chromosomes were made at zygotene in some cells, but XY synaptonemal complex was formed. The sex chromosomes were present as univalents at metaphase I, and germ-cell development was arrested between metaphase I and metaphase II in the vast majority of cells, consistent with the azoospermia observed in the patient. The failure of XY pairing in this individual indicates that the pseudoautosomal sequences play an important role in initiating XY pairing and formation of synaptonemal complex at meiosis. 36 refs., 6 figs.

  18. The development of a GeXP-based multiplex reverse transcription-PCR assay for simultaneous detection of sixteen human respiratory virus types/subtypes

    Directory of Open Access Journals (Sweden)

    Li Jin

    2012-08-01

    Full Text Available Abstract Background Existing standard non-molecular diagnostic methods such as viral culture and immunofluorescent (DFA are time-consuming, labor intensive or limited sensitivity. Several multiplex molecular assays are costly. Therefore, there is a need for the development of a rapid and sensitive diagnosis of respiratory viral pathogens. Methods A GeXP-based multiplex RT-PCR assay (GeXP assay was developed to detect simultaneously sixteen different respiratory virus types/subtypes. Seventeen sets of chimeric primers were used to initiate the RT-PCR, and one pair of universal primers was used for the subsequent cycles of the RT-PCR. The specificity of the GeXP assay was examined with positive controls for each virus type/subtype. The sensitivity was evaluated by performing the assay on serial ten-fold dilutions of in vitro-transcribed RNA of all RNA viruses and the plasmids containing the Adv and HBoV target sequence. GeXP assay was further evaluated using 126 clinical specimens and compared with Luminex xTAG RVP Fast assay. Results The GeXP assay achieved a sensitivity of 20–200 copies for a single virus and 1000 copies when all of the 16 pre-mixed viral targets were present. Analyses of 126 clinical specimens using the GeXP assay demonstrated that GeXP assay and the RVP Fast assay were in complete agreement for 109/126 (88.51% of the specimens. GeXP assay was more sensitive than the RVP Fast assay for the detection of HRV and PIV3, and slightly less sensitive for the detection of HMPV, Adv, RSVB and HBoV. The whole process of the GeXP assay for the detection of 12 samples was completed within 2.5 hours. Conclusions In conclusion, the GeXP assay is a rapid, cost-effective, sensitive, specific and high throughput method for the detection of respiratory virus infections.

  19. Metal-organic frameworks derived CoxFe1-xP nanocubes for electrochemical hydrogen evolution

    Science.gov (United States)

    Hao, Jinhui; Yang, Wenshu; Zhang, Zhe; Tang, Jilin

    2015-06-01

    Designing and developing active, cost-effective and stable electrocatalysts for hydrogen evolution reaction (HER) are still an ongoing challenge. Herein, we report the synthesis of binary transition metal phosphide (CoxFe1-xP) nanocubes with different Co and Fe ratios through a phosphidation process using metal-organic frameworks (MOFs) as templates. MOF templates contribute well-defined nanocube architectural features after phosphidation, while a suitable phosphidation temperature could allow formation of a crystal structure and maintain the well-defined structure. The incorporation of a binary transition metal results in redistribution of the valence electrons in CoxFe1-xP. The changes imply anionic states of the P and Fe atoms, which act as active sites and thus have stronger electron-donating ability. When CoxFe1-xP nanocubes are employed as electrocatalysts, these characteristic features facilitate the performance of HER. Remarkably, Co0.59Fe0.41P nanocubes prepared at 450 °C afford a current density of 10 mA cm-2 at a low overpotential of 72 mV in acidic conditions and 92 mV in alkaline conditions. Co0.59Fe0.41P nanocubes also exhibit a small Tafel slope of 52 mV decade-1 in acidic conditions and 72 mV decade-1 in alkaline conditions. Moreover, Co0.59Fe0.41P nanocubes show good stability in both acidic and alkaline conditions. Our method produces the highly active HER catalyst based on binary transition metal MOF templates, providing a new avenue for designing excellent electrocatalysts.Designing and developing active, cost-effective and stable electrocatalysts for hydrogen evolution reaction (HER) are still an ongoing challenge. Herein, we report the synthesis of binary transition metal phosphide (CoxFe1-xP) nanocubes with different Co and Fe ratios through a phosphidation process using metal-organic frameworks (MOFs) as templates. MOF templates contribute well-defined nanocube architectural features after phosphidation, while a suitable phosphidation

  20. Modeling of a lot scale rainwater tank system in XP-SWMM: a case study in Western Sydney, Australia.

    Science.gov (United States)

    van der Sterren, Marlène; Rahman, Ataur; Ryan, Garry

    2014-08-01

    Lot scale rainwater tank system modeling is often used in sustainable urban storm water management, particularly to estimate the reduction in the storm water run-off and pollutant wash-off at the lot scale. These rainwater tank models often cannot be adequately calibrated and validated due to limited availability of observed rainwater tank quantity and quality data. This paper presents calibration and validation of a lot scale rainwater tank system model using XP-SWMM utilizing data collected from two rainwater tank systems located in Western Sydney, Australia. The modeling considers run-off peak and volume in and out of the rainwater tank system and also a number of water quality parameters (Total Phosphorus (TP), Total Nitrogen (TN) and Total Solids (TS)). It has been found that XP-SWMM can be used successfully to develop a lot scale rainwater system model within an acceptable error margin. It has been shown that TP and TS can be predicted more accurately than TN using the developed model. In addition, it was found that a significant reduction in storm water run-off discharge can be achieved as a result of the rainwater tank up to about one year average recurrence interval rainfall event. The model parameter set assembled in this study can be used for developing lot scale rainwater tank system models at other locations in the Western Sydney region and in other parts of Australia with necessary adjustments for the local site characteristics.

  1. Definition of the neurological phenotype associated with dup (X)(p11.22-p11.23).

    Science.gov (United States)

    Broli, Marcella; Bisulli, Francesca; Mastrangelo, Massimo; Fontana, Elena; Fiocchi, Isabella; Zucca, Claudio; Bonaglia, Maria Clara; Buono, Serafino; Musumeci, Sebastiano Antonino; Romano, Corrado; Reitano, Santina; Savio, Maria; Vitello, Girolamo Aurelio; Bernardi, Bruno; Cevolani, Daniela; Agati, Raffaele; Poda, Roberto; Gallassi, Roberto; Giorda, Roberto; Zuffardi, Orsetta; Bernardina, Bernardo Dalla; Seri, Marco; Tinuper, Paolo

    2011-09-01

    The aim of this study was to describe in detail the neurological features of nine patients carrying the recently reported microduplication at Xp11.22-11.23. Clinical and neurological examination, brain magnetic resonance imaging (except for two patients), electroencephalography and a neuropsychological assessment specific for language disturbances were performed in nine patients with microduplication at Xp11.22-11.23, disclosed by comparative genomic hybridisation array. Six patients were familial cases belonging to three unrelated pedigrees and three were sporadic cases. The patients had the following characteristics: mild dysmorphic facial features (except for two patients), mental retardation with moderate to severe global language deterioration, electroencephalographic epileptiform discharges during wakefulness and especially during sleep or electrical status epilepticus during slow sleep in younger cases, and negative brain magnetic resonance imaging. The main clinical features of this new microduplication syndrome were mild facial dysmorphisms, from increased electroencephalogram abnormalities during sleep to electrical status epilepticus during slow sleep, and mental retardation mainly involving language function in the absence of detectable brain lesions. In the absence of detectable brain lesions, speech delay may be associated with electrical status epilepticus during slow sleep or, alternatively, related to abnormal brain expression of a dosage-sensitive gene contained within the duplication region.

  2. A grandpaternally derived de novo deletion within Xp21 initially presenting in carrier females diagnosed as Kugelberg-Welander syndrome.

    Science.gov (United States)

    Wood, S; Shukin, R J; McGillivray, B C; Ray, P N; Worton, R G

    1988-02-01

    We report on two sisters with a history of muscle weakness and an electromyogram (EMG) diagnosis of Kugelberg-Welander syndrome (KWS) or juvenile spinal muscular atrophy. A half-brother to these women was diagnosed to have Duchenne muscular dystrophy (DMD). Using molecular probes, we identified a deletion within Xp21 in this isolated case of DMD. Sequences detected by pXJ1.1 are deleted, while fragments detected by pERT87 are intact. Both of these probes are derived from the DMD locus. We have shown that the affected sisters share with their half-brother DNA markers that are linked to the DMD gene and inherited from their maternal grandfather. Dosage analysis of Southern blots show monosomy for pXJ1.1, which has allowed us to determine carrier status within this family and to show that the half-sisters are manifesting DMD carriers.

  3. Group A Streptococcus vulvovaginitis in breastfeeding women.

    Science.gov (United States)

    Rahangdale, Lisa; Lacy, Judith; Hillard, Paula A

    2008-08-01

    Group A beta-hemolytic streptococcus-associated vulvovaginitis is uncommon in adult women. Clinicians should include group A beta-hemolytic streptococcus as a possible cause of vulvovaginal symptoms in breastfeeding women. Along with appropriate antibiotic therapy, vaginal estrogen therapy may be considered to diminish susceptibility to recurrent infection in women with vaginal atrophy.

  4. Dataset of proinflammatory cytokine and cytokine receptor gene expression in rainbow trout (Oncorhynchus mykiss) measured using a novel GeXP multiplex, RT-PCR assay

    Science.gov (United States)

    A GeXP multiplex, RT-PCR assay was developed and optimized that simultaneously measures expression of a suite of immune-relevant genes in rainbow trout (Oncorhynchus mykiss), concentrating on tumor necrosis factor and interleukin-1 ligand/receptor systems and acute phase response genes. The dataset ...

  5. Experimental investigations of atomic ordering effects in the epitaxial Ga{sub x}In{sub 1-x}P, coherently grown on GaAs (100) substrates

    Energy Technology Data Exchange (ETDEWEB)

    Seredin, P.V., E-mail: paul@phys.vsu.ru [Voronezh State University, Universitetskaya pl., 1, 394006 Voronezh (Russian Federation); Goloshchapov, D.L.; Khudyakov, Yu.Yu.; Lenshin, A.S.; Lukin, A.N. [Voronezh State University, Universitetskaya pl., 1, 394006 Voronezh (Russian Federation); Arsentyev, I.N., E-mail: arsentyev@mail.ioffe.ru [Ioffe Physical and Technical Institute, Polytekhnicheskaya, 26, 194021 St-Petersburg (Russian Federation); Prutskij, Tatiana, E-mail: prutskij@yahoo.com [Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Privada 17 Norte, No 3417, Col San Miguel Hueyotlipan, 72050 Puebla, Puebla (Mexico)

    2017-03-15

    A range of structural and spectroscopic techniques were used for the study of the properties of epitaxial Ga{sub x}In{sub 1-x}P alloys with an ordered arrangement of atoms in a crystal lattice grown by MOCVD on single-crystalline substrates of GaAs (100). The appearance of atomic ordering in the coherent growth conditions of the ordered Ga{sub x}In{sub 1-x}P alloy on GaAs (100) resulted in cardinal changes of the structural and optical properties of semiconductor in comparison to disordered alloys, including the change of the crystal lattice parameter and, consequently, reduced crystal symmetry, decreased band gap and formation of two different types of surface nanorelief. This is the first report of the calculation of parameters of the crystal lattice in Ga{sub x}In{sub 1-x}P with ordering taking into account the elastic stresses dependent on long-range ordering. Based on the variance analysis data with regard to the IR-reflection spectra as well as the UV-spectroscopy data obtained in the transmission-reflection mode, the main optical characteristics of the ordered Ga{sub x}In{sub 1-x}P alloys were determined for the first time, namely, refractive index dispersion and high-frequency dielectric constant. All of the experimental results were in good agreement with the previously developed theoretical beliefs.

  6. Fine-scale mapping of type I allergy candidate loci suggests central susceptibility genes on chromosomes 3q, 4q and Xp

    DEFF Research Database (Denmark)

    Haagerup, A; Børglum, A D; Binderup, H G;

    2004-01-01

    and prevention. Like for other complex disorders, achievement of the knowledge necessary depends on confirmation of reported genomic candidate regions. METHODS: We performed a two-stage fine-scale linkage analysis in 11 selected candidate regions on chromosome 3p, 3q, 4p, 4q, 5q, 6p, 9p, 12q, 12qter, 18q and Xp...

  7. Experimental investigations of atomic ordering effects in the epitaxial GaxIn1-xP, coherently grown on GaAs (100) substrates

    Science.gov (United States)

    Seredin, P. V.; Goloshchapov, D. L.; Khudyakov, Yu. Yu.; Lenshin, A. S.; Lukin, A. N.; Arsentyev, I. N.; Prutskij, Tatiana

    2017-03-01

    A range of structural and spectroscopic techniques were used for the study of the properties of epitaxial GaxIn1-xP alloys with an ordered arrangement of atoms in a crystal lattice grown by MOCVD on single-crystalline substrates of GaAs (100). The appearance of atomic ordering in the coherent growth conditions of the ordered GaxIn1-xP alloy on GaAs (100) resulted in cardinal changes of the structural and optical properties of semiconductor in comparison to disordered alloys, including the change of the crystal lattice parameter and, consequently, reduced crystal symmetry, decreased band gap and formation of two different types of surface nanorelief. This is the first report of the calculation of parameters of the crystal lattice in GaxIn1-xP with ordering taking into account the elastic stresses dependent on long-range ordering. Based on the variance analysis data with regard to the IR-reflection spectra as well as the UV-spectroscopy data obtained in the transmission-reflection mode, the main optical characteristics of the ordered GaxIn1-xP alloys were determined for the first time, namely, refractive index dispersion and high-frequency dielectric constant. All of the experimental results were in good agreement with the previously developed theoretical beliefs.

  8. X-linked mental retardation: a comprehensive molecular screen of 47 candidate genes from a 7.4 Mb interval in Xp11.

    NARCIS (Netherlands)

    Jensen, L.R.; Lenzner, S.; Moser, B.; Freude, K.; Tzschach, A.; Wei, C.; Fryns, J.P.; Chelly, J.; Turner, G.; Moraine, C.; Hamel, B.C.J.; Ropers, H.H.; Kuss, A.W.

    2007-01-01

    About 30% of the mutations causing nonsyndromic X-linked mental retardation (MRX) are thought to be located in Xp11 and in the pericentromeric region, with a particular clustering of gene defects in a 7.4 Mb interval flanked by the genes ELK1 and ALAS2. To search for these mutations, 47 brain-expres

  9. Efficient transformation of the yellow fever mosquito Aedes aegypti using the piggyBac transposable element vector pBac[3xP3-EGFP afm].

    Science.gov (United States)

    Kokoza, V; Ahmed, A; Wimmer, E A; Raikhel, A S

    2001-11-01

    We report efficient germ-line transformation in the yellow fever mosquito Aedes aegypti accomplished using the piggyBac transposable element vector pBac[3xP3-EGFP afm]. Two transgenic lines were established and characterized; each contained the Vg-Defensin A transgene with strong eye-specific expression of the enhanced green fluorescent protein (EGFP) marker gene regulated by the artificial 3xP3 promoter. Southern blot hybridization and inverse PCR analyses of genomic DNA demonstrated a precise piggyBac-mediated, single copy insertion of the pBac[3xP3-EGFP afm,Vg-DefA] transposon in each transgenic line. For each line, genetic analysis confirmed stability and integrity of the entire transposon construct in the mosquito genome through the G2-G6 generations. Successful establishment of homozygous transgenic lines indicated that in both cases a non-lethal integration of the transposon into the mosquito genome had occurred. The 3xP3-EGFP marker was tested in mosquitoes with different genetic backgrounds. In white-eyed transgenic mosquitoes, the strong eye-specific expression of GFP was observed throughout all stages of development, starting from newly hatched first instar larvae to adults. A similar level and pattern of fluorescence was observed in red-eyed mosquitoes that were generated by crossing the 3xP3-EGFP transformants with the kh(w) white-eye mosquitoes transformed with the Drosophila cinnabar gene. Importantly, the utility of the 3xP3-EGFP, as marker gene for transformation of wild type mosquitoes, was demonstrated by strong eye-specific GFP expression in larval and pupal stages of black-eyed hybrids of the 3xP3-EGFP white-eye transformants and the wild type Rockefeller/UGAL strain. Finally, analysis of the Vg-DefA transgene expression in transformants from two established lines demonstrated strong blood-meal activation and fat-body-specific expression regulated by the Vg 1.8-kb 5' upstream region.

  10. Scarlet Fever: A Group A Streptococcal Infection

    Science.gov (United States)

    ... this? Submit Button Past Emails CDC Features Scarlet Fever: A Group A Streptococcal Infection Language: English Español ( ... red rash that feels rough, like sandpaper. Scarlet Fever Podcast A pediatrician explains the cause, treatment, and ...

  11. Interference Between Lactobacilli And Group A Streptococcus ...

    African Journals Online (AJOL)

    Interference Between Lactobacilli And Group A Streptococcus pyogenes : An Expansion To The Concept Of ... New Egyptian Journal of Microbiology ... However, little is known about their health benefits in respiratory and skin infections.

  12. Delfdroid y su comparación evaluativa con XP y Scrum mediante el método 4-DAT

    Directory of Open Access Journals (Sweden)

    Ernesto Avila Domenech

    2013-03-01

    Full Text Available Debido a las diferencias notables entre el desarrollo de software tradicional y el software para dispositivos móviles, es necesario que la metodología utilizada para guiar proyectos de desarrollo de aplicaciones para móviles tenga características no tradicionales. En el presente trabajo se propone una metodología ágil de desarrollo de software específica para dispositivos móviles. Para su descripción se han tomado algunos elementos de la propuesta de Alistair Cockburn, en la que se indica desglosar la metodología en diez elementos como mínimo: roles, destrezas, artefactos, actividades, valores, equipos, asignación de tareas, técnicas, herramientas y estándares. Además se realiza una evaluación comparativa con las metodologías ágiles XP y Scrum mediante el método 4-Dimensional Analytical Tool propuesto por Asif Qumer y Brian Henderson-Sellers.

  13. Development and physical analysis of YAC contigs covering 7 Mb of Xp22.3-p22.2

    Energy Technology Data Exchange (ETDEWEB)

    Herrell, S.; Novo, F.J.; Charlton, R. [Univ. of Cambridge (United Kingdom)] [and others

    1995-01-20

    A total of YAC clones have been isolated from the region of Xp22.2-p22.3 extending from the amelogenin gene locus to DXS31. Restriction analysis of these clones in association with STS contenting and end clone analysis has facilitated the construction of 6 contigs covering a total of 7 Mb in which 20 potential CpG islands have been located. Thirty new STSs have been developed from probe and YAC end clone sequences, and these have been used in the analysis of patients suffering from different combinations of chondrodysplasia punctata, mental retardation, X-linked ichthyosis, and Kallmann syndrome. The results suggest that (1) the gene for chondrodysplasia punctata must lie between the X chromosome pseudoautosomal boundary (PABX) and DXS1145; (2) a gene for mental retardation lies between DXS1145 and the sequence tagged site GS1; and (3) the gene for ocular albinism type 1 lies proximal to the STS G13. The CpG islands within the YAC contigs constitute valuable markers for the potential positions of genes. Genes found associated with any of these potential CpG islands would be possible candidates for the disease genes mentioned above. 47 refs., 3 figs., 5 tabs.

  14. The Role of ZnP2 Nanoclusters in the Vibrational Properties of Cd x Zn(1 - x)P2 Solid Solutions

    Science.gov (United States)

    Shportko, K.; Shoukavaya, T.; Trukhan, V.; Baran, J.; Starik, S.; Venger, E.

    2016-09-01

    This study reports an analysis of the IR reflectance and Raman spectra of Cd x Zn(1 - x)P2 solid solutions. We have analyzed the effect of the doping of the CdP2 single crystal by the ZnP2 nanoclusters on the vibrational properties of studied samples: ɛ 0, ɛ inf, phonon frequencies, and strengths. These dependencies might be used as an alternative non-destructive way for the control of the Cd x Zn(1 - x)P2 composition. The obtained results show that variation of the concentration of ZnP2 nanoclusters opens a space to design the tailored material properties for the industrial applications.

  15. Non-Bloch nature of alloy states in a conventional semiconductor alloy - GaxIn1-xP as an example

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lin-Wang; Zhang, Yong; Mascarenhas, Angelo; Wang, Lin-Wang

    2008-07-11

    Contrary to the conventional wisdom, electronic states in a 'well behaved' semiconductor alloy such as Ga{sub x}In{sub 1-x}P may drastically deviate from a Bloch state, which can be true even for band edge states if they are derived from degenerate critical points. For Ga{sub x}In{sub 1-x}P in the entire composition range, k-space spectral analyses are performed for the important critical points, revealing the significance of the (near) resonant inter-and intra-valley scatterings of the fluctuation potential in the alloy. The non-trivial implications of such scatterings on the transport and strain effect are discussed.

  16. Measurements of (n,xp), (n,xd) double differential cross sections of Al and C for neutrons at 75 and 65 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Nauchi, Yasushi; Baba, Mamoru; Iwasaki, Tomohiko [Tohoku Univ., Sendai (Japan). Faculty of Engineering] [and others

    1998-03-01

    The (n,xp) and (n,xd) double differential cross sections (DDXs) of Al and C were measured at 6 angles (12deg, 17deg, 25deg, 40deg, 55deg and 70deg) for neutrons En=65 and 75 MeV. These data are compared with theoretical calculations of ISOBAR and GNASH. A new wide range spectrometer under fabrication to down the detection threshold is also described. (author)

  17. 创建一个Microsoft Office XP外接程序%Creating a Microsoft Office XP COM Add-ins

    Institute of Scientific and Technical Information of China (English)

    杨之江; 王晖

    2002-01-01

    本文描述了如何用Microsoft Office XP Developer来开发一个COM外接程序,该外接程序可以创建一个适用于Microsoft FrontPage,Microsoft Word和Microsoft PowerPoint的简单的报表,报表中的数据来源于Microsoft Access数据库.

  18. Relaxor ferroeletric behavior in S r1 -xP rxTi O3 : Cooperation between polar and antiferrodistortive instabilities

    Science.gov (United States)

    Checchia, Stefano; Allieta, Mattia; Coduri, Mauro; Brunelli, Michela; Scavini, Marco

    2016-09-01

    Chemical doping at the Sr and Ti sites is a feasible way to alter the quantum paraelectric state of SrTi O3 perovskite. Doping with Pr is known to induce relaxor ferroelectricity at room temperature in the S r1 -xP rxTi O3 solid solution. The relationship between its dielectric properties and structural phase transition has been debated, but no definitive structural argument has been proposed. Here we present a systematic structural study of S r1 -xP rxTi O3 (0.020 ≤x ≤0.150 ). We establish the structural phase diagram using high-resolution x-ray powder diffraction by finding the antiferrodistortive structural phase transitions for all the compositions studied. By using pair distribution function analysis, we show the mismatch between local and long-range structures in terms of increased local order parameters. Finally, we propose a correlation between the local structural order parameters and the emergence of hard polar modes as found by Raman spectroscopy. Our results are quantitatively consistent with recent theoretical calculations showing that the increase of local tetragonality and local octahedral tilting above a critical value in fact underlie the polar instability. This confirms that structural orders involving both polar and antiferrodistortive characters compete and cooperate at different levels, promoting ferroelectricity in S r1 -xP rxTi O3 .

  19. Novel microduplications at Xp11.22 including HUWE1: clinical and molecular insights into these genomic rearrangements associated with intellectual disability.

    Science.gov (United States)

    Santos-Rebouças, Cíntia Barros; de Almeida, Luciana Guedes; Belet, Stefanie; Dos Santos, Suely Rodrigues; Ribeiro, Márcia Gonçalves; da Silva, Antônio Francisco Alves; Medina-Acosta, Enrique; Dos Santos, Jussara Mendonça; Gonçalves, Andressa Pereira; Bahia, Paulo Roberto Valle; Pimentel, Márcia Mattos Gonçalves; Froyen, Guy

    2015-04-01

    Recently, we defined a minimal overlapping region for causal Xp11.22 copy number gains in males with intellectual disability (ID), and identified HECT, UBA and WWE domain-containing protein-1 (HUWE1) as the primary dosage-sensitive gene, whose overexpression leads to ID. In the present study, we used this minimal interval to search for HUWE1 copy number variations by quantitative polymerase chain reaction in a large cohort of Brazilian males with idiopathic ID. We detected two unrelated sporadic individuals with syndromic ID carrying unique overlapping duplications encompassing HUWE1. Breakpoint junction analysis showed a simple tandem duplication in the first patient, which has probably arisen by microhomology-mediated break-induced repair mechanism. In the second patient, the rearrangement is complex having an insertion of an intrachromosomal sequence at its junction. This kind of rearrangement has not been reported in Xp11.22 duplications and might have emerged by a replication- or recombination-based mechanism. Furthermore, the presence of infantile seizures in the second family suggests a potential role of increased KDM5C expression on epilepsy. Our findings highlight the importance of microduplications at Xp11.22 to ID, even in sporadic cases, and reveal new clinical and molecular insight into HUWE1 copy number gains.

  20. Genome Sequence Comparative Analysis of Long Arm and Short Arm of Human X Chromosome%人X染色体长臂(Xq)和短臂(Xp)基因组学比较分析

    Institute of Scientific and Technical Information of China (English)

    吕占军; 宋淑霞; 翟羽; 侯杰; 韩丽枝; 王秀芳

    2005-01-01

    density.Nucleotide sequences on the X chromosome were divided into 50 kb per segment that was recorded as a set of frequency values of 7-nucleotide (7 nt) strings using all possible 7 nt strings (47=16 384).120 genes highly expressed in the tonsil germinal center B cells were selected for calculating the 7 nt string frequency values of all introns (intron 7nt).Intron 7nt was considered RNAs (RNA population) that simulated the total of small RNA fragments in cells.Knowing the 7 nt frequency values of DNA segments and the intron 7nt,we can calculate the binding density of DNA segments to the intron 7nt that was termed as RNA binding density.The RNA binding density was determined by the amount of complement sequences.The more amount of complement sequences,the more density of RNA binding.The RNA binding density simulated the total of small RNA fragments bound to the DNA segment.Several principal characteristics were observed for the first time: (1) The mean value of RNA binding density of DNA segments on Xp was significantly higher than that on Xq (P<0.001); (2) The numbers of DNA segments highly binding RNAs were more on Xp than on Xq (P<0.001); (3) The clusters of RNA highly binding DNA segments were associated with regions in which genes escape inactivation.It has been suggested that RNAs activate genes and the interaction of RNA-DNA in cells are extensive,for example,RNAs increase DNaseⅠsensitivity of DNA,there is plenty of nonprotein-coding RNAs in cells,the binding specificity of DNA-RNA is far higher than that of DNA-protein and the affinity of DNA with RNA is increased,as compared with DNA.The nonrandom properties of distribution of RNA highly binding segments between Xp and Xq,combined with the finding of RNA activating genes,provide a strong evidence that RNA highly binding segments may serve as DNA signals to propagate activation along a chromosome and vice versa,the DNA segments that less bind RNAs may silence the genes.

  1. Production of pinoresinol diglucoside, pinoresinol monoglucoside, and pinoresinol by Phomopsis sp. XP-8 using mung bean and its major components.

    Science.gov (United States)

    Zhang, Yan; Shi, Junling; Gao, Zhenhong; Yangwu, Ruiming; Jiang, Huanshi; Che, Jinxin; Liu, Yanlin

    2015-06-01

    Phomopsis sp. XP-8 is an endophytic fungus that has the ability to produce pinoresinol diglucoside (PDG) in vitro and thus has potential application for the biosynthesis of PDG independent of plants. When cultivated in mung bean medium, PDG production was significantly improved and pinoresinol monoglucoside (PMG) and pinoresinol (Pin) were also found in the culture medium. In this experiment, starch, protein, and polysaccharides were isolated from mung beans and separately used as the sole substrate in order to explore the mechanism of fermentation and identify the major substrates that attributed to the biotransformation of PDG, PMG, and Pin. The production of PDG, PMG, and Pin was monitored using high-performance liquid chromatography (HPLC) and confirmed using HPLC-MS. Activities of related enzymes, including phenylalanine ammonia-lyase (PAL), trans-cinnamate 4-hydroxylase (C4H), and 4-coumarate-CoA ligase (4CL) were analyzed and tracked during the cultivation. The reaction system contained the compounds isolated from mung bean in the designed amount. Accumulation of phenylalanine, cinnamic acid, p-coumaric acid, PDG, PMG, and Pin and the activities of PAL, C4H, and 4CL were measured during the bioconversion. PMG was found only when mung bean polysaccharide was analyzed, while production of PDG and Pin were found when both polysaccharide and starch were analyzed. After examining the monosaccharide composition of the mung bean polysaccharide and the effect of the different monosaccharides had on the production of PMG, PDG, and Pin, galactose in mung bean polysaccharide proved to be the major factor that stimulates the production of PMG.

  2. Successive Administration of Streptococcus Type 5 Group A Antigens and S. typhimurium Antigenic Complex Corrects Elevation of Serum Cytokine Concentration and Number of Bone Marrow Stromal Pluripotent Cells in CBA Mice Induced by Each Antigen Separately.

    Science.gov (United States)

    Gorskaya, Yu F; Danilova, T A; Grabko, V I; Nesterenko, V G

    2015-12-01

    Administration of bacterial antigens to CBA mice induced an increase in serum concentration of virtually all cytokines with a peak in 4 h after administration of S. typhimurium antigens and in 7 h after administration of streptococcus antigens. In 20 h, cytokine concentrations returned to the control level or were slightly below it. In 4 h after administration of S. typhimurium antigens preceded 3 h before by administration of streptococcus antigens, we observed a significant decrease in serum concentrations of IFN-γ, IL-10, GM-CSF, IL-12, and TNF-α, in comparison with injection S. typhimurium antigens alone and IL-5, IL-10, GM-CSF, and TNF-α in comparison with injection of streptococcus antigens alone; the concentrations of IL-2 and IFN-γ, in contrast, increased by 1.5 times in this case. In 20 h after administration of S. typhimurium antigens, the number of multipotential stromal cells (MSC) in the bone marrow and their cloning efficiency (ECF-MSC) increased by 4.8 and 4.4 times, respectively, in comparison with the control, while after administration of streptococcus antigens by 2.6 and 2.4 times, respectively. In 20 h after administration of S. typhimurium antigens preceded 3 h before by administration of streptococcus antigens, these parameters increased by 3.2 and 2.9 times, respectively, in comparison with the control, i.e. the observed increase in the level of MSC count and ECF-MSC is more consistent with the response of the stromal tissue to streptococcus antigens. Thus, successive administration of two bacterial antigens corrected both serum cytokine profiles and MSC response to administration of each antigen separately, which indicates changeability of the stromal tissue in response to changes in the immune response.

  3. A randomized prospective comparison of CartoMerge and CartoXP to guide circumferential pulmonary vein isolation for the treatment of paroxysmal atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    TANG Kai; MA Jian; ZHANG Shu; ZHANG Jing-ying; WEI Yi-dong; CHEN Yan-qing; YU Xue-jing; XU Ya-wei

    2008-01-01

    Background CartoXP and CartoMerge have been used to treat atrial fibrillation(AF)for several years.Our randomized prospective study compared clinical outcomes of these two versions of three dimensional electroanatomic mapping system in guiding catheter ablation for paroxysmal atrial fibrillation (PAF).Methods Eighty-one patients with symptomatic,drug refractory PAF were randomly assigned to CartoMerge group (n=42,mean age(54.5±13.1)years,history of AF=3.2 years)or CartoXP group(n=39,mean age(59.8±15.6)years,history of AF=2.9 years).All patients underwent 64-slice computed tomography(MSCT)1 to 3 days prior to ablation procedure.Using CartoMergeTM Image Integration Module,3D anatomical images of the left atrium(LA)and pulmonary veins(PVs)derived from MSCT of CartoMerge group were established and merged with the electroanatomical map.The integrated images were used to guide the procedure of circumferential pulmonary vein isolation (CPVI).In the other group,CPVI was guided just by CartoXP.The endpoint of CPVI in both groups was abolition or dissociation of pulmonary vein potentials(PVPs).Results Mapping points to establish the electroanatomical model of the LA/PVs were 48.7±13.4 in CartoMerge group and 62.5±15.7 in CartoXP group(P<0.001).Mean distance between mapping points and the MSCT surfaces in CartoMerge group was(1.59±0.33)mm.Accomplishment of abolition or dissociation of PVPs was achieved 95.2% in CartoMerge group and 92.3% in CartoXP group.Durations of procedure and exposure to X-ray were(156±25)minutes,(179±21)minutes(P<0.001) and(19.6±7.5)minutes,(28.5±12.8)minutes(P<0.001),respectively.After a follow-up with duration of(11.9±3.1)months vs (12.4±3.6)months post the first ablation procedure,patients free of AF were 33(78.6%)in CartoMerge group and 29(74.4%) in CartoXP group(P>0.50).No patient suffered pulmonary vein stenosis,alrioesophageal fistula,stroke or death.Conclusion Compared to CartoXP,CartoMerge shortened the catheter ablation

  4. Necrotizing fasciitis caused by group A streptococcus

    Directory of Open Access Journals (Sweden)

    Mikić Dragan

    2002-01-01

    Full Text Available The first case of the confirmed necrotizing fasciitis caused by Group A Streptococcus in Yugoslavia was presented. Male patient, aged 28, in good health, suddenly developed symptoms and signs of severe infective syndrome and intensive pain in the axillary region. Parenteral antibiotic, substitution and supportive therapy was conducted along with the radical surgical excision of the necrotizing tissue. The patient did not develop streptococcal toxic shock syndrome thanks to the early established diagnosis and timely applied aggressive treatment. He was released from the hospital as completely cured two months after the admission.

  5. The DNA damage-binding protein XPC is a frequent target for inactivation in squamous cell carcinomas.

    Science.gov (United States)

    de Feraudy, Sebastien; Ridd, Katie; Richards, Lauren M; Kwok, Pui-Yan; Revet, Ingrid; Oh, Dennis; Feeney, Luzviminda; Cleaver, James E

    2010-08-01

    XPC, the main damage-recognition protein responsible for nucleotide excision repair of UVB damage to DNA, is lost or mutated in xeroderma pigmentosum group C (XP-C), a rare inherited disease characterized by high incidence and early onset of non-melanoma and melanoma skin cancers. The high incidence of skin cancers in XP-C patients suggests that loss of expression of XPC protein might also provide a selective advantage for initiation and progression of similar cancers in non XP-C patients in the general population. To test whether XPC is selectively lost in squamous cell carcinomas from non XP-C patients, we examined XPC expression by immunohistochemistry on a tissue microarray with 244 tissue cores, including in situ and invasive squamous-cell carcinomas (SCCs), keratoacanthoma (KA), and normal skin samples from both immunocompetent and immunosuppressed patients. We found that XPC expression was lost in 49% of invasive squamous cell carcinomas from immunocompetent patients and 59% from immunosuppressed patients. Loss of expression was correlated with deletions of chromosomal 3p and mutations in the XPC gene. The XPC gene is consequently inactivated or lost in almost half of squamous cell carcinomas from non XP-C patients. Loss or mutation of XPC may be an early event during skin carcinogenesis that provides a selective advantage for initiation and progression of squamous cell carcinomas in non XP-C patients.

  6. [Group A streptococcal perineal infection in children].

    Science.gov (United States)

    Koskas, M; Levy, C; Romain, O; Schlemmer, C; Béchet, S; Bonacorsi, S; Bidet, Ph; Cohen, R

    2014-11-01

    Perineal diseases in children are usually caused by group A streptococcus (GAS). If the natural course of untreated cases is not known, it is well known that symptoms do not resolve spontaneously and can persist often for many months, until appropriate diagnosis and effective treatment are instituted. Furthermore, failures and recurrences after penicillin treatment are frequent. From 2009 to 2014, 165 perineal infections (median age: 48 months, extremes: 0.4-139) were enrolled by 15 pediatricians: 4 balanitis, 29 vulvo-vaginal diseases and 132 perianal infections. Painful defecation, anal fissures and macroscopic blood in stools were significantly more frequent in GAS perianal infections than negative GAS infections (p<0.01). The performance of GAS-rapid antigen test compared to the GAS culture was : sensitivity 97 % [CI 95 %: 89-100 %], specificity 76 % [CI 95 %: 66-84 %], negative predictive value 97 % [CI 95 %: 91-100 %], positive predictive value 71 % [CI 95 %: 60-80 %].

  7. A theoretical study of the XP and NEXAFS spectra of alanine: gas phase molecule, crystal, and adsorbate at the ZnO(10 ̅10) surface.

    Science.gov (United States)

    Gao, You Kun; Traeger, Franziska; Kotsis, Konstantinos; Staemmler, Volker

    2011-06-14

    The adsorption of alanine on the mixed-terminated ZnO(10 ̅10) surface is studied by means of quantum-chemical ab initio calculations. Using a finite cluster model and the adsorption geometry as obtained both by periodic CPMD and embedded cluster calculations, the C1s, N1s and O1s X-ray photoelectron spectra (XPS) and near-edge X-ray absorption fine structure (NEXAFS) spectra are calculated for single alanine molecules on ZnO(10 ̅10). These spectra are compared with the spectra calculated for alanine in the gas phase and in its crystalline form and with experimental XPS and NEXAFS data for the isolated alanine molecule and for alanine adsorbed on ZnO(10 ̅10) at multilayer and monolayer coverage. The excellent agreement between the experimental and calculated XP and NEXAFS spectra confirms the calculated adsorption geometry: A single alanine molecule is bound to ZnO(10 ̅10) in a dissociated bidentate form with the two O atoms of the acid group bound to two Zn atoms of the surface and the proton transferred to one O atom of the surface. Other possible structures, such as adsorption of alanine in one of its neutral or zwitterionic forms in which the proton of the -COOH group remains at this group or is transferred to the amino group, can be excluded since they would give rise to quite different XP spectra. In the multilayer coverage regime, on the other hand, alanine is in its crystalline form as is also shown by the analysis of the XP spectra.

  8. Chromosome engineering: generation of mono- and dicentric isochromosomes in a somatic cell hybrid system.

    Science.gov (United States)

    Higgins, A W; Schueler, M G; Willard, H F

    1999-08-01

    The most common isochromosome found in humans involves the long arm of the X, i(Xq), and is associated with a subset of Turner syndrome cases. To study the formation and behavior of isochromosomes in a more tractable experimental system, we have developed a somatic cell hybrid model system that allows for the selection of mono- or dicentric isochromosomes involving the short arm of the X, i(Xp). Simultaneous positive and negative counterselection of a mouse/human somatic cell hybrid containing a human X chromosome, selecting for retention of the UBE1 locus in Xp but against the HPRT locus in Xq, results in a variety of abnormalities of the X chromosome involving deletions of Xq. We have generated 70 such "Pushmi-Pullyu" hybrids derived from seven independent X chromosomes. Cytogenetic analysis of these hybrids using fluorescence in situ hybridization showed i(Xp) chromosomes in approximately 19% of the hybrids. Southern blot and polymerase chain reaction analyses of the Pushmi-Pullyu hybrids revealed a distribution of breakpoints along Xq. The distance between the centromeres of the dicentric i(Xp)s generated ranged from approximately 2 Mb to approximately 20 Mb. To examine centromeric activity in these dicentric i(Xp)s, we used indirect immunofluorescence with antibodies to centromere protein E (CENP-E). CENP-E was detected at only one of the centromeres of a dicentric i(Xp) with approximately 2-3 Mb of Xq DNA. In contrast, CENP-E was detected at both centromeres of a dicentric i(Xp) with approximately 14 Mb of Xq DNA. Two other dicentric i(Xp) chromosomes were heterogeneous with respect to centromeric activity, suggesting that centromeric activity and chromosome stability of dicentric chromosomes may be more complicated than previously thought. The Pushmi-Pullyu model system presented in this study may provide a tool for examining the structure and function of mammalian centromeres.

  9. X-linked mental retardation, short stature, microcephaly and hypogonadism maps to Xp22.1-p21.3 in a Belgian family.

    Science.gov (United States)

    Van Esch, Hilde; Zanni, Ginevra; Holvoet, Maureen; Borghgraef, Martine; Chelly, Jamel; Fryns, Jean-Pierre; Devriendt, Koenraad

    2005-01-01

    X-linked mental retardation (XLMR) is a heterogeneous disorder that can be classified as either non-specific (MRX), when mental retardation is the only feature, or as syndromic mental retardation (MRXS). Genetic defects underlying XLMR are being identified at a rapid pace, often starting from X-chromosomal aberrations and XLMR families with a well-defined linkage interval. Here, we present a new family with a syndromic form of XLMR, including mild mental retardation, short stature, microcephaly and hypogonadism. Two-point linkage analysis with 24 polymorphic markers spanning the entire X chromosome was carried out. We could assign the causative gene to a 6 cM interval in Xp22.1-p21.3, with a maximum LOD score of 2.61 for markers DXS989 and DXS1061 at theta = 0.00. No mutations were found in the presented family for two known MRX genes mapping to this interval, ARX and IL1RAPL-1. These data indicate that the interval Xp22.1-p21.3 contains at least one additional MRXS gene.

  10. 基于Windows XP+RTX的模拟测试系统开发%Development of Emulation and Test System Based on Windows Adding in RTX Technology

    Institute of Scientific and Technical Information of China (English)

    戴哲; 田颖; 胡春晓

    2016-01-01

    The emulation and test system,which is developed by model emulation technology, semi-physical emulation technology and Windows XP+RTX,is used to check and test the gunship weapon system and component equipment under the condition of complex battleground. This system provide a technical way and test method for fully checking gunship weapon system function,and now the system had applied to gunship weapon system engineering practice successfully.%采用建模仿真技术、半实物仿真技术和Windows XP+RTX技术开发研制的模拟测试系统,用于在复杂试验条件下,对舰炮武器系统及组成设备进行检验评估,是一种充分检验舰炮武器系统性能的技术途径和试验方法,目前该系统已成功应用于舰炮武器系统工程实践中。

  11. [X-chromosome-linked ichthyosis associated to epilepsy, hyperactivity, autism and mental retardation, due to the Xp22.31 microdeletion].

    Science.gov (United States)

    Carrascosa-Romero, M Carmen; Suela, Javier; Alfaro-Ponce, Blanca; Cepillo-Boluda, Antonio J

    2012-02-16

    X-chromosome-linked ichthyosis is caused by mutation or deletion of the STS gene associated with a deficiency of the enzyme steroid sulphatase, located in the distal part of the short arm of the X chromosome (Xp22.3-pter), close to the pseudo-autosomal region. Depending on its size, it can present as an isolated entity or combined with a syndrome caused by neighbouring genes, thus associating itself with other monogenic diseases as well as other mental disorders. The most relevant findings from the literature review are the importance of the Xp22.3-pter region and the higher incidence of neurological disorders among males (attention deficit hyperactivity disorder, autism and X-linked mental retardation). The role and implication of these genes in the disease are discussed and the authors suggest a possible contribution of the gene PNPLA4, which was originally described as GS2 and codes for calcium-independent phospholipase A2 beta, involved in lipoprotein metabolism, as one of the causes of autism. Improvements have been observed following treatment with citicoline, thanks to the role this nootropic plays in the biosynthesis of structural phospholipids involved in the formation and repair of the neuronal membrane.

  12. Localization of a new type of X-linked liver glycogenosis to the chromosomal region Xp22 containing the liver {alpha}-subunit of phosphorylase kinase (PHKA2)

    Energy Technology Data Exchange (ETDEWEB)

    Hendrickx, J.; Coucke, P.; Willems, P.J. [Univ. of Antwerp (Belgium)] [and others

    1994-06-01

    The authors describe here a new type of X-linked liver glycogen storage disease. The main symptoms include liver enlargement and growth retardation. The clinical and biochemical abnormalities of this glycogenosis are similar to those of classical X-linked liver glycogenosis due to phosphorylase kinase deficiency (XLG). However, in constrast to patients with XLG, the patients described here have no reduced phosphorylase kinase activity in erythrocytes and leukocytes, and no enzyme deficiency could be found. Linkage analysis of four families with this X-linked type of liver glycogenosis assigned the disease gene to Xp22. Lod scores obtained with the markers DXS987, DXS207, and DXS999 were 3.97, 2.71, and 2.40, respectively, all at 0% recombination. Multipoint linkage analysis localized the disease gene between DXS143 and DXS989 with a maximum lod score of 4.70 at {theta}=0, relative to DXS987. As both the classical XLG gene and the liver {alpha}-subunit of PHK (PHKA2) are also located in Xp22, this variant type of XLG may be allelic to classical XLG, and both diseases may be caused by mutations in PHKA2. Therefore, they propose to classify XLG as XLG type I (the classical type of XLG) and XLG type II (the variant type of XLG). 28 refs., 2 figs., 3 tabs.

  13. The ClpXP protease is responsible for the degradation of the Epsilon antidote to the Zeta toxin of the streptococcal pSM19035 plasmid.

    Science.gov (United States)

    Brzozowska, Iwona; Zielenkiewicz, Urszula

    2014-03-14

    Most bacterial genomes contain different types of toxin-antitoxin (TA) systems. The ω-ε-ζ proteinaceous type II TA cassette from the streptococcal pSM19035 plasmid is a member of the ε/ζ family, which is commonly found in multiresistance plasmids and chromosomes of various human pathogens. Regulation of type II TA systems relies on the proteolysis of antitoxin proteins. Under normal conditions, the Epsilon antidote neutralizes the Zeta toxin through the formation of a tight complex. In this study, we show, using both in vivo and in vitro analyses, that the ClpXP protease is responsible for Epsilon antitoxin degradation. Using in vivo studies, we examined the stability of the plasmids with active or inactive ω-ε-ζ TA cassettes in B. subtilis mutants that were defective for different proteases. Using in vitro assays, the degradation of purified His6-Epsilon by the His6-LonBs, ClpPBs, and ClpXBs proteases from B. subtilis was analyzed. Additionally, we showed that purified Zeta toxin protects the Epsilon protein from rapid ClpXP-catalyzed degradation.

  14. Survival and gill morphology of different life stages of Tilapia guineensis exposed to the drilling fluid XP-07 Sobrevivência e morfologia branquial de Tilapia guineensis expostos ao líquido de perfuração XP-07 em diferentes estágios de vida

    Directory of Open Access Journals (Sweden)

    Ijeoma Favour Vincent-Akpu

    2010-03-01

    Full Text Available The toxicity of drilling fluid XP-07 on gills of three life stages (fry, fingerling and post fingerling of Tilapia guineensis was evaluated in a 96h static bioassay. The mortality rates of the organisms were determined using the same concentrations of XP-07 in all the life stages. At the end of 96h, the gills were examined for histopathological changes. The 96h median lethal concentrations for fry (Fr, fingerlings (F and post fingerlings (PF were 5.03, 7.77 and 6.93% XP-07 respectively. The median lethal time values decreased as concentration and time of exposure increased. The histopathological studies carried out on gills of T. guineensis showed injuries, which increased progressively with the concentration of the fluid. The fry stage was the most susceptible to the drilling fluid. This states the need for care to be taken in handling drilling fluids in Niger delta, since this area serves as breeding and nursery ground for several fish species.A toxicidade do líquido de perfuração XP-07, nas brânquias de Tilapia guineensis, foi avaliada por meio de um bioensaio estático de 96h em três estágios da vida do peixe (larva, alevino e juvenil. As taxas de mortalidade do organismo foram avaliadas nas mesmas concentrações de XP-07 para todos os estágios de vida do peixe. As brânquias foram avaliadas ao final de 96 horas, com o objetivo de observarem-se mudanças histopatológicas. A concentração média letal para 96h foi de 5,03; 7,77 e 6,93% para larvas, alevinos e juvenis, respectivamente. O tempo médio letal diminuiu à medida que a concentração e o tempo de exposição aumentaram. Os estudos histopatológicos realizados nas brânquias de T. guineensis indicaram lesões que aumentaram progressivamente com a concentração do fluido. A fase larval é a mais suscetível ao fluido de perfuração. Concluiu-se que é necessário cuidado no manuseio de fluidos de perfuração no Delta do Niger, uma vez que esta é uma área de reprodu

  15. DSSC anchoring groups: a surface dependent decision.

    Science.gov (United States)

    O'Rourke, C; Bowler, D R

    2014-05-14

    Electrodes in dye sensitised solar cells are typically nanocrystalline anatase TiO2 with a majority (1 0 1) surface exposed. Generally the sensitising dye employs a carboxylic anchoring moiety through which it adheres to the TiO₂ surface. Recent interest in exploiting the properties of differing TiO₂ electrode morphologies, such as rutile nanorods exposing the (1 1 0) surface and anatase electrodes with high percentages of the (0 0 1) surface exposed, begs the question of whether this anchoring strategy is best, irrespective of the majority surface exposed. Here we address this question by presenting density functional theory calculations contrasting the binding properties of two promising anchoring groups, phosphonic acid and boronic acid, to that of carboxylic acid. Anchor-electrode interactions are studied for the prototypical anatase (1 0 1) surface, along with the anatase (0 0 1) and rutile (1 1 0) surfaces. Finally the effect of using these alternative anchoring groups to bind a typical coumarin dye (NKX-2311) to these TiO₂ substrates is examined. Significant differences in the binding properties are found depending on both the anchor and surface, illustrating that the choice of anchor is necessarily dependent upon the surface exposed in the electrode. In particular the boronic acid is found to show the potential to be an excellent anchor choice for electrodes exposing the anatase (0 0 1) surface.

  16. A high-resolution map of genes, microsatellite markers, and new dinucleotide repeats from UBE1 to the GATA locus in the region Xp11.23

    Energy Technology Data Exchange (ETDEWEB)

    Kwan, Sau-Ping; Hagemann, T.L. [Rush Medical School, Chicago, IL (United States); Rosen, F.S. [Harvard Medical School, Boston, MA (United States)] [and others

    1995-09-01

    Several new genes and markers have recently been identified on the proximal short arm of the human X chromosome in the area of Xp11.23. We had previously generated at YAC contig in this region extending from UBE1 to the OATL1 locus. In this report two polymorphic dinucleotide repeats, DXS6949 and DXS6950, were isolated and characterized from the OATL1 locus. A panel of YAC deletion derivatives from the distal portion of the contig was used in conjunction with the rest of the YAC map to position the new microsatellites and order other markers localizing to this interval. The marker order was determined to be DXS1367-ZNF81-DXS6849-ZNF21-DXS6616-DXS6950-DXS6949. In the proximal region below OATL1, we have isolated a pair of YACs from the GATA locus, B1026 and C01160. Mapping within these YACs indicates the orientation of DXS1126 and DXS1240, while a cosmid near the OATL1 region reveals the overlap between the YAC contigs from the two loci. This cosmid contains the gene responsible for Wiskott-Aldrich syndrome (WAS) and localizes the disease gene between OATL1 and GATA. These data enable the expansion of the present physical map of the X chromosome from UBE1 to the GATA locus, covering a large portion of the Xp11.23 region. Genetic crossovers in Xp11.23 support the marker orientation and the position of WAS, contrary to previous reports. With the integration of both physical and genetic maps we have predicted the following marker order: Xpter-UBE1-SYN1/ARAF1/TIMP1/DXS1367-ZNF81-DXS-6849-ZNF21-DXSy6616-(OATL1, DXS6950-DXS6949)-WAS-(GATA,DXS1126)-DXS12410-Xcen. This orientation identifies DXS6949 and DXS1126 as the nearest flanking polymorphic markers for WAS and provides useful anchor positions for the analysis of other disease genes that have been localized to this area including three different retinal defects and X-linked nephrolithiasis. 39 refs., 3 figs., 1 tab.

  17. Syndromic form of X-linked mental retardation with marked hypotonia in early life, severe mental handicap, and difficult adult behavior maps to Xp22.

    Science.gov (United States)

    Turner, Gillian; Gedeon, Agi; Kerr, Bronwyn; Bennett, Rachael; Mulley, John; Partington, Michael

    2003-03-15

    An X-linked recessive syndromic form of mental retardation is described in a family in which 10 males in four generations were affected. The main manifestations were severe to profound intellectual disability, muscular hypotonia in childhood, delayed walking, and difficult, aggressive behavior. There was a moderate reduction both in occipitofrontal circumference (OFC) and height and a similar facial appearance, triangular in shape with a high forehead, prominent ears, and a small pointed chin. Linkage analysis located the gene at Xp22 with maximum lod scores of 4.8 at theta = 0.0 for markers mapping between the closest recombination points at DXS7104 and DXS418. The physical length of this region is approximately 6 Mb. Mutations in the GRPR gene and M6b genes were excluded by sequence analysis. Nearby genes in which mutations are known to be associated with mental retardation (RPS6KA3, STK9, and VCXA, B and C), were excluded by position.

  18. Congenital nasal pyriform aperture stenosis and ocular albinism co-occurring in a sibship with a maternally-inherited 97 kb Xp22.2 microdeletion.

    Science.gov (United States)

    Somsen, David; Davis-Keppen, Laura; Crotwell, Patricia; Flanagan, Jason; Munson, Patrick; Stein, Quinn

    2014-05-01

    Congenital Nasal Pyriform Aperture Stenosis (CNPAS) is a rare congenital malformation caused by overgrowth of the maxillary bone. We report on two patients, brothers born 3 and 1½ years apart, both presented at birth with radiographically diagnosed CNPAS. Both siblings also were born with ocular albinism, which is known to have X-linked inheritance. Subsequent genetic testing demonstrated a 97 kb deletion in the p arm of the X chromosome in both siblings and their mother. This deletion encompasses a gene known to cause ocular albinism (GPR143), as well as partial deletion of two other genes, TBL1X and SHROOM2. This is the first reported case of CNPAS in siblings, both males, sharing a maternally inherited Xp22.2 deletion.

  19. Encephalopathy and bilateral cataract in a boy with an interstitial deletion of Xp22 comprising the CDKL5 and NHS genes.

    Science.gov (United States)

    Van Esch, Hilde; Jansen, Anna; Bauters, Marijke; Froyen, Guy; Fryns, Jean-Pierre

    2007-02-15

    We describe a male patient with a deletion at Xp22, detected by high resolution X-array CGH. The clinical phenotype present in this infant boy, consists of severe encephalopathy, congenital cataracts and tetralogy of Fallot and can be attributed to the deletion of the genes within the interval. Among these deleted genes are the gene for Nance-Horan syndrome and the cyclin-dependent kinase-like 5 gene (CDKL5), responsible for the early seizure variant of Rett syndrome. This is the first description of a male patient with a deletion of these genes, showing the involvement of CDKL5 in severe epileptic encephalopathy in males. Moreover it illustrates the added value of high resolution array-CGH in molecular diagnosis of mental retardation-multiple congenital anomaly cases.

  20. Superficial characterization by XP S of silver nanoparticles and their hydrothermal deposit over zircaloy; Caracterizacion superficial por XPS de nanoparticulas de plata y su deposito hidrotermal sobre zircaloy

    Energy Technology Data Exchange (ETDEWEB)

    Contreras R, A.; Gutierrez W, C.; Martinez M, I.; Medina A, A. L., E-mail: aida.contreras@inin.gob.mx [ININ, Departamento de Tecnologia de Materiales, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2012-10-15

    The analysis technique of X-ray photoelectron spectroscopy (XP S) is sensitive exclusively to the first layers of the solids surface, which allows obtaining information about the chemical, physical and electronic properties of them. The combustible elements of the boiling water nuclear reactors (BWR) are formed by zircaloy pipes that contain in their interior pellets or uranium dioxide. In this work is studied the zircaloy surface, oxidized zircaloy under similar conditions to those of a reactor BWR type and oxidized zircaloy with a hydrothermal deposit of silver nanoparticles and zinc. The silver deposit is a proposal of the Materials Technology Department of the Instituto Nacional de Investigaciones Nucleares (ININ) in Mexico, which has the same objective that the noble metals deposit (Pt, Pd, and Rh) that is practiced in some of the reactors BWR, in order to mitigating the speed of crack growth for IGSCC in stainless steels 304 Ss. (Author)

  1. An investigation of the predictors of photoprotection and UVR dose to the face in patients with XP: a protocol using observational mixed methods.

    Science.gov (United States)

    Walburn, Jessica; Sarkany, Robert; Norton, Sam; Foster, Lesley; Morgan, Myfanwy; Sainsbury, Kirby; Araújo-Soares, Vera; Anderson, Rebecca; Garrood, Isabel; Heydenreich, Jakob; Sniehotta, Falko F; Vieira, Rute; Wulf, Hans Christian; Weinman, John

    2017-08-21

    Xeroderma pigmentosum (XP) is a rare genetic condition caused by defective nucleotide excision repair and characterised by skin cancer, ocular and neurological involvement. Stringent ultraviolet protection is the only way to prevent skin cancer. Despite the risks, some patients' photoprotection is poor, with a potentially devastating impact on their prognosis. The aim of this research is to identify disease-specific and psychosocial predictors of photoprotection behaviour and ultraviolet radiation (UVR) dose to the face. Mixed methods research based on 45 UK patients will involve qualitative interviews to identify individuals' experience of XP and the influences on their photoprotection behaviours and a cross-sectional quantitative survey to assess biopsychosocial correlates of these behaviours at baseline. This will be followed by objective measurement of UVR exposure for 21 days by wrist-worn dosimeter and daily recording of photoprotection behaviours and psychological variables for up to 50 days in the summer months. This novel methodology will enable UVR dose reaching the face to be calculated and analysed as a clinically relevant endpoint. A range of qualitative and quantitative analytical approaches will be used, reflecting the mixed methods (eg, cross-sectional qualitative interviews, n-of-1 studies). Framework analysis will be used to analyse the qualitative interviews; mixed-effects longitudinal models will be used to examine the association of clinical and psychosocial factors with the average daily UVR dose; dynamic logistic regression models will be used to investigate participant-specific psychosocial factors associated with photoprotection behaviours. This research has been approved by Camden and King's Cross Research Ethics Committee 15/LO/1395. The findings will be published in peer-reviewed journals and presented at national and international scientific conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of

  2. Anti-adaptors use distinct modes of binding to inhibit the RssB-dependent turnover of RpoS (σS by ClpXP.

    Directory of Open Access Journals (Sweden)

    Dimce eMicevski

    2015-04-01

    Full Text Available In Escherichia coli, σS is the master regulator of the general stress response. The level of σS changes in response to multiple stress conditions and it is regulated at many levels including protein turnover. In the absence of stress, σS is rapidly degraded by the AAA+ protease, ClpXP in a regulated manner that depends on the adaptor protein RssB. This two-component response regulator mediates the recognition of σS and its delivery to ClpXP. The turnover of σS however, can be inhibited in a stress specific manner, by one of three anti-adaptor proteins. Each anti-adaptor binds to RssB and inhibits its activity, but how this is achieved is not fully understood at a molecular level. Here we describe details of the interaction between each anti-adaptor and RssB that leads to the stabilization of σS. By defining the domains of RssB using partial proteolysis we demonstrate that each anti-adaptor uses a distinct mode of binding to inhibit RssB activity. IraD docks specifically to the N-terminal domain of RssB, IraP interacts primarily with the C-terminal domain, while IraM interacts with both domains. Despite these differences in binding, we propose that docking of each anti-adaptor induces a conformational change in RssB, which resembles the inactive dimer of RssB. This dimer-like state of RssB not only prevents substrate binding but also triggers substrate release from a pre-bound complex.

  3. NAD+-Glycohydrolase Promotes Intracellular Survival of Group A Streptococcus.

    Directory of Open Access Journals (Sweden)

    Onkar Sharma

    2016-03-01

    Full Text Available A global increase in invasive infections due to group A Streptococcus (S. pyogenes or GAS has been observed since the 1980s, associated with emergence of a clonal group of strains of the M1T1 serotype. Among other virulence attributes, the M1T1 clone secretes NAD+-glycohydrolase (NADase. When GAS binds to epithelial cells in vitro, NADase is translocated into the cytosol in a process mediated by streptolysin O (SLO, and expression of these two toxins is associated with enhanced GAS intracellular survival. Because SLO is required for NADase translocation, it has been difficult to distinguish pathogenic effects of NADase from those of SLO. To resolve the effects of the two proteins, we made use of anthrax toxin as an alternative means to deliver NADase to host cells, independently of SLO. We developed a novel method for purification of enzymatically active NADase fused to an amino-terminal fragment of anthrax toxin lethal factor (LFn-NADase that exploits the avid, reversible binding of NADase to its endogenous inhibitor. LFn-NADase was translocated across a synthetic lipid bilayer in vitro in the presence of anthrax toxin protective antigen in a pH-dependent manner. Exposure of human oropharyngeal keratinocytes to LFn-NADase in the presence of protective antigen resulted in cytosolic delivery of NADase activity, inhibition of protein synthesis, and cell death, whereas a similar construct of an enzymatically inactive point mutant had no effect. Anthrax toxin-mediated delivery of NADase in an amount comparable to that observed during in vitro infection with live GAS rescued the defective intracellular survival of NADase-deficient GAS and increased the survival of SLO-deficient GAS. Confocal microscopy demonstrated that delivery of LFn-NADase prevented intracellular trafficking of NADase-deficient GAS to lysosomes. We conclude that NADase mediates cytotoxicity and promotes intracellular survival of GAS in host cells.

  4. Expression and cytotoxic effect of transmembrane form of human blood group A antigen mimotope vaccine in a malignant melanoma cell line B16%跨膜型血型A抗原模拟肽疫苗在黑素瘤细胞B16中表达及细胞毒效应检测

    Institute of Scientific and Technical Information of China (English)

    岑东芝; 孟辉; 张积仁

    2011-01-01

    Objective To establish a stable cell line expressing transmembrane form of human blood group A antigen mimotope vaccine by transfecting malignant melanoma cell line B16, and to detect the cytotoxicity of the vaccine against melanoma cells. Methods Cultured B16 cells were classified into 4 groups, i.e.,P/F-M-pIRES group [transfected with the recombinant plasmid mimotope peptide/Fas-macrophage inflammatory protein (Mip)-pIRES], P/F-pIRES group (transfected with the recombinant plasmid mimotope peptide/FaspIRES), M-pIRES group (transfected with the recombinant plasmid Mip-pIRES), and pIRES group (transfected with the empty plasmid pIRES). B 16 cells were transfected through Lipofectamine 2000. Subsequently, RT-PCR and Western blotting were performed to detect the mRNA and protein expressions of the mimotope peptide/Fas fusion gene and Mip3β in transfected B16 cells. Cell counting kit-8 (CCK-8) was used to evaluate the vaccinemediated complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC)against B16 cells. Results RT-PCR yielded specific DNA fragments with expected size. Western blotting revealed the anti-A antibody-binding activity of the recombinant mimotope peptide/Fas fusion protein. Factor analysis indicated significant differences in CDC (F = 244.522, P < 0.01 ) and ADCC (F = 71.593, P < 0.01 )against B16 cells between the 4 groups. Group comparisons demonstrated more intense CDC and ADCC in P/FM-pIRES and P/F-pIRES groups compared with M-plRES and pIRES groups, stronger ADCC in P/F-M-pIRES group in comparison with P/F-pIRES group (F = 15.42, P < 0.05), but no significant difference in CDC was observed between M-pIRES and pIRES group. Conclusions The transmembrane form of human blood group A antigen mimotope vaccine could be stably expressed in B16 cells, and mediate ADCC and CDC against B16 cells in vitro.%目的 建立稳定表达跨膜型血型A抗原模拟肽疫苗的恶性黑素瘤细胞株B16,并检

  5. 跨膜型血型A抗原模拟肽疫苗诱导黑色素瘤细胞凋亡的实验研究%Research on the apoptosis of malignant melanoma cell induced by transmembrane form of human blood group A mimotope vaccine

    Institute of Scientific and Technical Information of China (English)

    岑东芝; 李许锋; 邹建军; 罗敏; 张积仁

    2011-01-01

    Objective To investigate the apoptotic effect of the transmembrane form vaccine of human blood group A mimotope on malignant melanoma cell line B16. Methods B16 cells were transfected with different recombinant plasmid through Lipofectamine 2000 and incubated with different concentration of monoclonal anti-A antibody at 2.5 μg/ml, 5 μg/ml,10 μg/ml and 20 μg/ml. Apoptosis rate of cells was determined with Annexin Ⅴ/PI double staining by flow cytometry. Results Apoptosis rate to P/F-M-pIRES group B16 cells was 74.74% when anti-A monoclonal antibody concentration was 10 μg/ml; apoptosis rate of plasmids carrying peptide/Fas fusion gene such as P/F-M-pIRES group and P/F-pIRES group were significantly higher than M-pIRES group and pIRES group. The apoptosis rate was statistically significantly different between different recombinated plasmid groups (F=669.707,P<0.01). The apoptosis rate was statistically significantly different between different antibody groups (F=106.596,P<0.01). The interaction between recombinated plasmid groups and antibody groups was statistically significant (F=34.806,P<0.01). Conclusions The transmembrane form vaccine of human blood group A mimotope could induce B16 cell apoptosis in vitro. This vaccine may be a promising candidate for potential malignant melanoma therapy.%目的 研究跨膜型血型A抗原模拟肽疫苗诱导恶性黑色素瘤细胞B16凋亡的作用.方法 采用脂质体转染法分别将前期构建的模拟肽疫苗稳定转染B16细胞,加入终浓度为2.5 μg/ml、5 μg/ml、10 μg/ml及20 μg/ml的抗血型A单克隆抗体培养72 h,Annexin Ⅴ/PI双染法检测细胞凋亡率.结果 P/F-M-pIRES组的B16细胞经10 μg/ml抗血型A单克隆抗体诱导后凋亡率为74.74%,转染有模拟肽/Fas融合基因的P/F-M-pIRES组和P/F-pIRES组凋亡率明显高于未转染的M-pIRES组和pIRES组.析因设计的方差分析显示不同实验分组之间的差异主效应差异有统计学意义(F=669

  6. Mechanisms of group A Streptococcus resistance to reactive oxygen species.

    Science.gov (United States)

    Henningham, Anna; Döhrmann, Simon; Nizet, Victor; Cole, Jason N

    2015-07-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the 'top 10' causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•(-)), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress.

  7. Loss of SLC38A5 and FTSJ1 at Xp11.23 in three brothers with non-syndromic mental retardation due to a microdeletion in an unstable genomic region

    NARCIS (Netherlands)

    Froyen, Guy; Bauters, Marijke; Boyle, Jackie; Van Esch, Hilde; Govaerts, Karen; van Bokhoven, Hans; Ropers, Hans-Hilger; Moraine, Claude; Chelly, Jamel; Fryns, Jean-Pierre; Marynen, Peter; Gecz, Jozef; Turner, Gillian

    2007-01-01

    Using high resolution X chromosome array-CGH we identified an interstitial microdeletion at Xp11.23 in three brothers with moderate to severe mental retardation (MR) without dysmorphic features. The extent of the deletion was subsequently delineated to about 50 kb by regular PCR and included only th

  8. Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors

    DEFF Research Database (Denmark)

    Arendrup, M; Hansen, J E; Clausen, H;

    1991-01-01

    not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can...

  9. OMEGAHAB-XP a bioregenerative aquatic life support system designed to be used in Bion-M1 long term space flight

    Science.gov (United States)

    Hilbig, Reinhard; Lebert, Michael

    The OmegaHab XP Experiment will be based on the OmegaHab system successfully flown in the context of the FOTON M3 mission. OmegaHab XP -a refurbished OmegaHab for a long term mission -is in general assembled from four parts: an algae compartment, a nutrition com-partment for higher plants and crustaceens, a fish compartment and a filter compartment with biodegradant bacterias. The algae compartment (Euglena gracilis; unicellular, photosynthetic flagellate) will be illuminated with photosynthetic active radiation and will produce oxygen. The photosynthetic process also consumes carbon dioxide and if available ammonia. In addi-tion, nitrate will be taken up by the algae and by this means removed from the system. Via a gas-permeable membrane (gas/ion exchanger) the produced oxygen will be transported in a separate fish compartment. The metabolism of the fish will produce carbon dioxide and nitro-genic components. These components as well as the carbon dioxide will be transported back in the algae compartment and subsequently used by the algae. The transport of the components is enhanced by a counter flow inside the gas/ion exchanger driven by a pump. In addition, a filter system is installed which removes debris as well as ammonia by means of ammonia metabolizing bacteria. The nutrition compartment with higher plants and the crustaceans (e.g. Hyalella azteca; flown successfully aboard shuttles) builds the basis of this multi-trophic sys-tem. Hyalella azteca can reproduce in an adequate amount to replace external fish nutrition for Oreochromis mossambicus in large parts. The fish compartment is divided into two chambers: a hatchery chamber for larval fishes and an chamber for subadult Oreochromis mossambicus. The system is fully automatic and measures and stores all house-keeping data internally. These house-keeping data include light, temperature, acceleration and oxygen as well as many system related parameters. By means of Peltier-elements the system can be

  10. Characterization of a porcine enterocyte receptor for group A rotavirus.

    Science.gov (United States)

    Kuhlenschmidt, M S; Rolsma, M D; Kuhlenschmidt, T B; Gelberg, H B

    1997-01-01

    We have identified, purified to apparent homogeneity and chemically characterized a biologically-relevant porcine enterocyte receptor for group A porcine rotavirus. Ceramide glycanase digestion followed by acid hydrolysis and monosaccharide compositional analyses indicated the receptor is a family of two GM, gangliosides, one containing N-glycolyl-neuraminic acid and the other N-acetylneuraminic acid. Both gangliosides displayed dose-dependent inhibition of rotavirus binding to, and infectivity of, host cells. Inhibition of infectivity in a focus-forming-unit-reduction assay was achieved with as little as 2 nmols of NeuGcGM3 (50% inhibition with 3.97 nmol) or NeuAcGM3 (50% inhibition with 9.84 nmol) per 10(4) FFU of virus. Preliminary data suggest specific porcine GM3 carbohydrate fine structure or spatial orientation of the sialyloligosaccharide epitopes of the holoGM3 gangliosides may be crucial to enterocyte receptor recognition by rotavirus. We have quantified both NeuGcGM3 and NeuAcGM3 in enterocytes of various-aged pigs from newborn through 16 weeks and have found with increasing age the amount of both GM3 derivatives, especially NeuGcGM3 per gram (dry weight) intestinal brush border decreases rapidly from newborn through 4 weeks of age. These results may help explain the age-sensitivity of piglets to severe rotavirus diarrhea.

  11. Inhibitory effect of puerarin on proliferation of retinoblastoma cells ...

    African Journals Online (AJOL)

    Methods: The effect of puerarin was examined on human retinoblastoma Y79 cells ... International Pharmaceutical Abstract, Chemical Abstracts, Embase, Index Copernicus, EBSCO, African. Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, ..... Hou SZ, Su ZR, Chen SX, Ye MR, Huang S, Liu L, Lai. XP.

  12. The XPD subunit of TFIIH is required for transcription-associated but not DNA double-strand break-induced recombination in mammalian cells.

    Science.gov (United States)

    Savolainen, Linda; Cassel, Tobias; Helleday, Thomas

    2010-11-01

    Mutations in the XPD gene can give rise to three phenotypically distinct disorders: xeroderma pigmentosum (XP), trichothiodystrophy (TTD) or combined XP and Cockayne syndrome (CS) (XP/CS). The role of Xeroderma Pigmentosum group D protein (XPD) in nucleotide excision repair explains the increased risk of skin cancer in XP patients but not all the clinical phenotypes found in XP/CS or TTD patients. Here, we describe that the XPD-defective UV5 cell line is impaired in transcription-associated recombination (TAR), which can be reverted by the introduction of the wild-type XPD gene expressed from a vector. UV5 cells are defective in TAR, despite having intact transcription and homologous recombination (HR) repair of DNA double-strand breaks (DSBs). Interestingly, we find reduced spontaneous HR in XPD-defective cells, suggesting that transcription underlies a portion of spontaneous HR events. We also report that transcription-coupled repair (TCR)-defective cells, mutated in the Cockayne syndrome B (CSB) protein, have a defect in TAR, but not in DSB-induced HR. However, the TAR defect may be associated with a general transcription defect in CSB-deficient cells. In conclusion, we show a novel role for the XPD protein in TAR, linking TAR with TCR.

  13. X-linked dominant cone-rod degeneration: Linkage mapping of a new locus for retinitis pigmentosa (RP15) to Xp22.13-p22.11

    Energy Technology Data Exchange (ETDEWEB)

    McGuire, R.E.; Sullivan, L.S.; Daiger, S.P. [Univ. of Texas-Houston Health Science Center, TX (United States)] [and others

    1995-07-01

    Retinitis pigmentosa is the name given to a heterogeneous group of hereditary retinal degenerations characterized by progressive visual field loss, pigmentary changes of the retina, abnormal electroretinograms, and, frequently, night blindness. In this study, we investigated a family with dominant cone-rod degeneration, a variant form of retinitis pigmentosa. We used microsatellite markers to test for linkage to the disease locus and exluded all mapped autosomal loci. However, a marker from the short arm of the X chromosome, DXS989, showed 0% recombination to the disease locus, with a maximum lod (log-odds) score of 3.3. On the basis of this marker, the odds favoring X-linked dominant versus autosomal dominant inheritance are > 10{sup 5}:1. Haplotype analysis using an additional nine microsatellite markers places the disease locus in the Xp22.13-p22.11 region and excludes other X-linked disease loci causing retinal degeneration. The clinical expression of the retinal degeneration is consistent with X-linked dominant inheritance with milder, variable effects of Lyonization affecting expression in females. On the basis of these data we propose that this family has a novel form of dominant, X-linked cone-rod degeneration with the gene symbol {open_quotes}RP15{close_quotes}. 17 refs., 2 figs., 4 tabs.

  14. The parallel processing of EGS4 code on distributed memory scalar parallel computer:Intel Paragon XP/S15-256

    Energy Technology Data Exchange (ETDEWEB)

    Takemiya, Hiroshi; Ohta, Hirofumi; Honma, Ichirou

    1996-03-01

    The parallelization of Electro-Magnetic Cascade Monte Carlo Simulation Code, EGS4 on distributed memory scalar parallel computer: Intel Paragon XP/S15-256 is described. EGS4 has the feature that calculation time for one incident particle is quite different from each other because of the dynamic generation of secondary particles and different behavior of each particle. Granularity for parallel processing, parallel programming model and the algorithm of parallel random number generation are discussed and two kinds of method, each of which allocates particles dynamically or statically, are used for the purpose of realizing high speed parallel processing of this code. Among four problems chosen for performance evaluation, the speedup factors for three problems have been attained to nearly 100 times with 128 processor. It has been found that when both the calculation time for each incident particles and its dispersion are large, it is preferable to use dynamic particle allocation method which can average the load for each processor. And it has also been found that when they are small, it is preferable to use static particle allocation method which reduces the communication overhead. Moreover, it is pointed out that to get the result accurately, it is necessary to use double precision variables in EGS4 code. Finally, the workflow of program parallelization is analyzed and tools for program parallelization through the experience of the EGS4 parallelization are discussed. (author).

  15. Structural parameters, band-gap bowings and phase diagrams of zinc-blende Sc{sub 1−x}In{sub x}P ternary alloys: A FP-LAPW study

    Energy Technology Data Exchange (ETDEWEB)

    López-Pérez, William, E-mail: wlopez@uninorte.edu.co [Grupo de Investigación en Fısica Aplicada, Departamento de Fısica, Universidad del Norte, Barranquilla (Colombia); Simon-Olivera, Nicolás [Grupo de Investigación en Fısica Aplicada, Departamento de Fısica, Universidad del Norte, Barranquilla (Colombia); Molina-Coronell, Javier [Departamento de Ciencias Básicas, Universidad de la Costa, Barranquilla (Colombia); González-García, Alvaro; González-Hernández, Rafael [Grupo de Investigación en Fısica Aplicada, Departamento de Fısica, Universidad del Norte, Barranquilla (Colombia)

    2013-10-15

    Highlights: •Structural, electronic and thermodynamic properties of Sc{sub 1−x}In{sub x}P were theoretically studied. •The lattice constants of Sc{sub 1−x}In{sub x}P increase with concentration x, deviating from Vegard’s law. •A large difference in electronegativity between Sc and In atoms is main contribution to the bowing. •The Sc{sub 1−x}In{sub x}P Palloys are unstable at normal growth temperatures, and stable at hight temperature. -- Abstract: Using first-principles total-energy calculations, we investigate the structural, electronic and thermodynamic properties of the cubic Sc{sub 1−x}In{sub x}P semiconducting alloys. The calculations are based on the full-potential linearized-augmented plane wave (FP-LAPW) method within density functional theory (DFT). The exchange–correlation effect is treated by both local-density approximation (LDA) and generalized-gradient approximation (GGA). In the latter approach, both Perdew-Burke-Ernzerhof (PBE) and EngelVosko (EV) functional of the exchange–correlation energy were used. The effect of atomic composition on structural parameters, band-gap energy, mixing enthalpy and phase diagram was analyzed for x = 0, 0.25, 0.5, 0.75, 1. Lattice constant, bulk modulus, and band-gap energy for zinc-blende Sc{sub 1−x}In{sub x}P alloys show nonlinear dependence on the aluminium composition x. Deviations of the lattice constant from Vegard’s law, and deviations of the bulk modulus and band-gap energy from linear concentration dependence (LCD) were found. The variation of the calculated equilibrium lattice constant versus indium concentration shows a small deviation from Vegard’s law with upward bowing parameter of −0.043 Å and −0.058 Å for PBE and LDA, respectively. The bulk modulus as a function of indium composition shows a small deviation from the linear concentration dependence (LCD) with upward bowing equal to −0.790 GPa using PBE, and with net downward bowing of 0.847 GPa using LDA. The

  16. M1 Protein Allows Group A Streptococcal Survival in Phagocyte Extracellular Traps through Cathelicidin Inhibition

    OpenAIRE

    Lauth, Xavier; von Köckritz-Blickwede, Maren; McNamara, Case W; Myskowski, Sandra; Zinkernagel, Annelies S.; Beall, Bernard; Ghosh, Partho; Richard L Gallo; Nizet, Victor

    2009-01-01

    M1 protein contributes to Group A Streptococcus (GAS) systemic virulence by interfering with phagocytosis and through proinflammatory activities when released from the cell surface. Here we identify a novel role of M1 protein in the stimulation of neutrophil and mast cell extracellular trap formation, yet also subsequent survival of the pathogen within these DNA-based innate defense structures. Targeted mutagenesis and heterologous expression studies demonstrate M1 protein promotes resistance...

  17. High-density physical mapping of a 3-Mb region in Xp22.3 and refined localization of the gene for X-linked recessive chondrodysplasia punctata (CDPX1)

    Energy Technology Data Exchange (ETDEWEB)

    Wang, I.; Levilliers, J.; Petit, C. [Institut Pasteur, Paris (France)] [and others

    1995-03-20

    The study of patients with chromosomal rearrangements has led to the mapping of the gene responsible for X-linked recessive chondrodysplasia punctata (CDPX1; MIM 302950) to the distal part of the Xp22.3 region, between the loci PABX and DXS31. To refine this mapping, a yeast artificial chromosome (YAC) contig map spanning this region has been constructed. Together with the YAC contig of the pseudo-autosomal region that we previously established, this map covers the terminal 6 Mb of Xp, with an average density of 1 probe every 100 kb. Newly isolated probes that detect segmental X-Y homologies on Yp and Yq suggest multiple complex rearrangements of the ancestral pseudoautosomal region during evolution. Compilation of the data obtained from the study of individuals carrying various Xp22.3 deletions led us to conclude that the CDPX disease displays incomplete penetrance and, consequently, to refine the localization of CDPX1 to a 600-kb interval immediately adjacent to the pseudoautosomal boundary. This interval, in which 12 probes are ordered, provides the starting point for the isolation of CDPX1. 67 refs., 3 figs., 2 tabs.

  18. High mobility group A1 enhances tumorigenicity of human cholangiocarcinoma and confers resistance to therapy

    DEFF Research Database (Denmark)

    Quintavalle, Cristina; Burmeister, Katharina; Piscuoglio, Salvatore

    2017-01-01

    High mobility group A1 (HMGA1) protein has been described to play an important role in numerous types of human carcinoma. By the modulation of several target genes HMGA1 promotes proliferation and epithelial-mesenchymal transition of tumor cells. However, its role in cholangiocarcinoma (CCA) has ...

  19. Percutaneous intraluminal recanalization of long, chronic superficial femoral and popliteal occlusions using the Frontrunner XP CTO device: a single-center experience.

    Science.gov (United States)

    Charalambous, Nikolas; Schäfer, Philipp J; Trentmann, Jens; Hümme, Tim H; Stöhring, Christine; Müller-Hülsbeck, Stefan; Heller, Martin; Jahnke, Thomas

    2010-02-01

    The purpose of this study was to examine the safety and efficacy of the Frontrunner XP CTO (chronic total occlusion) Catheter (Cordis) for recanalization of long femoropopliteal artery occlusions. A Frontrunner catheter was used to treat 26 CTOs in SFA after guidewire failure (68.3 +/- 8.8 years). Sixty-seven percent of patients had severe claudication. Critical lower limb ischemia with rest pain or minor tissue loss was present in three and eight patients, respectively. All the lesions were considered complex (TASC B, C, and D); 68% of the lesions were heavily calcified. The mean lesion length was 17.6 cm (range, 10-42 cm). The initial attempt to cross the occlusion with the CTO guidewire V18 was unsuccessful in 26 of 76 limbs (34.26%). A secondary attempt using the Frontrunner catheter (crossover approach, 27%; antegrade, 73%) performed in all 26 failed cases was successful in 17 limbs (65.38%), increasing the technical success rate to 88.12%. The main reasons for failure with the Frontrunner were inability to cross the lesion due to heavy calcification (six of nine) and inability to re-enter the true lumen after subintimal passage of the occluded segment (three of nine). The mean fluoroscopy time was 22.9 min. Minor complications included one distal extension of the dissection with involvement of the first popliteal segment and one perforation in the occluded segment. No major complications were seen. In conclusion, recanalization with the Frontrunner CTO catheter is a simple and safe method with a high technical success rate in the endovascular treatment of long superficial femoral artery occlusions and should be an alternative method after guidewire failure.

  20. A 1. 8-Mb YAC contig in Xp11. 23: Identification of Cpg islands and physical mapping of CA repeats in a region of high gene density

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, M.P.; Nemeth, A.H.; Campbell, L.; Raut, C.P.; Davies, K.E. (Institute of Molecular Medicine, Oxford (United Kingdom)); Weissenbach, J. (Unite de Genetique Moleculaire Humaine, Paris (France))

    1994-05-15

    The genes ARAF1, SYN1, TIMP, and PFC are clustered within 70 kb of one another, and, as reported in the accompanying paper, at least four more genes map within 400 kb: a cluster of Krueppel-type zinc finger genes (including ZNF21, ZNF41, and ZNF81) and ELK-1, a member of the ets oncogene superfamily. This gene-rich region is of particular interest because of the large number of disease genes mapping to Xp11.23: At least three eye diseases (retinitis pigmentosa type 2, congenital stationary night blindness CSNB1, and Aland Island eye disease), Wiskott-Aldrich syndrome, X-linked nephrolithiasis, and a translocation breakpoint associated with synovial sarcoma. The authors have constructed a 1.8-Mb YAC contig in this region, confirming the link between TIMP and OATL1 reported by Knight et al. (1994) and extending the map in the distal direction. To investigate the likelihood that more genes are located within this region, they have carried out detailed mapping of rare-cutter restriction sites in these YACs and identified seven CpG islands. At least six of these islands are located over 50 kb from any known gene locations, suggesting that the region contains at least this many as yet unidentified genes. They have also mapped the physical locations of six highly polymorphic CA repeats within the contig, thus integrating the physical, genetic, and transcriptional maps of the region and facilitating the mapping and identification of disease genes. Together with the report by Knight et al., these data indicate the following order of loci: Xpter-DXS1264-DXS1055-DXS1003-DXS1146-DXS1266-(ZNF41, ARAF1)-SYN1 CA repeat-SYN1 (3[prime] end)-TIMP-SYN1 (5[prime] end)-PFC CA repeat-PFC-(DXS426, ELK1)-(DXS1265, ZNF81)-ZNF21-DXS1267-OATL1-Xcen. 40 refs., 4 figs., 3 tabs.

  1. A child with mild X-linked intellectual disability and a microduplication at Xp22.12 including RPS6KA3.

    Science.gov (United States)

    Tejada, María-Isabel; Martínez-Bouzas, Cristina; García-Ribes, Ainhoa; Larrucea, Susana; Acquadro, Francesco; Cigudosa, Juan-C; Belet, Stefanie; Froyen, Guy; López-Aríztegui, Maria-Asun

    2011-10-01

    Multiplex ligation-dependent probe amplification (MLPA) and array- comparative genomic hybridization analysis have been proven to be useful in the identification of submicroscopic copy-number imbalances in families with nonsyndromic X-linked intellectual disability (NS-XLID). Here we report the first description of a child with mild intellectual disability and a submicroscopic duplication at Xp22.12 identified by MLPA with a P106 MRX kit (MRC-Holland, Amsterdam, Netherlands) and further confirmed and characterized with a custom 244-k oligo-array, fluorescence in situ hybridization, quantitative polymerase chain reaction (qPCR), and immunoblotting. This 1.05-megabase duplication encompasses 7 genes, RPS6KA3 being the only of these genes known to be related to ID. The proband was an 8-year-old boy referred to the genetics unit for psychomotor retardation and learning disabilities. Both maternal brothers also showed learning difficulties and delayed language during childhood in a similar way to the proband. These boys also carried the duplication, as did the healthy mother and grandmother of the proband. The same duplication was also observed in the 5-year-old younger brother who presented with features of developmental delay and learning disabilities during the previous year. Increased RPS6KA3/RSK2 levels were demonstrated in the proband by qPCR and immunoblotting. To our knowledge, this is the first family identified with a submicroscopic duplication including the entire RPS6KA3/RSK2 gene, and our findings suggest that an increased dose of this gene is responsible for a mild form of NS-XLID.

  2. Contralateral compartment syndrome inoculated by invasive group A streptococcus

    Directory of Open Access Journals (Sweden)

    Huiwen Chen

    2016-10-01

    Full Text Available Compartment syndrome is a rare but a well-documented complication in patients with trauma-induced group A streptococcus infection. Here, we present a case of a male who developed compartment syndrome on the left lower extremity after an injury inoculated by group A streptococcus on the right lower extremity. The patient was resuscitated with antibiotics, urgent fasciotomy, and immunoglobulin. The patient was eventually transferred to a burn center for further care.

  3. Human group A rotavirus infections in children in Denmark

    DEFF Research Database (Denmark)

    Midgley, S; Böttiger, B; Jensen, T G

    2014-01-01

    One of the leading causes of severe childhood gastroenteritis are group A rotaviruses, and they have been found to be associated with similar to 40% of the annual gastroenteritis-associated hospitalizations in young Danish children......One of the leading causes of severe childhood gastroenteritis are group A rotaviruses, and they have been found to be associated with similar to 40% of the annual gastroenteritis-associated hospitalizations in young Danish children...

  4. Puerperal Group A Streptococcal Infections: A Case Series and Discussion

    Directory of Open Access Journals (Sweden)

    Mary T. Busowski

    2013-01-01

    Full Text Available Puerperal group A streptococcal infections, a major postpartum killer during the late 19th and early 20th centuries, have become (fortunately rare. We describe a cluster of 4 serious peripartum group A streptococcal infections occurring within the past five years at a single medical center. These cases were not epidemiologically linked and serve to illustrate the continuing risk of these potentially fulminant infections.

  5. Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors

    DEFF Research Database (Denmark)

    Arendrup, M; Hansen, J E; Clausen, H

    1991-01-01

    Three virus isolates HTLV-IIIB/lyA, HTLV-IIIB/lyB and HTLV-IIIB/lyO, obtained by passaging and propagating the HTLV-IIIB/H9 isolate in three separate cultures of mixed peripheral blood mononuclear cells (PBMC) from donors of blood type A, B or O, respectively, were tested for susceptibility...... for virus neutralization by the monoclonal antibody (MAb) AH16 directed against the blood group A epitope. MAb AH16 was previously shown to inhibit cell-free virus infection using HTLV-IIIB propagated in H9 cells. AH16 showed a concentration-dependent inhibition of the HTLV-IIIB/lyA isolate but did...... not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can...

  6. Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors

    DEFF Research Database (Denmark)

    Arendrup, M; Hansen, J E; Clausen, H;

    1991-01-01

    for virus neutralization by the monoclonal antibody (MAb) AH16 directed against the blood group A epitope. MAb AH16 was previously shown to inhibit cell-free virus infection using HTLV-IIIB propagated in H9 cells. AH16 showed a concentration-dependent inhibition of the HTLV-IIIB/lyA isolate but did...... not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can......Three virus isolates HTLV-IIIB/lyA, HTLV-IIIB/lyB and HTLV-IIIB/lyO, obtained by passaging and propagating the HTLV-IIIB/H9 isolate in three separate cultures of mixed peripheral blood mononuclear cells (PBMC) from donors of blood type A, B or O, respectively, were tested for susceptibility...

  7. Group A β-hemolytic streptococcal pharyngotonsillitis outbreak

    Science.gov (United States)

    Culqui, Dante R; Manzanares-Laya, Sandra; Van Der Sluis, Sarah Lafuente; Fanlo, Albert Anton; Comas, Rosa Bartolomé; Rossi, Marcello; Caylá, Joán A

    2014-01-01

    The aim was to describe an outbreak of group A β-hemolytic streptococcal pharyngotonsillitis in health care professionals. This is a cross-sectional descriptive study of 17 clients who dined at the same table in a restaurant in Barcelona in July 2012. The frequency, timing and severity of symptoms were analyzed, as were demographic variables and others concerning the food ingested. The attack rate was 58.8%. Six of the 10 clients were positive for group A β-hemolytic streptococcal. Six of the 13 individuals who handled the food involved in the dinner had symptoms. No association was identified with the food consumed. There is epidemiological evidence of foodborne group A β-hemolytic streptococcal transmission, but respiratory transmission could not be ruled out. PMID:24897054

  8. The Asymmetry in the Mature Amino-Terminus of ClpP Facilitates a Local Symmetry Match in ClpAP and ClpXP Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Bewley,M.; Graziano, V.; Griffin, K.; Flanagan, J.

    2006-01-01

    ClpP is a self-compartmentalized proteolytic assembly comprised of two, stacked, heptameric rings that, when associated with its cognate hexameric ATPase (ClpA or ClpX), form the ClpAP and ClpXP ATP-dependent protease, respectively. The symmetry mismatch is an absolute feature of this large energy-dependent protease and also of the proteasome, which shares a similar barrel-shaped architecture, but how it is accommodated within the complex has yet to be understood, despite recent structural investigations, due in part to the conformational lability of the N-termini. We present the structures of Escherichia coli ClpP to 1.9 Angstroms and an inactive variant that provide some clues for how this might be achieved. In the wild type protein, the highly conserved N-terminal 20 residues can be grouped into two major structural classes. In the first, a loop formed by residues 10-15 protrudes out of the central access channel extending {approx}12-15 Angstroms from the surface of the oligomer resulting in the closing of the access channel observed in one ring. Similar loops are implied to be exclusively observed in human ClpP and a variant of ClpP from Streptococcus pneumoniae. In the other ring, a second class of loop is visible in the structure of wt ClpP from E. coli that forms closer to residue 16 and faces toward the interior of the molecule creating an open conformation of the access channel. In both classes, residues 18-20 provide a conserved interaction surface. In the inactive variant, a third class of N-terminal conformation is observed, which arises from a conformational change in the position of F17. We have performed a detailed functional analysis on each of the first 20 amino acid residues of ClpP. Residues that extend beyond the plane of the molecule (10-15) have a lesser effect on ATPase interaction than those lining the pore (1-7 and 16-20). Based upon our structure-function analysis, we present a model to explain the widely disparate effects of individual

  9. Invasive Group A Streptococcal Disease. National Epidemiology and Genetic Analysis

    NARCIS (Netherlands)

    Vlaminckx, B.J.M.

    2006-01-01

    Infections with group A streptococci (GAS), or S. pyogenes, range from mild and superficial to very severe and lethal invasive disease. In severe invasive GAS infections, hypotension and multiorgan failure may develop rapidly resulting in the development of toxic shock-like syndrome (TSS). In the

  10. Rotavirus Group A in Danish Cattle and Swine Herds 2006

    DEFF Research Database (Denmark)

    Midgley, Sofie; Gram, Nina; Hjulsager, Charlotte Kristiane

    Rotavirus group A infection causes gastroenteritis in both humans and a variety of animal species. Both domestic pet species such as cats and dogs, and commercial species such as pigs and cows can be affected. Zoonotic transmission is a possibility and could lead to the introduction into human...... populations of novel rotavirus strains....

  11. Invasive Group A Streptococcal Disease. National Epidemiology and Genetic Analysis

    NARCIS (Netherlands)

    Vlaminckx, B.J.M.

    2006-01-01

    Infections with group A streptococci (GAS), or S. pyogenes, range from mild and superficial to very severe and lethal invasive disease. In severe invasive GAS infections, hypotension and multiorgan failure may develop rapidly resulting in the development of toxic shock-like syndrome (TSS). In the no

  12. Development of a GeXP Based Multiplex RT-PCR Assay for Simultaneous Detection of Eight Arboviruses Related to Encephalitis%8种脑炎相关虫媒病毒GeXP检测方法的初步建立

    Institute of Scientific and Technical Information of China (English)

    何玢; 王环宇; 张晨; 王淼; 秦萌; 王克霞; 马学军

    2012-01-01

    利用GeXP多重基因表达遗传分析系统,建立一种多重逆转录-聚合酶链反应( mRT-PCR)方法,同时检测与病毒性脑炎相关的乙型脑炎病毒(Japanese encephalitis virus,JEV)等8种虫媒病毒.优化多重反应体系及反应条件,分别以病毒分离培养物和阳性标本来验证多重反应体系的特异性,以克隆质粒体外转录的RNA梯度稀释液来检测多重检测体系的灵敏度.结果表明,优化后的多重检测体系,可扩增出各病毒对应的特异片段,并可在102拷贝/μL水平同时并特异地检测出8种(共13个特异片段)脑炎相关病毒RNA.该方法具有高通量、灵敏度高、特异性强且快速等优点,对病毒性脑炎的分子诊断及流行病学调查具有重要意义.%Multiplex reverse transcription-polymerase chain reaction (mRT-PCR) is currently available in virus detection and defined as the simultaneous amplification of two or more DNA/RNA targets in a single reaction vessel. In this study, we attempted to modify the conventional mRT-PCR technique on a basis of GenomeLab Genetic Analysis System (GeXP). Initially, we optimized the analytical validation of the GeXP analyzer and its design of workflow and simultaneously detected eight arboviruses that related to epidemic encephalitis by verifying the specificity of mRT-PCR with Japanese encephalitis virus(JEV) cell cultures and positive strains identified previously and determining the sensitivity with in vitro-transcribed RNA of serial dilutions. The GeXP system after optimization could amplify the specific fragments related to the viruses and exposed specifically a total of 13 target genes out of eight types of arboviruses at the level of 102 copies/μL, and the findings suggest that the novel protocol we developed can be high-throughput and highly specific and sensitive as well as quickness in screening of the encephalitis viruses, and is promising in detection of encephalitis-associated viruses for molecular

  13. Epitaxial lateral overgrowth of Ga{sub x}In{sub 1-x}P toward direct Ga{sub x}In{sub 1-x}P/Si heterojunction

    Energy Technology Data Exchange (ETDEWEB)

    Omanakuttan, Giriprasanth; Stergiakis, Stamoulis; Sychugov, Ilya; Lourdudoss, Sebastian; Sun, Yan-Ting [Department of Materials and Nano Physics, School of Information and Communication Technology, Royal Institute of Technology-KTH, Kista (Sweden); Sahgal, Abhishek [Department of Materials and Nano Physics, School of Information and Communication Technology, Royal Institute of Technology-KTH, Kista (Sweden); Department of Physics, Indian Institute of Technology Delhi, New Delhi (India)

    2017-03-15

    The growth of GaInP by hydride vapor phase epitaxy (HVPE) was studied on planar GaAs, patterned GaAs for epitaxial lateral overgrowth (ELOG), and InP/Si seed templates for corrugated epitaxial lateral overgrowth (CELOG). First results on the growth of direct GaInP/Si heterojunction by CELOG is presented. The properties of Ga{sub x}In{sub (1-x)}P layer and their dependence on the process parameters were investigated by X-ray diffraction, including reciprocal lattice mapping (XRD-RLM), scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy (SEM-EDS), photoluminescence (PL), and Raman spectroscopy. The fluctuation of Ga composition in the Ga{sub x}In{sub (1-x)}P layer was observed on planar substrate, and the strain caused by the composition variation is retained until relaxation occurs. Fully relaxed GaInP layers were obtained by ELOG and CELOG. Raman spectroscopy reveals that there is a certain amount of ordering in all of the layers except those grown at high temperatures. Orientation dependent Ga incorporation in the CELOG, but not in the ELOG Ga{sub x}In{sub (1-x)}P layer, and Si incorporation in the vicinity of direct Ga{sub x}In{sub (1-x)}P/Si heterojunction from CELOG are observed in the SEM-EDS analyses. The high optical quality of direct GaInP/Si heterojunction was observed by cross-sectional micro-PL mapping and the defect reduction effect of CELOG was revealed by high PL intensity in GaInP above Si. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  14. DNase expression allows the pathogen group A streptococcus to escape killing in neutrophil extracellular traps

    OpenAIRE

    Buchanan, John T; Simpson, Amelia J; Aziz, Ramy K.; Liu, George Y.; Kristian, Sascha A.; Kotb, Malak; Feramisco, James; Nizet, Victor

    2006-01-01

    The innate immune response plays a crucial role in satisfactory host resolution of bacterial infection. In response to chemotactic signals, neutrophils are early responding cells that migrate in large numbers to sites of infection. The recent discovery of secreted neutrophil extracellular traps (NETs) composed of DNA and histones opened a novel dimension in our understanding of the microbial killing capacity of these specialized leukocytes. M1 serotype strains of the pathogen Group A Streptoc...

  15. Ditching Tests of a 1/18-Scale Model of the Navy XP4M-1 Airplane in Langley Tank No. 2 and on an Outdoor Catapult, TED No. NACA 2362

    Science.gov (United States)

    Fisher, Lloyd J.; Hoffman, Edward L.

    1947-01-01

    Tests with a dynamically similar model of the Navy XP4M-1 airplane were made to determine the best way to land the airplane in calm and rough water, to determine its probable ditching performance, and to determine practicable modifications which could be incorporated in the design of the airplane that would improve its ditching characteristics. The results were obtained by making visual observations, by recording longitudinal decelerations,a nd by taking motion pictures of the landings. A list of conclusions from the test results is included.

  16. 极限编程(XP)在工程质量监管系统中的应用%Applying Extreme Programming for Information Systems of Engineering Quality Monitoring and Controlling

    Institute of Scientific and Technical Information of China (English)

    夏静清

    2006-01-01

    "极限编程"(eXtreme Programming,简称XP)是目前最流行的敏捷软件开发方法(Agile Software Development,ASD).通过XP在实际项目中的应用"实践",本文将对XP的理论和实践方法进行探讨,并衡量XP方法在项目中的应用效果,给出实际应用XP方法的一些建议.

  17. Genetic Manipulation of Streptococcus pyogenes (The Group A Streptococcus, GAS)

    OpenAIRE

    Le Breton, Yoann; McIver, Kevin S.

    2013-01-01

    Streptococcus pyogenes (the group A streptococcus, GAS) is a Gram-positive bacterium responsible for a wide spectrum of diseases ranging from mild superficial infections (pharyngitis, impetigo) to severe often life-threatening invasive diseases (necrotizing fasciitis, streptococcal toxic shock syndrome) in humans. This unit describes molecular techniques for the genetic manipulation of S. pyogenes with detailed protocols for transformation, gene disruption, allelic exchange, transposon mutage...

  18. Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors

    DEFF Research Database (Denmark)

    Arendrup, M; Hansen, J E; Clausen, H

    1991-01-01

    Three virus isolates HTLV-IIIB/lyA, HTLV-IIIB/lyB and HTLV-IIIB/lyO, obtained by passaging and propagating the HTLV-IIIB/H9 isolate in three separate cultures of mixed peripheral blood mononuclear cells (PBMC) from donors of blood type A, B or O, respectively, were tested for susceptibility...... not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can...

  19. Decrease of FOXP3 mRNA in CD4~+ T cells in latent autoimmune diabetes in adult

    Institute of Scientific and Technical Information of China (English)

    杨治芳

    2006-01-01

    Objective To study the percentage of peripheral blood CD4+ CD25+ T cells and the expression of F0XP3 mRNA in patients with latent autoimmune diabetes in adult (LADA). Methods Fresh peripheral blood samples were obtained from 60 patients with LADA,30 patients with type 2 diabetes and 30 age- and sex-matched

  20. Rapid detection of infectious rotavirus group A using a molecular beacon assay.

    Science.gov (United States)

    Bertol, Jéssica Wildgrube; Gatti, Maria Silvia Viccari

    2016-08-01

    Rapid, sensitive and specific methods are necessary to detect and quantify infectious viruses. Cultivating and detecting enteric viruses in cell culture are difficult, thus impairing the advancement of knowledge regarding virus-induced diarrhea. Rotavirus (RV) detection has been conducted by serological or molecular biology methods, which do not provide information regarding viral infectivity. Molecular beacons (MBs) have demonstrated efficacy for viral detection in cell culture. We propose a MB assay to detect human rotavirus group A (HuRVA) in cell culture. MA104 cells were mock-infected or infected with HuRVA strains (RotaTeq(®) vaccine and K8 strains), and a specific MB for the HuRVA VP6 gene was used for virus detection. Mock-infected cells showed basal fluorescence, while infected cells exhibited increased fluorescence emission. MB hybridization to the viral mRNA target of HuRVA was confirmed. Fluorescence increased according to the increase in the number of infectious viral particles per cell (MOI 0.5-MOI 1). This technique provides quick and efficient HuRVA detection in cell culture without a need for viral culture for several days or many times until cytopathic effects are visualized. This methodology could be applied in the selection of samples for developing RV vaccines.

  1. Biofilm in group A streptococcal necrotizing soft tissue infections

    DEFF Research Database (Denmark)

    Siemens, Nikolai; Chakrakodi, Bhavya; Shambat, Srikanth Mairpady

    2016-01-01

    Necrotizing fasciitis caused by group A streptococcus (GAS) is a life-threatening, rapidly progressing infection. At present, biofilm is not recognized as a potential problem in GAS necrotizing soft tissue infections (NSTI), as it is typically linked to chronic infections or associated with foreign...... devices. Here, we present a case of a previously healthy male presenting with NSTI caused by GAS. The infection persisted over 24 days, and the surgeon documented the presence of a "thick layer biofilm" in the fascia. Subsequent analysis of NSTI patient tissue biopsies prospectively included...

  2. Suspected zoonotic transmission of rotavirus group A in Danish adults

    DEFF Research Database (Denmark)

    Midgley, S. E.; Hjulsager, Charlotte Kristiane; Larsen, Lars Erik

    2012-01-01

    Group A rotaviruses infect humans and a variety of animals. In July 2006 a rare rotavirus strain with G8P[14] specificity was identified in the stool samples of two adult patients with diarrheoa, who lived in the same geographical area in Denmark. Nucleotide sequences of the VP7, VP4, VP6, and NSP4...... genes of the identified strains were identical. Phylogenetic analyses showed that both Danish G8P[14] strains clustered with rotaviruses of animal, mainly, bovine and caprine, origin. The high genetic relatedness to animal rotaviruses and the atypical epidemiological features suggest that these human G8...

  3. Construction of two YAC contigs in human xp11.23-p11.22, one encompassing the loci OATL1, GATA, TFE3, and SYP, the other linking DXS255 to DXS146

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, S.E.; Hatchwell, E.; Chand, A.; Ockenden, N.; Craig, I.W. [Univ. of Oxford, Oxford (United Kingdom)] [and others

    1995-09-20

    We have constructed two YAC contigs in the Xp11.23-p11.22 interval of the human X chromosome, a region that was previously poorly characterized. One contig, of at least 1.4 Mb, links the pseudogene OATL1 to the genes GATA1, TFE3, and SYP and also contains loci implicated in Wiskott-Aldrich syndrome and synovial sarcoma. A second contig, mapping proximal to the first, is estimated to be over 2.1 Mb and links the hypervariable locus DXS255 to DXS146, and also contains a chloride channel gene that is responsible for hereditary nephrolithiasis. We have used plasmid rescue, inverse PCR, and Alu-PCR to generate 20 novel markers from this region, 1 of which is polymorphic, and have positioned these relative to one another on the basis of YAC analysis. The order of previously known markers within our contigs, Xpter-OATL1-GATA-TFE3-SYP-DXS255-DXS146-Xcen, agrees with genomic pulsed-field maps of the region. In addition, we have constructed a rare-cutter restriction map for a 710-kb region of the DXS255-DXS146 contig and have identified three CpG islands. These contigs and new markers will provide a useful resource for more detailed analysis of Xp11.23-p11.22, a region implicated in several genetic diseases. 32 refs., 2 figs., 2 tabs.

  4. The effect of PO 4 doping on the luminescent properties of Sr 3-3zEu 2zV 2-xP xO 8

    Science.gov (United States)

    Cao, S.; Ma, Y. Q.; Yang, K.; Zhu, W. L.; Yin, W. J.; Zheng, G. H.; Wu, M. Z.; Sun, Z. Q.

    2010-07-01

    The luminescent properties of Sr 3V 2-xP xO 8 (0 ⩽ x ⩽ 2), Eu 3+ doped Sr 2.7Eu 0.2V 2-yP yO 8 (0 ⩽ y ⩽ 2) and Sr 3-3zEu 2zV 0.8P 1.2O 8 (0 < z ⩽ 0.3) have been investigated. For the Sr 3V 2-xP xO 8 (0 ⩽ x ⩽ 2) samples, the VO43- activation and emission intensity reaches the strongest as x = 1.6. For the Sr 2.7Eu 0.2V 2-yP yO 8 (0 ⩽ y ⩽ 2) samples, an appropriate amount of phosphorus doping enhances the Eu 3+ emission with the strongest emission occurring at y = 1.2. For the Sr 3-3zEu 2zV 0.8P 1.2O 8 (0 < z ⩽ 0.3) sample with the phosphorus content fixed at 1.2, it exhibits the most intense emission as Eu 3+ concentration reaches at z = 0.2. Our results indicate that the introduction of the PO43- plays an important role in the photoluminescence properties of the studied samples and the relevant mechanism has been discussed.

  5. Viable group A streptococci in macrophages during acute soft tissue infection.

    Directory of Open Access Journals (Sweden)

    Pontus Thulin

    2006-03-01

    Full Text Available Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells.We characterized in vivo interactions between group A streptococci (GAS and cells involved in innate immune responses, using human biopsies (n = 70 collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria.This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis of streptococcal soft tissue infections

  6. Viable Group A Streptococci in Macrophages during Acute Soft Tissue Infection.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells. METHODS AND FINDINGS: We characterized in vivo interactions between group A streptococci (GAS and cells involved in innate immune responses, using human biopsies (n = 70 collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria. CONCLUSIONS: This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis

  7. Genotypification of bovine group A rotavirus in México.

    Science.gov (United States)

    Rodríguez-Limas, William A; Flores-Samaniego, Beatriz; de la Mora, Germán; Ramírez, Octavio T; Palomares, Laura A

    2009-10-30

    Bovine scours, frequently provoked by rotavirus infection, causes significant economic losses. Nevertheless, no information exists about the bovine rotavirus genotypes present in Mexico. This information is necessary for designing efficient vaccines. In this work, 128 samples from diarrheic calves were collected between 2005 and 2006 in 26 dairy and/or beef cattle herds located in 10 regions of Mexico, and analyzed for the presence of group A rotavirus. G and P genotypes were determined by PCR in rotavirus-positive samples (12/128). Three different genotype combinations were found, G10, P[11]; G6, P[5]; and G10, P[5]; in 67, 25 and 8% of the positive samples, respectively. Some rotavirus-positive animals had been vaccinated with an inactivated rotavirus strain of a different genotype.

  8. [Characteristics of group A streptococcal meningitis in children].

    Science.gov (United States)

    Levy, C; Bidet, Ph; Bonacorsi, S; Béchet, S; Cohen, R

    2014-11-01

    Group A streptococcal (GAS) meningitis in children are rare. The aim of this study was to analyze the clinical, biological and outcome data on GAS meningitis recorded in the Bacterial Meningitis (BM) French Surveillance Network (GPIP/ACTIV). From 2001 through 2012, 4,564 children suffering from proven bacterial meningitis were recorded in the data base. Among them, 0.7 % were GAS infections. The median age was 5.6 years. A history of community acquired infection before the onset of GAS meningitis was frequent. Apart from the identification of the bacterial species, GAS meningitis were clinically and biologically indistinguishable from meningitis caused by other pathogens notably S. pneumoniae. Case fatality rate was 8 %.

  9. Recurrent group A streptococcal vulvovaginitis in adult women: family epidemiology.

    Science.gov (United States)

    Sobel, Jack D; Funaro, Deana; Kaplan, Edward L

    2007-03-01

    Group A beta-hemolytic streptococcal (GAS) vulvovaginitis has been reported in prepubertal girls. In adult women, a vaginal carrier state has been described, but vulvovaginitis is rarely reported. We describe 2 cases of recurrent GAS vulvovaginitis in women whose husbands were gastrointestinal carriers of GAS. Characterization of the isolated strains demonstrated that identical emm types of GAS were shared by partners. Treatment of both partners resulted in resolution of vaginitis. On the basis of negative vaginal culture results obtained after treatment of each individual episode of vaginitis, we believe that the female patients were reinfected as a result of exposure to their husbands, with shedding likely to have occurred in bed. These cases reiterate the necessity for adequate screening of the patient's family and contacts in cases of recurrent GAS infection by culturing all potential areas of GAS carriage.

  10. Group a streptococcal cellulitis in the early puerperium

    Directory of Open Access Journals (Sweden)

    Nikolić Branka

    2011-01-01

    Full Text Available Introduction. Infectious diseases caused by Streptococcus pyogenes, a member of the group A Streptococci (GAS are among the most common life threatening ones. Patients with GAS infections have a poor survival rate. Cellulitis is a severe invasive GAS infection and the most common clinical presentation of the disease associated with more deaths than it can be seen in other GAS infections. According to the literature data, most cases of GAS toxic shock syndrome are developed in the puerperium. However, there are two main problems with GAS infection in early puerperium and this case report is aimed at reminding on them. The first problem is an absence of awareness that it can be postpartal invasive GAS infection before the microbiology laboratory confirms it, and the second one is that we have little knowledge about GAS infection, in general. Case report. A 32- year-old healthy woman, gravida 1, para 1, was hospitalized three days after vaginal delivery with a 38-hour history of fever, pain in the left leg (under the knee, and head injury after short period of conscious lost. Clinical picture of GAS infection was cellulites. Group A Streptoccocus pyogenes was isolated in vaginal culture. Rapid antibiotic and supportive treatment stopped development of streptococcal toxic shock syndrome (STSS and potential multiorganic failure. Signs and symptoms of the infection lasted 25 days, and complete recovery of the patient almost 50 days. Conclusion. In all women in childbed with a history of fever early after delivery, vaginal and cervical culture specimens should be taken as soon as possible. Early recognition of GAS infection in early puerperium and prompt initiation of antimicrobial drug and supportive therapy can prevent development of STSS and lethal outcome.

  11. Transient correction of excision repair defects in fibroblasts of 9 xeroderma pigmentosum complementation groups by microinjection of crude human cell extract.

    NARCIS (Netherlands)

    W. Vermeulen (Wim); P. Osseweijer; A.J.R. de Jonge; J.H.J. Hoeijmakers (Jan)

    1986-01-01

    textabstractCrude extracts from human cells were microinjected into the cytoplasm of cultured fibroblasts from 9 excision-deficient xeroderma pigmentosum (XP) complementation groups. The level of UV-induced unscheduled DNA synthesis (UDS) was measured to determine the effect of the extract on the re

  12. Streptolysin O Rapidly Impairs Neutrophil Oxidative Burst and Antibacterial Responses to Group A Streptococcus

    OpenAIRE

    Uchiyama, Satoshi; Döhrmann, Simon; Anjuli M. Timmer; Dixit, Neha; Ghochani, Mariam; Bhandari, Tamara; Timmer, John C.; Sprague, Kimberly; Bubeck-Wardenburg, Juliane; Simon, Scott I.; Nizet, Victor

    2015-01-01

    Group A Streptococcus (GAS) causes a wide range of human infections, ranging from simple pharyngitis to life-threatening necrotizing fasciitis and toxic shock syndrome. A globally disseminated clone of M1T1 GAS has been associated with an increase in severe, invasive GAS infections in recent decades. The secreted GAS pore-forming toxin streptolysin O (SLO), which induces eukaryotic cell lysis in a cholesterol-dependent manner, is highly upregulated in the GAS M1T1 clone during bloodstream dis...

  13. Streptolysin O Rapidly Impairs Neutrophil Oxidative Burst and Antibacterial Responses to Group A Streptococcus

    OpenAIRE

    Satoshi Uchiyama; Simon Döhrmann; Anjuli M. Timmer; Neha Dixit; Mariam Ghochani; Tamara Bhandari; Timmer, John C.; Kimberly Sprague; Juliane Bubeck Wardenburg; Simon, Scott I.; Victor Nizet

    2016-01-01

    Group A Streptococcus (GAS) causes a wide range of human infections, ranging from simple pharyngitis to life-threatening necrotizing fasciitis and toxic shock syndrome. A globally disseminated clone of M1T1 GAS has been associated with an increase in severe, invasive GAS infections in recent decades. The secreted GAS pore-forming toxin streptolysin O (SLO), which induces eukaryotic cell lysis in a cholesterol-dependent manner, is highly upregulated in the GAS M1T1 clone during bloodstream dis...

  14. [Management of severe invasive group A streptococcal infections].

    Science.gov (United States)

    Faye, A; Lorrot, M; Bidet, Ph; Bonacorsi, S; Cohen, R

    2014-11-01

    The group A streptococcus (GAS) is the 5(th) responsible pathogen of invasive infections in children in France. These particularly severe diseases are dominated in children by soft tissue infection, isolated bacteremia but also osteoarthritis. Other complications are rare in France such as lung infections, necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS). More unusual localizations such as meningitis, neonatal infections, severe ear and throat and gastrointestinal infections and vascular disorders are also described. Based on published series, mortality ranging from 0-8 % of cases, is high but still lower than that observed in adults. Probabilistic antibiotherapy includes a β-lactam with anti-SGA but also anti-staphylococcal (predominantly methi-S in France) activity such as clavulanic acid- amoxicillin followed by amoxicillin as soon as identification of SGA is performed. The addition of an anti-toxin antibiotic such as clindamycin is recommended particularly in NF or STSS or clinical signs suggestive of toxin production by the SGA (rash, gastrointestinal signs, hemodynamic disorders). The use of intravenous polyvalent immunoglobulins must also be discussed in NF and STSS. In all cases surgery should be discussed. The prognosis of these potentially very severe infections is related to their early diagnosis and treatment. A better understanding of the pathophysiology of these infections may optimize their management but also their prevention.

  15. Adaptation of group A Streptococcus to human amniotic fluid.

    Directory of Open Access Journals (Sweden)

    Izabela Sitkiewicz

    Full Text Available BACKGROUND: For more than 100 years, group A Streptococcus has been identified as a cause of severe and, in many cases, fatal infections of the female urogenital tract. Due to advances in hospital hygiene and the advent of antibiotics, this type of infection has been virtually eradicated. However, within the last three decades there has been an increase in severe intra- and post-partum infections attributed to GAS. METHODOLOGY: We hypothesized that GAS alters its transcriptome to survive in human amniotic fluid (AF and cause disease. To identify genes that were up or down regulated in response to growth in AF, GAS was grown in human AF or standard laboratory media (THY and samples for expression microarray analysis were collected during mid-logarithmic, late-logarithmic, and stationary growth phases. Microarray analysis was performed using a custom Affymetrix chip and normalized hybridization values derived from three biological replicates were collected at each growth point. Ratios of AF/THY above a 2-fold change and P-value <0.05 were considered significant. PRINCIPAL FINDINGS: The majority of changes in the GAS transcriptome involved down regulation of multiple adhesins and virulence factors and activation of the stress response. We observed significant changes in genes involved in the arginine deiminase pathway and in the nucleotide de novo synthesis pathway. CONCLUSIONS/SIGNIFICANCE: Our work provides new insight into how pathogenic bacteria respond to their environment to establish infection and cause disease.

  16. Streptococcal toxic shock syndrome secondary to group A Streptococcus vaginitis.

    Science.gov (United States)

    Hikone, Mayu; Kobayashi, Ken-Ichiro; Washino, Takuya; Ota, Masayuki; Sakamoto, Naoya; Iwabuchi, Sentaro; Ohnishi, Kenji

    2015-12-01

    Streptococcal toxic shock syndrome (TSS) is a systemic illness usually caused in the setting of infection by group A Streptococcus (GAS). The primary infections are often invasive infections of the respiratory tract or necrotizing infections of the skin and soft tissue, but some infections occur without relevant focus. GAS vaginitis is a rare condition among adult women and is accordingly thought to be uncommon as a cause of streptococcal TSS. Here we report the cases of two postmenopausal women with streptococcal TSS secondary to GAS vaginitis, one aged 55 and one aged 60. Both came to our emergency department with complaints or symptoms of abdominal pain, fever, hypotension, and multi-organ failure. In both cases, the relevant factor associated with streptococcal infection was a recent episode of GAS vaginitis. Both underwent fluid management and 14 days of antibiotic treatment and fully recovered without complications. Vaginitis was likely to be the primary infectious trigger of TSS in these two cases. Intrauterine device insertion, endometrial biopsy, and post-partum state have all been previously reported in TSS patients, and the female genital tract has been described as a portal of entry. GAS vaginitis warrants appropriate treatment as it may progress to severe systemic infection as described. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  17. Invasive Group A Streptococcus Infection among Children, Rural Kenya.

    Science.gov (United States)

    Seale, Anna C; Davies, Mark R; Anampiu, Kirimi; Morpeth, Susan C; Nyongesa, Sammy; Mwarumba, Salim; Smeesters, Pierre R; Efstratiou, Androulla; Karugutu, Rosylene; Mturi, Neema; Williams, Thomas N; Scott, J Anthony G; Kariuki, Samuel; Dougan, Gordon; Berkley, James A

    2016-02-01

    To determine the extent of group A Streptococcus (GAS) infections in sub-Saharan Africa and the serotypes that cause disease, we analyzed surveillance data for 64,741 hospital admissions in Kilifi, Kenya, during 1998-2011. We evaluated incidence, clinical presentations, and emm types that cause invasive GAS infection. We detected 370 cases; of the 369 for which we had data, most were skin and soft tissue infections (70%), severe pneumonia (23%), and primary bacteremia (14%). Overall case-fatality risk was 12%. Incidence of invasive GAS infection was 0.6 cases/1,000 live births among neonates, 101/100,000 person-years among children <1 year of age, and 35/100,000 among children <5 years of age. Genome sequencing identified 88 emm types. GAS causes serious disease in children in rural Kenya, especially neonates, and the causative organisms have considerable genotypic diversity. Benefit from the most advanced GAS type-specific vaccines may be limited, and efforts must be directed to protect against disease in regions of high incidence.

  18. Identification of group A Streptococcus antigenic determinants upregulated in vivo.

    Science.gov (United States)

    Salim, Kowthar Y; Cvitkovitch, Dennis G; Chang, Peter; Bast, Darrin J; Handfield, Martin; Hillman, Jeffrey D; de Azavedo, Joyce C S

    2005-09-01

    Group A Streptococcus (GAS) causes a range of diseases in humans, from mild noninvasive infections to severe invasive infections. The molecular basis for the varying severity of disease remains unclear. We identified genes expressed during invasive disease using in vivo-induced antigen technology (IVIAT), applied for the first time in a gram-positive organism. Convalescent-phase sera from patients with invasive disease were pooled, adsorbed against antigens derived from in vitro-grown GAS, and used to screen a GAS genomic expression library. A murine model of invasive GAS disease was included as an additional source of sera for screening. Sequencing DNA inserts from clones reactive with both human and mouse sera indicated 16 open reading frames with homology to genes involved in metabolic activity to genes of unknown function. Of these, seven genes were assessed for their differential expression by quantitative real-time PCR both in vivo, utilizing a murine model of invasive GAS disease, and in vitro at different time points of growth. Three gene products-a putative penicillin-binding protein 1A, a putative lipoprotein, and a conserved hypothetical protein homologous to a putative translation initiation inhibitor in Vibrio vulnificus-were upregulated in vivo, suggesting that these genes play a role during invasive disease.

  19. Precipitating the Decline of Terrorist Groups: A Systems Analysis

    Science.gov (United States)

    1994-03-24

    Act on April 30, 1971, signifming the end of the FLQ crisis ."’ 3. Post Critica Error Phase The police lid not want to break up the Viger cell because...36 . The FLQ’s Pre Critical Error Phase . .................... 37 2. The Critical Error Phase: The October Crisis ............... 45 3...organizational crisis ."" These radical innovations are a response by the terrorists to relieve the anxiety Ř|Edgar H. Schein, The Mechanisms of Channe in

  20. Inclusive Spectra of (p,xp) and (p,xd) Reactions on $^{90,92}$Zr and $^{92}$Mo Nuclei at E$_{p}$=30.3 MeV

    CERN Document Server

    Duisebayev, A; Boztosun, I

    2003-01-01

    New experimental data for the inclusive reactions (p,xp) and (p,xd) on isotopes of the nuclei $^{90,92}$Zr and $^{92}$Mo, have been measured at E$_{p}$=30.3 MeV, which has not been investigated in detail so far. We show the extension of the pre-equilibrium reactions to this energy region and interpret the results of these experiments. Moreover, we display the mechanism of the reaction and the level of energy-dependence. The adequacy of the theoretical models in explaining the measured experimental data is also discussed. In our theoretical analysis, the contributions of multi-step direct and compound processes in the formation of cross-sections are determined and we assert that the traditional frameworks are valid for the description of the experimental data.

  1. Differences between Belgian and Brazilian group A Streptococcus epidemiologic landscape.

    Directory of Open Access Journals (Sweden)

    Pierre Robert Smeesters

    Full Text Available BACKGROUND: Group A Streptococcus (GAS clinical and molecular epidemiology varies with location and time. These differences are not or are poorly understood. METHODS AND FINDINGS: We prospectively studied the epidemiology of GAS infections among children in outpatient hospital clinics in Brussels (Belgium and Brasília (Brazil. Clinical questionnaires were filled out and microbiological sampling was performed. GAS isolates were emm-typed according to the Center for Disease Control protocol. emm pattern was predicted for each isolate. 334 GAS isolates were recovered from 706 children. Skin infections were frequent in Brasília (48% of the GAS infections, whereas pharyngitis were predominant (88% in Brussels. The mean age of children with GAS pharyngitis in Brussels was lower than in Brasília (65/92 months, p<0.001. emm-typing revealed striking differences between Brazilian and Belgian GAS isolates. While 20 distinct emm-types were identified among 200 Belgian isolates, 48 were found among 128 Brazilian isolates. Belgian isolates belong mainly to emm pattern A-C (55% and E (42.5% while emm pattern E (51.5% and D (36% were predominant in Brasília. In Brasília, emm pattern D isolates were recovered from 18.5% of the pharyngitis, although this emm pattern is supposed to have a skin tropism. By contrast, A-C pattern isolates were infrequently recovered in a region where rheumatic fever is still highly prevalent. CONCLUSIONS: Epidemiologic features of GAS from a pediatric population were very different in an industrialised country and a low incomes region, not only in term of clinical presentation, but also in terms of genetic diversity and distribution of emm patterns. These differences should be taken into account for designing treatment guidelines and vaccine strategies.

  2. Cloning of aminopeptidase Npromoter and its activity in hematopoietic cell and different tumor cell lines

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Aminopeptidase N (APN) promoter region was cloned and sequenced from peripheral blood mononuclear cells. The recombinant reporter construct containing the promoter and luciferase gene, designated pXP1-APNLuc, was introduced into myeloblastic cell line, T lymphocyte cell line and various tumor cell lines. Luciferase assay showed that APN upstream promoter is myeloid-specific for high expression in myeloblastic cell line and much lower expres sion in T lymphocyte cell line. The promoter activity was relatively high in lung adenoma cell line compared with other tumor cell lines including hepatoma cell line, tong cancer cell line and esophageal cancer cell line in which the promoter activity significantly diminished or was almost undetectable. The characteristics of APN promoter may pro vide a new strategy for specific myeloprotection while tumor patients are being treated with chemotherapy and/or radio therapy.

  3. Invasive Group A streptococcal disease in Ireland, 2004 to 2010.

    LENUS (Irish Health Repository)

    Martin, J

    2011-01-01

    Invasive group A streptococcal infections (iGAS) are a major clinical and public health challenge. iGAS is a notifiable disease in Ireland since 2004. The aim of this paper is to describe the epidemiology of iGAS in Ireland for the first time over the seven-year period from 2004 to 2010. The Irish national electronic infectious disease reporting system was used by laboratories to enter the source of iGAS isolates, and by departments of public health to enter clinical and epidemiological details. We extracted and analysed data from 1 January 2004 to 31 December 2010. Over the study period, 400 iGAS cases were notified. The annual incidence of iGAS doubled, from 0.8 per 100,000 population in 2004 to 1.6 in 2008, and then remained the same in 2009 and 2010. The reported average annual incidence rates were highest among children up to five years of age (2.3\\/100,000) and adults aged over 60 years (3.2\\/100,000). The most common risk factors associated with iGAS were skin lesions or wounds. Of the 174 people for whom clinical syndrome information was available, 28 (16%) cases presented with streptococcal toxic shock syndrome and 19 (11%) with necrotising fasciitis. Of the 141 cases for whom seven-day outcomes were recorded, 11 people died with iGAS identified as the main cause of death (seven-day case fatality rate 8%). The notification rate of iGAS in Ireland was lower than that reported in the United Kingdom, Nordic countries and North America but higher than southern and eastern European countries. The reasons for lower notification rates in Ireland compared with other countries may be due to a real difference in incidence, possibly due to prescribing practices, or due to artefacts resulting from the specific Irish case definition and\\/or low reporting in the early stages of a new surveillance system. iGAS disease remains an uncommon but potentially severe disease in Ireland. Ongoing surveillance is required in order to undertake appropriate control measures and

  4. Blood Group Antigen Recognition via the Group A Streptococcal M Protein Mediates Host Colonization

    Science.gov (United States)

    De Oliveira, David M. P.; Hartley-Tassell, Lauren; Everest-Dass, Arun; Day, Christopher J.; Dabbs, Rebecca A.; Ve, Thomas; Kobe, Bostjan; Nizet, Victor; Packer, Nicolle H.; Walker, Mark J.; Jennings, Michael P.

    2017-01-01

    ABSTRACT Streptococcus pyogenes (group A streptococcus [GAS]) is responsible for over 500,000 deaths worldwide each year. The highly virulent M1T1 GAS clone is one of the most frequently isolated serotypes from streptococcal pharyngitis and invasive disease. The oral epithelial tract is a niche highly abundant in glycosylated structures, particularly those of the ABO(H) blood group antigen family. Using a high-throughput approach, we determined that a strain representative of the globally disseminated M1T1 GAS clone 5448 interacts with numerous, structurally diverse glycans. Preeminent among GAS virulence factors is the surface-expressed M protein. M1 protein showed high affinity for several terminal galactose blood group antigen structures. Deletion mutagenesis shows that M1 protein mediates glycan binding via its B repeat domains. Association of M1T1 GAS with oral epithelial cells varied significantly as a result of phenotypic differences in blood group antigen expression, with significantly higher adherence to those cells expressing H antigen structures compared to cells expressing A, B, or AB antigen structures. These data suggest a novel mechanism for GAS attachment to host cells and propose a link between host blood group antigen expression and M1T1 GAS colonization. PMID:28119471

  5. Evaluation of simplified dna extraction methods for EMM typing of group a streptococci

    Directory of Open Access Journals (Sweden)

    Jose JJM

    2006-01-01

    Full Text Available Simplified methods of DNA extraction for amplification and sequencing for emm typing of group A streptococci (GAS can save valuable time and cost in resource crunch situations. To evaluate this, we compared two methods of DNA extraction directly from colonies with the standard CDC cell lysate method for emm typing of 50 GAS strains isolated from children with pharyngitis and impetigo. For this, GAS colonies were transferred into two sets of PCR tubes. One set was preheated at 94oC for two minutes in the thermal cycler and cooled while the other set was frozen overnight at -20oC and then thawed before adding the PCR mix. For the cell lysate method, cells were treated with mutanolysin and hyaluronidase before heating at 100oC for 10 minutes and cooling immediately as recommended in the CDC method. All 50 strains could be typed by sequencing the hyper variable region of the emm gene after amplification. The quality of sequences and the emm types identified were also identical. Our study shows that the two simplified DNA extraction methods directly from colonies can conveniently be used for typing a large number of GAS strains easily in relatively short time.

  6. Addiction protein Phd of plasmid prophage P1 is a substrate of the ClpXP serine protease of Escherichia coli.

    OpenAIRE

    Lehnherr, H; Yarmolinsky, M B

    1995-01-01

    Plasmid-encoded addiction genes augment the apparent stability of various low copy number bacterial plasmids by selectively killing plasmid-free (cured) segregants or their progeny. The addiction module of plasmid prophage P1 consists of a pair of genes called phd and doc. Phd serves to prevent host death when the prophage is retained and, should retention mechanisms fail, Doc causes death on curing. Doc acts as a cell toxin to which Phd is an antidote. In this study we show that host mutants...

  7. GeXP多重PCR技术同时检测12种常见呼吸道病毒%A GeXP based Multiplex RT-PCR Assay for Simultaneous Detection of Twelve Human Respiratory Viruses

    Institute of Scientific and Technical Information of China (English)

    李瑾; 毛乃颖; 秦萌; 胡秀梅; 杨梦婕; 王淼; 张晨; 许文波; 马学军

    2011-01-01

    本研究建立了一种基于GeXP多重基因表达遗传分析系统的多重RT-PCR检测方法,该方法可以同时检测12种呼吸道病毒,包括流感病毒A型和B型、季节性H1N1、副流感病毒1~3型、人鼻病毒、人偏肺病毒、腺病毒、呼吸道合胞病毒A型和B型、人博卡病毒.针对病原体保守区序列设计12种病毒的特异性引物,分别用已验证的阳性标本为模板检验多重体系的特异性.多重检测体系在103拷贝/μL水平可同时检测到12种病毒.另检测24份临床标本,以real-time RT-PCR为参考标准,进一步验证检测体系.结果表明,这种基于GeXP系统的新方法灵敏度高、特异性强,可以快速同时检测12种常见呼吸道病毒.%A GeXP based multiplex RT-PCR assay was developed to simultaneously detect twelve different respiratory viruses types/subtypes including influenza A virus, influenza B virus, influenza A virus sHlNl, parainfluenza virus type 1, parainfluenza virus type 2, parainfluenza virus type 3 , human rhinovi-rus, human metapneumovirus, adenovirus, respiratory syncytial virus A, respiratory syncytial virus B and human bocavirus. Twelve sets of specific primers were designed based on the conserved sequences of available respiratory-virus sequence database The specificity of the multiplex system was examined by positive specimens confirmed previously. The sensitivity to detect twelve respiratory viruses simultaneously was 103 copies/μL. Twenty four clinical specimens were further detected by this novel assay and the results were compared with that of the real-time RT-PCR. These results showed that this novel assay based on GeXP is a fast, sensitive, and high throughput test for the detection of respiratory virus infections.

  8. Genetic Correction of Stem Cells in the Treatment of Inherited Diseases and Focus on Xeroderma Pigmentosum

    Directory of Open Access Journals (Sweden)

    Françoise Bernerd

    2013-10-01

    Full Text Available Somatic stem cells ensure tissue renewal along life and healing of injuries. Their safe isolation, genetic manipulation ex vivo and reinfusion in patients suffering from life threatening immune deficiencies (for example, severe combined immunodeficiency (SCID have demonstrated the efficacy of ex vivo gene therapy. Similarly, adult epidermal stem cells have the capacity to renew epidermis, the fully differentiated, protective envelope of our body. Stable skin replacement of severely burned patients have proven life saving. Xeroderma pigmentosum (XP is a devastating disease due to severe defects in the repair of mutagenic DNA lesions introduced upon exposure to solar radiations. Most patients die from the consequences of budding hundreds of skin cancers in the absence of photoprotection. We have developed a safe procedure of genetic correction of epidermal stem cells isolated from XP patients. Preclinical and safety assessments indicate successful correction of XP epidermal stem cells in the long term and their capacity to regenerate a normal skin with full capacities of DNA repair.

  9. Loss of SLC38A5 and FTSJ1 at Xp11.23 in three brothers with non-syndromic mental retardation due to a microdeletion in an unstable genomic region.

    Science.gov (United States)

    Froyen, Guy; Bauters, Marijke; Boyle, Jackie; Van Esch, Hilde; Govaerts, Karen; van Bokhoven, Hans; Ropers, Hans-Hilger; Moraine, Claude; Chelly, Jamel; Fryns, Jean-Pierre; Marynen, Peter; Gecz, Jozef; Turner, Gillian

    2007-06-01

    Using high resolution X chromosome array-CGH we identified an interstitial microdeletion at Xp11.23 in three brothers with moderate to severe mental retardation (MR) without dysmorphic features. The extent of the deletion was subsequently delineated to about 50 kb by regular PCR and included only the SLC38A5 and FTSJ1 genes. The loss of the FTSJ1 MR gene in males is expected to result in the observed phenotype but the contribution of the deletion of the solute carrier SLC38A5 gene is less clear. Their mother also carries the deletion and completely inactivates the aberrant X chromosome. Interestingly, the distal breakpoint is situated within a 200 kb SSX repeat region that appears to stimulate recombination since subtle copy number changes often occur at this location and it is frequently involved in translocations in tumours. Since this apparent SSX unstable structure is flanked proximally by FTSJ1 and PQBP1, subtle deletions or duplications at this location would be expected to cause MR, as in our family. So far, we have screened a cohort of 300 patients but did not find additional aberrations at the FTSJ1 locus indicating that the frequency is likely to be low.

  10. Highly Transparent Compositionally Graded Buffers for New Metamorphic Multijunction Solar Cell Designs

    Energy Technology Data Exchange (ETDEWEB)

    Schulte, Kevin L.; France, Ryan M.; Geisz, John F.

    2017-01-01

    The development of compositionally graded buffer layers (CGBs) with enhanced transparency would enable novel five and six junction solar cells, with efficiencies approaching 50% under high concentration. We demonstrate highly transparent grades between the GaAs and InP lattice constants on both A- and B-miscut GaAs substrates, employing AlxGayIn1-x-yAs and highly Se-doped Burstein-Moss (BM) shifted GaxIn 1-xP. Transparency to >810 and >890 nm wavelengths is demonstrated with BM-shifted GaxIn1-xP on B-miscut substrates and AlxGayIn1-x-yAs/GaxIn1-xP(Se) combined grades on A-miscut substrates, respectively. 0.74 eV GaInAs solar cells grown on these transparent CGBs exhibit Woc = 0.41 V at mA/ cm2, performance comparable with the state-of-the-art GaxIn1-xP grade employed in the four-junction-inverted metamorphic multijunction (IMM) cell. A GaAs/0.74cV GaInAs tandem cell was grown with a transparent BM-shifted GaxIn1-xP CGB to verify the CGB performance in a multijunction device structure. Quantum efficiency measurements indicate that the CGB is completely transparent to photons below the GaAs bandedge, validating its use in 4-6 junction IMM devices with a single-graded buffer. This tandem represents a highly efficient two-junction band gap combination, achieving 29.6% +/- 1.2% efficiency under the AM1.5 global spectrum, demonstrating how the additional transparency enables new device structures.

  11. Repair of DNA lesions induced by ultraviolet irradiation and aromatic amines in normal and repair-deficient human lymphoblastoid cell lines

    DEFF Research Database (Denmark)

    Stevnsner, Tinna; Frandsen, Henrik; Autrup, Herman

    1995-01-01

    A host cell reactivation (HCR) assay was employed to study the capacity of a normal and three repair-deficient human lymphoblastoid cell lines to repair DNA damage induced by UV irradiation and the aromatic amines 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and N-acetyl-2-aminofluorene....... In the XP-D cell line, which had practically no DNA repair capacity, AAF adducts had a more potent inhibitory effect on gene expression than UV and PhIP adducts. When corrected for this inhibitory effect, the wild-type, XP-C and CS-B cell lines repaired low levels of AAF and UV adducts with similar...

  12. Blockade of invariant TCR-CD1d interaction specifically inhibits antibody production against blood group A carbohydrates

    Science.gov (United States)

    Tazawa, Hirofumi; Irei, Toshimitsu; Tanaka, Yuka; Igarashi, Yuka; Tashiro, Hirotaka

    2013-01-01

    Previously, we detected B cells expressing receptors for blood group A carbohydrates in the CD11b+CD5+ B-1a subpopulation in mice, similar to that in blood group O or B in humans. In the present study, we demonstrate that CD1d-restricted natural killer T (NKT) cells are required to produce anti-A antibodies (Abs), probably through collaboration with B-1a cells. After immunization of wild-type (WT) mice with human blood group A red blood cells (A-RBCs), interleukin (IL)-5 exclusively and transiently increased and the anti-A Abs were elevated in sera. However, these reactions were not observed in CD1d−/− mice, which lack NKT cells. Administration of anti-mouse CD1d blocking monoclonal Abs (mAb) prior to immunization abolished IL-5 production by NKT cells and anti-A Ab production in WT mice. Administration of anti-IL-5 neutralizing mAb also diminished anti-A Ab production in WT mice, suggesting that IL-5 secreted from NKT cells critically regulates anti-A Ab production by B-1a cells. In nonobese diabetic/severe combined immunodeficient (NOD/SCID/γcnull) mice, into which peripheral blood mononuclear cells from type O human volunteers were engrafted, administration of anti-human CD1d mAb prior to A-RBC immunization completely inhibited anti-A Ab production. Thus, anti-CD1d treatment might constitute a novel approach that could help in evading Ab-mediated rejection in ABO-incompatible transplant recipients. PMID:23943651

  13. Dextromethorphan Efficiently Increases Bactericidal Activity, Attenuates Inflammatory Responses, and Prevents Group A Streptococcal Sepsis▿ †

    Science.gov (United States)

    Li, Ming-Han; Luo, Yueh-Hsia; Lin, Chiou-Feng; Chang, Yu-Tzu; Lu, Shiou-Ling; Kuo, Chih-Feng; Hong, Jau-Shyong; Lin, Yee-Shin

    2011-01-01

    Group A streptococcus (GAS) is an important human pathogen that causes a wide spectrum of diseases, ranging from mild throat and skin infections to severe invasive diseases such as necrotizing fasciitis and streptococcal toxic shock syndrome. Dextromethorphan (DM), a dextrorotatory morphinan and a widely used antitussive drug, has recently been reported to possess anti-inflammatory properties. In this study, we investigated the potential protective effect of DM in GAS infection using an air pouch infection mouse model. Our results showed that DM treatment increased the survival rate of GAS-infected mice. Bacterial numbers in the air pouch were lower in mice treated with DM than in those infected with GAS alone. The bacterial elimination efficacy was associated with increased cell viability and bactericidal activity of air-pouch-infiltrating cells. Moreover, DM treatment prevented bacterial dissemination in the blood and reduced serum levels of the proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-1β and the chemokines monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 2 (MIP-2), and RANTES. In addition, GAS-induced mouse liver injury was reduced by DM treatment. Taken together, DM can increase bacterial killing and reduce inflammatory responses to prevent sepsis in GAS infection. The consideration of DM as an adjunct treatment in combination with antibiotics against bacterial infection warrants further study. PMID:21199930

  14. Combination of immunohistochemistry, FISH and RT-PCR shows high incidence of Xp11 translocation RCC: comparison of three different diagnostic methods.

    Science.gov (United States)

    Lee, Hyun Jung; Shin, Dong Hoon; Noh, Gyu You; Kim, Young Keum; Kim, Ahrong; Shin, Nari; Lee, Jung Hee; Choi, Kyung Un; Kim, Jee Yeon; Lee, Chang Hun; Sol, Mee Young; Rha, Seo Hee; Park, Sung Woo

    2017-05-09

    We evaluated the frequency of translocation renal cell carcinoma (RCC) by reverse transcription polymerase chain reaction (RT-PCR) and how well the TFE3 immunoreactivity is concordant with TFE3 gene translocation status proved by fluorescence in situ hybridization (FISH) assay and RT-PCR. TFE3 and Cathepsin K expression was analyzed by immunohistochemistry in 185 RCC cases, and 48 cases either of more than weak expression of TFE3 or of positivity for Cathepsin K were done for FISH analysis and RT-PCR. All the RT-PCR positive cases were confirmed by cloning and sequencing. Of the 14 cases with strong nuclear TFE3 expression, 12 showed a break-apart signal by FISH. ASPL- and PRCC-TFE3 translocations were detected in 13 and one case, respectively, by RT-PCR. Of 21 cases with weak TFE3 expression, five were translocation-positive by FISH. ASPL-, PRCC-, and PSF-TFE3 translocations were detected by RT-PCR (n=3, 3, and 1, respectively). All 13 TFE3-negative/cathepsin K-positive cases were negative by FISH and two each harbored ASPL- and PRCC-TFE3 translocations that were detected by RT-PCR. A high rate of TFE3 immunoreactivity (8.6%) was confirmed by RT-PCR (13.5%) and FISH (9.7%). Higher translocation rate of RT-PCR means RT-PCR detected translocation in TFE3 weak expression group and only cathepsin K positive group more specifically than FISH. Thus, RT-PCR would complement FISH analysis for detecting translocation RCC with fusion partners.

  15. Genetic switch to hypervirulence reduces colonization phenotypes of the globally disseminated group A streptococcus M1T1 clone.

    Science.gov (United States)

    Hollands, Andrew; Pence, Morgan A; Timmer, Anjuli M; Osvath, Sarah R; Turnbull, Lynne; Whitchurch, Cynthia B; Walker, Mark J; Nizet, Victor

    2010-07-01

    The recent resurgence of invasive group A streptococcal disease has been paralleled by the emergence of the M1T1 clone. Recently, invasive disease initiation has been linked to mutations in the covR/S 2-component regulator. We investigated whether a fitness cost is associated with the covS mutation that counterbalances hypervirulence. Wild-type M1T1 group A Streptococcus and an isogenic covS-mutant strain derived from animal passage were compared for adherence to human laryngeal epithelial cells, human keratinocytes, or fibronectin; biofilm formation; and binding to intact mouse skin. Targeted mutagenesis of capsule expression of both strains was performed for analysis of its unique contribution to the observed phenotypes. The covS-mutant bacteria showed reduced capacity to bind to epithelial cell layers as a consequence of increased capsule expression. The covS-mutant strain also had reduced capacity to bind fibronectin and to form biofilms on plastic and epithelial cell layers. A defect in skin adherence of the covS-mutant strain was demonstrated in a murine model. Reduced colonization capacity provides a potential explanation for why the covS mutation, which confers hypervirulence, has not become fixed in the globally disseminated M1T1 group A Streptococcus clone, but rather may arise anew under innate immune selection in individual patients.

  16. 矿物钠快离子导体Na1+3x+yAlxNdyTi2-x-ySi2xP3-2xO12合成与表征%Synthesis and characterization of Na1+3x+yAlxNdyTi2-x-ySi2xP3-2xO12 mineral sodium fast ionic conductors

    Institute of Scientific and Technical Information of China (English)

    曾飞; 蔡增良; 王文继

    2006-01-01

    Na1+3x+yAlxNdyTi2-x-ySi2xP3-2xO12钠快离子导体(以下简称Al-Nd-Nasicon)可以用精选的天然叶腊石A12[Si4O10](OH)2为起始原料与其它化合物,经过高温(900~1100℃)固相反应约15h制得.在y=0.3,x≤0.3和y=0.5,x≤0.2的组成范围内可得到具有Nasicon的三方结构空间群属于R3C的固溶体.该相具有较高的电导率,其中起始组成y=0.3,x=0.1的合成物在350℃时电导率为1.80×10-2S/cm.

  17. Initially unrecognised group A streptococcal pelvic inflammatory disease in a postmenopausal woman.

    Science.gov (United States)

    Kouijzer, I J E; Polderman, F N; Bekers, E M; Bloks, P H C J; Schneeberger, P M; de Jager, C P C

    2014-11-01

    Invasive group A streptococcal infection is a severe disease with high mortality. Invasive group A streptococcal infection may arise after pelvic inflammatory disease. Pelvic inflammatory disease in postmenopausal women is rare. Here, we report a unique case of a postmenopausal woman with fatal invasive group A streptococcal infection due to pelvic inflammatory disease and an extraordinary course of diagnosis.

  18. Two group A streptococcal peptide pheromones act through opposing Rgg regulators to control biofilm development.

    Science.gov (United States)

    Chang, Jennifer C; LaSarre, Breah; Jimenez, Juan C; Aggarwal, Chaitanya; Federle, Michael J

    2011-08-01

    Streptococcus pyogenes (Group A Streptococcus, GAS) is an important human commensal that occasionally causes localized infections and less frequently causes severe invasive disease with high mortality rates. How GAS regulates expression of factors used to colonize the host and avoid immune responses remains poorly understood. Intercellular communication is an important means by which bacteria coordinate gene expression to defend against host assaults and competing bacteria, yet no conserved cell-to-cell signaling system has been elucidated in GAS. Encoded within the GAS genome are four rgg-like genes, two of which (rgg2 and rgg3) have no previously described function. We tested the hypothesis that rgg2 or rgg3 rely on extracellular peptides to control target-gene regulation. We found that Rgg2 and Rgg3 together tightly regulate two linked genes encoding new peptide pheromones. Rgg2 activates transcription of and is required for full induction of the pheromone genes, while Rgg3 plays an antagonistic role and represses pheromone expression. The active pheromone signals, termed SHP2 and SHP3, are short and hydrophobic (DI[I/L]IIVGG), and, though highly similar in sequence, their ability to disrupt Rgg3-DNA complexes were observed to be different, indicating that specificity and differential activation of promoters are characteristics of the Rgg2/3 regulatory circuit. SHP-pheromone signaling requires an intact oligopeptide permease (opp) and a metalloprotease (eep), supporting the model that pro-peptides are secreted, processed to the mature form, and subsequently imported to the cytoplasm to interact directly with the Rgg receptors. At least one consequence of pheromone stimulation of the Rgg2/3 pathway is increased biogenesis of biofilms, which counteracts negative regulation of biofilms by RopB (Rgg1). These data provide the first demonstration that Rgg-dependent quorum sensing functions in GAS and substantiate the role that Rggs play as peptide receptors across the

  19. covR Mediated Antibiofilm Activity of 3-Furancarboxaldehyde Increases the Virulence of Group A Streptococcus.

    Directory of Open Access Journals (Sweden)

    Ganapathy Ashwinkumar Subramenium

    Full Text Available Group A streptococcus (GAS, Streptococcus pyogenes, a multi-virulent, exclusive human pathogen responsible for various invasive and non-invasive diseases possesses biofilm forming phenomenon as one of its pathogenic armaments. Recently, antibiofilm agents have gained prime importance, since inhibiting the biofilm formation is expected to reduce development of antibiotic resistance and increase their susceptibility to the host immune cells.The current study demonstrates the antibiofilm activity of 3Furancarboxaldehyde (3FCA, a floral honey derived compound, against GAS biofilm, which was divulged using crystal violet assay, light microscopy, and confocal laser scanning microscopy. The report is extended to study its effect on various aspects of GAS (morphology, virulence, aggregation at its minimal biofilm inhibitory concentration (132μg/ml. 3FCA was found to alter the growth pattern of GAS in solid and liquid medium and increased the rate of auto-aggregation. Electron microscopy unveiled the increase in extra polymeric substances around cell. Gene expression studies showed down-regulation of covR gene, which is speculated to be the prime target for the antibiofilm activity. Increased hyaluronic acid production and down regulation of srtB gene is attributed to the enhanced rate of auto-aggregation. The virulence genes (srv, mga, luxS and hasA were also found to be over expressed, which was manifested with the increased susceptibility of the model organism Caenorhabditis elegans to 3FCA treated GAS. The toxicity of 3FCA was ruled out with no adverse effect on C. elegans.Though 3FCA possess antibiofilm activity against GAS, it was also found to increase the virulence of GAS. This study demonstrates that, covR mediated antibiofilm activity may increase the virulence of GAS. This also emphasizes the importance to analyse the acclimatization response and virulence of the pathogen in the presence of antibiofilm compounds prior to their clinical trials.

  20. Two group A streptococcal peptide pheromones act through opposing Rgg regulators to control biofilm development.

    Directory of Open Access Journals (Sweden)

    Jennifer C Chang

    2011-08-01

    Full Text Available Streptococcus pyogenes (Group A Streptococcus, GAS is an important human commensal that occasionally causes localized infections and less frequently causes severe invasive disease with high mortality rates. How GAS regulates expression of factors used to colonize the host and avoid immune responses remains poorly understood. Intercellular communication is an important means by which bacteria coordinate gene expression to defend against host assaults and competing bacteria, yet no conserved cell-to-cell signaling system has been elucidated in GAS. Encoded within the GAS genome are four rgg-like genes, two of which (rgg2 and rgg3 have no previously described function. We tested the hypothesis that rgg2 or rgg3 rely on extracellular peptides to control target-gene regulation. We found that Rgg2 and Rgg3 together tightly regulate two linked genes encoding new peptide pheromones. Rgg2 activates transcription of and is required for full induction of the pheromone genes, while Rgg3 plays an antagonistic role and represses pheromone expression. The active pheromone signals, termed SHP2 and SHP3, are short and hydrophobic (DI[I/L]IIVGG, and, though highly similar in sequence, their ability to disrupt Rgg3-DNA complexes were observed to be different, indicating that specificity and differential activation of promoters are characteristics of the Rgg2/3 regulatory circuit. SHP-pheromone signaling requires an intact oligopeptide permease (opp and a metalloprotease (eep, supporting the model that pro-peptides are secreted, processed to the mature form, and subsequently imported to the cytoplasm to interact directly with the Rgg receptors. At least one consequence of pheromone stimulation of the Rgg2/3 pathway is increased biogenesis of biofilms, which counteracts negative regulation of biofilms by RopB (Rgg1. These data provide the first demonstration that Rgg-dependent quorum sensing functions in GAS and substantiate the role that Rggs play as peptide

  1. Streptolysin O Rapidly Impairs Neutrophil Oxidative Burst and Antibacterial Responses to Group A Streptococcus

    Directory of Open Access Journals (Sweden)

    Satoshi Uchiyama

    2016-11-01

    Full Text Available Group A Streptococcus (GAS causes a wide range of human infections, ranging from simple pharyngitis to life-threatening necrotizing fasciitis and toxic shock syndrome. A globally disseminated clone of M1T1 GAS has been associated with an increase in severe, invasive GAS infections in recent decades. The secreted GAS pore-forming toxin streptolysin O (SLO, which induces eukaryotic cell lysis in a cholesterol-dependent manner, is highly upregulated in the GAS M1T1 clone during bloodstream dissemination. SLO is known to promote GAS resistance to phagocytic clearance by neutrophils, a critical first element of host defense against invasive bacterial infection. Here we examine the role of SLO in modulating specific neutrophil functions during their early interaction with GAS. We find that SLO at subcytotoxic concentrations and time points is necessary and sufficient to suppress neutrophil oxidative burst, in a manner reversed by free cholesterol and anti-SLO blocking antibodies. In addition, SLO at subcytotoxic concentrations blocked neutrophil degranulation, interleukin-8 secretion and responsiveness, and elaboration of DNA-based neutrophil extracellular traps (NETs, cumulatively supporting a key role for SLO in GAS resistance to immediate neutrophil killing. A non-toxic SLO derivate elicits protective immunity against lethal GAS challenge in a murine infection model. We conclude that SLO exerts a novel cytotoxic-independent function at early stages of invasive infections (< 30 min, contributing to GAS escape from neutrophil clearance.

  2. Treatment Challenges of Group A Beta-hemolytic Streptococcal Pharyngo-Tonsillitis

    Science.gov (United States)

    Brook, Itzhak

    2017-01-01

    Introduction  Despite its in vitro efficacy, penicillin often fails to eradicate Group A β-hemolytic streptococci (GABHS) from patients with acute and relapsing pharyngo-tonsillitis (PT). Objective  This review of the literature details the causes of penicillin failure to eradicate GABHS PT and the therapeutic modalities to reduce and overcome antimicrobial failure. Data Synthesis  The causes of penicillin failure in eradicating GABHS PT include the presence of β lactamase producing bacteria (BLPB) that “protect” GABHS from any penicillin; the absence of bacteria that interfere with the growth of GABHS; co-aggregation between GABHS and Moraxella catarrhalis; and the poor penetration of penicillin into the tonsillar tissues and the tonsillo-pharyngeal cells, which allows intracellular GABHS and Staphylococcus aureus to survive. The inadequate intracellular penetration of penicillin can allow intracellular GABHS and S. aureus to persist. In the treatment of acute tonsillitis, the use of cephalosporin can overcome these interactions by eradicating aerobic BLPB (including M. catarrhalis), while preserving the potentially interfering organisms and eliminating GABHS. Conclusion  In treatment of recurrent and chronic PT, the administration of clindamycin, or amoxicillin-clavulanic acid, can eradicate both aerobic and anaerobic BLPB, as well as GABHS. The superior intracellular penetration of cephalosporin and clindamycin also enhances their efficacy against intracellular GABHS and S. aureus. PMID:28680500

  3. Group A Streptococcus exploits human plasminogen for bacterial translocation across epithelial barrier via tricellular tight junctions

    Science.gov (United States)

    Sumitomo, Tomoko; Nakata, Masanobu; Higashino, Miharu; Yamaguchi, Masaya; Kawabata, Shigetada

    2016-01-01

    Group A Streptococcus (GAS) is a human-specific pathogen responsible for local suppurative and life-threatening invasive systemic diseases. Interaction of GAS with human plasminogen (PLG) is a salient characteristic for promoting their systemic dissemination. In the present study, a serotype M28 strain was found predominantly localized in tricellular tight junctions of epithelial cells cultured in the presence of PLG. Several lines of evidence indicated that interaction of PLG with tricellulin, a major component of tricellular tight junctions, is crucial for bacterial localization. A site-directed mutagenesis approach revealed that lysine residues at positions 217 and 252 within the extracellular loop of tricellulin play important roles in PLG-binding activity. Additionally, we demonstrated that PLG functions as a molecular bridge between tricellulin and streptococcal surface enolase (SEN). The wild type strain efficiently translocated across the epithelial monolayer, accompanied by cleavage of transmembrane junctional proteins. In contrast, amino acid substitutions in the PLG-binding motif of SEN markedly compromised those activities. Notably, the interaction of PLG with SEN was dependent on PLG species specificity, which influenced the efficiency of bacterial penetration. Our findings provide insight into the mechanism by which GAS exploits host PLG for acceleration of bacterial invasion into deeper tissues via tricellular tight junctions. PMID:26822058

  4. Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation*

    Science.gov (United States)

    Sumitomo, Tomoko; Nakata, Masanobu; Higashino, Miharu; Terao, Yutaka; Kawabata, Shigetada

    2013-01-01

    Group A Streptococcus (GAS) is an important human pathogen that possesses an ability to translocate across the epithelial barrier. In this study, culture supernatants of tested GAS strains showed proteolytic activity against human occludin and E-cadherin. Utilizing various types of protease inhibitors and amino acid sequence analysis, we identified SpeB (streptococcal pyrogenic exotoxin B) as the proteolytic factor that cleaves E-cadherin in the region neighboring the calcium-binding sites within the extracellular domain. The cleaving activities of culture supernatants from several GAS isolates were correlated with the amount of active SpeB, whereas culture supernatants from an speB mutant showed no such activities. Of note, the wild type strain efficiently translocated across the epithelial monolayer along with cleavage of occludin and E-cadherin, whereas deletion of the speB gene compromised those activities. Moreover, destabilization of the junctional proteins was apparently relieved in cells infected with the speB mutant, as compared with those infected with the wild type. Taken together, our findings indicate that the proteolytic efficacy of SpeB in junctional degradation allows GAS to invade deeper into tissues. PMID:23532847

  5. Asymptomatic carriage of group A streptococcus is associated with elimination of capsule production.

    Science.gov (United States)

    Flores, Anthony R; Jewell, Brittany E; Olsen, Randall J; Shelburne, Samuel A; Fittipaldi, Nahuel; Beres, Stephen B; Musser, James M

    2014-09-01

    Humans commonly carry pathogenic bacteria asymptomatically, but despite decades of study, the underlying molecular contributors remain poorly understood. Here, we show that a group A streptococcus carriage strain contains a frameshift mutation in the hasA gene resulting in loss of hyaluronic acid capsule biosynthesis. This mutation was repaired by allelic replacement, resulting in restoration of capsule production in the isogenic derivative strain. The "repaired" isogenic strain was significantly more virulent than the carriage strain in a mouse model of necrotizing fasciitis and had enhanced growth ex vivo in human blood. Importantly, the repaired isogenic strain colonized the mouse oropharynx with significantly greater bacterial burden and had significantly reduced ability to internalize into cultured epithelial cells than the acapsular carriage strain. We conducted full-genome sequencing of 81 strains cultured serially from 19 epidemiologically unrelated human subjects and discovered the common theme that mutations negatively affecting capsule biosynthesis arise in vivo in the has operon. The significantly decreased capsule production is a key factor contributing to the molecular détente between pathogen and host. Our discoveries suggest a general model for bacterial pathogens in which mutations that downregulate or ablate virulence factor production contribute to carriage.

  6. Scrum en XP frisse wind in onderwijs

    NARCIS (Netherlands)

    Blom, G. (Gerben); Leeuwen, van H. (Henk)

    2009-01-01

    Projecten in het hbo kenmerken zich meestal door een strakke rolverdeling, een flinke hoeveelheid documentatie en een watervalaanpak. De resultaten met een Agile-werkwijze zijn echter bemoedigend. Studenten zijn enthousiast door de continue focus op werkende software en de verbeterde communicatie in

  7. XP in a Small Software Development Business

    DEFF Research Database (Denmark)

    Babb, Jeffry; Hoda, Rashina; Nørbjerg, Jacob

    2014-01-01

    While small software development shops have trended towards the adoption of Agile methods, local conditions and high iteration pressure typically cause adaptations and appropriations of Agile methods. This paper shares evidence from a study concerning how a small software development company adopts...... most sustainable for small shop teams, with process maintenance and viability as a goal, are highlighted....

  8. XP in a Small Software Development Business

    DEFF Research Database (Denmark)

    Babb, Jeffry; Hoda, Rashina; Nørbjerg, Jacob

    2014-01-01

    While small software development shops have trended towards the adoption of Agile methods, local conditions and high iteration pressure typically cause adaptations and appropriations of Agile methods. This paper shares evidence from a study concerning how a small software development company adopts...

  9. Initially unrecognised group A streptococcal pelvic inflammatory disease in a postmenopausal woman

    NARCIS (Netherlands)

    Kouijzer, I.J.; Polderman, F.N.; Bekers, E.M.; Bloks, P.H.; Schneeberger, P.M.; Jager, C.P. de

    2014-01-01

    Invasive group A streptococcal infection is a severe disease with high mortality. Invasive group A streptococcal infection may arise after pelvic inflammatory disease. Pelvic inflammatory disease in postmenopausal women is rare. Here, we report a unique case of a postmenopausal woman with fatal

  10. GeXP多重基因表达遗传分析系统在手足口病病原分型检测中的应用%Development of a GeXP based Multiplex RT-PCR Assay for Simultaneous Differentiation of Nine Human Hand Food Mouth Disease Pathogens

    Institute of Scientific and Technical Information of China (English)

    胡秀梅; 许文波; 马学军; 张勇; 徐邦牢; 杨梦; 王淼; 张晨; 李瑾; 白如银; 周小棉

    2011-01-01

    利用GeXP多重基因表达遗传分析系统,建立一种多重逆转录-聚合酶链反应(RT-PCR)方法,同时检测引起手足口病的9种常见的人肠道病毒一人肠道病毒71型(HEV71)、柯萨奇病毒A组(CVA)16、4、5、9、10型和柯萨奇病毒B组(CVB)1、3、5型.优化多重反应体系中针对5'UTR区的肠道病毒通用引物和11对针对9种血清型人肠道病毒VP1区的特异性引物的浓度比例,分别以病毒细胞培养物和阳性粪便标本来验证多重反应体系的特异性,以TCID50定量的细胞培养物和克隆质粒体外转录的RNA梯度稀释液来检测多重检测体系的灵敏度.结果表明,优化后的多重检测体系,可扩增出人肠道病毒共有的保守片段的和型特异性片段,HEV71和CVA16细胞培养物的检测下限为100.5TCID50/μL,并可在103copies/μL水平同时、特异地检测出9种病毒RNA.该方法灵敏度高、特异性强,可快速对大量临床样本进行高通量检测,用于手足口病的分子流行病学调查.%A multiplex RT-PCR assay based on GeXP system was developed in order to detect simultaneously human enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) and other coxsackieviruses (CVA4, 5,9 and 10, CVB1, 3 and 5). Enterovirus detection was performed with a mixture of 12 pairs of oligonu-cleotide primers including one pair of published primers for amplifying all known pan-enterovirus genomes and eleven primer pairs specific for detection of the VP1 genes of EV71, C A16, CVA4, CVA5, CVA9,CVA10, CVB1, CVB3 and CVB5, respectively. The specificity of multiplex RT-PCR system was examined using enterovirus cell cultures and positive strains identified previously from hand-foot-and-mouth disease (HFMD) patients. Serial dilution of titrated EV71 and C A16 cell cultures and in vitro transcripted RNA of enterovirus VP1 regions were used to detect the sensitivity of the multiplex RT-PCR system. The limit of detection for this multiplex RT-PCR system was 100

  11. UVB-induced cell death signaling is associated with G1-S progression and transcription inhibition in primary human fibroblasts.

    Directory of Open Access Journals (Sweden)

    Tatiana Grohmann Ortolan

    Full Text Available DNA damage induced by ultraviolet (UV radiation can be removed by nucleotide excision repair through two sub-pathways, one general (GGR and the other specific for transcribed DNA (TCR, and the processing of unrepaired lesions trigger signals that may lead to cell death. These signals involve the tumor suppressor p53 protein, a central regulator of cell responses to DNA damage, and the E3 ubiquitin ligase Mdm2, that forms a feedback regulatory loop with p53. The involvement of cell cycle and transcription on the signaling to apoptosis was investigated in UVB-irradiated synchronized, DNA repair proficient, CS-B (TCR-deficient and XP-C (GGR-deficient primary human fibroblasts. Cells were irradiated in the G1 phase of the cell cycle, with two doses with equivalent levels of apoptosis (low and high, defined for each cell line. In the three cell lines, the low doses of UVB caused only a transient delay in progression to the S phase, whereas the high doses induced permanent cell cycle arrest. However, while accumulation of Mdm2 correlated well with the recovery from transcription inhibition at the low doses for normal and CS-B fibroblasts, for XP-C cells this protein was shown to be accumulated even at UVB doses that induced high levels of apoptosis. Thus, UVB-induced accumulation of Mdm2 is critical for counteracting p53 activation and apoptosis avoidance, but its effect is limited due to transcription inhibition. However, in the case of XP-C cells, an excess of unrepaired DNA damage would be sufficient to block S phase progression, which would signal to apoptosis, independent of Mdm2 accumulation. The data clearly discriminate DNA damage signals that lead to cell death, depending on the presence of UVB-induced DNA damage in replicating or transcribing regions.

  12. Comorbidity of Kawasaki disease and group A streptococcal pleural effusion in a healthy child: a case report

    Directory of Open Access Journals (Sweden)

    Alhammadi AH

    2013-07-01

    Full Text Available Ahmed H Alhammadi, Mohamed A HendausGeneral Pediatrics Section, Department of Pediatrics, Hamad Medical Corporation, Doha, QatarBackground: Kawasaki disease is an acute self-limiting vasculitis that affects children. The most dreaded complication of Kawasaki disease reported in the literature over the years is coronary artery disease, which is considered as the main cause of acquired heart disease. However, pulmonary associations with Kawasaki disease have been overlooked. We present a rare, if not unique, case of Kawasaki disease associated with group A streptococcus pleural effusion in the English language literature. A search of the PubMed database was carried out, using a combination of the terms “Kawasaki disease”, “pneumonia”, and “group A streptococcus”. The majority of studies conducted in children with Kawasaki disease have concentrated on the coronary artery implications. Kawasaki disease is considered a self-limiting illness, but can have detrimental consequences if not diagnosed early. When there is a prolonged inflammatory reaction, with no infectious agent identified or remittent fever unresponsive to antibiotics, Kawasaki disease should be taken into consideration. Elevated Vβ2+ T cells compared with healthy controls suggest possible involvement of a superantigen in the etiology of Kawasaki disease, so it is wise that the health care provider concentrates not only on the cardiac consequences, but also on pulmonary associations.Keywords: Kawasaki disease, pneumonia, group A streptococcus

  13. Manganese Homeostasis in Group A Streptococcus Is Critical for Resistance to Oxidative Stress and Virulence

    Science.gov (United States)

    Turner, Andrew G.; Ong, Cheryl-lynn Y.; Gillen, Christine M.; Davies, Mark R.; West, Nicholas P.; McEwan, Alastair G.

    2015-01-01

    ABSTRACT Streptococcus pyogenes (group A Streptococcus [GAS]) is an obligate human pathogen responsible for a spectrum of human disease states. Metallobiology of human pathogens is revealing the fundamental role of metals in both nutritional immunity leading to pathogen starvation and metal poisoning of pathogens by innate immune cells. Spy0980 (MntE) is a paralog of the GAS zinc efflux pump CzcD. Through use of an isogenic mntE deletion mutant in the GAS serotype M1T1 strain 5448, we have elucidated that MntE is a manganese-specific efflux pump required for GAS virulence. The 5448ΔmntE mutant had significantly lower survival following infection of human neutrophils than did the 5448 wild type and the complemented mutant (5448ΔmntE::mntE). Manganese homeostasis may provide protection against oxidative stress, explaining the observed ex vivo reduction in virulence. In the presence of manganese and hydrogen peroxide, 5448ΔmntE mutant exhibits significantly lower survival than wild-type 5448 and the complemented mutant. We hypothesize that MntE, by maintaining homeostatic control of cytoplasmic manganese, ensures that the peroxide response repressor PerR is optimally poised to respond to hydrogen peroxide stress. Creation of a 5448ΔmntE-ΔperR double mutant rescued the oxidative stress resistance of the double mutant to wild-type levels in the presence of manganese and hydrogen peroxide. This work elucidates the mechanism for manganese toxicity within GAS and the crucial role of manganese homeostasis in maintaining GAS virulence. PMID:25805729

  14. Vismodegib Therapy for Basal Cell Carcinoma in an 8-Year-Old Chinese Boy with Xeroderma Pigmentosum.

    Science.gov (United States)

    Fife, Douglas; Laitinen, Marko A; Myers, David J; Landsteiner, Pamela B

    2017-03-01

    Vismodegib is an oral inhibitor of the Hedgehog signaling pathway and has been used to treat basal cell carcinoma (BCC) in adults. This article reports clearance of a nodular BCC of the nasal tip in an 8-year-old boy with xeroderma pigmentosum (XP). BCC can pose therapeutic challenges when located in areas that are not amenable to traditional therapies such as Mohs micrographic surgery or topical agents. Vismodegib was used at a dose of 150 mg/day to treat the boy's BCC. After 4 months of therapy, we achieved complete clinical clearance. During 21 months of follow-up, the patient's nose remained clinically clear of tumor. Vismodegib was successfully used to treat a child with XP and nodular BCC. Our goal in using vismodegib was tumor regression while avoiding cosmetic and functional disfigurement. Vismodegib was effective in clinically clearing the tumor, and the patient has shown no signs of recurrence. Further studies are warranted.

  15. Induction of Endoplasmic Reticulum Stress and Unfolded Protein Response Constitutes a Pathogenic Strategy of group A Streptococcus

    Directory of Open Access Journals (Sweden)

    Emanuel eHanski

    2014-08-01

    Full Text Available The connection between bacterial pathogens and unfolded protein response (UPR is poorly explored. In this review we highlight the evidence showing that group A streptococcus (GAS induces endoplasmic reticulum (ER stress and UPR through which it captures the amino acid asparagine (ASN from the host. GAS acts extracellularly and during adherence to host cells it delivers the hemolysin toxins; streptolysin O (SLO and streptolysin S (SLS. By poorly understood pathways, these toxins trigger UPR leading to the induction of the transcriptional regulator ATF4 and consequently to the upregulation of asparagine synthetase (ASNS transcription leading to production and release of ASN. GAS senses ASN and alters gene expression profile accordingly, and increases the rate of multiplication. We suggest that induction of UPR by GAS and by other bacterial pathogens represent means through which bacterial pathogens gain nutrients from the host, obviating the need to become internalized or inflict irreversible cell damage.

  16. Group A PP2Cs evolved in land plants as key regulators of intrinsic desiccation tolerance.

    Science.gov (United States)

    Komatsu, Kenji; Suzuki, Norihiro; Kuwamura, Mayuri; Nishikawa, Yuri; Nakatani, Mao; Ohtawa, Hitomi; Takezawa, Daisuke; Seki, Motoaki; Tanaka, Maho; Taji, Teruaki; Hayashi, Takahisa; Sakata, Yoichi

    2013-01-01

    Vegetative desiccation tolerance is common in bryophytes, although this character has been lost in most vascular plants. The moss Physcomitrella patens survives complete desiccation if treated with abscisic acid (ABA). Group A protein phosphatases type 2C (PP2C) are negative regulators of abscisic acid signalling. Here we show that the elimination of Group A PP2C is sufficient to ensure P. patens survival to full desiccation, without ABA treatment, although its growth is severely hindered. Microarray analysis shows that the Group A PP2C-regulated genes exclusively overlap with genes exhibiting a high level of ABA induction. Group A PP2C disruption weakly affects ABA-activated kinase activity, indicating Group A PP2C action downstream of these kinases in the moss. We propose that Group A PP2C emerged in land plants to repress desiccation tolerance mechanisms, possibly facilitating plants propagation on land, whereas ABA releases the intrinsic desiccation tolerance from Group A PP2C regulation.

  17. Cells

    Directory of Open Access Journals (Sweden)

    Zhao-Hui Jin

    2012-11-01

    Full Text Available As cancer stem cells (CSCs are postulated to play critical roles in cancer development, including metastasis and recurrence, CSC imaging would provide valuable information for cancer treatment and lead to CSC-targeted therapy. To assess the possibility of in vivo CSC targeting, we conducted basic studies on radioimmunotargeting of cancer cells positive for CD133, a CSC marker recognized in various cancers. Antibodies against CD133 were labeled with 125I, and their in vitro cell binding properties were tested. Using the same isotype IgG as a control, in vivo biodistribution of the labeled antibody retaining immunoreactivity was examined in mice bearing an HCT116 xenograft in which a population of the cancer cells expressed CD133. Intratumoral distribution of the labeled antibody was examined and compared to the CD133 expression pattern. The 125I-labeled anti-CD133 antibody showed a modest but significantly higher accumulation in the HCT116 xenograft compared to the control IgG. The intratumoral distribution of the labeled antibody mostly overlapped with the CD133 expression, whereas the control IgG was found in the area close to the necrotic tumor center. Our results indicate that noninvasive in vivo targeting of CSCs could be possible with radiolabeled antibodies against cell membrane markers.

  18. Multi-reassortant G3P[3] group A rotavirus in a horseshoe bat in Zambia.

    Science.gov (United States)

    Sasaki, Michihito; Orba, Yasuko; Sasaki, Satoko; Gonzalez, Gabriel; Ishii, Akihiro; Hang'ombe, Bernard M; Mweene, Aaron S; Ito, Kimihito; Sawa, Hirofumi

    2016-10-01

    Group A rotavirus is a major cause of diarrhoea in humans, especially in young children. Bats also harbour group A rotaviruses, but the genetic backgrounds of bat rotavirus strains are usually distinct from those of human rotavirus strains. We identified a new strain of group A rotavirus in the intestinal contents of a horseshoe bat in Zambia. Whole genome sequencing revealed that the identified virus, named RVA/Bat-wt/ZMB/LUS12-14/2012/G3P[3], possessed the genotype constellation G3-P[3]-I3-R2-C2-M3-A9-N2-T3-E2-H3. Several genome segments of LUS12-14 were highly similar to those of group A rotaviruses identified from humans, cows and antelopes, indicating interspecies transmission of rotaviruses between bats and other mammals with possible multiple genomic reassortment events.

  19. Genetic Architecture of Group A Streptococcal Necrotizing Soft Tissue Infections in the Mouse

    DEFF Research Database (Denmark)

    Chella Krishnan, Karthickeyan; Mukundan, Santhosh; Alagarsamy, Jeyashree;

    2016-01-01

    Host genetic variations play an important role in several pathogenic diseases, and we have previously provided strong evidences that these genetic variations contribute significantly to differences in susceptibility and clinical outcomes of invasive Group A Streptococcus (GAS) infections, includi...

  20. 78 FR 61387 - Supermedia LLC, Publishing Operations Divison, Account Management Group, a Subsidiary of Dex...

    Science.gov (United States)

    2013-10-03

    ... Employment and Training Administration Supermedia LLC, Publishing Operations Divison, Account Management..., Florida; Supermedia LLC, Publishing Operations Divison, Listing Management Group, a Subsidiary of Dex... Operation Division, Account Management Group, Internet Publishing Operations Group, and Listing...

  1. The expansion of thymopoiesis in neonatal mice is dependent on expression of high mobility group a 2 protein (Hmga2).

    Science.gov (United States)

    Berent-Maoz, Beata; Montecino-Rodriguez, Encarnacion; Fice, Michael; Casero, David; Seet, Christopher S; Crooks, Gay M; Lowry, William; Dorshkind, Kenneth

    2015-01-01

    Cell number in the mouse thymus increases steadily during the first two weeks after birth. It then plateaus and begins to decline by seven weeks after birth. The factors governing these dramatic changes in cell production are not well understood. The data herein correlate levels of High mobility group A 2 protein (Hmga2) expression with these temporal changes in thymopoiesis. Hmga2 is expressed at high levels in murine fetal and neonatal early T cell progenitors (ETP), which are the most immature intrathymic precursors, and becomes almost undetectable in these progenitors after 5 weeks of age. Hmga2 expression is critical for the initial, exponential expansion of thymopoiesis, as Hmga2 deficient mice have a deficit of ETPs within days after birth, and total thymocyte number is repressed compared to wild type littermates. Finally, our data raise the possibility that similar events occur in humans, because Hmga2 expression is high in human fetal thymic progenitors and falls in these cells during early infancy.

  2. The expansion of thymopoiesis in neonatal mice is dependent on expression of high mobility group a 2 protein (Hmga2.

    Directory of Open Access Journals (Sweden)

    Beata Berent-Maoz

    Full Text Available Cell number in the mouse thymus increases steadily during the first two weeks after birth. It then plateaus and begins to decline by seven weeks after birth. The factors governing these dramatic changes in cell production are not well understood. The data herein correlate levels of High mobility group A 2 protein (Hmga2 expression with these temporal changes in thymopoiesis. Hmga2 is expressed at high levels in murine fetal and neonatal early T cell progenitors (ETP, which are the most immature intrathymic precursors, and becomes almost undetectable in these progenitors after 5 weeks of age. Hmga2 expression is critical for the initial, exponential expansion of thymopoiesis, as Hmga2 deficient mice have a deficit of ETPs within days after birth, and total thymocyte number is repressed compared to wild type littermates. Finally, our data raise the possibility that similar events occur in humans, because Hmga2 expression is high in human fetal thymic progenitors and falls in these cells during early infancy.

  3. Global Analysis and Comparison of the Transcriptomes and Proteomes of Group A Streptococcus Biofilms

    Science.gov (United States)

    Freiberg, Jeffrey A.; Le Breton, Yoann; Tran, Bao Q.; Scott, Alison J.; Harro, Janette M.; Ernst, Robert K.; Goo, Young Ah; Mongodin, Emmanuel F.; Goodlett, David R.; McIver, Kevin S.

    2016-01-01

    ABSTRACT To gain a better understanding of the genes and proteins involved in group A Streptococcus (GAS; Streptococcus pyogenes) biofilm growth, we analyzed the transcriptome, cellular proteome, and cell wall proteome from biofilms at different stages and compared them to those of plankton-stage GAS. Using high-throughput RNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) shotgun proteomics, we found distinct expression profiles in the transcriptome and proteome. A total of 46 genes and 41 proteins showed expression across the majority of biofilm time points that was consistently higher or consistently lower than that seen across the majority of planktonic time points. However, there was little overlap between the genes and proteins on these two lists. In line with other studies comparing transcriptomic and proteomic data, the overall correlation between the two data sets was modest. Furthermore, correlation was poorest for biofilm samples. This suggests a high degree of regulation of protein expression by nontranscriptional mechanisms. This report illustrates the benefits and weaknesses of two different approaches to global expression profiling, and it also demonstrates the advantage of using proteomics in conjunction with transcriptomics to gain a more complete picture of global expression within biofilms. In addition, this report provides the fullest characterization of expression patterns in GAS biofilms currently available. IMPORTANCE Prokaryotes are thought to regulate their proteomes largely at the level of transcription. However, the results from this first set of global transcriptomic and proteomic analyses of paired microbial samples presented here show that this assumption is false for the majority of genes and their products in S. pyogenes. In addition, the tenuousness of the link between transcription and translation becomes even more pronounced when microbes exist in a biofilm or a stationary planktonic state

  4. Characterization of DNA repair phenotypes of Xeroderma pigmentosum cell lines by a paralleled in vitro test; Phenotypage de la reparation de l'ADN de lignees Xeroderma pigmentosum, par un test in vitro multiparametrique

    Energy Technology Data Exchange (ETDEWEB)

    Raffin, A.L.

    2009-06-15

    DNA is constantly damaged modifying the genetic information for which it encodes. Several cellular mechanisms as the Base Excision Repair (BER) and the Nucleotide Excision Repair (NER) allow recovering the right DNA sequence. The Xeroderma pigmentosum is a disease characterised by a deficiency in the NER pathway. The aim of this study was to propose an efficient and fast test for the diagnosis of this disease as an alternative to the currently available UDS test. DNA repair activities of XP cell lines were quantified using in vitro miniaturized and paralleled tests in order to establish DNA repair phenotypes of XPA and XPC deficient cells. The main advantage of the tests used in this study is the simultaneous measurement of excision or excision synthesis (ES) of several lesions by only one cellular extract. We showed on one hand that the relative ES of the different lesions depend strongly on the protein concentration of the nuclear extract tested. Working at high protein concentration allowed discriminating the XP phenotype versus the control one, whereas it was impossible under a certain concentration's threshold. On the other hand, while the UVB irradiation of control cells stimulated their repair activities, this effect was not observed in XP cells. This study brings new information on the XPA and XPC protein roles during BER and NER and underlines the complexity of the regulations of DNA repair processes. (author)

  5. Regulated proteolysis of a transcription factor complex is critical to cell cycle progression in Caulobacter crescentus.

    Science.gov (United States)

    Gora, Kasia G; Cantin, Amber; Wohlever, Matthew; Joshi, Kamal K; Perchuk, Barrett S; Chien, Peter; Laub, Michael T

    2013-03-01

    Cell cycle transitions are often triggered by the proteolysis of key regulatory proteins. In Caulobacter crescentus, the G1-S transition involves the degradation of an essential DNA-binding response regulator, CtrA, by the ClpXP protease. Here, we show that another critical cell cycle regulator, SciP, is also degraded during the G1-S transition, but by the Lon protease. SciP is a small protein that binds directly to CtrA and prevents it from activating target genes during G1. We demonstrate that SciP must be degraded during the G1-S transition so that cells can properly activate CtrA-dependent genes following DNA replication initiation and the reaccumulation of CtrA. These results indicate that like CtrA, SciP levels are tightly regulated during the Caulobacter cell cycle. In addition, we show that formation of a complex between CtrA and SciP at target promoters protects both proteins from their respective proteases. Degradation of either protein thus helps trigger the destruction of the other, facilitating a cooperative disassembly of the complex. Collectively, our results indicate that ClpXP and Lon each degrade an important cell cycle regulator, helping to trigger the onset of S phase and prepare cells for the subsequent programmes of gene expression critical to polar morphogenesis and cell division.

  6. Immunoglobulin G antibody reactivity to a group A Plasmodium falciparum erythrocyte membrane protein 1 and protection from em>P. falciparum malaria

    DEFF Research Database (Denmark)

    Magistrado, Pamela A; Lusingu, John; Vestergaard, Lasse S;

    2007-01-01

    Variant surface antigens (VSA) on the surface of Plasmodium falciparum-infected red blood cells play a major role in the pathogenesis of malaria and are key targets for acquired immunity. The best-characterized VSA belong to the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. In areas...... where P. falciparum is endemic, parasites causing severe malaria and malaria in young children with limited immunity tend to express semiconserved PfEMP1 molecules encoded by group A var genes. Here we investigated antibody responses of Tanzanians who were 0 to 19 years old to PF11_0008, a group A PfEMP...

  7. The prevalence of group A streptococcal throat carriage in Al Ain, United Arab Emirates.

    Science.gov (United States)

    Dawson, K P; Ameen, A S; Nsanze, H; Bin-Othman, S; Mustafa, N

    1996-06-01

    The aim of this study was to establish the carrier rate of group A beta haemolytic streptococci in school children in Al Ain, United Arab Emirates. One thousand and two randomly selected school children aged 5-7 years had their throats swabbed twice for both culture and direct antigen detection of group A streptococci. One hundred and fourteen children (11.3%) had both a positive antigen and culture test, while 216 (21.6%) had antigen-positive tests only and 16 (1.5%) had a positive culture only. Thus, the combination of culture and antigen detection revealed a carrier rate of 35.4% in the children examined. We conclude that in an affluent but isolated desert area on the Tropic of Cancer, group A streptococcal carriage rate is high. Antigen detection is superior to culture techniques in asymptomatic carrier studies.

  8. [Epidemiology of invasive group A streptococcal infections in developed countries : the Canadian experience with necrotizing fasciitis].

    Science.gov (United States)

    Ovetchkine, Ph; Bidet, Ph; Minodier, Ph; Frère, J; Bingen, E

    2014-11-01

    In industrialized countries, group A streptococcal infections were a source of concern, mainly due to the occurrence of rheumatic fever and its cardiac complications. At present, the incidence of rheumatic fever is decreasing in these countries, giving way to an increasing occurrence of invasive streptococcal group A infections with high level of morbidity and mortality. Streptococcal necrotizing fasciitis, a specific entity, emerged these last decades, often in association with chickenpox. The introduction of the varicella vaccine in the province of Quebec routine immunization program, was followed by a significant decrease in the number of necrotizing fasciitis or other skin and soft-tissues infections in our pediatric population. However, in our experience at the CHU Sainte-Justine, this immunization program has not been helpful to reduce the overall incidence of invasive group A streptococcal infections. Conversely, an increase in the number of pleuro-pulmonary and osteo-articular infections was observed.

  9. [Research progress of real-time quantitative PCR method for group A rotavirus detection].

    Science.gov (United States)

    Guo, Yan-Qing; Li, Dan-Di; Duan, Zhao-Jun

    2013-11-01

    Group A rotavirus is one of the most significant etiological agents which causes acute gastroenteritis among infants and young children worldwide. So far, several method which includes electron microscopy (EM), enzyme immunoassay (EIA), reverse transcription-polymerase chain reaction (RT-PCR)and Real-time Quantitative PCR has been established for the detection of rotavirus. Compared with other methods, Real-time quantitative PCR have advantages in specificity, sensitivity, genotyping and quantitative accuracy. This article shows a overview of the application of real-time quantitative PCR technique to detecte group A rotavirus.

  10. Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors

    DEFF Research Database (Denmark)

    Ermert, David; Shaughnessy, Jutamas; Joeris, Thorsten;

    2015-01-01

    Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is an important human bacterial pathogen that can cause invasive infections. Once it colonizes its exclusively human host, GAS needs to surmount numerous innate immune defense mechanisms, including opsonization by complement and c...... in studies of GAS pathogenesis and for developing vaccines and therapeutics that rely on human complement activation for efficacy.......Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is an important human bacterial pathogen that can cause invasive infections. Once it colonizes its exclusively human host, GAS needs to surmount numerous innate immune defense mechanisms, including opsonization by complement...

  11. Comorbidity of Kawasaki disease and group a streptococcal pleural effusion in a healthy child: a case report.

    Science.gov (United States)

    Alhammadi, Ahmed H; Hendaus, Mohamed A

    2013-01-01

    Kawasaki disease is an acute self-limiting vasculitis that affects children. The most dreaded complication of Kawasaki disease reported in the literature over the years is coronary artery disease, which is considered as the main cause of acquired heart disease. However, pulmonary associations with Kawasaki disease have been overlooked. We present a rare, if not unique, case of Kawasaki disease associated with group A streptococcus pleural effusion in the English language literature. A search of the PubMed database was carried out, using a combination of the terms "Kawasaki disease", "pneumonia", and "group A streptococcus". The majority of studies conducted in children with Kawasaki disease have concentrated on the coronary artery implications. Kawasaki disease is considered a self-limiting illness, but can have detrimental consequences if not diagnosed early. When there is a prolonged inflammatory reaction, with no infectious agent identified or remittent fever unresponsive to antibiotics, Kawasaki disease should be taken into consideration. Elevated Vβ2+ T cells compared with healthy controls suggest possible involvement of a superantigen in the etiology of Kawasaki disease, so it is wise that the health care provider concentrates not only on the cardiac consequences, but also on pulmonary associations.

  12. Immunization with a streptococcal multiple-epitope recombinant protein protects mice against invasive group A streptococcal infection

    Science.gov (United States)

    Kuo, Chih-Feng; Tsao, Nina; Hsieh, I-Chen; Lin, Yee-Shin; Wu, Jiunn-Jong; Hung, Yu-Ting

    2017-01-01

    Streptococcus pyogenes (group A Streptococcus; GAS) causes clinical diseases, including pharyngitis, scarlet fever, impetigo, necrotizing fasciitis and streptococcal toxic shock syndrome. A number of group A streptococcus vaccine candidates have been developed, but only one 26-valent recombinant M protein vaccine has entered clinical trials. Differing from the design of a 26-valent recombinant M protein vaccine, we provide here a vaccination using the polyvalence epitope recombinant FSBM protein (rFSBM), which contains four different epitopes, including the fibronectin-binding repeats domain of streptococcal fibronectin binding protein Sfb1, the C-terminal immunogenic segment of streptolysin S, the C3-binding motif of streptococcal pyrogenic exotoxin B, and the C-terminal conserved segment of M protein. Vaccination with the rFSBM protein successfully prevented mortality and skin lesions caused by several emm strains of GAS infection. Anti-FSBM antibodies collected from the rFSBM-immunized mice were able to opsonize at least six emm strains and can neutralize the hemolytic activity of streptolysin S. Furthermore, the internalization of GAS into nonphagocytic cells is also reduced by anti-FSBM serum. These findings suggest that rFSBM can be applied as a vaccine candidate to prevent different emm strains of GAS infection. PMID:28355251

  13. Streptolysin O and its co-toxin NAD-glycohydrolase protect group A Streptococcus from Xenophagic killing.

    Directory of Open Access Journals (Sweden)

    Maghnus O'Seaghdha

    Full Text Available Group A Streptococcus (Streptococcus pyogenes or GAS causes pharyngitis, severe invasive infections, and the post-infectious syndromes of glomerulonephritis and rheumatic fever. GAS can be internalized and killed by epithelial cells in vitro, a process that may contribute to local innate defense against pharyngeal infection. Secretion of the pore-forming toxin streptolysin O (SLO by GAS has been reported to stimulate targeted autophagy (xenophagy upon internalization of the bacteria by epithelial cells. Whereas this process was associated with killing of GAS in HeLa cells, studies in human keratinocytes found SLO production enhanced intracellular survival. To reconcile these conflicting observations, we now report in-depth investigation of xenophagy in response to GAS infection of human oropharyngeal keratinocytes, the predominant cell type of the pharyngeal epithelium. We found that SLO expression was associated with prolonged intracellular survival; unexpectedly, expression of the co-toxin NADase was required for this effect. Enhanced intracellular survival was lost upon deletion of NADase or inactivation of its enzymatic activity. Shortly after internalization of GAS by keratinocytes, SLO-mediated damage to the bacteria-containing vacuole resulted in exposure to the cytosol, ubiquitination of GAS and/or associated vacuolar membrane remnants, and engulfment of GAS in LC3-positive vacuoles. We also found that production of streptolysin S could mediate targeting of GAS to autophagosomes in the absence of SLO, a process accompanied by galectin 8 binding to damaged GAS-containing endosomes. Maturation of GAS-containing autophagosome-like vacuoles to degradative autolysosomes was prevented by SLO pore-formation and by SLO-mediated translocation of enzymatically active NADase into the keratinocyte cytosol. We conclude that SLO stimulates xenophagy in pharyngeal keratinocytes, but the coordinated action of SLO and NADase prevent maturation of GAS

  14. A Two-Component Regulatory System Impacts Extracellular Membrane-Derived Vesicle Production in Group A Streptococcus

    Directory of Open Access Journals (Sweden)

    Ulrike Resch

    2016-11-01

    Full Text Available Export of macromolecules via extracellular membrane-derived vesicles (MVs plays an important role in the biology of Gram-negative bacteria. Gram-positive bacteria have also recently been reported to produce MVs; however, the composition and mechanisms governing vesiculogenesis in Gram-positive bacteria remain undefined. Here, we describe MV production in the Gram-positive human pathogen group A streptococcus (GAS, the etiological agent of necrotizing fasciitis and streptococcal toxic shock syndrome. M1 serotype GAS isolates in culture exhibit MV structures both on the cell wall surface and in the near vicinity of bacterial cells. A comprehensive analysis of MV proteins identified both virulence-associated protein substrates of the general secretory pathway in addition to “anchorless surface proteins.” Characteristic differences in the contents, distributions, and fatty acid compositions of specific lipids between MVs and GAS cell membrane were also observed. Furthermore, deep RNA sequencing of vesicular RNAs revealed that GAS MVs contained differentially abundant RNA species relative to bacterial cellular RNA. MV production by GAS strains varied in a manner dependent on an intact two-component system, CovRS, with MV production negatively regulated by the system. Modulation of MV production through CovRS was found to be independent of both GAS cysteine protease SpeB and capsule biosynthesis. Our data provide an explanation for GAS secretion of macromolecules, including RNAs, lipids, and proteins, and illustrate a regulatory mechanism coordinating this secretory response.

  15. A Genetic Switch to Hypervirulence Reduces Colonization Phenotypes of the Globally Disseminated Group A Streptococcus M1T1 Clone

    Science.gov (United States)

    Hollands, Andrew; Pence, Morgan A.; Timmer, Anjuli M.; Osvath, Sarah R.; Turnbull, Lynne; Whitchurch, Cynthia B.; Walker, Mark J.; Nizet, Victor

    2010-01-01

    Background The recent resurgence of invasive group A streptococcal disease has been paralleled by the emergence of the M1T1 clone. Recently, invasive disease initiation to has been linked to mutations in the covR/S two-compnent regulator. Here we investigate if a fitness cost is associated with covS mutation that counterbalances hypervirulence. Methods Wild-type M1T1 GAS and an isogenic covS mutant derived from animal passage were compared for adherence to human laryngeal epithelial cells, keratinocytes or fibronectin, biofilm formation, and binding to intact mouse skin. Targeted mutagenesis of capsule expression from both strains was performed for analysis of its unique contribution to the observed phenotypes. Results The covS mutant bacteria showed reduced capacity to bind to epithelial cell layers as a consequence of increased capsule expression. The covS mutant strain also had reduced capacity to bind fibronectin and to form biofilms on plastic and epithelial cell layers. A defect in skin adherence of the covS mutant strain was demonstrated in a murine model. Conclusions Reduced colonization capacity provides a potential explanation as to why the covS mutation conferring hypervirulence has not become fixed in the globally-disseminated M1T1 GAS clone, but rather may arise anew under innate immune selection in individual patients. PMID:20507231

  16. Contribution of AmyA, an extracellular alpha-glucan degrading enzyme, to group A streptococcal host-pathogen interaction.

    Science.gov (United States)

    Shelburne, Samuel A; Keith, David B; Davenport, Michael T; Beres, Stephen B; Carroll, Ronan K; Musser, James M

    2009-10-01

    alpha-Glucans such as starch and glycogen are abundant in the human oropharynx, the main site of group A Streptococcus (GAS) infection. However, the role in pathogenesis of GAS extracellular alpha-glucan binding and degrading enzymes is unknown. The serotype M1 GAS genome encodes two extracellular proteins putatively involved in alpha-glucan binding and degradation; pulA encodes a cell wall anchored pullulanase and amyA encodes a freely secreted putative cyclomaltodextrin alpha-glucanotransferase. Genetic inactivation of amyA, but not pulA, abolished GAS alpha-glucan degradation. The DeltaamyA strain had a slower rate of translocation across human pharyngeal epithelial cells. Consistent with this finding, the DeltaamyA strain was less virulent following mouse mucosal challenge. Recombinant AmyA degraded alpha-glucans into beta-cyclomaltodextrins that reduced pharyngeal cell transepithelial resistance, providing a physiologic explanation for the observed transepithelial migration phenotype. Higher amyA transcript levels were present in serotype M1 GAS strains causing invasive infection compared with strains causing pharyngitis. GAS proliferation in a defined alpha-glucan-containing medium was dependent on the presence of human salivary alpha-amylase. These data delineate the molecular mechanisms by which alpha-glucan degradation contributes to GAS host-pathogen interaction, including how GAS uses human salivary alpha-amylase for its own metabolic benefit.

  17. [A postpartum woman with toxic shock syndrome: group A streptococcal infection, a much feared postpartum complication.

    NARCIS (Netherlands)

    Abbink, K.; Kortekaas, J.C.; Buise, M.P.; Dokter, J.; Kuppens, S.M.; Hasaart, T.H.M.

    2016-01-01

    BACKGROUND: The development of toxic shock syndrome (TSS) after an invasive group A streptococcal (GAS) infection in the postpartum period is a much feared complication. The mortality rate of TSS with necrotizing fasciitis is 30 to 50%. CASE DESCRIPTION: We present the case of a woman with atypical

  18. Identification and Characterization of Peptide Mimics of Blood Group A Antigen

    Institute of Scientific and Technical Information of China (English)

    Zhaoming TANG; Lin WANG; Lihua HU; Yirong LI; Tianpen CUI; Juan XIONG; Lifang DOU

    2008-01-01

    In order to investigate peptide mimics of carbohydrate blood group A antigen, a phage display 12-met peptide library was screened with a monoclonal antibody against blood group A antigen, NaM87-1F6. The antibody-binding properties of the selected phage peptides were evaluated by phage ELISA and phage capture assay. The peptides were co-expressed as glutathione S-transferase (GST) fusion proteins. RBC agglutination inhibition assay was performed to assess the natural blood group A antigen-mimicking ability of the fusion proteins. The results showed that seven phage clones selected bound to NaM87-1F6 specifically, among which, 6 clones bore the same peptide sequence, EYWYCGMNRTGC and another harbored a different one QIWYERTLPFrF. The two peptides were successfully expressed at the N terminal of GST protein. Both of the fusion proteins inhibited the RBC agglutination mediated by anti-A serum in a concentration-dependent manner. These results suggested that the fusion proteins based on the selected peptides could mimic the blood group A an- tigen and might be used as anti-A antibody-adsorbing materials when immunoabsorption was applied in ABO incompatible transplantation.

  19. OCCURRENCE OF ANTIBIOTIC-RESISTANT UROPATHOGENIC ESCHERICHIA COLI CLONAL GROUP A IN WASTEWATER EFFLUENTS

    Science.gov (United States)

    Isolates of Escherichia coli belonging to clonal group A (CGA), a recently described disseminated cause of drug-resistant urinary tract infections in humans, were present in four of seven sewage effluents collected from geographically dispersed areas of the United States. ...

  20. Biosynthetic basis of incompatible histo-blood group A antigen expression

    DEFF Research Database (Denmark)

    David, L; Leitao, D; Sobrinho-Simoes, M

    1993-01-01

    , we have screened 31 cases of gastric tumors of phenotype O for the expression of blood group A gene-defined glycosyltransferase by immunohistology on frozen sections using newly developed monoclonal antibodies to the transferases. Three cases were positive, and transferase expression was confirmed...

  1. Napa River Restoration Project: Oakville to Oak Knoll Reach, Group A Sites 21-23

    Science.gov (United States)

    Information about the SFBWQP Napa River Restoration Project: Oakville to Oak Knoll Reach, Group A Sites 21-23, part of an EPA competitive grant program to improve SF Bay water quality focused on restoring impaired waters and enhancing aquatic resources

  2. Reassortment Group A Rotavirus from Straw-colored Fruit Bat (Eidolon helvum)

    Centers for Disease Control (CDC) Podcasts

    2010-12-02

    In this podcast, Dr. Mathew Esona of the Division of Viral Diseases at CDC describes the discovery of a unique Group A rotavirus isolated from fruit bats in Kenya.  Created: 12/2/2010 by National Center for Emerging and Zoonotic Infectious Diseases, National Center for Immunization and Respiratory Diseases.   Date Released: 12/2/2010.

  3. OCCURRENCE OF ANTIBIOTIC-RESISTANT UROPATHOGENIC ESCHERICHIA COLI CLONAL GROUP A IN WASTEWATER EFFLUENTS

    Science.gov (United States)

    Isolates of Escherichia coli belonging to clonal group A (CGA), a recently described disseminated cause of drug-resistant urinary tract infections in humans, were present in four of seven sewage effluents collected from geographically dispersed areas of the United States. ...

  4. Xeroderma pigmentosum group A protein loads as a separate factor onto DNA lesions

    NARCIS (Netherlands)

    S. Rademakers (Suzanne); M. Volker (Marcel); D. Hoogstraten (Deborah); A.L. Nigg (Alex); M.J. Mone; A.A. van Zeeland (Albert); A.B. Houtsmuller (Adriaan); W. Vermeulen (Wim); J.H.J. Hoeijmakers (Jan)

    2003-01-01

    textabstractNucleotide excision repair (NER) is the main DNA repair pathway in mammals for removal of UV-induced lesions. NER involves the concerted action of more than 25 polypeptides in a coordinated fashion. The xeroderma pigmentosum group A protein (XPA) has been suggested to function as a centr

  5. Two cases of group A streptococcal vulvovaginitis in premenopausal adults in a sexual health setting.

    Science.gov (United States)

    Bray, Susan; Morgan, Jane

    2006-09-01

    Two cases of group A streptococcus (GAS) causing vulvovaginitis in premenopausal adults are described. A review of the literature of genital GAS is made, as this is an uncommon cause of vulvovaginitis in premenopausal adults. Contrasts are made between anogenital carriage of GAS and group B streptococcus (GBS) to highlight the differences in anogenital carriage between these two organisms.

  6. Homomorphisms of the alternating group A_5 into a reductive group

    OpenAIRE

    2002-01-01

    We show that any two homomorphisms of the alternating group A_5 into E_8 (over the complex numbers) whose images has finite centralizers are conjugate under E_8. This, in conjunction with earlier work of Frey, completes the classification up to G-conjugacy of homomorphisms of A_5 into a simple adjoint algebraic group over the complex numbers.

  7. Hypervirulent emm59 Clone in Invasive Group A Streptococcus Outbreak, Southwestern United States.

    Science.gov (United States)

    Engelthaler, David M; Valentine, Michael; Bowers, Jolene; Pistole, Jennifer; Driebe, Elizabeth M; Terriquez, Joel; Nienstadt, Linus; Carroll, Mark; Schumacher, Mare; Ormsby, Mary Ellen; Brady, Shane; Livar, Eugene; Yazzie, Del; Waddell, Victor; Peoples, Marie; Komatsu, Kenneth; Keim, Paul

    2016-04-01

    The hyper-virulent emm59 genotype of invasive group A Streptococcus was identified in northern Arizona in 2015. Eighteen isolates belonging to a genomic cluster grouped most closely with recently identified isolates in New Mexico. The continued transmission of emm59 in the southwestern United States poses a public health concern.

  8. An outbreak of food-borne group A Streptococcus (GAS) tonsillopharyngitis among residents of a dormitory.

    Science.gov (United States)

    Sarvghad, M R; Naderi, H R; Naderi-Nassab, M; Majdzadeh, R; Javanian, M; Faramarzi, H; Fatehmanesh, P

    2005-01-01

    Epidemics of food-borne pharyngitis due to group A Streptococcus are rarely reported. Here we present an outbreak of food-borne tonsillopharyngitis in female dormitories in the Islamic Republic of Iran. Throat swabs and cultures were performed on a number of patients, and of specimens from the nasopharynx and hands of staff who were involved in food processing. We planned a case-control study for assessing the source of epidemics. 11 out of 17 throat swabs of students were positive for Streptococcus group A and also 2 throat samples from asymptomatic cooks were positive. A DNA fingerprinting study showed that Streptococcus group A strains of 11 students and 1 cook had the same T agglutination pattern and M protein factor (M3/T13). It is suggested that group A streptococci as well as group C and G streptococci can cause epidemic food-borne pharyngitis. Regular health surveillance of food handlers and food preparation processes are important for prevention of such outbreaks.

  9. Whole-exome sequencing of fibroblast and its iPS cell lines derived from a patient diagnosed with xeroderma pigmentosum

    Directory of Open Access Journals (Sweden)

    Kohji Okamura

    2015-12-01

    Full Text Available Cells from a patient with a DNA repair-deficiency disorder are anticipated to bear a large number of somatic mutations. Because such mutations occur independently in each cell, there is a high degree of mosaicism in patients' tissues. While major mutations that have been expanded in many cognate cells are readily detected by sequencing, minor ones are overlaid with a large depth of non-mutated alleles and are not detected. However, cell cloning enables us to observe such cryptic mutations as well as major mutations. In the present study, we focused on a fibroblastic cell line that is derived from a patient diagnosed with xeroderma pigmentosum (XP, which is an autosomal recessive disorder caused by a deficiency in nucleotide excision repair. By making a list of somatic mutations, we can expect to see a characteristic pattern of mutations caused by the hereditary disorder. We cloned a cell by generating an iPS cell line and performed a whole-exome sequencing analysis of the progenitor and its iPS cell lines. Unexpectedly, we failed to find causal mutations in the XP-related genes, but we identified many other mutations including homozygous deletion of GSTM1 and GSTT1. In addition, we found that the long arm of chromosome 9 formed uniparental disomy in the iPS cell line, which was also confirmed by a structural mutation analysis using a SNP array. Type and number of somatic mutations were different from those observed in XP patients. Taken together, we conclude that the patient might be affected by a different type of the disorder and that some of the mutations that we identified here may be responsible for exhibiting the phenotype. Sequencing and SNP-array data have been submitted to SRA and GEO under accession numbers SRP059858 and GSE55520, respectively.

  10. A key role for the urokinase plasminogen activator (uPA) in invasive Group A streptococcal infection.

    Science.gov (United States)

    Sanderson-Smith, Martina L; Zhang, Yueling; Ly, Diane; Donahue, Deborah; Hollands, Andrew; Nizet, Victor; Ranson, Marie; Ploplis, Victoria A; Walker, Mark J; Castellino, Francis J

    2013-01-01

    Recruitment of the serine protease plasmin is central to the pathogenesis of many bacterial species, including Group A streptococcus (GAS), a leading cause of morbidity and mortality globally. A key process in invasive GAS disease is the ability to accumulate plasmin at the cell surface, however the role of host activators of plasminogen in this process is poorly understood. Here, we demonstrate for the first time that the urokinase-type plasminogen activator (uPA) contributes to plasmin recruitment and subsequent invasive disease initiation in vivo. In the absence of a source of host plasminogen activators, streptokinase (Ska) was required to facilitate cell surface plasmin acquisition by GAS. However, in the absence of Ska, host activators were sufficient to promote cell surface plasmin acquisition by GAS strain 5448 during incubation with plasminogen or human plasma. Furthermore, GAS were able mediate a significant increase in the activation of zymogen pro-uPA in human plasma. In order to assess the contribution of uPA to invasive GAS disease, a previously undescribed transgenic mouse model of infection was employed. Both C57/black 6J, and AlbPLG1 mice expressing the human plasminogen transgene, were significantly more susceptible to invasive GAS disease than uPA-/- mice. The observed decrease in virulence in uPA-/-mice was found to correlate directly with a decrease in bacterial dissemination and reduced cell surface plasmin accumulation by GAS. These findings have significant implications for our understanding of GAS pathogenesis, and research aimed at therapeutic targeting of plasminogen activation in invasive bacterial infections.

  11. A key role for the urokinase plasminogen activator (uPA in invasive Group A streptococcal infection.

    Directory of Open Access Journals (Sweden)

    Martina L Sanderson-Smith

    Full Text Available Recruitment of the serine protease plasmin is central to the pathogenesis of many bacterial species, including Group A streptococcus (GAS, a leading cause of morbidity and mortality globally. A key process in invasive GAS disease is the ability to accumulate plasmin at the cell surface, however the role of host activators of plasminogen in this process is poorly understood. Here, we demonstrate for the first time that the urokinase-type plasminogen activator (uPA contributes to plasmin recruitment and subsequent invasive disease initiation in vivo. In the absence of a source of host plasminogen activators, streptokinase (Ska was required to facilitate cell surface plasmin acquisition by GAS. However, in the absence of Ska, host activators were sufficient to promote cell surface plasmin acquisition by GAS strain 5448 during incubation with plasminogen or human plasma. Furthermore, GAS were able mediate a significant increase in the activation of zymogen pro-uPA in human plasma. In order to assess the contribution of uPA to invasive GAS disease, a previously undescribed transgenic mouse model of infection was employed. Both C57/black 6J, and AlbPLG1 mice expressing the human plasminogen transgene, were significantly more susceptible to invasive GAS disease than uPA-/- mice. The observed decrease in virulence in uPA-/-mice was found to correlate directly with a decrease in bacterial dissemination and reduced cell surface plasmin accumulation by GAS. These findings have significant implications for our understanding of GAS pathogenesis, and research aimed at therapeutic targeting of plasminogen activation in invasive bacterial infections.

  12. The X-linked F cell production locus: Genetic mapping and role in fetal hemoglobin production

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Y.C.; Smith, K.D.; Moore, R.D. [John Hopkins Univ., Baltimore, MD (United States)] [and others

    1994-09-01

    Postnatal fetal hemoglobin (Hb F) production is confined to a subset of erythocytes termed F-cells. There is a 10-20 fold variation in F-cell production in sickle cell disease (SCD) and normal individuals. Most of the variation in F-cell production has been attributed to a diallelic (High, Low) X-linked gene, the F-cell production (FCP) locus that we recently mapped to Xp22.2-22.3 (LOD=4.56, theta=0.04). Using multiple regression analysis in 262 Jamaican SCD patients we determined the relative contribution of the FCP locus and other variables previously associated with variation in Hb F level (gender, age, beta-globin haplotypes, number of alpha-globin genes and the FCP locus phenotypes). When the FCP locus is in the regression model, the FCP locus alone accounts for approximately 40% of the variation in Hb F level while the contribution of age, alpha-globin gene number, and beta-globin haplotypes was insignificant. When individuals with High FCP allele are removed from the analysis, the beta globin haplotype now contribute to >10% of the Hb F variation. We conclude that the X-linked FCP locus is the major determinant of all known variables in Hb F production. Using 4 highly polymorphic dinucleotide repeat markers that we identified from cosmids in Xp22.2-22.3, have localized the FCP locus to a 1 Mb minimal candidate region between DXS143 and DXS410.

  13. The efficacy of the inhalation of an aerosolized Group A streptococcal preparation in the treatment of lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jun Liu; Xiang Liu; Fei Cui; Guoqin Chen; Yubao Guan; Jianxing He

    2012-01-01

    Objective:To observe the efficacy of the inhalation of an aerosolized group A streptococcal (GAS) preparation in treating orthotopic lung cancer in mouse models and assess the feasibility,safety,and effectiveness of this administration mode for lung cancer.Methods:Lewis lung carcinoma (LLC) cell strains were administered via intrathoracic injection to establish orthotopic lung cancer mouse models.After the tumor-bearing models were successfully established,as confirmed by computed tomography,the mice were administered by inhalation with an aerosolized GAS preparation (GAS group) or aerosolized normal saline (control group).The anti-tumor effect of the aerosolized GAS preparation was evaluated histologically; meanwhile,the survival and quality of life were compared between these two groups.Results:The aerosolized GAS preparation showed remarkably anti-tumor effect,causing the necrosis of the orthotopic lung cancer cells in tumor-bearing mice.Furthermore,mice in the GAS group had significantly better quality of life and longer survival than those in control group.conclusions:The inhalation of aerosolized GAS preparation may be a feasible,safe and effective solution for lung cancer.

  14. Severe monobacterial necrotizing soft tissue infection by group A Streptococcus:A surgical emergency

    Institute of Scientific and Technical Information of China (English)

    Lanitis S; Khan MAA; Sgourakis G; Kontovounisios C; Papaconstandinou T; Karaliotas C

    2012-01-01

    Eight percent of necrotizing soft tissue infections (NSTI) are attributable to group A Streptococci (GAS), and among these, 50% develop streptococcal toxic shock syndrome. The reported mortality associated with NSTI reaches 32%. We present cases of two healthy individuals with minor GAS skin infection which developed to a rapidly progressed NSTI and sepsis despite of the antibiotic treatment, aiming to discuss the lessons learned from the course and management of these patients.

  15. Group A Streptococcus Gene Expression in Humans and Cynomolgus Macaques with Acute Pharyngitis

    OpenAIRE

    2003-01-01

    The molecular mechanisms used by group A Streptococcus (GAS) to survive on the host mucosal surface and cause acute pharyngitis are poorly understood. To provide new information about GAS host-pathogen interactions, we used real-time reverse transcription-PCR (RT-PCR) to analyze transcripts of 17 GAS genes in throat swab specimens taken from 18 pediatric patients with pharyngitis. The expression of known and putative virulence genes and regulatory genes (including genes in seven two-component...

  16. Population-Based Surveillance of Invasive Group A Streptococcal Disease in British Columbia: 1996-1998

    OpenAIRE

    Gordean L Bjornson; Scheifele, David W; Alison Bell; Arlene King

    2001-01-01

    OBJECTIVE: To identify and describe all cases of invasive group A streptococcal (GAS) infection occurring in British Columbia during a two-year period.DESIGN: Active, laboratory-based surveillance with supplemental case description.SETTING: Forty community and regional hospitals and the provincial laboratory participated, encompassing all health regions.POPULATION STUDIED: Entire provincial population from April 1, 1996 to March 31, 1998.MAIN RESULTS: Over the 24-month surveillance period, 18...

  17. An aggressive group a streptococcal cellulitis of the hand and forearm requiring surgical debridement.

    Science.gov (United States)

    Bharucha, Neil J; Alaia, Michael J; Paksima, Nader; Christoforou, Dimitrios; Gupta, Salil

    2011-01-03

    Group A streptococcus is responsible for a diverse range of soft tissue infections. Manifestations range from minor oropharyngeal and cellulitic skin infections to more severe conditions such as necrotizing fasciitis and septic shock. Troubling increases in the incidence and the severity of streptococcal infections have been reported over the past 25 years. Cases of streptococcal necrotizing fasciitis have received significant attention in the literature, with prompt surgical debridement being the mainstay of treatment. However, cases of rapidly progressing upper extremity streptococcal cellulitis leading to shock and a subsequent surgical intervention have not been well described. This article presents a case of an 85-year-old woman with a rapidly progressing, erythematous, painful, swollen hand associated with fever, hypotension, and mental status change. Due to a high clinical suspicion for necrotizing fasciitis, the patient was rapidly resuscitated and underwent immediate surgical irrigation and debridement. All intraoperative fascial pathology specimens were negative for necrotizing fasciitis, leading to a final diagnosis of Group A streptococcal cellulitis. Although surgical intervention is not commonly considered in patients with cellulitis, our patient benefited from irrigation and debridement with soft tissue decompression. In cases of necrotizing fasciitis as well as rapidly progressive cellulitis, prompt diagnosis and aggressive treatment may help patients avoid the catastrophic consequences of rapidly progressive group A streptococcal infections.

  18. Searching for neuKREEP: An EMP study of Apollo 11 Group A basalts

    Science.gov (United States)

    Jerde, Eric A.; Taylor, Lawrence A.

    1993-01-01

    The Apollo 11 and 17 landing sites are characterized by the presence of high-Ti basalts (TiO2 greater than 6 percent). The Group A basalts of Apollo 11 have elevated K compositions (greater than 2000 ppm); and are enriched in incompatible trace elements relative to the other types of high-Ti basalt found in the region. These unique basalts also are the youngest of all high-Ti basalts, with an age of 3.56 +/- 0.02 Ga. Recent modelling of the Apollo 11 Group A basalts by Jerde et al. has demonstrated that this unique variety of high-Ti basalt may have formed through fractionation of a liquid with the composition of the Apollo 11 orange glass, coupled with assimilation of evolved material (dubbed neuKREEP and having similarities to lunar quartz monzodiorite). Assimilation of this material would impart its REE signature on the liquid, resulting in the elevated REE abundances observed. Minerals such as whitlockite which contain a large portion of the REE budget can be expected to reflect the REE characteristics of the assimilant. To this end, an examination of the whitlockite present in the Apollo 11 Group A basalts was undertaken to search for evidence of the neuKREEP material assimilated.

  19. Targeted gene therapy of xeroderma pigmentosum cells using meganuclease and TALEN™.

    Directory of Open Access Journals (Sweden)

    Aurélie Dupuy

    Full Text Available Xeroderma pigmentosum group C (XP-C is a rare human syndrome characterized by hypersensitivity to UV light and a dramatic predisposition to skin neoplasms. XP-C cells are deficient in the nucleotide excision repair (NER pathway, a complex process involved in the recognition and removal of DNA lesions. Several XPC mutations have been described, including a founder mutation in North African patients involving the deletion of a TG dinucleotide (ΔTG located in the middle of exon 9. This deletion leads to the expression of an inactive truncated XPC protein, normally involved in the first step of NER. New approaches used for gene correction are based on the ability of engineered nucleases such as Meganucleases, Zinc-Finger nucleases or TALE nucleases to accurately generate a double strand break at a specific locus and promote correction by homologous recombination through the insertion of an exogenous DNA repair matrix. Here, we describe the targeted correction of the ΔTG mutation in XP-C cells using engineered meganuclease and TALEN™. The methylated status of the XPC locus, known to inhibit both of these nuclease activities, led us to adapt our experimental design to optimize their in vivo efficacies. We show that demethylating treatment as well as the use of TALEN™ insensitive to CpG methylation enable successful correction of the ΔTG mutation. Such genetic correction leads to re-expression of the full-length XPC protein and to the recovery of NER capacity, attested by UV-C resistance of the corrected cells. Overall, we demonstrate that nuclease-based targeted approaches offer reliable and efficient strategies for gene correction.

  20. Targeted gene therapy of xeroderma pigmentosum cells using meganuclease and TALEN™.

    Science.gov (United States)

    Dupuy, Aurélie; Valton, Julien; Leduc, Sophie; Armier, Jacques; Galetto, Roman; Gouble, Agnès; Lebuhotel, Céline; Stary, Anne; Pâques, Frédéric; Duchateau, Philippe; Sarasin, Alain; Daboussi, Fayza

    2013-01-01

    Xeroderma pigmentosum group C (XP-C) is a rare human syndrome characterized by hypersensitivity to UV light and a dramatic predisposition to skin neoplasms. XP-C cells are deficient in the nucleotide excision repair (NER) pathway, a complex process involved in the recognition and removal of DNA lesions. Several XPC mutations have been described, including a founder mutation in North African patients involving the deletion of a TG dinucleotide (ΔTG) located in the middle of exon 9. This deletion leads to the expression of an inactive truncated XPC protein, normally involved in the first step of NER. New approaches used for gene correction are based on the ability of engineered nucleases such as Meganucleases, Zinc-Finger nucleases or TALE nucleases to accurately generate a double strand break at a specific locus and promote correction by homologous recombination through the insertion of an exogenous DNA repair matrix. Here, we describe the targeted correction of the ΔTG mutation in XP-C cells using engineered meganuclease and TALEN™. The methylated status of the XPC locus, known to inhibit both of these nuclease activities, led us to adapt our experimental design to optimize their in vivo efficacies. We show that demethylating treatment as well as the use of TALEN™ insensitive to CpG methylation enable successful correction of the ΔTG mutation. Such genetic correction leads to re-expression of the full-length XPC protein and to the recovery of NER capacity, attested by UV-C resistance of the corrected cells. Overall, we demonstrate that nuclease-based targeted approaches offer reliable and efficient strategies for gene correction.

  1. The effect of hydrophobicity of group a beta-hemolytic streptococcus in the process of adherence and biofilm production

    Directory of Open Access Journals (Sweden)

    Šmitran Aleksandra

    2014-01-01

    Full Text Available Introduction. Bacterial cell hydrophobicity and adherence to a substrate are one of the most important factors in biofilm formation. Group A streptococcus is an unstable and low biofilm productor. Importance of biofilm production in streptococcal pathogenesis is still unknown. Objective. The aim of this study was to determine the impact of hydrophobicity and adherence on the biofilm production of group A streptococcal invasive and noninvasive isolates, and also to evaluate the stability of biofilm production in time function. Methods. Adherence, hydrophobicity and biofilm production were investigated in a total of 172 isolates divided into three groups: noninvasive, low invasive and highly invasive. Adherence to uncoated and laminin-coated microtiter plates and biofilm production after 12, 24 and 48 hours of incubation was determined using the method described by Stepanović et al. Hydrophobicity was measured using the MATH test by Rosenberg and SAT test by Lindhal. Results. Correlation between adherence and biofilm production was detected in the group of noninvasive isolates. These isolates were stable biofilm productors during all three time periods of biofilm production. In the groups of invasive and noninvasive isolates no statistical correlation was detected among the analysed variables. The invasive isolates were unstable biofilm productors. Conclusion. Noninvasive isolates were stable biofilm producers; as detected, they showed a direct correlation between adherence and biofilm production, and a negative impact of hydrophobicity on the biofilm production. Invasive isolates were unstable biofilm productors; it was observed that there was no correlation between adherence and hydrophobicity with biofilm production. [Projekat Ministarstva nauke Republike Srbije, br. 175039: Bakterije rezistentne na antibiotike u Srbiji: fenotipska i genotipska rezistencija

  2. Primary Peritonitis due to Group A Streptococcus in a Previously Healthy Pediatric Patient

    Directory of Open Access Journals (Sweden)

    R Holden

    2012-01-01

    Full Text Available Primary peritonitis remains a rare disease in otherwise healthy children, with group A Streptococcus (GAS being a particularly unusual cause. A case involving a 14-year-old girl, who presented with an ‘acute abdomen’ and was taken to the operating room for urgent laparoscopy, is reported. Abdominal and pelvic structures were only minimally inflamed, as was the appendix. Peritoneal fluid and blood cultures both grew pure cultures of GAS. The patient’s course was complicated by streptococcal toxic shock syndrome. She fortunately made a full recovery. The present report highlights the diagnostic and treatment dilemmas associated with GAS primary peritonitis.

  3. Invasive group A Streptococcus resulting in sepsis and abdominal wall abscess after adenotonsillectomy.

    Science.gov (United States)

    Wilson, Paul F; Wannemuehler, Todd J; Matt, Bruce H

    2015-05-01

    Systemic infectious complications following adenotonsillectomy are exceedingly rare. We describe an otherwise healthy 2-year-old patient who developed group A beta-hemolytic Streptococcus sepsis and presumptive scarlet fever 3 days after an uncomplicated adenotonsillectomy. After resolution of fever, rash, and discharge home on antibiotics, the patient returned on postoperative day 10 with an abdominal wall abscess. This is the first reported case of an abdominal wall abscess as a complication of adenotonsillectomy. This case demonstrates that an awareness of unexpected infectious complications of adenotonsillectomy should be a part of postsurgical management. Laryngoscope, 125:1230-1232, 2015.

  4. The association between invasive group A streptococcal diseases and viral respiratory tract infections

    Directory of Open Access Journals (Sweden)

    Andrea L Herrera

    2016-03-01

    Full Text Available Viral infections of the upper respiratory tract are associated with a variety of invasive diseases caused by Streptococcus pyogenes, the group A streptococcus, including pneumonia, necrotizing fasciitis, toxic shock syndrome, and bacteremia. While these polymicrobial infections, or superinfections, are complex, progress has been made in understanding the molecular basis of disease. Areas of investigation have included the characterization of virus-induced changes in innate immunity, differences in bacterial adherence and internalization following viral infection, and the efficacy of vaccines in mitigating the morbidity and mortality of superinfections. Here, we briefly summarize viral-S. pyogenes superinfections with an emphasis on those affiliated with influenza viruses.

  5. Identification of uropathogenic Escherichia coli clonal group A (CgA in hospitalised patients

    Directory of Open Access Journals (Sweden)

    Rubens CS Dias

    2009-08-01

    Full Text Available This study provides the first description of healthcare-associated infections with Escherichia coli clonal group A (CgA isolates in Latin America. Isolates were typed by enterobacterial repetitive intergenic consensus-PCR, pulsed-field gel electrophoresis, E. coli phylogenetic grouping, multilocus sequence typing and fimH single nucleotide polymorphism analysis. Out of 42 E. coli hospital isolates studied, three belonged to E. coli phylogenetic group D and ST69 and had fimH sequences identical to that of the CgA reference strain ATCC BAA-457. E. coli CgA is another potential source of resistant infections in hospitals.

  6. Group A streptococcal genotypes from throat and skin isolates in the United Arab Emirates

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    Alfaresi Mubarak S

    2010-04-01

    Full Text Available Abstract Background The bacterium Streptococcus pyogenes causes a variety of human diseases that range from relatively mild skin infections to severe invasive diseases, such as acute rheumatic fever, glomerulonephritis, puerperal sepsis, necrotizing fasciitis, meningitis, and streptococcal toxic shock syndrome. Accurate identification and typing of group A hemolytic streptococci (GAS is essential for epidemiological and pathogenetic studies of streptococcal diseases. For this reason, The genetic diversity of group A streptococcal (GAS isolates from subjects in the United Arab Emirates with streptococcal disease was studied using emm gene sequence analysis. The emm typing system which is based on sequence analysis of PCR products of the N-terminal hypervariable region of the M protein gene, concurs with M serotyping almost 1:1. Findings A total of 38 GAS isolates were analyzed, including 35 isolates from throat and 3 from skin. Among the 38 isolates, a total of 25 different emm/st types were detected: 20 isolates (53% belonged to 16 validated standard reference emm types and 18 isolates (47% belonged to 9 recognized sequence types. Conclusions This is the first emm typing study in the United Arab Emirates to demonstrate the heterogeneity of the GAS population.

  7. Group A rotavirus gastroenteritis: post-vaccine era, genotypes and zoonotic transmission.

    Science.gov (United States)

    Luchs, Adriana; Timenetsky, Maria do Carmo Sampaio Tavares

    2016-01-01

    ABSTRACTThis article provides a review of immunity, diagnosis, and clinical aspects of rotavirus disease. It also informs about the changes in epidemiology of diarrheal disease and genetic diversity of circulating group A rotavirus strains following the introduction of vaccines. Group A rotavirus is the major pathogen causing gastroenteritis in animals. Its segmented RNA genome can lead to the emergence of new or unusual strains in human populations via interspecies transmission and/or reassortment events.RESUMOEste artigo fornece uma revisão sobre imunidade, diagnóstico e aspectos clínicos da doença causada por rotavírus. Também aponta as principais mudanças no perfil epidemiológico da doença diarreica e na diversidade genética das cepas circulantes de rotavírus do grupo A, após a introdução vacinal. O rotavírus do grupo A é o principal patógeno associado à gastroenterite em animais. Seu genoma RNA segmentado pode levar ao surgimento de cepas novas ou incomuns na população humana, por meio de transmissão entre espécies e eventos de rearranjo.

  8. NCBI nr-aa BLAST: CBRC-MDOM-06-0050 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MDOM-06-0050 ref|XP_510783.2| PREDICTED: cell death inducing protein isoform 4... [Pan troglodytes] ref|XP_001168950.1| PREDICTED: cell death inducing protein isoform 2 [Pan troglodytes] re...f|XP_001168974.1| PREDICTED: cell death inducing protein isoform 3 [Pan troglodytes] XP_510783.2 1e-66 69% ...

  9. NCBI nr-aa BLAST: CBRC-MLUC-01-1044 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MLUC-01-1044 ref|XP_510783.2| PREDICTED: cell death inducing protein isoform 4... [Pan troglodytes] ref|XP_001168950.1| PREDICTED: cell death inducing protein isoform 2 [Pan troglodytes] re...f|XP_001168974.1| PREDICTED: cell death inducing protein isoform 3 [Pan troglodytes] XP_510783.2 3e-73 73% ...

  10. DNase Sda1 allows invasive M1T1 Group A Streptococcus to prevent TLR9-dependent recognition.

    Directory of Open Access Journals (Sweden)

    Satoshi Uchiyama

    Full Text Available Group A Streptococcus (GAS has developed a broad arsenal of virulence factors that serve to circumvent host defense mechanisms. The virulence factor DNase Sda1 of the hyperinvasive M1T1 GAS clone degrades DNA-based neutrophil extracellular traps allowing GAS to escape extracellular killing. TLR9 is activated by unmethylated CpG-rich bacterial DNA and enhances innate immune resistance. We hypothesized that Sda1 degradation of bacterial DNA could alter TLR9-mediated recognition of GAS by host innate immune cells. We tested this hypothesis using a dual approach: loss and gain of function of DNase in isogenic GAS strains and presence and absence of TLR9 in the host. Either DNA degradation by Sda1 or host deficiency of TLR9 prevented GAS induced IFN-α and TNF-α secretion from murine macrophages and contributed to bacterial survival. Similarly, in a murine necrotizing fasciitis model, IFN-α and TNF-α levels were significantly decreased in wild type mice infected with GAS expressing Sda1, whereas no such Sda1-dependent effect was seen in a TLR9-deficient background. Thus GAS Sda1 suppressed both the TLR9-mediated innate immune response and macrophage bactericidal activity. Our results demonstrate a novel mechanism of bacterial innate immune evasion based on autodegradation of CpG-rich DNA by a bacterial DNase.

  11. Superoxide anions produced by Streptococcus pyogenes group A-stimulated keratinocytes are responsible for cellular necrosis and bacterial growth inhibition.

    Science.gov (United States)

    Regnier, Elodie; Grange, Philippe A; Ollagnier, Guillaume; Crickx, Etienne; Elie, Laetitia; Chouzenoux, Sandrine; Weill, Bernard; Plainvert, Céline; Poyart, Claire; Batteux, Frédéric; Dupin, Nicolas

    2016-02-01

    Gram-positive Streptococcus pyogenes (group A Streptococcus or GAS) is a major skin pathogen and interacts with keratinocytes in cutaneous tissues. GAS can cause diverse suppurative and inflammatory infections, such as cellulitis, a common acute bacterial dermo-hypodermitis with a high morbidity. Bacterial isolation yields from the lesions are low despite the strong local inflammation observed, raising numerous questions about the pathogenesis of the infection. Using an in vitro model of GAS-infected keratinocytes, we show that the major ROS produced is the superoxide anion ([Formula: see text]), and that its production is time- and dose-dependent. Using specific modulators of ROS production, we show that [Formula: see text] is mainly synthesized by the cytoplasmic NADPH oxidase. Superoxide anion production leads to keratinocyte necrosis but incomplete inhibition of GAS growth, suggesting that GAS may be partially resistant to the oxidative burst. In conclusion, GAS-stimulated keratinocytes are able to develop an innate immune response based on the production of ROS. This local immune response limits GAS development and induces keratinocyte cell death, resulting in the skin lesions observed in patients with cellulitis.

  12. Study of the IgG endoglycosidase EndoS in group A streptococcal phagocyte resistance and virulence

    Directory of Open Access Journals (Sweden)

    Collin Mattias

    2011-05-01

    Full Text Available Abstract Background The secreted enzyme EndoS, an endoglycosidase from Streptococcus pyogenes, hydrolyzes the N-linked glycan of the constant region of immunoglobulin G (IgG heavy chain and renders the antibody unable to interact with Fc receptors and elicit effector functions. In this study we couple targeted allelic replacement mutagenesis and heterologous expression to elucidate the contribution of EndoS to group A Streptococcus (GAS phagocyte resistance and pathogenicity in vitro and in vivo. Results Knocking out the EndoS gene in GAS M1T1 background revealed no significant differences in bacterial survival in immune cell killing assays or in a systemic mouse model of infection. However, exogenous addition and heterologous expression of EndoS was found to increase GAS resistance to killing by neutrophils and monocytes in vitro. Additionally, heterologous expression of EndoS in M49 GAS increased mouse virulence in vivo. Conclusions We conclude that in a highly virulent M1T1 background, EndoS has no significant impact on GAS phagocyte resistance and pathogenicity. However, local accumulation or high levels of expression of EndoS in certain GAS strains may contribute to virulence.

  13. DNase Sda1 allows invasive M1T1 Group A Streptococcus to prevent TLR9-dependent recognition.

    Directory of Open Access Journals (Sweden)

    Satoshi Uchiyama

    Full Text Available Group A Streptococcus (GAS has developed a broad arsenal of virulence factors that serve to circumvent host defense mechanisms. The virulence factor DNase Sda1 of the hyperinvasive M1T1 GAS clone degrades DNA-based neutrophil extracellular traps allowing GAS to escape extracellular killing. TLR9 is activated by unmethylated CpG-rich bacterial DNA and enhances innate immune resistance. We hypothesized that Sda1 degradation of bacterial DNA could alter TLR9-mediated recognition of GAS by host innate immune cells. We tested this hypothesis using a dual approach: loss and gain of function of DNase in isogenic GAS strains and presence and absence of TLR9 in the host. Either DNA degradation by Sda1 or host deficiency of TLR9 prevented GAS induced IFN-α and TNF-α secretion from murine macrophages and contributed to bacterial survival. Similarly, in a murine necrotizing fasciitis model, IFN-α and TNF-α levels were significantly decreased in wild type mice infected with GAS expressing Sda1, whereas no such Sda1-dependent effect was seen in a TLR9-deficient background. Thus GAS Sda1 suppressed both the TLR9-mediated innate immune response and macrophage bactericidal activity. Our results demonstrate a novel mechanism of bacterial innate immune evasion based on autodegradation of CpG-rich DNA by a bacterial DNase.

  14. Development of a Real-time PCR test for porcine group A rotavirus diagnosis

    Directory of Open Access Journals (Sweden)

    Elizabeth C.M. Marconi

    2015-01-01

    Full Text Available Group A Rotavirus (RVA is one of the most common causes of diarrhea in humans and several animal species. A SYBR-Green Real-Time polymerase chain reaction (PCR was developed to diagnose RVA from porcine fecal samples, targeting amplification of a 137-bp fragment of nonstructural protein 5 (NSP5 gene using mRNA of bovine NADH-desidrogenase-5 as exogenous internal control. Sixty-five samples were tested (25 tested positive for conventional PCR and genetic sequencing. The overall agreement (kappa was 0.843, indicating 'very good' concordance between tests, presenting 100% of relative sensitivity (25+ Real Time PCR/25+ Conventional PCR and 87.5% of relative sensitivity (35- Real Time PCR/40- Conventional PCR. The results also demonstrated high intra- and inter-assay reproducibility (coefficient of variation ≤1.42%; thus, this method proved to be a fast and sensitive approach for the diagnosis of RVA in pigs.

  15. SUMMARY OF GENERAL WORKING GROUP A+B+D: CODES BENCHMARKING.

    Energy Technology Data Exchange (ETDEWEB)

    WEI, J.; SHAPOSHNIKOVA, E.; ZIMMERMANN, F.; HOFMANN, I.

    2006-05-29

    Computer simulation is an indispensable tool in assisting the design, construction, and operation of accelerators. In particular, computer simulation complements analytical theories and experimental observations in understanding beam dynamics in accelerators. The ultimate function of computer simulation is to study mechanisms that limit the performance of frontier accelerators. There are four goals for the benchmarking of computer simulation codes, namely debugging, validation, comparison and verification: (1) Debugging--codes should calculate what they are supposed to calculate; (2) Validation--results generated by the codes should agree with established analytical results for specific cases; (3) Comparison--results from two sets of codes should agree with each other if the models used are the same; and (4) Verification--results from the codes should agree with experimental measurements. This is the summary of the joint session among working groups A, B, and D of the HI32006 Workshop on computer codes benchmarking.

  16. [Use of group A streptococcal rapid diagnostic test in extra-pharyngeal infections].

    Science.gov (United States)

    Wollner, A; Levy, C; Benani, M; Thollot, F; Béchet, S; Cohen, J; Bonacorsi, S; Bidet, Ph; Cohen, R

    2014-11-01

    The purpose of this study was to assess the performances of the group A streptococcus (GAS) rapid antigen diagnostic tests (RADTs) in extra-pharyngeal infections. Between October 2009 and June 2014, 368 patients (median age: 48 months) were enrolled. The pathologies involved were : 160 perineal infections (44 %), 69 blistering distal dactylitis (19 %), 55 cervical lymphadenitis (15 %), 31 crusty or bleeding rhinitis (8 %), and 53 other diseases (14 %). The sensitivity of GAS-RADT used was 96 % (95 % CI: 92-99 %), the specificity 81 % (95 % CI: 75- 86 %), the negative predictive value 97 % (CI 95 %: 93-99 %), and the positive predictive value 79 % (95 % CI: 73-85 %). Finally, positive and negative likelihood ratio were 5 (95 % CI: 4-7) and 0.05 (95 % CI: 0.02-0.11) respectively. The GAS-RADTs developed for pharyngitis have comparable performances in these settings and therefore can be used.

  17. [Clustered cases of intrafamily invasive Streptococcus pyogenes infection (or group A streptococcus)].

    Science.gov (United States)

    Caillet-Gossot, S; Rousset-Rouviere, C; Arlaud, K; Dubus, J-C; Bosdure, E

    2011-12-01

    Streptococcus pyogenes or group A streptococcus (GAS) is responsible for serious invasive infections with a risk of secondary infection in patients with more contact than in the general population. Regardless of clustering, few intrafamilial invasive infections have been reported despite a recent increase in the incidence of invasive GAS disease. We report the cases of two brothers, one a boy of 8.5 years with toxic shock syndrome with no bacteria identified and the second, 1 week later, his 14.5-year-old brother in hospital for sepsis due to GAS. The occurrence of a confirmed case of invasive GAS and a probable case within such a short period met the definition of clustered cases. Both brothers showed no risk factors for invasive disease and no gateway including skin was found. Antibiotic therapy was initiated in the family as recommended by the French Higher Council of Public Hygiene.

  18. [Necrotizing fasciitis and group A streptococcal toxic shock syndrome in two patients without risk factors].

    Science.gov (United States)

    Ayala-Gaytán, Juan Jacobo; Guajardo-Lara, Claudia Elena; Valdovinos-Chávez, Salvador Bruno

    2011-01-01

    Necrotizing fasciitis associated to group A streptococcus (S. pyogenes) infection is a deep-seated infection of the subcutaneous tissue that results in progressive destruction of fascia and fat, with a high mortality rate due to a rapid progression of the illness to shock and multiple organ dysfunction. The challenge is to perform a prompt diagnosis because it is often confused with a minor soft-tissue infection. This infection should be aggressively treated with systemic antimicrobials, surgical debridement, and critical care. We present two cases of necrotizing fasciitis associated to infection with Streptococcus pyogenes patients developed myonecrosis and toxic shock syndrome within the following 24 hours after admission. In addition, we reviewed the pathogenic mechanism, diagnosis and treatment of this syndrome and discuss published treatment recommendations.

  19. Escherichia coli clonal group A causing bacteraemia of urinary tract origin

    DEFF Research Database (Denmark)

    Skjøt-Rasmussen, L; Olsen, S S; Jakobsen, L

    2013-01-01

    Clin Microbiol Infect ABSTRACT: Escherichia coli clonal group A (CgA) causes disease in humans. This is the first study investigating the prevalence of CgA among E. coli from non-urine, extraintestinal infections in a northern European country. E. coli blood (n = 196) and paired urine (n = 195......) isolates from the same patients with bacteraemia of urinary tract origin were analysed. The isolates were collected from January 2003 through May 2005 at four hospitals in Copenhagen, Denmark. Pulsed-field gel electrophoresis (PFGE) patterns, antimicrobial resistance and patient characteristics were...... a distinctive VAG profile. The blood and urine isolates from each pair were found to be related in 26 of 27 CgA blood/urine pairs, confirming a urinary tract origin of infection. Furthermore, a relationship between the PFGE patterns of CgA blood/urine isolates and CgA isolates from UTI patients in general...

  20. Correlates of Protection for M Protein-Based Vaccines against Group A Streptococcus

    Directory of Open Access Journals (Sweden)

    Shu Ki Tsoi

    2015-01-01

    Full Text Available Group A streptococcus (GAS is known to cause a broad spectrum of illness, from pharyngitis and impetigo, to autoimmune sequelae such as rheumatic heart disease, and invasive diseases. It is a significant cause of infectious disease morbidity and mortality worldwide, but no efficacious vaccine is currently available. Progress in GAS vaccine development has been hindered by a number of obstacles, including a lack of standardization in immunoassays and the need to define human correlates of protection. In this review, we have examined the current immunoassays used in both GAS and other organisms, and explored the various challenges in their implementation in order to propose potential future directions to identify a correlate of protection and facilitate the development of M protein-based vaccines, which are currently the main GAS vaccine candidates.

  1. Asymptomatic Group A Streptococcus carriage in children with recurrent tonsillitis and tonsillar hypertrophy.

    Science.gov (United States)

    Pontin, Isabela P Olivetti; Sanchez, Daniela Cristina Janolli; Di Francesco, Renata

    2016-07-01

    Group A Streptococcus (GAS) is the most important bacterial cause of acute tonsillitis in children. Some children are chronic GAS carriers, and this carriage is poorly understood. We determined the frequency of GAS detection using a rapid antigen detection test in pediatric patients with indications for tonsillectomy due to adenotonsillar hypertrophy or recurrent GAS infections. Seventy-two patients underwent a tonsil swab for a rapid antigen detection test. The GAS rapid antigen detection test was positive in 18.1% of children. GAS was not associated with sex, age or previous history of recurrent tonsillitis. Also, the prevalence of GAS was similar between patients with either recurrent tonsillitis or tonsil hypertrophy. In our study, the GAS carriage rate was similar to other reports, and GAS carrier state was not correlated with recurrent tonsillitis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Group A rotavirus in Brazilian bats: description of novel T15 and H15 genotypes.

    Science.gov (United States)

    Asano, Karen Miyuki; Gregori, Fabio; Hora, Aline Santana; Scheffer, Karin Corrêa; Fahl, Willian Oliveira; Iamamoto, Keila; Mori, Enio; Silva, Fernanda Dornelas Florentino; Taniwaki, Sueli Akemi; Brandão, Paulo Eduardo

    2016-11-01

    This study aimed to survey for group A rotaviruses (RVA) in bats from Brazil and to perform phylogenetic inferences for VP4, VP7, NSP3, NSP4 and NSP5 genes. RVA was found in 9.18 % (28/305) of tested samples. The partial genotype constellation of a Molossus molossus RVA strain was G3-P[3]-Ix-Rx-Cx-Mx-Ax-Nx-T3-E3-H6, and that of a Glossophaga soricina RVA strain was G20-P[x]-Ix-Rx-Cx-Mx-Ax-Nx-T15-Ex-H15. These findings demonstrate an important role of bats in RVA epidemiology and provide evidence of participation of bat RVA strains in interspecies transmission and reassortment events.

  3. Group A Streptococcal Endometritis: Report of an Outbreak and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ziad A Memish

    1994-01-01

    Full Text Available Two cases of group A streptococcus (gas postpartum endometritis were diagnosed within 24 h following uncomplicated vaginal delivery. Investigation by the infection control service identified all 10 obstetric personnel who performed any invasive procedure on both cases. These personnel were questioned about a recent history of sore throat, skin lesions, vaginal or rectal symptoms. Throat and rectal cultures were obtained for gas from all 10 personnel. A carrier was identified among the personnel screened. This nurse was removed from direct patient care and treated with a two-week course of oral clindamycin and rifampin with documentation of carrier eradication of gas at the end of therapy, 30 days, 60 days and six months post-treatment. All three isolated strains were identical by restriction endonuclease analysis and by M and T typing. Rapid implementation of infection control measures were successful in arresting this outbreak, with no further cases of gas occurring in the subsequent year.

  4. Group A streptococcal toxic shock syndrome secondary to necrotizing pelvic inflammatory disease in a postmenopausal woman

    Directory of Open Access Journals (Sweden)

    Qiwei Paulson

    2016-01-01

    Full Text Available Group A β-hemolytic streptococcus (GAS is well known to cause upper respiratory tract or cutaneous infections, but some more virulent species of GAS can lead to a rapidly progressive life threatening soft tissue necrotizing infection and streptococcal toxic shock syndrome (STSS. In the modern era, GAS infections within the female reproductive tract leading to STSS are unusual and are often the result of retained products of conception or intrauterine devices. This report describes a case of GAS necrotizing pelvic infection in a previously healthy menopausal woman with no obvious portal of entry. Her clinical course rapidly progressed to septic shock and multiorgan failure. She required multiple surgeries in addition to targeted antimicrobials and aggressive management of shock and organ failures. After a prolonged hospital stay, she had a full recovery.

  5. Coiled-Coil Irregularities and Instabilities in Group A Streptococcus M1 Are Required for Virulence

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, Case; Zinkernagel, Annelies S.; Macheboeuf, Pauline; Cunningham, Madeleine W.; Nizet, Victor; Ghosh, Partho (UO-HSC); (UCSD)

    2008-07-21

    Antigenically variable M proteins are major virulence factors and immunogens of the human pathogen group A Streptococcus (GAS). Here, we report the -3 angstrom resolution structure of a GAS M1 fragment containing the regions responsible for eliciting type-specific, protective immunity and for binding fibrinogen, which promotes M1 proinflammatory and antiphagocytic functions. The structure revealed substantial irregularities and instabilities throughout the coiled coil of the M1 fragment. Similar structural irregularities occur in myosin and tropomyosin, explaining the patterns of cross-reactivity seen in autoimmune sequelae of GAS infection. Sequence idealization of a large segment of the M1 coiled coil enhanced stability but diminished fibrinogen binding, proinflammatory effects, and antibody cross-reactivity, whereas it left protective immunogenicity undiminished. Idealized M proteins appear to have promise as vaccine immunogens.

  6. Surveillance and molecular characterization of group A rotaviruses in Goroka, Papua New Guinea.

    Science.gov (United States)

    Horwood, Paul Francis; Luang-Suarkia, Dagwin; Bebes, Sauli; Boniface, Karen; Datta, Siddhartha Sankar; Siba, Peter Max; Kirkwood, Carl Dunn

    2012-12-01

    In this study, we investigated the molecular epidemiology of group A rotaviruses in cases of acute gastroenteritis in Goroka, Papua New Guinea. From April 2008 through November 2010, 813 diarrheal stool samples were collected from children < 5 years of age hospitalized with acute gastroenteritis. Rotavirus antigen was detected in 31.2% of samples using a commercial enzyme-linked immunosorbent assay. Genotyping revealed the presence of the globally circulating strains G1P[8] (50.0%), G3P[8] (23.0%), and G2P[4] (8.2%). The globally emerging strains G9 and G12 were detected in 1.2% and 6.1% of samples, respectively. Mixed infections were detected in a high proportion of samples (11.9%), with 9.0% and 3.7% of samples displaying multiple G and P genotypes, respectively.

  7. Liposome-based intranasal delivery of lipopeptide vaccine candidates against group A streptococcus.

    Science.gov (United States)

    Ghaffar, Khairunnisa Abdul; Marasini, Nirmal; Giddam, Ashwini Kumar; Batzloff, Michael R; Good, Michael F; Skwarczynski, Mariusz; Toth, Istvan

    2016-09-01

    Group A streptococcus (GAS), an exclusively human pathogen, causes a wide range of diseases ranging from trivial to life threatening. Treatment of infection is often ineffective following entry of bacteria into the bloodstream. To date, there is no vaccine available against GAS. In this study, cationic liposomes encapsulating lipopeptide-based vaccine candidates against GAS have been employed for intranasal vaccine delivery. Cationic liposomes were prepared with dimethyldioctadecylammonium bromide (DDAB) using the film hydration method. Female Swiss mice were immunized intranasally with the liposomes. In contrast to unmodified peptides, lipopeptides entrapped by liposomes induced both mucosal and systemic immunity, IgA and IgG (IgG1 and IgG2a) production in mice, respectively. High levels of antibody (IgA and IgG) titres were detected even five months post immunization. Thus, the combination of lipopeptides and liposomes generates a very promising delivery system for intranasal vaccines. Group A streptococcus, causing rheumatic heart diseases, kills approximately half a million people annually. There is no vaccine available against the infection. Mucosal immunity is vital in ensuring an individual is protected as this gram positive bacteria initially colonizes at the throat. Herein, we demonstrated that lipopeptides entrapped by liposomes induced both mucosal and systemic immunity. High levels of antibody (IgA and IgG) titres were detected even five months post immunization and lead vaccine candidate was able to induce humoral immune responses even after single immunization. Thus, the combination of lipopeptides and liposomes generates a very promising delivery system for intranasal vaccines. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  8. Rapid antigen group A streptococcus test to diagnose pharyngitis: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Emily H Stewart

    Full Text Available BACKGROUND: Pharyngitis management guidelines include estimates of the test characteristics of rapid antigen streptococcus tests (RAST using a non-systematic approach. OBJECTIVE: To examine the sensitivity and specificity, and sources of variability, of RAST for diagnosing group A streptococcal (GAS pharyngitis. DATA SOURCES: MEDLINE, Cochrane Reviews, Centre for Reviews and Dissemination, Scopus, SciELO, CINAHL, guidelines, 2000-2012. STUDY SELECTION: Culture as reference standard, all languages. DATA EXTRACTION AND SYNTHESIS: Study characteristics, quality. MAIN OUTCOME(S AND MEASURE(S: Sensitivity, specificity. RESULTS: We included 59 studies encompassing 55,766 patients. Forty three studies (18,464 patients fulfilled the higher quality definition (at least 50 patients, prospective data collection, and no significant biases and 16 (35,634 patients did not. For the higher quality immunochromatographic methods in children (10,325 patients, heterogeneity was high for sensitivity (inconsistency [I(2] 88% and specificity (I(2 86%. For enzyme immunoassay in children (342 patients, the pooled sensitivity was 86% (95% CI, 79-92% and the pooled specificity was 92% (95% CI, 88-95%. For the higher quality immunochromatographic methods in the adult population (1,216 patients, the pooled sensitivity was 91% (95% CI, 87 to 94% and the pooled specificity was 93% (95% CI, 92 to 95%; however, heterogeneity was modest for sensitivity (I(2 61% and specificity (I(2 72%. For enzyme immunoassay in the adult population (333 patients, the pooled sensitivity was 86% (95% CI, 81-91% and the pooled specificity was 97% (95% CI, 96 to 99%; however, heterogeneity was high for sensitivity and specificity (both, I(2 88%. CONCLUSIONS: RAST immunochromatographic methods appear to be very sensitive and highly specific to diagnose group A streptococcal pharyngitis among adults but not in children. We could not identify sources of variability among higher quality studies. The

  9. The Plasminogen-Binding Group A Streptococcal M Protein-Related Protein Prp Binds Plasminogen via Arginine and Histidine Residues▿

    OpenAIRE

    Martina L. Sanderson-Smith; Dowton, Mark; Ranson, Marie; Walker, Mark J.

    2006-01-01

    The migration of the human pathogen Streptococcus pyogenes (group A streptococcus) from localized to deep tissue sites may result in severe invasive disease, and sequestration of the host zymogen plasminogen appears crucial for virulence. Here, we describe a novel plasminogen-binding M protein, the plasminogen-binding group A streptococcal M protein (PAM)-related protein (Prp). Prp is phylogenetically distinct from previously described plasminogen-binding M proteins of group A, C, and G strep...

  10. Diagnostic accuracy of clinical symptoms and rapid diagnostic test in group A streptococcal perianal infections in children.

    Science.gov (United States)

    Cohen, Robert; Levy, Corinne; Bonacorsi, Stéphane; Wollner, Alain; Koskas, Marc; Jung, Camille; Béchet, Stéphane; Chalumeau, Martin; Cohen, Jérémie; Bidet, Philippe

    2015-01-15

    From 2009 to 2014, we prospectively enrolled 132 children with perianal infections. The presentation of painful defecation, anal fissures, and macroscopic blood in stools was highly suggestive of group A streptococcal perianal infection (probability 83.3%). We found a high sensitivity of a group A streptococcal rapid diagnostic testing (98%) but relatively low specificity (72.8%).

  11. Serological Evidence of Immune Priming by Group A Streptococci in Patients with Acute Rheumatic Fever

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    Jeremy M Raynes

    2016-07-01

    Full Text Available Acute rheumatic fever (ARF is an autoimmune response to Group A Streptococcus (GAS infection. Repeated GAS exposures are proposed to ‘prime’ the immune system for autoimmunity. This notion of immune-priming by multiple GAS infections was first postulated in the 1960s, but direct experimental evidence to support the hypothesis has been lacking. Here we present novel methodology, based on antibody responses to GAS T‑antigens, that enables previous GAS exposures to be mapped in patient sera. T-antigens are surface expressed, type specific antigens and GAS strains fall into 18 major clades or T-types. A panel of recombinant T-antigens was generated and immunoassays were performed in parallel with serum depletion experiments allowing type-specific T‑antigen antibodies to be distinguished from cross-reactive antibodies. At least two distinct GAS exposures were detected in each of the ARF sera tested. Furthermore, no two sera had the same T-antigen reactivity profile suggesting that each patient was exposed to a unique series of GAS T‑types prior to developing ARF. The methods have provided much-needed experimental evidence to substantiate the immune-priming hypothesis, and will facilitate further serological profiling studies that explore the multifaceted interactions between GAS and the host.

  12. Group A Streptococcus pharyngitis outbreak among university students in a judo club.

    Science.gov (United States)

    Aoki, Akiko; Ashizawa, Tatsuto; Ebata, Akira; Nasu, Yutaka; Fujii, Takeshi

    2014-03-01

    We report on an outbreak of Group A Streptococcus (GAS) pharyngitis among university students in a judo club. Eventually, 14 of total 23 club members developed acute pharyngitis clinically. In a span of 15 days in April 2013, 12 students visited our hospital complaining of sore throat and high fever. All were men with a median age of 19.5 years (interquartile range, 18-21). The rapid streptococcal antigen test was positive in 3 of 4 patients (75%) without previous antibiotic treatment, and in 2 of 8 patients (25%) with previous antibiotic treatment. The definitive diagnosis of GAS pharyngitis was made by either a positive RADT or positive throat culture of GAS when patients had more than 2 findings from the Centor scoring system in this study. 5 students received the definitive diagnosis. The throat culture results showed that 1 out of 9 asymptomatic students was GAS-positive. The outbreak might have occurred by person-to-person contact while living in a dormitory and during judo training, which is a highly close-contact sport. However, there was also the possibility of oral transmission by the shared use of water bottles, although the culture from 1 bottle was negative. Some students continued to participate in the judo club activities after the onset of sore throat or fever. Healthcare professionals, teachers, and coaches should be aware of the potential outbreaks of infectious diseases among university students engaged in athletic activities. Furthermore, it is important to educate athletes about infectious diseases.

  13. Invasive Group A Streptococcal Infection and Vaccine Implications, Auckland, New Zealand

    Science.gov (United States)

    Safar, Atheer; Stewart, Joanna; Trenholme, Adrian; Drinkovic, Dragana; Peat, Briar; Taylor, Susan; Read, Kerry; Roberts, Sally; Voss, Lesley

    2011-01-01

    We aimed to assess the effect of invasive group A streptococcal (GAS) infection and the potential effects of a multivalent GAS vaccine in New Zealand. During January 2005–December 2006, we conducted prospective population-based laboratory surveillance of Auckland residents admitted to all public hospitals with isolation of GAS from normally sterile sites. Using emm typing, we identified 225 persons with confirmed invasive GAS infection (median 53 years of age; range 0–97 years). Overall incidence was 8.1 cases per 100,00 persons per year (20.4/100,000/year for Maori and Pacific Islanders; 24.4/100,000/year for persons >65 years of age; 33/100,000/year for infants <1 year of age). Nearly half (49%) of all cases occurred in Auckland’s lowest socioeconomic quintile. Twenty-two persons died, for an overall case-fatality rate of 10% (63% for toxic shock syndrome). Seventy-four percent of patients who died had an underlying condition. To the population in our study, the proposed 26-valent vaccine would provide limited benefit. PMID:21749758

  14. Maternal and Fetal Death following Group A Streptococcal Meningitis in Mid-Term Pregnancy

    Science.gov (United States)

    Kamaledeen, Abderahman; Law, Penelope

    2014-01-01

    Background. Group A streptococcal (GAS) meningitis is rarely seen in the antenatal period, but it is associated with significant mortality. We present a case of a mid-trimester woman who developed fulminant meningitis following a rapid onset atypical presentation of infection with this organism. Case. A multiparous 23+5-week woman presented with a 10-day history of a non-productive cough associated with pyrexia. Within minutes of her admission she collapsed and lost consciousness; sepsis was suspected and cross-specialty care was initiated. She was managed empirically in extremis with broad-spectrum antibiotics and mannitol with 3% hypertonic saline for suspected infection and raised intracranial pressure, respectively. Despite intensivist management, a CT head revealed diffuse oedema with coning of the cerebellar tonsils. Brainstem death was certified within 19 hours of admission and fetal death ensued. Postmortem bacteriology confirmed GAS meningitis. Conclusion. Through raising awareness of this patient and her disease course, we hope that future policy decisions, primary care, and hospital level management will be informed accordingly for treatment of pregnant women with suspected GAS infection. PMID:24883215

  15. Maternal and Fetal Death following Group A Streptococcal Meningitis in Mid-Term Pregnancy

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    Sayinthen Vivekanantham

    2014-01-01

    Full Text Available Background. Group A streptococcal (GAS meningitis is rarely seen in the antenatal period, but it is associated with significant mortality. We present a case of a mid-trimester woman who developed fulminant meningitis following a rapid onset atypical presentation of infection with this organism. Case. A multiparous 23+5-week woman presented with a 10-day history of a non-productive cough associated with pyrexia. Within minutes of her admission she collapsed and lost consciousness; sepsis was suspected and cross-specialty care was initiated. She was managed empirically in extremis with broad-spectrum antibiotics and mannitol with 3% hypertonic saline for suspected infection and raised intracranial pressure, respectively. Despite intensivist management, a CT head revealed diffuse oedema with coning of the cerebellar tonsils. Brainstem death was certified within 19 hours of admission and fetal death ensued. Postmortem bacteriology confirmed GAS meningitis. Conclusion. Through raising awareness of this patient and her disease course, we hope that future policy decisions, primary care, and hospital level management will be informed accordingly for treatment of pregnant women with suspected GAS infection.

  16. Effects of meteorologic factors and schooling on the seasonality of group A streptococcal pharyngitis

    Science.gov (United States)

    Hervás, Daniel; Hervás-Masip, Juan; Ferrés, Laia; Ramírez, Antonio; Pérez, José L.; Hervás, Juan A.

    2016-05-01

    The objective of this study was to determine the seasonal pattern of group A streptococcal pharyngitis in children attended at a hospital emergency department in the Mediterranean island of Mallorca (Spain), and its association with meteorologic factors and schooling. We conducted a retrospective review of the medical records of children aged 1-15 years with a diagnosis of Streptococcus pyogenes pharyngitis between January 2006 and December 2011. The number of S. pyogenes pharyngitis was correlated to temperature, humidity, rainfall, atmospheric pressure, wind speed, solar radiation, and schooling, using regression and time series techniques. A total of 906 patients (median, 4 years old) with S. pyogenes pharyngitis, confirmed by throat culture, were attended during the study period. A seasonal pattern was observed with a peak activity in June and a minimum in September. Mean temperature, solar radiation, and school holidays were the best predicting variables ( R 2 = 0.68; p pyogenes activity increased with the decrease of mean temperature ( z = -2.4; p pyogenes pharyngitis had a clear seasonality predominating in springtime, and an association with mean temperature, solar radiation, and schooling was observed. The resulting model predicted 68 % of S. pyogenes pharyngitis.

  17. Molecular characterization of Streptococcus pyogenes group A isolates from a tertiary hospital in Lebanon.

    Science.gov (United States)

    Karaky, Nathalie M; Araj, George F; Tokajian, Sima T

    2014-09-01

    Streptococcus pyogenes [Group A Streptococcus (GAS)] is one of the most important human pathogens, responsible for numerous diseases with diverse clinical manifestations. As the epidemiology of GAS infections evolves, a rapid and reliable characterization of the isolates remains essential for epidemiological analysis and infection control. This study investigated the epidemiological patterns and genetic characteristics of 150 GAS isolates from a tertiary hospital in Lebanon by emm typing, superantigens (SAgs) detection, PFGE and antibiotic profiling. The results revealed 41 distinct emm types, the most prevalent of which were emm89 (16 %), emm12 (10 %), emm2 (9 %) and emm1 (8 %). Testing for the presence of superantigens showed that speB (87 %), ssa (36 %) and speG (30 %) were predominant. PFGE detected 39 pulsotypes when a similarity cut-off value of 80 % was implemented. Antibiotic-susceptibility testing against seven different classes of antibiotics showed that 9 % of the isolates were resistant to clindamycin, 23 % were resistant to erythromycin and 4 % showed the macrolide-lincosamide-streptogramin B (MLSB) phenotype. The emergence of tetracycline-resistant strains (37 %) was high when compared with previous reports from Lebanon. This study provided comprehensive evidence of the epidemiology of GAS in Lebanon, highlighting the association between emm types and toxin genes, and providing valuable information about the origin and dissemination of this pathogen.

  18. Distribution of emm types in invasive and non-invasive group A and G streptococci.

    Science.gov (United States)

    Vähäkuopus, S; Vuento, R; Siljander, T; Syrjänen, J; Vuopio, J

    2012-06-01

    Our study describes the emm type distributions of invasive and non-invasive group A streptococci (GAS) and group G streptococci (GGS) strains in one of the biggest Health Districts in Finland. A total of 571 GAS or GGS were recovered from patients with invasive or non-invasive infections during a 1-year period in 2008-2009 in Pirkanmaa Health District in Finland. We describe here the emm type distributions of GAS and GGS collected from throat (n = 246), pus (n = 217), deep tissue (n = 56) and blood (n = 52). The most common emm types among GAS were emm77, emm1, emm28, emm89 and emm12. Among GGS, the most common emm types were stG480, stG643, stG6, stC6979 and stG485. Some emm types were found to associate with certain infection focus. In GAS, emm77 associated with pus isolates, whereas emm1 and emm12 were more frequent among throat isolates. In GGS, stG480 was more commonly found from throat isolates.

  19. Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A

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    Rie Miyata

    2016-01-01

    Full Text Available Xeroderma pigmentosum group A (XPA is a genetic disorder in DNA nucleotide excision repair (NER with severe neurological disorders, in which oxidative stress and disturbed melatonin metabolism may be involved. Herein we confirmed the diurnal variation of melatonin metabolites, oxidative stress markers, and antioxidant power in urine of patients with XPA and age-matched controls, using enzyme-linked immunosorbent assay (ELISA. The peak of 6-sulfatoxymelatonin, a metabolite of melatonin, was seen at 6:00 in both the XPA patients and controls, though the peak value is lower, specifically in the younger age group of XPA patients. The older XPA patients demonstrated an increase in the urinary levels of 8-hydroxy-2′-deoxyguanosine and hexanoyl-lysine, a marker of oxidative DNA damage and lipid peroxidation, having a robust peak at 6:00 and 18:00, respectively. In addition, the urinary level of total antioxidant power was decreased in the older XPA patients. Recently, it is speculated that oxidative stress and antioxidant properties may have a diurnal variation, and the circadian rhythm is likely to influence the NER itself. We believe that the administration of melatonin has the possibility of ameliorating the augmented oxidative stress in neurodegeneration, especially in the older XPA patients, modulating the melatonin metabolism and the circadian rhythm.

  20. Frequency of the Group A Beta Hemolytic Streptococcus Infection in Children Presenting with Acute Tonsillopharyngitis

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    Özgül Yiğit

    2009-06-01

    Full Text Available Aim: The aim of this study was to evaluate the frequency of group A beta hemolytic streptococcus (GABHS in children with tonsillopharyngitis and to assess their complaints and clinical findings.Materials and Method: A total of 420 children who presented to our outpatient department with acute tonsillopharyngitis were enrolled to the study. The clinical features of patients with positive throat cultures for GABHS were compared to those with negative culture results. Presence of fever (≥37.50C, axilary, vomiting, coryza, sore throat, cough, abdominal pain, tenderness of cervical lymph nodes, and tonsillopharyngitis were recorded. Results: The mean age of the patients was 6.5±3.4 years (range, 1 to 14 years. The positive throat culture rate for GABHS was 22.62% (95 of 420 patients. It was found that fever, sore throat, cough, abdominal pain and tender cervical lymph nodes were significantly more frequent in patients with positive throat culture for GABHS than those with negative result for GABHS.Conclusion: GABHS should be firstly considered in patients presenting with symptoms of fever, sore throat, cough, abdominal pain and tenderness of cervical lymph nodes. (Journal of Current Pediatrics 2009; 7: 13-7

  1. High burden of invasive group A streptococcal disease in the Northern Territory of Australia.

    Science.gov (United States)

    Boyd, R; Patel, M; Currie, B J; Holt, D C; Harris, T; Krause, V

    2016-04-01

    Although the incidence of invasive group A streptococcal disease in northern Australia is very high, little is known of the regional epidemiology and molecular characteristics. We conducted a case series of Northern Territory residents reported between 2011 and 2013 with Streptococcus pyogenes isolates from a normally sterile site. Of the 128 reported episodes, the incidence was disproportionately high in the Indigenous population at 69·7/100 000 compared to 8·8/100 000 in the non-Indigenous population. Novel to the Northern Territory is the extremely high incidence in haemodialysis patients of 2205·9/100 000 population; and for whom targeted infection control measures could prevent transmission. The incidences in the tropical north and semi-arid Central Australian regions were similar. Case fatality was 8% (10/128) and streptococcal toxic shock syndrome occurred in 14 (11%) episodes. Molecular typing of 82 isolates identified 28 emm types, of which 63 (77%) were represented by four emm clusters. Typing confirmed transmission between infant twins. While the diverse range of emm types presents a challenge for effective coverage by vaccine formulations, the limited number of emm clusters raises optimism should cluster-specific cross-protection prove efficacious. Further studies are required to determine effectiveness of chemoprophylaxis for contacts and to inform public health response.

  2. [Rapid antigen detection tests for group A streptococcus in children with pharyngitis].

    Science.gov (United States)

    Cohen, J; Levy, C; Chalumeau, M; Bidet, Ph; Cohen, R

    2014-11-01

    Group A streptococcus (GAS) is the most frequently identified bacterium in children with acute pharyngitis. Clinical signs and symptoms cannot distinguish accurately between viral and GAS pharyngitis. Rapid antigen detection tests (RADTs) can identify GAS by an immunologic reaction within a few minutes. Compared to throat culture, most RADTs have a high specificity (around 95 %), allowing antibiotic prescribing on the basis of a positive RADT result. Similarly, the negative predictive value of RADTs seems sufficiently high (around 95 %) to ensure against the presence of GAS in case of a negative RADT result. Among several factors affecting RADT sensitivity, the training and expertise of the person performing the test and the quality of the throat swab specimen seem to be key determinants. Available evidence suggests that clinical prediction rules for the triage of children who should undergo GAS testing are not sufficiently accurate. Implementing RADTs into clinical practice has an important impact on antibiotic prescription rates, for a reduction of about 30 %. French guidelines that recommend using RADTs in all children above 3 years of age presenting with pharyngitis without backup culture of negative tests seem relevant in this context.

  3. [Group A streptococcus-induced toxic shock syndrome in pregnancy: a case report of cesarean section].

    Science.gov (United States)

    Yamada, Kumiko; Fukuda, Taeko; Kimura, Maiko; Hagiya, Keiichi; Danmura, Masato; Nakayama, Shin; Ogura, Tsuyoshi; Tanaka, Makoto

    2012-12-01

    Group A streptococcus (GAS)-induced toxic shock syndrome (TSS) in pregnancy is rare, but its clinical course is fulminant. The mortality rates of mother and fetus are reported to be 58 and 66%, respectively. We report a case of GAS-TSS after cesarean section. A 38-year-old pregnant woman of 38 weeks gestation was admitted to our hospital because of vomiting, fever of 39 degrees C, and continuous abdominal pain with scanty genital bleeding. She had complained of sore throat several days before. One hour after admission, external fetal monitoring revealed periodic pulse deceleration to 90 x beats min(-1). The emergent cesarean section was performed under general anesthesia. Approximately 8 hours after the cesarean section, she developed coma, shock and respiratory insufficiency requiring intubation. Streptococcus pyogens were isolated from her blood sample and the patient met criteria for GAS-TSS. She was treated with antibiotics (penicillin and clindamycin), antithrombin III, recomodulin, catecholamins, and continuous hemodialysis with filtration of toxins. Although the patient recovered and was discharged on 63rd day, the infant died on postpartum day 4. Early recognition and intensive treatment for GAS is recommended in a late stage pregnancy with an episode of sore throat, vomiting, high fever, strong labor pain, and DIC signs.

  4. Mutual Exclusivity of Hyaluronan and Hyaluronidase in Invasive Group A Streptococcus*

    Science.gov (United States)

    Henningham, Anna; Yamaguchi, Masaya; Aziz, Ramy K.; Kuipers, Kirsten; Buffalo, Cosmo Z.; Dahesh, Samira; Choudhury, Biswa; Van Vleet, Jeremy; Yamaguchi, Yuka; Seymour, Lisa M.; Ben Zakour, Nouri L.; He, Lingjun; Smith, Helen V.; Grimwood, Keith; Beatson, Scott A.; Ghosh, Partho; Walker, Mark J.; Nizet, Victor; Cole, Jason N.

    2014-01-01

    A recent analysis of group A Streptococcus (GAS) invasive infections in Australia has shown a predominance of M4 GAS, a serotype recently reported to lack the antiphagocytic hyaluronic acid (HA) capsule. Here, we use molecular genetics and bioinformatics techniques to characterize 17 clinical M4 isolates associated with invasive disease in children during this recent epidemiology. All M4 isolates lacked HA capsule, and whole genome sequence analysis of two isolates revealed the complete absence of the hasABC capsule biosynthesis operon. Conversely, M4 isolates possess a functional HA-degrading hyaluronate lyase (HylA) enzyme that is rendered nonfunctional in other GAS through a point mutation. Transformation with a plasmid expressing hasABC restored partial encapsulation in wild-type (WT) M4 GAS, and full encapsulation in an isogenic M4 mutant lacking HylA. However, partial encapsulation reduced binding to human complement regulatory protein C4BP, did not enhance survival in whole human blood, and did not increase virulence of WT M4 GAS in a mouse model of systemic infection. Bioinformatics analysis found no hasABC homologs in closely related species, suggesting that this operon was a recent acquisition. These data showcase a mutually exclusive interaction of HA capsule and active HylA among strains of this leading human pathogen. PMID:25266727

  5. Comparison of Gen-Probe Group A streptococcus Direct Test with culture for diagnosing streptococcal pharyngitis.

    Science.gov (United States)

    Pokorski, S J; Vetter, E A; Wollan, P C; Cockerill, F R

    1994-01-01

    The Group A Streptococcus Direct Test (GP-ST test; Gen-Probe, Inc., San Diego, Calif.) was compared with culture for the detection of Streptococcus pyogenes from throat swabs of 767 patients with pharyngitis. Swabs were tested by the GP-ST test after inoculating a 5% sheep blood agar (SBA) plate. SBA plates were incubated at 35 degrees C in room air for 72 h. SBA plates with no evidence of beta-hemolytic colonies after 18 to 24 h of incubation were subcultured by taking a swipe across the primary inoculum from the SBA plate to an agar selective for Streptococcus spp. In a low-prevalence (11.9%) population and in comparison with the number of positive cultures detected by the 72-h single-culture method (SBA plate method), the GP-ST test had a sensitivity of 88.6%, a specificity of 97.8%, a positive predictive value of 83.9%, and a negative predictive value of 98.5%. In comparison with the growth of any colonies of S. pyogenes on the 72-h SBA plates plus a subculture onto selective blood agar, the sensitivities and specificities were as follows: 72-h SBA plate method, 96.7 and 100%, respectively; GP-ST test, 85.7 and 97.8%, respectively. The GP-ST test is an easy-to-perform, reliable test for batch screening of throat swabs for S. pyogenes. PMID:8077386

  6. Lower respiratory tract infection in cynomolgus macaques (Macaca fascicularis) infected with group A Streptococcus.

    Science.gov (United States)

    Olsen, Randall J; Ashraf, Madiha; Gonulal, Vedia E; Ayeras, Ara A; Cantu, Concepcion; Shea, Patrick R; Carroll, Ronan K; Humbird, Tammy; Greaver, Jamieson L; Swain, Jody L; Chang, Ellen; Ragasa, Willie; Jenkins, Leslie; Lally, Kevin P; Blasdel, Terry; Cagle, Philip; Musser, James M

    2010-12-01

    Group A Streptococcus (GAS), a human-specific pathogen, is best known for causing pharyngitis ("strep-throat") and necrotizing fasciitis ("flesh-eating disease"). However, the organism is also an uncommon but important cause of community-acquired bronchopneumonia, an infection with an exceptionally high mortality rate. Inasmuch as little is known about the molecular pathogenesis of GAS lower respiratory tract infection, we sought to develop a relevant human infection model. Nine cynomolgus macaques were infected by intra-bronchial instillation of either sterile saline or GAS (10(5) or 10(7) CFU). Animals were continuously monitored and sacrificed at five days post-inoculation. Serial bronchial alveolar lavage specimens and tissues collected at necropsy were used for histologic and immunohistochemical examination, quantitative microbial culture, lung and blood biomarker analysis, and in vivo GAS gene expression studies. The lower respiratory tract disease observed in cynomolgus macaques mimicked the clinical and pathological features of severe GAS bronchopneumonia in humans. This new monkey model will be useful for testing hypotheses bearing on the molecular pathogenesis of GAS in the lower respiratory tract.

  7. Immunization with Streptococcal Heme Binding Protein (Shp) Protects Mice Against Group A Streptococcus Infection.

    Science.gov (United States)

    Zhang, Xiaolan; Song, Yingli; Li, Yuanmeng; Cai, Minghui; Meng, Yuan; Zhu, Hui

    2017-01-01

    Streptococcal heme binding protein (Shp) is a surface protein of the heme acquisition system that is an essential iron nutrient in Group A Streptococcus (GAS). Here, we tested whether Shp immunization protects mice from subcutaneous infection. Mice were immunized subcutaneously with recombinant Shp and then challenged with GAS. The protective effects against GAS challenge were evaluated two weeks after the last immunization. Immunization with Shp elicited a robust IgG response, resulting in high anti-Shp IgG titers in the serum. Immunized mice had a higher survival rate and smaller skin lesions than adjuvant control mice. Furthermore, immunized mice had lower GAS numbers at the skin lesions and in the liver, spleen and lung. Histological analysis with Gram staining showed that GAS invaded the surrounding area of the inoculation sites in the skin in control mice, but not in immunized mice. Thus, Shp immunization enhances GAS clearance and reduces GAS skin invasion and systemic dissemination. These findings indicate that Shp is a protective antigen.

  8. Evolution of human G4P[8] group A rotavirus strains circulating in Italy in 2013.

    Science.gov (United States)

    Ianiro, Giovanni; Delogu, Roberto; Fiore, Lucia; Ruggeri, Franco M

    2015-06-02

    Group A rotaviruses (RVA) are the leading cause of acute gastroenteritis in young (humans worldwide are associated with the five major G/P combinations G1P[8], G2P[4], G3P[8], G4P[8] and G9P[8]. During RVA gastroenteritis surveillance in Italy, a total of 1112 samples collected from children hospitalized with acute gastroenteritis in 2013 were RVA positive and were genotyped following standardized protocols from the EuroRotaNet. Most strains analyzed belonged to the five major human genotypes. Among these common strains, 22 G4P[8] RVA strains from different Italian regions were subjected to nucleotide sequencing of their VP4, VP6, VP7 and NSP4 genes to investigate their evolution. The phylogenetic analysis showed that the Italian strains belonged to lineage G4-I for VP7 and to lineage P[8]-III for VP4, in line with the modern G4P[8] RVA strains detected in children worldwide. The phylogenetic trees revealed high degrees of nucleotide identity between the RVA strains involved in this study and G4P[8] strains detected previously in Europe, Asia and Africa, but also demonstrated at least three separate evolution clusters within the same lineage. Based on the amino acid sequences deduced for their hypervariable regions, both the VP7 and VP8* proteins of the Italian G4P[8] RVA strains presented amino acid substitutions near known neutralizing epitopes.

  9. Regulatory gene mutation: a driving force behind group a Streptococcus strain- and serotype-specific variation.

    Science.gov (United States)

    Sarkar, Poulomee; Sumby, Paul

    2017-02-01

    Data from multiple bacterial pathogens are consistent with regulator-encoding genes having higher mutation frequencies than the genome average. Such mutations drive both strain- and type- (e.g., serotype, haplotype) specific phenotypic heterogeneity, and may challenge public health due to the potential of variants to circumvent established treatment and/or preventative regimes. Here, using the human bacterial pathogen the group A Streptococcus (GAS; S. pyogenes) as a model organism, we review the types and regulatory-, phenotypic-, and disease-specific consequences of naturally occurring regulatory gene mutations. Strain-specific regulator mutations that will be discussed include examples that transform isolates into hyper-invasive forms by enhancing expression of immunomodulatory virulence factors, and examples that promote asymptomatic carriage of the organism. The discussion of serotype-specific regulator mutations focuses on serotype M3 GAS isolates, and how the identified rewiring of regulatory networks in this serotype may be contributing to a decades old epidemiological association of M3 isolates with particularly severe invasive infections. We conclude that mutation plays an outsized role in GAS pathogenesis and has clinical relevance. Given the phenotypic variability associated with regulatory gene mutations, the rapid examination of these genes in infecting isolates may inform with respect to potential patient complications and treatment options.

  10. Molecular epidemiology of group A streptococcus causing scarlet fever in northern Taiwan, 2001-2002.

    Science.gov (United States)

    Chen, Ying-Yan; Huang, Chung-Ter; Yao, Shu-Man; Chang, Yi-Ching; Shen, Pei-Wun; Chou, Chen-Ying; Li, Shu-Ying

    2007-07-01

    In this study, 830 Streptococcus pyogenes isolates collected between 2001 and 2002 from patients with scarlet fever in northern Taiwan were analyzed by M protein gene (emm) sequence typing, pulsed-field gel electrophoresis (PFGE), and antimicrobial susceptibility testing. A total of 21 emm types and 56 PFGE patterns were identified. The most frequent emm types were emm1 (29.2%), emm4 (24.1%), emm12 (19.0%), emm6 (15.8%), stIL103 (5.7%), and emm22 (1.9%). Antimicrobial resistance profiles were determined, and resistance to erythromycin (24.6%), clindamycin (2.0%), and chloramphenicol (1.3%) was detected. Five major emm types (emm4, emm12, emm1, emm22, and emm6) accounted for 95.6% of the erythromycin-resistant isolates. The decreased prevalence of erythromycin-resistant emm12 strains coincided with the overall decrease in erythromycin resistance from 32.1% in 2001 to 21.1% in 2002 in Taiwan. Five major clones (emm4/2000, emm12/0000, emm4/2010, emm1/1000, and emm22/8100) represented 72.1% of the erythromycin-resistant isolates. The survey of group A Streptococcus emm types, genetic diversity, and antibiotic resistance has direct relevance to current antimicrobial use policies and potential vaccine development strategies.

  11. Differing Efficacies of Lead Group A Streptococcal Vaccine Candidates and Full-Length M Protein in Cutaneous and Invasive Disease Models

    Directory of Open Access Journals (Sweden)

    Tania Rivera-Hernandez

    2016-06-01

    Full Text Available Group A Streptococcus (GAS is an important human pathogen responsible for both superficial infections and invasive diseases. Autoimmune sequelae may occur upon repeated infection. For this reason, development of a vaccine against GAS represents a major challenge, since certain GAS components may trigger autoimmunity. We formulated three combination vaccines containing the following: (i streptolysin O (SLO, interleukin 8 (IL-8 protease (Streptococcus pyogenes cell envelope proteinase [SpyCEP], group A streptococcal C5a peptidase (SCPA, arginine deiminase (ADI, and trigger factor (TF; (ii the conserved M-protein-derived J8 peptide conjugated to ADI; and (iii group A carbohydrate lacking the N-acetylglucosamine side chain conjugated to ADI. We compared these combination vaccines to a “gold standard” for immunogenicity, full-length M1 protein. Vaccines were adjuvanted with alum, and mice were immunized on days 0, 21, and 28. On day 42, mice were challenged via cutaneous or subcutaneous routes. High-titer antigen-specific antibody responses with bactericidal activity were detected in mouse serum samples for all vaccine candidates. In comparison with sham-immunized mice, all vaccines afforded protection against cutaneous challenge. However, only full-length M1 protein provided protection in the subcutaneous invasive disease model.

  12. Translesion synthesis mechanisms depend on the nature of DNA damage in UV-irradiated human cells

    Science.gov (United States)

    Quinet, Annabel; Martins, Davi Jardim; Vessoni, Alexandre Teixeira; Biard, Denis; Sarasin, Alain; Stary, Anne; Menck, Carlos Frederico Martins

    2016-01-01

    Ultraviolet-induced 6-4 photoproducts (6-4PP) and cyclobutane pyrimidine dimers (CPD) can be tolerated by translesion DNA polymerases (TLS Pols) at stalled replication forks or by gap-filling. Here, we investigated the involvement of Polη, Rev1 and Rev3L (Polζ catalytic subunit) in the specific bypass of 6-4PP and CPD in repair-deficient XP-C human cells. We combined DNA fiber assay and novel methodologies for detection and quantification of single-stranded DNA (ssDNA) gaps on ongoing replication forks and postreplication repair (PRR) tracts in the human genome. We demonstrated that Rev3L, but not Rev1, is required for postreplicative gap-filling, while Polη and Rev1 are responsible for TLS at stalled replication forks. Moreover, specific photolyases were employed to show that in XP-C cells, CPD arrest replication forks, while 6-4PP are responsible for the generation of ssDNA gaps and PRR tracts. On the other hand, in the absence of Polη or Rev1, both types of lesion block replication forks progression. Altogether, the data directly show that, in the human genome, Polη and Rev1 bypass CPD and 6-4PP at replication forks, while only 6-4PP are also tolerated by a Polζ-dependent gap-filling mechanism, independent of S phase. PMID:27095204

  13. Telomerase activation in posterior fossa group A ependymomas is associated with dismal prognosis and chromosome 1q gain.

    Science.gov (United States)

    Gojo, Johannes; Lötsch, Daniela; Spiegl-Kreinecker, Sabine; Pajtler, Kristian W; Neumayer, Katharina; Korbel, Pia; Araki, Asuka; Brandstetter, Anita; Mohr, Thomas; Hovestadt, Volker; Chavez, Lukas; Kirchhofer, Dominik; Ricken, Gerda; Stefanits, Harald; Korshunov, Andrey; Pfister, Stefan M; Dieckmann, Karin; Azizi, Amedeo A; Czech, Thomas; Filipits, Martin; Kool, Marcel; Peyrl, Andreas; Slavc, Irene; Berger, Walter; Haberler, Christine

    2017-09-01

    Ependymomas account for up to 10% of childhood CNS tumors and have a high rate of tumor recurrence despite gross total resection. Recently, classification into molecular ependymoma subgroups has been established, but the mechanisms underlying the aggressiveness of certain subtypes remain widely enigmatic. The aim of this study was to dissect the clinical and biological role of telomerase reactivation, a frequent mechanism of cancer cells to evade cellular senescence, in pediatric ependymoma. We determined telomerase enzymatic activity, hTERT mRNA expression, promoter methylation, and the rs2853669 single nucleotide polymorphism located in the hTERT promoter in a well-characterized cohort of pediatric intracranial ependymomas. In posterior fossa ependymoma group A (PF-EPN-A) tumors, telomerase activity varied and was significantly associated with dismal overall survival, whereas telomerase reactivation was present in all supratentorial RelA fusion-positive (ST-EPN-RELA) ependymomas. In silico analysis of methylation patterns showed that only these two subgroups harbor hypermethylated hTERT promoters suggesting telomerase reactivation via epigenetic mechanisms. Furthermore, chromosome 1q gain, a well-known negative prognostic factor, was strongly associated with telomerase reactivation in PF-EPN-A. Additional in silico analyses of gene expression data confirmed this finding and further showed enrichment of the E-twenty-six factor, Myc, and E2F target genes in 1q gained ependymomas. Additionally, 1q gained tumors showed elevated expression of ETV3, an E-twenty-six factor gene located on chromosome 1q. Taken together we describe a subgroup-specific impact of telomerase reactivation on disease progression in pediatric ependymoma and provide preliminary evidence for the involved molecular mechanisms.

  14. [Clinical characteristics and antimicrobial resistance of invasive group A β-hemolytic streptococcus infection in children].

    Science.gov (United States)

    Fan, Jiemin; Dong, Lin; Chen, Zhaoxing; Bei, Dandan

    2014-01-01

    Group A β-hemolytic streptococcus (GAS) or Streptococcus pyogenes may be encountered in diverse clinical situations in children. A rising incidence of invasive group A streptococcus (IGAS) infections has been noted in children in the past three decades. The aim of this study was to summarize the clinical characteristics and antimicrobial resistance of IGAS in children, and to raise the level of diagnosis and treatment of this infection. The clinical data from 19 cases of IGAS younger than 14 years old seen from January 2004 to December 2011 treated in the authors' hospital were analyzed. IGAS infections are defined as the isolation of GAS from a normally sterile site in patients. The 19 cases were identified as IGAS infections, among whom 15 were male and 4 were female, and the ratio of them was 3.75. The age ranged from 1 day to 14 years, with a median age of 4 years. The course of disease was 4 h-10 days. The average length of stay was 12.2 days. In 13 cases the episodes of the infection occurred in winter and spring. In 18 cases the infection was community-acquired. Overall, 10 cases had neck or foot dorsum abscess, four cases had purulent peritonitis, and 3 cases were diagnosed as streptococcal toxic shock syndrome (STSS) complicated with empyema, pyopneumothorax occurred in 1 case and neonatal septicemia in another. Three cases had an underlying disease, including 2 cases wounded in a car accident and 1 case of congenital esophageal atresia and tracheoesophageal fistula. Before the isolation of GAS, 5 cases had stayed in ICUs, the length of ICU stay was 1-32 days, 4 cases had received intubation and mechanical ventilation, the ventilation time was 8 h-24 days, 2 cases had received major surgery; 5 cases had other pathogen coinfection, including 4 cases of abdominal pus at the same time and Escherichia coli was isolated, and 1 case had parainfluenza virus type I coinfection. Peripheral blood leucocyte increased in 18 cases, one case dropped off. The C

  15. How dietary intake methodology is adapted for use in European immigrant population groups - a review.

    Science.gov (United States)

    Ngo, Joy; Gurinovic, Mirjana; Frost-Andersen, Lene; Serra-Majem, Lluís

    2009-07-01

    Immigrants comprise a noteworthy segment of the European population whose numbers are increasing. Research on the dietary habits of immigrants is critical for correctly providing diet counselling and implementing effective interventions. The aim of the present study was to identify the presently used methods and adaptations required for measuring dietary intake in European immigrant groups. A comprehensive review strategy included a structured MEDLINE search, related references and key expert consultations. The review targeted adults from non-European union (European union-15 countries) ethnic groups having the largest populations in Europe. As studies evaluating nutrient intake were scarce, papers evaluating intake at the level of foods were included. Forty-six papers were selected. Although Eastern Europe, Turkey, Africa (North, Sub-Saharan and Afro-Caribbean), Asia and Latin America represented the most numerous immigrant groups, papers on dietary intake were not available for all populations. Interview-administered FFQ and repeated 24 hour recalls were the most frequently applied instruments. Inclusion of ethnic foods and quantification of specific portion sizes of traditional foods and dishes in assessment tools as well as food composition databases were commonly identified problems. For FFQ, food list elaboration required particular consideration to reflect key ethnic foods and relative contribution to nutrient intake. Extra efforts were observed to overcome cultural barriers to study participation. Evaluating dietary intake of immigrant populations requires special attention to various methodological aspects (sampling, recruiting, instruments used, method of administration, food composition database, acculturation, etc.) so as to adequately address the range of socio-cultural factors inherent in these nutritionally at risk target groups.

  16. Regulation of Polysaccharide Utilization Contributes to the Persistence of Group A Streptococcus in the Oropharynx▿

    Science.gov (United States)

    Shelburne, Samuel A.; Okorafor, Nnaja; Sitkiewicz, Izabela; Sumby, Paul; Keith, David; Patel, Payal; Austin, Celest; Graviss, Edward A.; Musser, James M.

    2007-01-01

    Group A Streptococcus (GAS) genes that encode proteins putatively involved in polysaccharide utilization show growth phase-dependent expression in human saliva. We sought to determine whether the putative polysaccharide transcriptional regulator MalR influences the expression of such genes and whether MalR helps GAS infect the oropharynx. Analysis of 32 strains of 17 distinct M protein serotypes revealed that MalR is highly conserved across GAS strains. malR transcripts were detectable in patients with GAS pharyngitis, and the levels increased significantly during growth in human saliva compared to the levels during growth in glucose-containing or nutrient-rich media. To determine if MalR influenced the expression of polysaccharide utilization genes, we compared the transcript levels of eight genes encoding putative polysaccharide utilization proteins in the parental serotype M1 strain MGAS5005 and its ΔmalR isogenic mutant derivative. The transcript levels of all eight genes were significantly increased in the ΔmalR strain compared to the parental strain, especially during growth in human saliva. Following experimental infection, the ΔmalR strain persistently colonized the oropharynx in significantly fewer mice than the parental strain colonized, and the numbers of ΔmalR strain CFU recovered were significantly lower than the numbers of the parental strain CFU recovered. These data led us to conclude that MalR influences the expression of genes putatively involved in polysaccharide utilization and that MalR contributes to the persistence of GAS in the oropharynx. PMID:17403878

  17. A genome-wide analysis of small regulatory RNAs in the human pathogen group A Streptococcus.

    Directory of Open Access Journals (Sweden)

    Nataly Perez

    Full Text Available The coordinated regulation of gene expression is essential for pathogens to infect and cause disease. A recently appreciated mechanism of regulation is that afforded by small regulatory RNA (sRNA molecules. Here, we set out to assess the prevalence of sRNAs in the human bacterial pathogen group A Streptococcus (GAS. Genome-wide identification of candidate GAS sRNAs was performed through a tiling Affymetrix microarray approach and identified 40 candidate sRNAs within the M1T1 GAS strain MGAS2221. Together with a previous bioinformatic approach this brings the number of novel candidate sRNAs in GAS to 75, a number that approximates the number of GAS transcription factors. Transcripts were confirmed by Northern blot analysis for 16 of 32 candidate sRNAs tested, and the abundance of several of these sRNAs were shown to be temporally regulated. Six sRNAs were selected for further study and the promoter, transcriptional start site, and Rho-independent terminator identified for each. Significant variation was observed between the six sRNAs with respect to their stability during growth, and with respect to their inter- and/or intra-serotype-specific levels of abundance. To start to assess the contribution of sRNAs to gene regulation in M1T1 GAS we deleted the previously described sRNA PEL from four clinical isolates. Data from genome-wide expression microarray, quantitative RT-PCR, and Western blot analyses are consistent with PEL having no regulatory function in M1T1 GAS. The finding that candidate sRNA molecules are prevalent throughout the GAS genome provides significant impetus to the study of this fundamental gene-regulatory mechanism in an important human pathogen.

  18. Escherichia coli clonal group A among uropathogenic infections in Mexico City.

    Science.gov (United States)

    Manjarrez-Hernandez, Angel; Molina-López, José; Gavilanes-Parra, Sandra; Hernandez-Castro, Rigoberto

    2016-12-01

    Escherichia coli clonal group A (CGA) causes urinary tract and other extra-intestinal infections in humans. CGA is an important cause of trimethoprim/sulfamethoxazole (SXT) resistance in extra-intestinal pathogens. We examined the extent to which resistance in this area is related to CGA dissemination of E. coli from urinary tract infections (UTIs) in Mexico City. The virulence backgrounds of the isolates were also characterized. In this study, the frequency of resistance to SXT used for UTI treatment was high (56-65 %), and CGA isolates accounted for 9 of the 78 SXT-resistant isolates (11.5 %). Although all CGA isolates were found to be multidrug resistant (MDR), none of them were extended-spectrum β-lactamase-producing organisms. The prevalence of CGA among the 45 MDR isolates that we identified was 20 %, indicating that this clonal group moderately contributes to the antibiotic resistance of uropathogenic E. coli isolates in this region. Most of the nine CGA isolates carried transferable, large-size plasmids of approximately 80 to 100 kb, which were able to transfer antimicrobial resistance to E. coli J53 in mating assays. CGA isolates mainly belonged to phylogenetic groups F and D. We found no association between antimicrobial resistance and virulence-associated genes: the median virulence scores of CGA isolates were slightly higher (4.6) than those of non-CGA isolates, whether they were susceptible (3.7) or resistant (3.5) to SXT. Our results indicate that CGA is not a major contributor to the high level of resistance to SXT in this region but, instead, seems to be an important constituent of MDR isolates from UTIs.

  19. Statistics on Lie groups: A need to go beyond the pseudo-Riemannian framework

    Science.gov (United States)

    Miolane, Nina; Pennec, Xavier

    2015-01-01

    Lie groups appear in many fields from Medical Imaging to Robotics. In Medical Imaging and particularly in Computational Anatomy, an organ's shape is often modeled as the deformation of a reference shape, in other words: as an element of a Lie group. In this framework, if one wants to model the variability of the human anatomy, e.g. in order to help diagnosis of diseases, one needs to perform statistics on Lie groups. A Lie group G is a manifold that carries an additional group structure. Statistics on Riemannian manifolds have been well studied with the pioneer work of Fréchet, Karcher and Kendall [1, 2, 3, 4] followed by others [5, 6, 7, 8, 9]. In order to use such a Riemannian structure for statistics on Lie groups, one needs to define a Riemannian metric that is compatible with the group structure, i.e a bi-invariant metric. However, it is well known that general Lie groups which cannot be decomposed into the direct product of compact and abelian groups do not admit a bi-invariant metric. One may wonder if removing the positivity of the metric, thus asking only for a bi-invariant pseudo-Riemannian metric, would be sufficient for most of the groups used in Computational Anatomy. In this paper, we provide an algorithmic procedure that constructs bi-invariant pseudo-metrics on a given Lie group G. The procedure relies on a classification theorem of Medina and Revoy. However in doing so, we prove that most Lie groups do not admit any bi-invariant (pseudo-) metric. We conclude that the (pseudo-) Riemannian setting is not the richest setting if one wants to perform statistics on Lie groups. One may have to rely on another framework, such as affine connection space.

  20. Meningococcal meningitis group A: a successful control of an outbreak by mass vaccination.

    Science.gov (United States)

    Bushra, H E; Mawlawi, M Y; Fontaine, R E; Afif, H

    1995-11-01

    Jeddah is the main point of entry to the holy places in Saudi Arabia. An outbreak of meningococcal disease (MCD) occurred during the fasting lunar month for Muslims, Ramadan (March-April) of 1992. To assess the threat of local spread of MCD within Jeddah, the effects of previous and a mass vaccination programme against MCD during the outbreak, we reviewed the medical records of confirmed cases (CC) of MCD (defined as a bacteriologically confirmed case or a case diagnosed by latex test) and their vaccination status in the last five years before the outbreak. There were 41 CC of meningitis due to Neisseria meningitidis (group A). The ratio of males to females was 4.1:1. Thirty two percent of the cases were religious visitors. About one fourth (22%) of the cases were Pakistani. More than half (57%) of the cases, who were residents of Jeddah, lived in the north-eastern part of the city, as did half of the Pakistani cases. The case-fatality rate among CC was 19.5%. Persons who visited the Makkah (Mecca) during Ramadan were more likely to get the disease than those who did not (odds ratio [OR] = 6.1; 95% confidence interval [CI] 1.4-40.7). Unvaccinated persons were more likely to get the disease than those who were vaccinated against MCD (OR = 13.9; 95% CI 1.8-296). Meningococcal vaccine (MCV) against MCD was effective in preventing the disease. However, MCV was of no protective value if it had been administered more than five years before the outbreak. The reason mentioned most frequently for not being vaccinated by both cases (84%) and controls (57%) was lack of knowledge about the disease. Health education programmes should be strengthened and promoted. A good collaborative surveillance system between Jeddah and other holy cities, especially Makkah, is needed to abort outbreaks among religious visitors and to prevent the spread of MCD outbreaks.

  1. Trivalent M-related protein as a component of next generation group A streptococcal vaccines

    Science.gov (United States)

    2017-01-01

    Purpose There is a need to broaden protective coverage of M protein–based vaccines against group A streptococci (GAS) because coverage of the current 30-valent M protein vaccine does not extend to all emm types. An additional GAS antigen and virulence factor that could potentially extend vaccine coverage is M-related protein (Mrp). Previous work indicated that there are three structurally related families of Mrp (MrpI, MrpII, and MrpIII) and peptides of all three elicited bactericidal antibodies against multiple emm types. The purpose of this study was to determine if a recombinant form containing Mrp from the three families would evoke bactericidal antiserum and to determine if this antiserum could enhance the effectiveness of antisera to the 30-valent M protein vaccine. Materials and Methods A trivalent recombinant Mrp (trMrp) protein containing N-terminal fragments from the three families (trMrp) was constructed, purified and used to immunize rabbits. Anti-trMrp sera contained high titers of antibodies against the trMrp immunogen and recombinant forms representing MrpI, MrpII, and MrpIII. Results The antisera opsonized emm types of GAS representing each Mrp family and also opsonized emm types not covered by the 30-valent M protein–based vaccine. Importantly, a combination of trMrp and 30-valent M protein antiserum resulted in higher levels of opsonization of GAS than either antiserum alone. Conclusion These findings suggest that trMrp may be an effective addition to future constructs of GAS vaccines. PMID:28168173

  2. Epidemiology and emm types of invasive group A streptococcal infections in Finland, 2008-2013.

    Science.gov (United States)

    Smit, P W; Lindholm, L; Lyytikäinen, O; Jalava, J; Pätäri-Sampo, A; Vuopio, J

    2015-10-01

    Invasive Streptococcus pyogenes (group A streptococcus, GAS) infections are a major global cause of morbidity and mortality. We analysed the surveillance data on invasive GAS and the microbiological characteristics of corresponding isolates to assess the incidence and emm type distribution of invasive GAS infections in Finland. Cases defined as patients with isolations of blood and cerebrospinal fluid S. pyogenes are mandatorily notified to the National Infectious Disease Registry and sent to the national reference laboratory for emm typing. Antimicrobial data were collected through the network including all clinical microbiology laboratories. Pulsed-field gel electrophoresis (PFGE) analysis was performed to assess clonality. In total, 1165 cases of invasive GAS were reported in Finland during 2008-2013; the median age was 52 years (range, 0-100) and 54% were male. The overall day 7 case fatality rate was 5.1% (59 cases). The average annual incidence was 3.6 cases per 100,000 population. A total of 1122 invasive GAS isolates (96%) were analysed by emm typing; 72 different emm types were identified, of which emm28 (297 isolates, 26%), emm89 (193 isolates, 12%) and emm1 (132 isolates, 12%) were the most common types. During 2008-2013, an increase of erythromycin resistance (1.9% to 8.7%) and clindamycin (0.9% to 9.2%) was observed. This resistance increase was in parallel with the introduction of a novel clone emm33 into Finland. The overall incidence of invasive GAS infections remained stable over the study period in Finland. We identified clonal spread of macrolide-resistant invasive emm33 GAS type, highlighting the importance of molecular surveillance.

  3. Molecular and Clinical Diagnosis of Group A Streptococcal Pharyngitis in Children

    Science.gov (United States)

    Faddoul, Diala; Sposto, Richard; Batoon, Kristine; Polanco, Claudia M.; Dien Bard, Jennifer

    2014-01-01

    Group A Streptococcus (GAS) pharyngitis is a very common condition causing significant morbidity in children. Accurate diagnosis followed by appropriate antimicrobial therapy is recommended to prevent postinfectious sequelae. Diagnosis of GAS pharyngitis by a rapid antigen detection test (RADT) or culture in the absence of discriminating clinical findings remains challenging. Validation of new sensitive rapid diagnostic tests is therefore a priority. The performance of a loop-mediated isothermal amplification (LAMP) assay (illumigene assay) for the diagnosis of GAS pharyngitis was compared with that of a RADT and standard culture in 361 pediatric throat swab samples. Discrepant results were resolved using an alternate molecular assay. Test results were correlated with clinical presentations in patients positive by either method. The closest estimate of the true prevalence of GAS pharyngitis was 19.7% (71/361 samples). The illumigene assay alone detected 70/71 GAS-positive samples; RADT and culture detected 35/71 and 55/71 samples, respectively. RADT followed by culture confirmation of RADT-negative specimens detected 58/71 cases. The illumigene assay increased identification among children eligible for testing by American College of Physicians (ACP)/American Academy of Family Physicians (AAFP) criteria from 31 to 39 positive cases, five of which were false positives. Analysis of clinical data in GAS-positive patients indicated that a significantly greater proportion of children with McIsaac scores of ≥4 tested positive by the illumigene assay versus RADT and culture. Overall, the illumigene assay was much more sensitive and was similarly specific for GAS detection, compared to culture alone, RADT alone, or the ACP/AAFP RADT/culture algorithm. Combining high sensitivity with rapidly available results, the illumigene GAS assay is an appropriate alternative to culture for the laboratory diagnosis of GAS pharyngitis in patients for whom testing is clinically

  4. Group A Streptococcus gene expression in humans and cynomolgus macaques with acute pharyngitis.

    Science.gov (United States)

    Virtaneva, Kimmo; Graham, Morag R; Porcella, Stephen F; Hoe, Nancy P; Su, Hua; Graviss, Edward A; Gardner, Tracie J; Allison, James E; Lemon, William J; Bailey, John R; Parnell, Michael J; Musser, James M

    2003-04-01

    The molecular mechanisms used by group A Streptococcus (GAS) to survive on the host mucosal surface and cause acute pharyngitis are poorly understood. To provide new information about GAS host-pathogen interactions, we used real-time reverse transcription-PCR (RT-PCR) to analyze transcripts of 17 GAS genes in throat swab specimens taken from 18 pediatric patients with pharyngitis. The expression of known and putative virulence genes and regulatory genes (including genes in seven two-component regulatory systems) was studied. Several known and previously uncharacterized GAS virulence gene regulators were highly expressed compared to the constitutively expressed control gene proS. To examine in vivo gene transcription in a controlled setting, three cynomolgus macaques were infected with strain MGAS5005, an organism that is genetically representative of most serotype M1 strains recovered from pharyngitis and invasive disease episodes in North America and Western Europe. These three animals developed clinical signs and symptoms of GAS pharyngitis and seroconverted to several GAS extracellular proteins. Real-time RT-PCR analysis of throat swab material collected at intervals throughout a 12-day infection protocol indicated that expression profiles of a subset of GAS genes accurately reflected the profiles observed in the human pediatric patients. The results of our study demonstrate that analysis of in vivo GAS gene expression is feasible in throat swab specimens obtained from infected human and nonhuman primates. In addition, we conclude that the cynomolgus macaque is a useful nonhuman primate model for the study of molecular events contributing to acute pharyngitis caused by GAS.

  5. A locus of group A Streptococcus involved in invasive disease and DNA transfer.

    Science.gov (United States)

    Hidalgo-Grass, Carlos; Ravins, Miriam; Dan-Goor, Mary; Jaffe, Joseph; Moses, Allon E; Hanski, Emanuel

    2002-10-01

    Group A streptococcus (GAS) causes diseases ranging from benign to severe infections such as necrotizing fasciitis (NF). The reasons for the differences in severity of streptococcal infections are unexplained. We developed the polymorphic-tag-lengths-transposon-mutagenesis (PTTM) method to identify virulence genes in vivo. We applied PTTM on an emm14 strain isolated from a patient with NF and screened for mutants of decreased virulence, using a mouse model of human soft-tissue infection. A mutant that survived in the skin but was attenuated in its ability to reach the spleen and to cause a lethal infection was identified. The transposon was inserted into a small open reading frame (ORF) in a locus termed sil, streptococcal invasion locus. sil contains at least five genes (silA-E) and is highly homologous to the quorum-sensing competence regulons of Streptococcus pneumoniae. silA and silB encode a putative two-component system whereas silD and silE encode two putative ABC transporters. silC is a small ORF of unknown function preceded by a combox promoter. Insertion and deletion mutants of sil had a diminished lethality in the animal model. Virulence of a deletion mutant of silC was restored when injected together with the avirulent emm14-deletion mutant, but not when these mutants were injected into opposite flanks of a mouse. DNA transfer between these mutants occurred in vivo but could not account for the complementation of virulence. DNA exchange between the emm14-deletion mutant and mutants of sil occurred also in vitro, at a frequency of approximately 10-8 for a single antibiotic marker. Whereas silC and silD mutants exchanged markers with the emm14 mutant, silB mutant did not. Thus, we identified a novel locus, which controls GAS spreading into deeper tissues and could be involved in DNA transfer.

  6. Expression and Immunoreactivity of a Human Group A Rotavirus Vp4

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Rotavirus capsid protein Vp4 plays an important role in the virus adhering and entering the cells. In this study, a Vp4 gene cloned from a rotavirus strain TB-Chen was highly expressed in E.coli BL21 (DE3). The results of the Western blot showed that the protein possesses specific immuno-reactivities and can be specifically recognized by guinea pig antibodies against rotavirus strain SA11 or Wa. Some Vp4 dimers were formed during renaturation. These data obtained from this study provide a strong basis for further study on the structure and function of the Vp4.

  7. Synthesis of dopamine analogue containing benzeneboronic acid group, a target compound for BNCT

    Energy Technology Data Exchange (ETDEWEB)

    Mizuno, T.; Yoshino, K. [Shinshu Univ., Faculty of Science, Matsumoto, Nagano (Japan); Hiratsuka, J. [Kawasaki Medical School, Dept. of Radiation Oncology, Kurashiki, Okayama (Japan); Ichihashi, M. [Kobe Univ. (Japan). School of Medicine

    2000-10-01

    Melanin synthesis is accentuated in the melanoma cells. DOPA is one of the melanin precursors, and has been found to be the substrates for tyrosinase. Since Dopamine has the similar structure to DOPA, we have thought that the Dopamine containing boron atom has a possibility to be incorporated into the melanin synthesis pathway, resulting in both higher {sup 10}B-delivery and long lasting {sup 10}B-accumulation in melanoma. Thus, we tried to synthesize a new amide compound between Dopamine and p-carboxybenzeneboronic acid (PCBA). (author)

  8. MiT family translocation renal cell carcinoma.

    Science.gov (United States)

    Argani, Pedram

    2015-03-01

    The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Erythromycin-resistant genes in group A β-haemolytic Streptococci in Chengdu, Southwestern China

    Directory of Open Access Journals (Sweden)

    W Zhou

    2014-01-01

    Full Text Available Context: The management of Group A β-haemolytic Streptococci (Streptococcus pyogenes or GAS infection include the use of penicillins, cephalosporins or macrolides for treatment. A general increase in macrolides resistance in GAS has been observed in recent years. Differences in rates of resistance to these agents have existed according to geographical location and investigators. Aims: To investigate the antibiotic pattern and erythromycin-resistant genes of GAS isolates associated with acute tonsillitis and scarlet fever in Chengdu, southwestern China. Settings and Design: To assess the macrolide resistance, phenotype, and genotypic characterization of GAS isolated from throat swabs of children suffering from different acute tonsillitis or scarlet fever between 2004 and 2011 in the city of Chengdu, located in the southwestern region of China. Materials and Methods: Minimal inhibitory concentration with seven antibiotics was performed on 127 GAS isolates. Resistance phenotypes of erythromycin-resistant GAS isolates were determined by the double-disk test. Their macrolide-resistant genes (mefA, ermB and ermTR were amplified by PCR. Results: A total of 98.4% (125/127 of the isolates exhibited resistance to erythromycin, clindamycin and tetracycline. All isolates were sensitive to penicillin G and cefotaxime. Moreover, 113 ermB-positive isolates demonstrating the cMLS phenotype of erythromycin resistance were predominant (90.4% and these isolates showed high-level resistance to both erythromycin and clindamycin (MIC 90 > 256 μg/ml; 12 (9.6% isolates demonstrating the MLS phenotype of erythromycin resistance carried the mefA gene, which showed low-level resistance to both erythromycin (MIC 90 = 8 μg/ml and clindamycin (MIC 90 = 0.5 μg/ml; and none of the isolates exhibited the M phenotype. Conclusions: The main phenotype is cMLS, and the ermB gene code is the main resistance mechanism against macrolides in GAS. Penicillin is the most beneficial

  10. An emm5 Group A Streptococcal Outbreak Among Workers in a Factory Manufacturing Telephone Accessories.

    Science.gov (United States)

    Chen, Mingliang; Wang, Wenqing; Tu, Lihong; Zheng, Yaxu; Pan, Hao; Wang, Gangyi; Chen, Yanxin; Zhang, Xi; Zhu, Linying; Chen, Jian; Chen, Min

    2017-01-01

    Ranked among the top10 infectious causes of death worldwide, group A Streptococcus (GAS) causes small- and large-scale outbreaks, depending on the trigger as transmission of a GAS strain or expansion of predominant clones. In China, GAS infections other than scarlet fever are not notifiable. In Shanghai, an epidemiological investigation was initiated after two successive severe pneumonia cases with one death in a digital factory, from where outbreaks are less widely reported. The investigation was performed using emm typing, pulsed-field gel electrophoresis (PFGE) typing, superantigen profiling, and genome analysis. This enabled characterization of relatedness among the outbreak isolates and identification of the mobile genetic elements present. Among 57 patients with respiratory symptoms investigated in the factory, emm5 GAS strains were isolated from 8 patients. The eight GAS infection cases comprising one fatal severe pneumonia case, six influenza-like illness cases, and one pharyngitis case. Two risk factors were identified: adult with an age of 18-20 years and close contact with a GAS patient or carrier. GAS attack rate was 14.0% (8/57), and GAS carriage rate was probably around 2.7% (14/521) based on surveys in two nearby districts. All the 10 outbreak associated isolates were assigned to emm5 and sequence type ST-99 (emm5/ST-99), harbored superantigen genes speC, speG, and smeZ, and were assigned to two similar PFGE patterns (clones). Among the outbreak associated isolates, all carried ermA with resistance to erythromycin and inducible resistance to clindamycin, and eight (80%) carried a tetM gene with resistance to tetracycline. Among the 14 carriage isolates, 12 were emm12/ST-36, and 2 were emm1/ST-28, all with superantigen genes speC, speG, ssa, and smeZ. All the carriage isolates harbored ermB and tetM with resistance to erythromycin, clindamycin, and tetracycline. Genome analysis showed the two outbreak clones were closely related and possessed new

  11. Preferences for health outcomes associated with Group A Streptococcal disease and vaccination

    Directory of Open Access Journals (Sweden)

    Gay Charlene

    2010-03-01

    Full Text Available Abstract Background A 26-valent Group A Streptococcus (GAS vaccine candidate has been developed that may provide protection against pharyngitis, invasive disease and rheumatic fever. However, recommendations for the use of a new vaccine must be informed by a range of considerations, including parents' preferences for different relevant health outcomes. Our objectives were to: (1 describe parent preferences for GAS disease and vaccination using willingness-to-pay (WTP and time trade-off (TTO methods; and (2 understand how parents' implied WTP for a quality-adjusted life year (QALY gained might vary depending on the particular health outcome considered (e.g. averted GAS disease vs. vaccine adverse events. Methods Telephone interviews were conducted with parents of children diagnosed with GAS pharyngitis at 2 pediatric practice sites in the Boston metropolitan area. WTP and TTO (trading parental longevity for child's health questions for 2 vaccine and 4 disease-associated health states were asked using a randomly selected opening bid, followed by a 2nd bid and a final open-ended question about the amount willing to pay or trade. Descriptive analyses included medians and interquartile ranges for WTP and TTO estimates. The Wilcoxon signed-rank test was used to assess differences in WTP/QALY values for vaccine adverse events vs. disease states. Results Of 119 respondents, 100 (84% and 96 (81% provided a complete set of responses for WTP and TTO questions, respectively. The median WTP and discounted (at 3% per year TTO values to avoid each health state were as follows: local reaction, $30, 0.12 days; systemic reaction, $50, 0.22 days; impetigo, $75, 1.25 days; strep throat, $75, 2.5 days; septic arthritis, $1,000, 6.6 days; and toxic shock syndrome, $3,000, 31.0 days. The median WTP/QALY was significantly higher for vaccine adverse events (~$60,000/QALY compared to disease states ($18,000 to $36,000/QALY. Conclusions Parents strongly prefer to prevent

  12. Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors.

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    David Ermert

    2015-07-01

    Full Text Available Streptococcus pyogenes, also known as Group A Streptococcus (GAS, is an important human bacterial pathogen that can cause invasive infections. Once it colonizes its exclusively human host, GAS needs to surmount numerous innate immune defense mechanisms, including opsonization by complement and consequent phagocytosis. Several strains of GAS bind to human-specific complement inhibitors, C4b-binding protein (C4BP and/or Factor H (FH, to curtail complement C3 (a critical opsonin deposition. This results in diminished activation of phagocytes and clearance of GAS that may lead to the host being unable to limit the infection. Herein we describe the course of GAS infection in three human complement inhibitor transgenic (tg mouse models that examined each inhibitor (human C4BP or FH alone, or the two inhibitors together (C4BPxFH or 'double' tg. GAS infection with strains that bound C4BP and FH resulted in enhanced mortality in each of the three transgenic mouse models compared to infection in wild type mice. In addition, GAS manifested increased virulence in C4BPxFH mice: higher organism burdens and greater elevations of pro-inflammatory cytokines and they died earlier than single transgenic or wt controls. The effects of hu-C4BP and hu-FH were specific for GAS strains that bound these inhibitors because strains that did not bind the inhibitors showed reduced virulence in the 'double' tg mice compared to strains that did bind; mortality was also similar in wild-type and C4BPxFH mice infected by non-binding GAS. Our findings emphasize the importance of binding of complement inhibitors to GAS that results in impaired opsonization and phagocytic killing, which translates to enhanced virulence in a humanized whole animal model. This novel hu-C4BPxFH tg model may prove invaluable in studies of GAS pathogenesis and for developing vaccines and therapeutics that rely on human complement activation for efficacy.

  13. Bovine coronavirus detection in a collection of diarrheic stool samples positive for group a bovine rotavirus

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    Aline Fernandes Barry

    2009-11-01

    Full Text Available Neonatal diarrhea is an important cause of economic losses for cattle farmers. The main viral etiologies of enteric diseases are group A rotaviruses (GARV and the bovine coronavirus (BCoV. Although both viruses infect calves of the same age, the occurrence of mixed infections is still under studied. The present study describes the co-infection of BCoV and GARV in stool samples. Forty-four diarrheic fecal samples from calves up to 60 days old that had previously tested positive for GARV by SS-PAGE were analyzed using semi-nested PCR for BCoV. A product with 251 bp of the BCoV nucleoprotein gene was amplified in 15.9% (7/44 of the samples, demonstrating that co-infection is not an unusual event. These results reinforce the need for testing for both GARV and BCoV, even in fecal samples that previously tested positive for one virus.A diarreia neonatal é uma importante causa de perdas econômicas para a criação de bovinos. Os principais agentes etiológicos virais das doenças entéricas são o rotavírus bovino grupo A (GARV e o coronavírus bovino (BCoV. Embora ambos os vírus infectem bezerros na mesma faixa etária, infecções mistas ainda são pouco estudadas. O presente trabalho descreve a identificação do BCoV em amostras de fezes positivas para o GARV, caracterizando a ocorrência de infecções mistas. Quarenta e quatro amostras de fezes diarreicas de bezerros com até 60 dias de idade, previamente identificadas como positivas para o GARV bovino por meio da técnica de SS-PAGE, foram avaliadas quanto a presença do BCoV pela técnica de semi-nested PCR. Um produto com 251 pb do gene da nucleoproteína do BCoV foi amplificado em 15,9% (7/44 das amostras de fezes demonstrando que a co-infecção não é um evento raro. Esse resultado enfatizada a importância da realização simultânea do diagnóstico para esses dois importantes vírus entéricos de bezerros em surtos de diarreia neonatal tanto em rebanhos bovinos leiteiros quanto de

  14. Checkpoint Kinase ATR Promotes Nucleotide Excision Repair of UV-induced DNA Damage via Physical Interaction with Xeroderma Pigmentosum Group A*

    Science.gov (United States)

    Shell, Steven M.; Li, Zhengke; Shkriabai, Nikolozi; Kvaratskhelia, Mamuka; Brosey, Chris; Serrano, Moises A.; Chazin, Walter J.; Musich, Phillip R.; Zou, Yue

    2009-01-01

    In response to DNA damage, eukaryotic cells activate a series of DNA damage-dependent pathways that serve to arrest cell cycle progression and remove DNA damage. Coordination of cell cycle arrest and damage repair is critical for maintenance of genomic stability. However, this process is still poorly understood. Nucleotide excision repair (NER) and the ATR-dependent cell cycle checkpoint are the major pathways responsible for repair of UV-induced DNA damage. Here we show that ATR physically interacts with the NER factor Xeroderma pigmentosum group A (XPA). Using a mass spectrometry-based protein footprinting method, we found that ATR interacts with a helix-turn-helix motif in the minimal DNA-binding domain of XPA where an ATR phosphorylation site (serine 196) is located. XPA-deficient cells complemented with XPA containing a point mutation of S196A displayed a reduced repair efficiency of cyclobutane pyrimidine dimers as compared with cells complemented with wild-type XPA, although no effect was observed for repair of (6-4) photoproducts. This suggests that the ATR-dependent phosphorylation of XPA may promote NER repair of persistent DNA damage. In addition, a K188A point mutation of XPA that disrupts the ATR-XPA interaction inhibits the nuclear import of XPA after UV irradiation and, thus, significantly reduced DNA repair efficiency. By contrast, the S196A mutation has no effect on XPA nuclear translocation. Taken together, our results suggest that the ATR-XPA interaction mediated by the helix-turn-helix motif of XPA plays an important role in DNA-damage responses to promote cell survival and genomic stability after UV irradiation. PMID:19586908

  15. The group A3 chondrules of Krymka: Further evidence for major evaporative loss during the formation of chondrules

    Science.gov (United States)

    Huang, S.; Benoit, P. H.; Sears, D. W. G.

    1993-01-01

    Like Semarkona (type 3.0), Krymka (type 3.1) contains two distinct types of chondrule (namely groups A and B) which differ in their bulk compositions, phase compositions, and CL properties. The group A chondrules in both meteorites show evidence for major loss of material by evaporation(i.e. elemental abundance patterns, size, redox state, olivine-pyroxene abundances). Group A and B chondrules probably formed from common or very similar precursors by the same processes acting with different intensities, group A suffering greater mass-loss by evaporation and reduction of FeO and SiO2. While Krymka chondrules share many primary mineralogical and compositional properties with Semarkona chondrules, the minimal metamorphism it has suffered has also had a significant effect on its chondrules.

  16. Perbandingan Daya Hambat Madu Alami dengan Madu Kemasan secara In Vitro terhadap Streptococcus beta hemoliticus Group A sebagai Penyebab Faringitis

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    Elsi Wineri

    2014-09-01

    Full Text Available AbstrakMadu merupakan substansi alam yang dihasilkan oleh lebah yang diketahui memiliki manfaat, salah satunya untuk mengobati faringitis yang disebabkan Streptococcus beta hemoliticus Group A. Efek antibakteri dari madu dapat menghambat pertumbuhan  Streptococcus beta hemoliticus Group A. Berdasarkan cara pembuatannya madu terdiri dari madu alami dan madu kemasan. Penelitian ini bertujuan untuk mengetahui perbedaan daya hambat madu alami dengan madu kemasan secara in vitro terhadap Streptococcus beta hemoliticus Group A. sebagai penyebab faringitis. Jenis penelitian ini adalah eksperimental dengan rancangan posttest only control group design yang dilaksanakan dari September sampai Desember 2013 di laboratorium Mikrobiologi Fakultas Kedokteran Universitas Andalas. Hasil penelitian menunjukan madu alami dan madu kemasan dapat menghambat pertumbuhan Streptococcus beta hemoliticus Group A dengan diameter daya hambat terbesar pada madu alami adalah 14 mm dan madu kemasan 11 mm. Berdasarkan uji analisis Kruskal-Wallis yang dilanjutkan dengan post-hoc Mann-Whitney terdapat perbedaan yang signifikan antara daya hambat  madu alami dengan madu kemasan dengan nilaip=0,004 (p<0,05. Kesimpulan hasil penelitian adalah madu alami dan madu kemasan memiliki daya hambat terhadap pertumbuhan Streptococcus beta hemoliticus Group A. Madu alami memiliki daya hambat yang lebih kuat dibandingkan madu kemasan.Kata kunci: madu alami, madu kemasan, Streptococcus beta hemoliticus Group A, antibakteri, faringitis AbstractHoney is a natural substance that produced by bees which is known have many benefits, one of them is to treat pharyngitis that caused by Streptococcus beta hemoliticus Group A. The antibacterial effect of honey can inhibit bacterial growth. By way of making, honey is divided to natural honey dan packing honey. The purpose of this study was to see comparison of the antibacterial effect of natural honey and packing honey againt Streptococcus beta

  17. Molecular epidemiology of the human group A rotavirus in the Paraná State, Brazil

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    Jucélia Stadinicki dos Santos

    2008-04-01

    Full Text Available From January/2000 to December/2003, 550 diarrheic fecal samples from the children and adults were collected in several geographical regions of Paraná State, Brazil. The enzyme immunoassay showed 120 (21.8% samples positive for the group A rotaviruses. One hundred and fourteen samples were genotyped by multiplex-nested-PCR assay. The highest frequency (77.5% of the positive samples (n=93 was observed in the children under 5 years old. Rotavirus diarrhea was more frequent in the cold and dry seasons of the four evaluated years. The most frequent genotypes were: G1 (50.9%, G4 (9.6%, G9 (7.0%, G2 (1.7%, G3 (0.9%, P[ 8] (71.9%, and P[ 4] (3.5%. The P[ 8] G1 (46.5% and P[ 8] G4 (9.6% were the main combinations found to P and G genotypes. The mixed infections, characterized by the rotaviruses with more than one genotype G or P, and nontypeable rotavirus were observed in 8.8, 3.5, and 16.7% of the samples, respectively. The identification of the G9 genotype in the rotavirus strains tested along the four years of studies ratifies the emergency of this genotype also in Paraná State, South region of Brazil, as the worldwide.No período de janeiro de 2000 a dezembro de 2003 foram colhidas, em várias regiões geográficas do Estado do Paraná, 550 amostras fecais de crianças e adultos com quadro clínico de diarréia aguda. Por meio de ensaio imunoenzimático comercial, 120 (21,8% amostras foram positivas para o rotavírus grupo A. Dessas, 114 amostras foram genotipadas por meio da multiplex-nested-PCR. A maior freqüência (77,5% de amostras positivas (n=93 foi observada em crianças menores de cinco anos de idade. A maior concentração de casos positivos para o rotavírus ocorreu nos meses frios e secos dos quatro anos avaliados. Os genotipos de maior ocorrência foram: G1 (50,9%, G4 (9,6%, G9 (7,0%, G2 (1,7%, G3 (0,9%, P[ 8] (71,9% e P[ 4] (3,5%. P[ 8] G1 (46,5% e P[ 8] G4 (9,6% foram as associações de genotipos P e G mais encontradas. Infec

  18. Prognostic Factors for Renal Cell Carcinoma Subtypes Diagnosed According to the 2016 WHO Renal Tumor Classification: a Study Involving 928 Patients.

    Science.gov (United States)

    Kuthi, Levente; Jenei, Alex; Hajdu, Adrienn; Németh, István; Varga, Zoltán; Bajory, Zoltán; Pajor, László; Iványi, Béla

    2017-07-01

    The morphotype and grade of renal cell carcinoma (RCC) in 928 nephrectomies were reclassified according to the 2016 WHO classification in order to analyze the distribution and outcomes of RCC subtypes in Hungary, to assess whether microscopic tumor necrosis is an independent prognostic factor in clear cell RCC, and to study whether a two-tiered grading (low/high) for clear cell and papillary RCC provides similar prognostic information to that of the four-tiered ISUP grading system. 83.4% of the cohort were clear cell, 6.9% papillary, 4.5% chromophobe, 2.3% unclassified, 1.1% Xp11 translocation, 1.1% clear cell papillary, 0.3% collecting duct and 0.1% mucinous tubular and spindle cell RCCs. RCC occurred in 16 patients with end-stage kidney disease and none of them displayed features of acquired cystic kidney disease-associated RCC. The 5-year survival rates were as follows: chromophobe 100%, clear cell papillary 100%, clear cell low-grade 96%, papillary type 1 92%, clear cell high-grade 63%, papillary type 2 65%, unclassified 46%, Xp11 translocation 20%, and collecting duct 0%. The 5-year survival rates in low-grade and high-grade papillary RCC were 95% and 59%, respectively. In clear cell RCC, only the grade, the stage and the positive surgical margin proved to be independent prognostic factors statistically. Overall, papillary RCC occurred relatively infrequently; microscopic tumor necrosis in clear cell RCC did not predict the outcome independently of the tumor grading; and the assignment of clear cell and papillary RCCs into low-grade or high-grade tumors was in terms of survival no worse than the ISUP grading.

  19. "Love's labours lost": failure to implement mass vaccination against group A meningococcal meningitis in sub-Saharan Africa.

    Science.gov (United States)

    Robbins, J B; Towne, D W; Gotschlich, E C; Schneerson, R

    1997-09-20

    Despite the availability of a safe, effective polysaccharide vaccine, group A meningococcal meningitis epidemics persist in sub-Saharan Africa. In October 1996, there were almost 150,000 reported cases and 15,000 deaths, the majority of which involved children. At 3 months of age, induction of protective group A meningococcal antibody levels requires 2 injections at least 1 month apart. Reinjection of 5-year-old children increases group A antibodies to long-term protective levels. During meningitis epidemics in Nigeria, Mali, and Rwanda, fatality was significantly reduced in areas where scarce vaccine was administered selectively. Although effective on an individual basis, selective vaccination is unable to control meningitis epidemics. In Chad, mass vaccination of the entire population (excluding infants under 12 months) eliminated the disease. Successful mass vaccination against group A meningococcal epidemics also has been reported in Saudi Arabia, China, and refugee camps in Africa. Although cost is cited as an obstacle to routine mass vaccination to prevent meningococcal meningitis in South Africa, prevention is the least expensive approach to disease control. It is recommended that the entire population of Africa's meningitis belt receive group A meningococcal vaccine in accordance with the recommended age schedule in a mass vaccination program.

  20. Pyogenic knee arthritis caused by group A β-hemolytic Streptococcus: a toxic shock-prevented case.

    Science.gov (United States)

    Goto, Masafumi; Gotoh, Masafumi; Mitsui, Yasuhiro; Shibata, Hideaki; Okawa, Takahiro; Higuchi, Fujio; Shiba, Naoto

    2014-01-01

    Pyogenic knee arthritis caused by group A β-hemolytic Streptococcus (GAS) is rare. GAS sometimes causes group A β-hemolytic streptococcal toxic shock syndrome. We encountered a case of pyogenic knee arthritis caused by GAS that resolved after appropriate treatment (emergency arthroscopic synovectomy and medication) administered within 48 h of onset. In cases of a history of another infection with acute knee joint pain, the possibility of GAS-induced pyogenic knee arthritis should be considered, and proper treatment should be administered immediately.

  1. Development of primers for sequencing the NSP1, NSP3, and VP6 genes of the group A porcine rotavirus

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    Fernanda Dornelas Florentino Silva

    2014-02-01

    Full Text Available Rotavirus is the causative pathogen of diarrhea in humans and in several animal species. Eight pairs of primers were developed and used for Sanger sequencing of the coding region of the NSP1, NSP3, and VP6 genes based on the conserved regions of the genome of the group A porcine rotavirus. Three samples previously screened as positive for group A rotaviruses were subjected to gene amplification and sequencing to characterize the pathogen. The information generated from this study is crucial for the understanding of the epidemiology of the disease.

  2. Respiratory syncytial virus groups A and B in Porto Alegre, Brazil, from 1990 to 1995 and 1998

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    Straliotto Selir M

    2001-01-01

    Full Text Available We analyzed the respiratory syncytial virus (RSV groups and their epidemiological pattern that were detected over the course of seven years in southern Brazil. The two RSV groups co-circulated each year, but frequencies of groups A and B varied both between and within yearly outbreaks. In 1991, group A predominated over group B (p=0.0016. RSV outbreaks analyzed showed a temperature-dependent pattern and no association with rainfall, similarly to other countries from southern South America. Knowledge of the variants is important in terms of both diagnosis and definition of a vaccine composition.

  3. Divergence in the plasminogen-binding group a streptococcal M protein family: functional conservation of binding site and potential role for immune selection of variants.

    Science.gov (United States)

    Sanderson-Smith, Martina; Batzloff, Michael; Sriprakash, Kabada S; Dowton, Mark; Ranson, Marie; Walker, Mark J

    2006-02-10

    Group A streptococci (GAS) display receptors for the human zymogen plasminogen on the cell surface, one of which is the plasminogen-binding group A streptococcal M protein (PAM). Characterization of PAM genes from 12 GAS isolates showed significant variation within the plasminogen-binding repeat motifs (a1/a2) of this protein. To determine the impact of sequence variation on protein function, recombinant proteins representing five naturally occurring variants of PAM, together with a recombinant M1 protein, were expressed and purified. Equilibrium dissociation constants for the interaction of PAM variants with biotinylated Glu-plasminogen ranged from 1.58 to 4.99 nm. Effective concentrations of prototype PAM required for 50% inhibition of plasminogen binding to immobilized PAM variants ranged from 0.68 to 22.06 nm. These results suggest that although variation in the a1/a2 region of the PAM protein does affect the comparative affinity of PAM variants, the functional capacity to bind plasminogen is conserved. Additionally, a potential role for the a1 region of PAM in eliciting a protective immune response was investigated by using a mouse model for GAS infection. The a1 region of PAM was found to protect immunized mice challenged with a PAM-positive GAS strain. These data suggest a link between selective immune pressure against the plasminogen-binding repeats and the functional conservation of the binding domain in PAM variants.

  4. High mobility group A-interacting proteins in cancer: focus on chromobox protein homolog 7, homeodomain interacting protein kinase 2 and PATZ

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    Monica Fedele

    2012-03-01

    Full Text Available The High Mobility Group A (HMGA proteins, a family of DNA architectural factors, by interacting with different proteins play crucial roles in neoplastic transformation of a wide range of tissues. Therefore, the search for HMGA-interacting partners was carried out by several laboratories in order to investigate the mechanisms underlying HMGA-dependent tumorigenesis. Three of the several HMGA-binding proteins are discussed in this review. These are the Chromobox family protein (chromobox protein homolog 7, CBX7, the homeodomain interacting protein kinase 2 (HIPK2 and the POZ/domain and Kruppel zinc finger family member, PATZ. All of them play a critical role in tumorigenesis, and may also be independent markers of cancer. Their activities are linked to cell cycle, apoptosis and senescence. In this review, we discuss the properties of each protein, including their effect on HMGA1 functions, and propose a model accounting for how their activities might be coordinated.

  5. Characterization of streptokinases from group A Streptococci reveals a strong functional relationship that supports the coinheritance of plasminogen-binding M protein and cluster 2b streptokinase.

    Science.gov (United States)

    Zhang, Yueling; Liang, Zhong; Hsueh, Hsing-Tse; Ploplis, Victoria A; Castellino, Francis J

    2012-12-07

    Group A streptococcus (GAS) strains secrete the protein streptokinase (SK), which functions by activating host human plasminogen (hPg) to plasmin (hPm), thus providing a proteolytic framework for invasive GAS strains. The types of SK secreted by GAS have been grouped into two clusters (SK1 and SK2) and one subcluster (SK2a and SK2b). SKs from cluster 1 (SK1) and cluster 2b (SK2b) display significant evolutionary and functional differences, and attempts to relate these properties to GAS skin or pharynx tropism and invasiveness are of great interest. In this study, using four purified SKs from each cluster, new relationships between plasminogen-binding group A streptococcal M (PAM) protein and SK2b have been revealed. All SK1 proteins efficiently activated hPg, whereas all subclass SK2b proteins only weakly activated hPg in the absence of PAM. Surface plasmon resonance studies revealed that the lower affinity of SK2b to hPg served as the basis for the attenuated activation of hPg by SK2b. Binding of hPg to either human fibrinogen (hFg) or PAM greatly enhanced activation of hPg by SK2b but minimally influenced the already effective activation of hPg by SK1. Activation of hPg in the presence of GAS cells containing PAM demonstrated that PAM is the only factor on the surface of SK2b-expressing cells that enabled the direct activation of hPg by SK2b. As the binding of hPg to PAM is necessary for hPg activation by SK2b, this dependence explains the coinherant relationship between PAM and SK2b and the ability of these particular strains to generate the proteolytic activity that disrupts the innate barriers that limit invasiveness.

  6. Necrotizing Fasciitis Resulting from Human Bites: A Report of Two Cases of Disease Caused by Group A Streptococci

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    Christopher A Sikora

    2005-01-01

    Full Text Available Necrotizing fasciitis is a serious and potentially life-threatening condition. Although bite wounds are common, they are not frequently reported as a cause of necrotizing fasciitis. In the present article, two cases of bite-associated necrotizing fasciitis caused by group A streptococcus are reported. Previously published cases are also reviewed.

  7. Invasive group A streptococcal disease in The Netherlands : Evidence for a protective role of anti-exotoxin A antibodies

    NARCIS (Netherlands)

    Mascini, EM; Jansze, M; Schellekens, JFP; Musser, JM; Faber, JAJ; Verhoef-Verhage, LAE; Schouls, L; van Leeuwen, WJ; Verhoef, J; van Dijk, H

    As part of a nationwide surveillance in The Netherlands during 1994-1997, 53 patients with invasive group A streptococcal (GAS) infections were evaluated for medical history, symptoms, and outcome. Patients' isolates were tested for the production of pyrogenic exotoxins A (SPE-A) and B (SPE-B).

  8. Inference of Antibiotic Resistance and Virulence Among Diverse Group A Streptococcus Strains Using emm Sequencing and Multilocus Genotyping Methods

    Science.gov (United States)

    2009-09-04

    pneumonia . Less frequently, it can cause severe symptoms such as toxic shock syndrome, necrotizing fasciitis, and sterile rheumatic sequelae [1]. Penicillin ... Pneumonia outbreak associated with group A Streptococcus at a military training facility. Clin Infect Dis 40: 511–518. 17. Lamagni TL, Neal S, Keshishian C...Macrolide resistance and erythromycin resistance determinants among Belgian Streptococcus pyogenes and Streptococcus pneumoniae isolates. J Antimicrob

  9. Molecular epidemiology of the sil streptococcal invasive locus in group A streptococci causing invasive infections in French children.

    Science.gov (United States)

    Bidet, Philippe; Courroux, Céline; Salgueiro, Christophe; Carol, Agnès; Mariani-Kurkdjian, Patricia; Bonacorsi, Stéphane; Bingen, Edouard

    2007-06-01

    We found 31 different emm-toxin genotypes among 74 group A streptococcal isolates causing invasive infections in French children. The predominant emm types were emm1 (25%), emm3 (8%), emm4 (8%), emm6 (7%), and emm89 (9%). Sixteen percent of isolates harbored the streptococcal invasive locus, half of them belonging to emm4.

  10. Clinical and Microbiological Characteristics of Invasive Group A Streptococcal Infections Before and After Implementation of a Universal Varicella Vaccine Program.

    Science.gov (United States)

    Frère, Julie; Bidet, Philippe; Tapiéro, Bruce; Rallu, Fabien; Minodier, Philippe; Bonacorsi, Stephane; Bingen, Edouard; Ovetchkine, Philippe

    2016-01-01

    Since the introduction of the varicella vaccine to the routine immunization schedule, we have observed a 70% reduction in the rate of varicella-associated invasive group A streptococcal infections (IGASI). In the mean time, the clinical presentation of IGASI and microbiological characteristics of GAS strains have changed significantly.

  11. Invasive group A streptococcal disease in The Netherlands : Evidence for a protective role of anti-exotoxin A antibodies

    NARCIS (Netherlands)

    Mascini, EM; Jansze, M; Schellekens, JFP; Musser, JM; Faber, JAJ; Verhoef-Verhage, LAE; Schouls, L; van Leeuwen, WJ; Verhoef, J; van Dijk, H

    2000-01-01

    As part of a nationwide surveillance in The Netherlands during 1994-1997, 53 patients with invasive group A streptococcal (GAS) infections were evaluated for medical history, symptoms, and outcome. Patients' isolates were tested for the production of pyrogenic exotoxins A (SPE-A) and B (SPE-B). Acut

  12. Invasive group A streptococcal diseases and pyrogenic exotoxins A and B : an update on pathogenesis and management

    NARCIS (Netherlands)

    Mascini, EM; Verhoef-Verhage, EAE; van Dijk, H

    2000-01-01

    Since the mid-1980s, there have been increasing numbers of reports on the resurgence of severe invasive group A streptococcal infections world-wide. Despite prompt therapy with penicillin and/or clindamycin, the mortality rates of these infections, including streptococcal toxic shock-like syndrome,

  13. EVALUATION OF THE MOST USED AGILE METHODS (XP, LEAN, SCRUM

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    BODJE N’KAUH NATHAN-REGIS

    2012-01-01

    Full Text Available With the emergence of Agile Software Development technologies, the software community is expecting in a large impact on producing quality. The Agile Software Development ideas were presentedin the form of Agile Manifesto which consists of four values and twelve principles. Toyota System production, set also a series of principles and practices which has lead Toyota Motor Corporationcommonly known simply as Toyota (multinational automaker on the top of the car industry market by achieving a reputation for the production of very high quality vehicles in all countries around the world. The main question that each new technology must pass through with success is: How much it’s worth? This paper propose a model for determining the significance worth of quality into the most used agilemethods (eXtreme programming, Scrum, Lean inspired by the Toyota Production System(TPS.

  14. 04033 XP13512在亚洲上市

    Institute of Scientific and Technical Information of China (English)

    李雅娟(摘)

    2006-01-01

    美国Xenoport公司与日本Astellas Pharma公司就前者的主导产品加巴喷丁(gabapentin)前药XPl3512(Ⅰ)签署第一个许可协议。Astellas公司已经获得在日本和五个亚洲国家独家开发和上市这种持续释放化合物的权力。该协议价值达2千5百万,给了Xenoport公司。进一步开发的总价值将达6千万美元,包括支付(Ⅰ)用于不安定腿综合征的Xenoport的美国Ⅲ期试验,计划在2006年前半年开始。

  15. Immunochemical determination of an initial step in thymine dimer excision repair in xeroderma pigmentosum variant fibroblasts and biopsy material from the normal population and patients with basal cell carcinoma and melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Roth, M.; Mueller, H.B.; Boyle, J.M.

    1987-09-01

    A monoclonal antibody specific for u.v.-induced thymine-thymine dimers in single-stranded DNA has been used in an enzyme immunoassay to investigate the loss of antigenicity associated with repair of this lesion in the first 2 h following 10 J/m/sup 2/ 254 nm radiation. Variances of +/- 10% for the method and +/- 6.5% for individuals were established using primary cultures of biopsies from healthy individuals. No differences in the rate of loss of antigenicity was observed between 20 normal lymphocyte samples and 10 normal skin biopsies. Of three xeroderma pigmentosum (XP) variant cell lines tested, GM3617 could not be distinguished from normal cells but GM1227 and GM3053 showed lower rates of loss than any of the healthy samples. When the group mean values were compared there was no significant difference between normals and biopsies from sun-shielded skin areas from 16 basal cell carcinomas but similar material from 10 melanoma patients showed a significantly reduced (P = 0.001) rate of loss of antigenicity. Since the rate of loss of antigenicity in normal and XP variant cells reflected their relative abilities to perform unscheduled DNA synthesis, our results suggest that some melanoma patients may also have a minor deficiency in an early stage of excision repair.

  16. Group A Streptococcal Infections

    Science.gov (United States)

    ... of Award Clinical Terms of Award Restriction for China Clinical Terms Guidance Compliance Sample Letter Inclusion Codes ... Division of AIDS Division of Allergy, Immunology, and Transplantation Division of Microbiology and Infectious Diseases Division of ...

  17. Solvability of the Diophantine equations xp + 22m y4 = pk z2 and xp + y2 = pk z4

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    We study the solvability of two classes of Diophantine equations by using some new methods and new results in this paper.Letp be an odd prime and Bn denote nth Bernoulli number.We prove that ifp ≡ 1(mod 4)andp |B(p-1)/2,then the equationxp +22mn4 = pky2,m,n,k ∈ N ,k > 1,gcd(x,py)= 1,and the equationxp +y2 =pkz4,k ∈ N,gcd(x,y)= 1,k > 1,21 y have no integral solutions respectively.

  18. Fatal group A streptococcal necrotizing fasciitis and toxic shock syndrome in a patient with psoriasis and chronic renal impairment.

    Science.gov (United States)

    Chong, Alvin H; Burrows, Nigel P

    2002-08-01

    A 78-year-old woman presented with rapid onset of skin pain which evolved into oedema, discoloration and infarction. She was diagnosed with group A beta-haemolytic streptococcus (Streptococcus pyogenes) necrotizing fasciitis and streptococcal toxic shock syndrome. The patient had a past history of psoriasis and end-stage renal impairment. Despite treatment with multiple antibiotics in an intensive care unit, the skin infarction involving the upper trunk continued to expand and the patient died within 24 hours of hospital admission. Group A streptococcus and Staphylococcus aureus were cultured from a tissue biopsy. Renal failure and compromised skin barrier function are known to predispose to invasive streptococcal infections, but necrotizing fasciitis has only rarely been reported in association with psoriasis. This case illustrates the fulminant nature of the infection.

  19. Novel group A rotavirus G8 P[1] as primary cause of an ovine diarrheic syndrome outbreak in weaned lambs

    OpenAIRE

    Galindo-Cardiel, I.; Fernández-Jiménez, M.; Luján, L.; Buesa, J.; Espada, J.; Fantova, E.; Blanco, J; Segalés, J.; Badiola, J. J.

    2011-01-01

    Abstract Rotavirus is a worldwide major cause of diarrhea outbreaks in neonatal ruminants. An outbreak of ovine diarrheic syndrome (ODS) in 50-75 days-old lambs (weaned lambs) is described. Fecal immunochromatography and intestinal immunohistochemistry for rotavirus group A were performed. In addition, semi-nested multiplex RT-PCR for G and P rotavirus genotyping in combination with sequencing were performed, to support the diagnosis and identify the viral strain. A novel ovine rot...

  20. Conformational energy calculations and proton nuclear overhauser enhancements reveal a unique conformation for blood group A oligosaccharides

    Energy Technology Data Exchange (ETDEWEB)

    Bush, C.A.; Yan, Z.Y.; Rao, B.N.N.

    1986-10-01

    The H NMR spectra of a series of blood group A active oligosaccharides containing from four to ten sugar residues have been completely assigned, and quantitative nuclear Overhauser enhancements (NOE) have been measured between protons separated by known distances within the pyranoside ring. The observation of NOE between anomeric protons and those of the aglycon sugar as well as small effects between protons of distant rings suggests that the oligosaccharides have well-defined conformations. Conformational energy calculations were carried out on a trisaccharide, Fuc( -1 2)(GalNAc( -1 3))-GalUS -O-me, which models the nonreducing terminal fragments of the blood group A oligosaccharides. The results of calculations with three different potential energy functions which have been widely used in peptides and carbohydrates gave several minimum energy conformations. In NOE calculations from conformational models, the rotational correlation time was adjusted to fit T1's and intra-ring NOE. Comparison of calculated maps of NOE as a function of glycosidic dihedral angles showed that only a small region of conformational space was consistent with experimental data on a blood group A tetrasaccharide alditol. This conformation occurs at an energy minimum in all three energy calculations. Temperature dependence of the NOE implies that the oligosaccharides adopt single rigid conformations which do not change with temperature.

  1. Association between group A beta-haemolytic streptococci and vulvovaginitis in adult women: a case-control study.

    Science.gov (United States)

    Bruins, M J; Damoiseaux, R A M J; Ruijs, G J H M

    2009-08-01

    Guidelines for the management of vaginal discharge mention Candida albicans, Trichomonas vaginalis, bacterial vaginosis, Chlamydia trachomatis and Neisseria gonorrhoeae as causes and do not recommend full microbiological culture. The role of non-group B beta-haemolytic streptococci in vaginal cultures is unclear, except for group A streptococci that are known to cause vulvovaginitis in children. In a case-control study, we investigated the association between non-group B beta-haemolytic streptococci and vulvovaginitis in adult women. Cases were women with recurrent vaginal discharge from whom a sample was cultured. Controls were asymptomatic women who consented to submitting a vaginal swab. Group A streptococci were isolated from 49 (4.9%) of 1,010 cases and not from the 206 controls (P < 0.01). Isolation rates of group C, F and G streptococci were low and did not differ statistically between cases and controls. Group A beta-haemolytic streptococci are associated with vaginal discharge in adult women. The other non-group B streptococci require more study. For the adequate management of vaginal discharge, culturing is necessary if initial treatment fails. Guidelines should be amended according to these results.

  2. The Plasminogen-Binding Group A Streptococcal M Protein-Related Protein Prp Binds Plasminogen via Arginine and Histidine Residues▿

    Science.gov (United States)

    Sanderson-Smith, Martina L.; Dowton, Mark; Ranson, Marie; Walker, Mark J.

    2007-01-01

    The migration of the human pathogen Streptococcus pyogenes (group A streptococcus) from localized to deep tissue sites may result in severe invasive disease, and sequestration of the host zymogen plasminogen appears crucial for virulence. Here, we describe a novel plasminogen-binding M protein, the plasminogen-binding group A streptococcal M protein (PAM)-related protein (Prp). Prp is phylogenetically distinct from previously described plasminogen-binding M proteins of group A, C, and G streptococci. While competition experiments indicate that Prp binds plasminogen with a lower affinity than PAM (50% effective concentration = 0.34 μM), Prp nonetheless binds plasminogen with high affinity and at physiologically relevant concentrations of plasminogen (Kd = 7.8 nM). Site-directed mutagenesis of the putative plasminogen binding site indicates that unlike the majority of plasminogen receptors, Prp does not interact with plasminogen exclusively via lysine residues. Mutagenesis to alanine of lysine residues Lys96 and Lys101 reduced but did not abrogate plasminogen binding by Prp. Plasminogen binding was abolished only with the additional mutagenesis of Arg107 and His108 to alanine. Furthermore, mutagenesis of Arg107 and His108 abolished plasminogen binding by Prp despite the presence of Lys96 and Lys101 in the binding site. Thus, binding to plasminogen via arginine and histidine residues appears to be a conserved mechanism among plasminogen-binding M proteins. PMID:17012384

  3. The plasminogen-binding group A streptococcal M protein-related protein Prp binds plasminogen via arginine and histidine residues.

    Science.gov (United States)

    Sanderson-Smith, Martina L; Dowton, Mark; Ranson, Marie; Walker, Mark J

    2007-02-01

    The migration of the human pathogen Streptococcus pyogenes (group A streptococcus) from localized to deep tissue sites may result in severe invasive disease, and sequestration of the host zymogen plasminogen appears crucial for virulence. Here, we describe a novel plasminogen-binding M protein, the plasminogen-binding group A streptococcal M protein (PAM)-related protein (Prp). Prp is phylogenetically distinct from previously described plasminogen-binding M proteins of group A, C, and G streptococci. While competition experiments indicate that Prp binds plasminogen with a lower affinity than PAM (50% effective concentration = 0.34 microM), Prp nonetheless binds plasminogen with high affinity and at physiologically relevant concentrations of plasminogen (K(d) = 7.8 nM). Site-directed mutagenesis of the putative plasminogen binding site indicates that unlike the majority of plasminogen receptors, Prp does not interact with plasminogen exclusively via lysine residues. Mutagenesis to alanine of lysine residues Lys(96) and Lys(101) reduced but did not abrogate plasminogen binding by Prp. Plasminogen binding was abolished only with the additional mutagenesis of Arg(107) and His(108) to alanine. Furthermore, mutagenesis of Arg(107) and His(108) abolished plasminogen binding by Prp despite the presence of Lys(96) and Lys(101) in the binding site. Thus, binding to plasminogen via arginine and histidine residues appears to be a conserved mechanism among plasminogen-binding M proteins.

  4. Antimicrobial activity of essential oils and carvacrol, and synergy of carvacrol and erythromycin, against clinical, erythromycin-resistant Group A Streptococci.

    Directory of Open Access Journals (Sweden)

    Gloria eMagi

    2015-03-01

    Full Text Available In the present study, we have evaluated the in vitro antibacterial activity of essential oils from Origanum vulgare, Thymus vulgaris, Lavandula angustifolia, Mentha piperita, and Melaleuca alternifolia against 32 erythromycin-resistant [MIC ≥1 µg/mL; inducible, constitutive, and efflux-mediated resistance phenotype; erm(TR, erm(B, and mef(A genes] and cell-invasive Group A streptococci (GAS isolated from children with pharyngotonsillitis in Italy. Over the past decades erythromycin resistance in GAS has emerged in several countries; strains combining erythromycin resistance and cell invasiveness may escape β-lactams because of intracellular location and macrolides because of resistance, resulting in difficulty of eradication and recurrent pharyngitis. Thyme and origanum essential oils demonstrated the highest antimicrobial activity with MICs ranging from 256 to 512 µg/mL. The phenolic monoterpene carvacrol [2-Methyl-5-(1-methylethyl phenol] is a major component of the essential oils of Origanum and Thymus plants. MICs of carvacrol ranged from 64 to 256 µg/mL. In the live/dead assay several dead cells were detected as early as 1 h after incubation with carvacrol at the MIC. In single-step resistance selection studies no resistant mutants were obtained. A synergistic action of carvacrol and erythromycin was detected by the checkerboard assay and calculation of the FIC Index. A 2- to 2048-fold reduction of the erythromycin MIC was documented in checkerboard assays. Synergy (FIC Index ≤0.5 was found in 21/32 strains and was highly significant (p <0.01 in strains where resistance is expressed only in presence of erythromycin. Synergy was confirmed in 17/23 strains using 24-h time-kill curves in presence of carvacrol and erythromycin. Our findings demonstrated that carvacrol acts either alone or in combination with erythromycin against erythromycin-resistant GAS and could potentially serve as a novel therapeutic tool.

  5. Oral Immunization with a Recombinant Lactococcus lactis-Expressing HIV-1 Antigen on Group A Streptococcus Pilus Induces Strong Mucosal Immunity in the Gut.

    Science.gov (United States)

    Chamcha, Venkateswarlu; Jones, Andrew; Quigley, Bernard R; Scott, June R; Amara, Rama Rao

    2015-11-15

    The induction of a potent humoral and cellular immune response in mucosal tissue is important for the development of an effective HIV vaccine. Most of the current HIV vaccines under development use the i.m. route for immunization, which is relatively poor in generating potent and long-lived mucosal immune responses. In this article, we explore the ability of an oral vaccination with a probiotic organism, Lactococcus lactis, to elicit HIV-specific immune responses in the mucosal and systemic compartments of BALB/c mice. We expressed the HIV-1 Gag-p24 on the tip of the T3 pilus of Streptococcus pyogenes as a fusion to the Cpa protein (LL-Gag). After four monthly LL-Gag oral immunizations, we observed strong Gag-specific IgG and IgA responses in serum, feces, and vaginal secretions. However, the Gag-specific CD8 T cell responses in the blood were at or below our detection limit. After an i.m. modified vaccinia Ankara/Gag boost, we observed robust Gag-specific CD8 T cell responses both in systemic and in mucosal tissues, including intraepithelial and lamina propria lymphocytes of the small intestine, Peyer's patches, and mesenteric lymph nodes. Consistent with strong immunogenicity, the LL-Gag induced activation of CD11c(+) CD11b(+) dendritic cells in the Peyer's patches after oral immunization. Our results demonstrate that oral immunization with L. lactis expressing an Ag on the tip of the group A Streptococcus pilus serves as an excellent vaccine platform to induce strong mucosal humoral and cellular immunity against HIV.

  6. Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency.

    Directory of Open Access Journals (Sweden)

    Sander Barnhoorn

    2014-10-01

    Full Text Available As part of the Nucleotide Excision Repair (NER process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS, or the infantile lethal cerebro-oculo-facio-skeletal (COFS syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional Xpg-/- mouse model which -in a C57BL6/FVB F1 hybrid genetic background- displays many progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4-5 months. We show that deletion of XPG specifically in the liver reproduces the progeroid features in the liver, yet abolishes the effect on growth or lifespan. In addition, specific XPG deletion in neurons and glia of the forebrain creates a progressive neurodegenerative phenotype that shows many characteristics of human XPG deficiency. Our findings therefore exclude that both the liver as well as the neurological phenotype are a secondary consequence of derailment in other cell types, organs or tissues (e.g. vascular abnormalities and support a cell-autonomous origin caused by the DNA repair defect itself. In addition they allow the dissection of the complex aging process in tissue- and cell-type-specific components. Moreover, our data highlight the critical importance of genetic background in mouse aging studies, establish the Xpg-/- mouse as a valid model for the severe form of human XPG patients and segmental accelerated aging, and strengthen the link between DNA damage and aging.

  7. Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease XPG deficiency.

    Directory of Open Access Journals (Sweden)

    Sander Barnhoorn

    2014-10-01

    Full Text Available As part of the Nucleotide Excision Repair (NER process, the endonuclease XPG is involved in repair of helix-distorting DNA lesions, but the protein has also been implicated in several other DNA repair systems, complicating genotype-phenotype relationship in XPG patients. Defects in XPG can cause either the cancer-prone condition xeroderma pigmentosum (XP alone, or XP combined with the severe neurodevelopmental disorder Cockayne Syndrome (CS, or the infantile lethal cerebro-oculo-facio-skeletal (COFS syndrome, characterized by dramatic growth failure, progressive neurodevelopmental abnormalities and greatly reduced life expectancy. Here, we present a novel (conditional Xpg-/- mouse model which -in a C57BL6/FVB F1 hybrid genetic background- displays many progeroid features, including cessation of growth, loss of subcutaneous fat, kyphosis, osteoporosis, retinal photoreceptor loss, liver aging, extensive neurodegeneration, and a short lifespan of 4-5 months. We show that deletion of XPG specifically in the liver reproduces the progeroid features in the liver, yet abolishes the effect on growth or lifespan. In addition, specific XPG deletion in neurons and glia of the forebrain creates a progressive neurodegenerative phenotype that shows many characteristics of human XPG deficiency. Our findings therefore exclude that both the liver as well as the neurological phenotype are a secondary consequence of derailment in other cell types, organs or tissues (e.g. vascular abnormalities and support a cell-autonomous origin caused by the DNA repair defect itself. In addition they allow the dissection of the complex aging process in tissue- and cell-type-specific components. Moreover, our data highlight the critical importance of genetic background in mouse aging studies, establish the Xpg-/- mouse as a valid model for the severe form of human XPG patients and segmental accelerated aging, and strengthen the link between DNA damage and aging.

  8. Identifikasi Carrier Bakteri Streptococcus β hemolyticus Group A pada Murid SD Negeri 13 Padang Berdasarkan Perbedaan Umur dan Jenis Kelamin

    Directory of Open Access Journals (Sweden)

    Fadhila Aini

    2016-01-01

    Full Text Available AbstrakStreptococcus β hemolyticus Grup A atau yang disebut juga Streptococcus pyogenes merupakan salah satu bakteri patogen yang banyak menginfeksi manusia.Bakteri ini dapat ditemukan sebagai carrier di saluran pernafasan terutama pada anak-anak, tidak menimbulkan penyakit tetapi berisiko untuk menyebarkan penyakit. Tujuan penelitian ini adalah menentukan jumlah carrier  bakteri Streptococcus β hemolyticus Grup A pada murid berdasarkan perbedaan umur dan jenis kelamin. Jenis penelitian ini adalah deskriptif cross-sectional dengan menggunakan sampel seluruh murid SD Negeri 13 Padang. Hasil penelitian adalah didapatkan 2 orang murid yang menderita carrier, yaitu pada kelompok usia>8-9 tahun dan >11 tahun. Berdasarkan jenis kelamin yang terdiri dari 54 orang laki-laki dan 50 orang perempuan, didapatkan 2 orang carrier yaitu hanya pada anak laki-laki. Hasil penelitian menunjukkan bahwa carrier bakteri Streptococcus β hemolyticus Group  A terdapat pada anak usia tersebut karena masih kurangnya pengetahuan tentang kebersihan. Carrier yang ditemukan hanya pada anak laki-laki kemungkinan disebabkan mereka lebih sering bermain di luar rumah dan terpapar dengan berbagai bakteri patogen dan kurang memperhatikan kebersihan diri.Kata kunci: carrier, streptococcus β hemolyticus grup A, umur, jenis kelamin AbstractGroup A Streptococcus β hemolyticus or also called Streptococcus pyogenes is one of many pathogenic bacteria that infect humans. These bacteria can be found as a carrier in the respiratory tract especially in children, do not cause disease but can be a risk for spreading the disease. This objective of this study was to determine the amount of the carrier of bacteria group A Streptococcus β hemolyticus based on age and gender differences. This research is a descriptive cross - sectional study using a sample of all students of SD Negeri 13 Padang. Based on the age of 104 students found that students who suffer 2 carrier, which is in the age

  9. [Streptococcal toxic shock syndrome or Kawasaki disease? Two case studies of children with group A streptococcal pneumonia empyema].

    Science.gov (United States)

    Bosland, A; Arlaud, K; Rousset-Rouvière, C; Fouilloux, V; Paut, O; Dubus, J-C; Bosdure, E

    2011-12-01

    We report 2 cases of children with group A streptococcus pyogenes pleuropneumonia, in one child associated with Kawasaki disease and in the other with streptococcal toxic shock syndrome. These 2 features, with theoretically well-defined clinical and biological criteria, are difficult to differentiate in clinical practice, however, likely due to their pathophysiological links. In case of clinical doubt, an echocardiography needs to be performed to search for coronary involvement and treatment including intravenous immunoglobulins, and an antibiotic with an anti-toxin effect such as clindamycin has to be started early.

  10. Regulatory T cell memory

    OpenAIRE

    Rosenblum, Md; Way, SS; Abbas, AK

    2015-01-01

    © 2015 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. Memory for antigen is a defining feature of adaptive immunity. Antigen-specific lymphocyte populations show an increase in number and function after antigen encounter and more rapidly re-expand upon subsequent antigen exposure. Studies of immune memory have primarily focused on effector B cells and T cells with microbial specificity, using prime–challenge models of infection. However, recent work ...

  11. Balanced Tripartite Entanglement, the Alternating Group A4 and the Lie Algebra $sl(3,C) \\oplus u(1)$

    CERN Document Server

    Planat, Michel; Saniga, Metod

    2009-01-01

    We discuss three important classes of three-qubit entangled states and their encoding into quantum gates, finite groups and Lie algebras. States of the GHZ and W-type correspond to pure tripartite and bipartite entanglement, respectively. We introduce another generic class B of three-qubit states, that have balanced entanglement over two and three parties. We show how to realize the largest cristallographic group $W(E_8)$ in terms of three-qubit gates (with real entries) encoding states of type GHZ or W [M. Planat, {\\it Clifford group dipoles and the enactment of Weyl/Coxeter group $W(E_8)$ by entangling gates}, Preprint 0904.3691 (quant-ph)]. Then, we describe a peculiar "condensation" of $W(E_8)$ into the four-letter alternating group $A_4$, obtained from a chain of maximal subgroups. Group $A_4$ is realized from two B-type generators and found to correspond to the Lie algebra $sl(3,\\mathbb{C})\\oplus u(1)$. Possible applications of our findings to particle physics and the structure of genetic code are also ...

  12. Translesion synthesis mechanisms depend on the nature of DNA damage in UV-irradiated human cells.

    Science.gov (United States)

    Quinet, Annabel; Martins, Davi Jardim; Vessoni, Alexandre Teixeira; Biard, Denis; Sarasin, Alain; Stary, Anne; Menck, Carlos Frederico Martins

    2016-07-08

    Ultraviolet-induced 6-4 photoproducts (6-4PP) and cyclobutane pyrimidine dimers (CPD) can be tolerated by translesion DNA polymerases (TLS Pols) at stalled replication forks or by gap-filling. Here, we investigated the involvement of Polη, Rev1 and Rev3L (Polζ catalytic subunit) in the specific bypass of 6-4PP and CPD in repair-deficient XP-C human cells. We combined DNA fiber assay and novel methodologies for detection and quantification of single-stranded DNA (ssDNA) gaps on ongoing replication forks and postreplication repair (PRR) tracts in the human genome. We demonstrated that Rev3L, but not Rev1, is required for postreplicative gap-filling, while Polη and Rev1 are responsible for TLS at stalled replication forks. Moreover, specific photolyases were employed to show that in XP-C cells, CPD arrest replication forks, while 6-4PP are responsible for the generation of ssDNA gaps and PRR tracts. On the other hand, in the absence of Polη or Rev1, both types of lesion block replication forks progression. Altogether, the data directly show that, in the human genome, Polη and Rev1 bypass CPD and 6-4PP at replication forks, while only 6-4PP are also tolerated by a Polζ-dependent gap-filling mechanism, independent of S phase. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Molecular genetics of pediatric renal cell carcinoma%青少年肾细胞癌分子遗传学研究进展

    Institute of Scientific and Technical Information of China (English)

    饶秋

    2012-01-01

    青少年肾细胞癌少见,占青少年肾肿瘤的2%~6%.该类肿瘤可能与希佩尔-林道(von Hippel-Lindau,VHL)病相关,但大多数为散发性,表现Xp11.2易位/转录因子E3(transcription factor E3,TFE3)基因融合相关性肾癌和t(6;11)(p21;q12) 转录因子EB(transcription factor EB,TFEB)基因融合相关性肾癌.文中就青少年肾细胞癌的分子遗传学研究进展作一综述.%Pediatric renal cell carcinoma ( RCC ) is relatively rare and represent approximately 2% -6% of all renal neoplasms in children and young adults. RCC may be associated with von Hippel-Lindau (VHL) disease, mostly sporadic and correlated with Xp11.2 translocation/TFE3 gene fusion and t(6;11 )( p21 ;ql2 )/Alpha-TFEB gene fusion. This article focuses on the molecular genetics of pediatric RCC.

  14. Stem cells from umbilical cord blood do have myogenic potential, with and without differentiation induction in vitro

    Directory of Open Access Journals (Sweden)

    Gollop Thomaz R

    2009-01-01

    Full Text Available Abstract The dystrophin gene, located at Xp21, codifies dystrophin, which is part of a protein complex responsible for the membrane stability of muscle cells. Its absence on muscle causes Duchenne Muscular Dystrophy (DMD, a severe disorder, while a defect of muscle dystrophin causes Becker Muscular Dystrophy (DMB, a milder disease. The replacement of the defective muscle through stem cells transplantation is a possible future treatment for these patients. Our objective was to analyze the potential of CD34+ stem cells from umbilical cord blood to differentiate in muscle cells and express dystrophin, in vitro. Protein expression was analyzed by Immunofluorescence, Western Blotting (WB and Reverse Transcriptase – Polymerase Chain Reaction (RT-PCR. CD34+ stem cells and myoblasts from a DMD affected patient started to fuse with muscle cells immediately after co-cultures establishment. Differentiation in mature myotubes was observed after 15 days and dystrophin-positive regions were detected through Immunofluorescence analysis. However, WB or RT-PCR analysis did not detect the presence of normal dystrophin in co-cultures of CD34+ and DMD or DMB affected patients' muscle cells. In contrast, some CD34+ stem cells differentiated in dystrophin producers' muscle cells, what was observed by WB, reinforcing that this progenitor cell has the potential to originate muscle dystrophin in vitro, and not just in vivo like reported before.

  15. Similar Ability of FbaA with M Protein to Elicit Protective Immunity Against Group A Streptococcus Challenge in Mice

    Institute of Scientific and Technical Information of China (English)

    Cuiqing Ma; Caihong Li; Xiurong Wang; Ruihong Zeng; Xiaolin Yin; Huidong Feng; Lin Wei

    2009-01-01

    Group A streptococcus (GAS), an important human pathogen, can cause various kinds of infections including superficial infections and potentially lethal infections, and the search for an effective vaccine to prevent GAS infections has been ongoing for many years. This paper compares the immunogenicity and immunoprotection of FbaA (an Fn-binding protein expressed on the surface of GAS) with that of M protein, the best immunogen of GAS. Assay for immune response showed that FbaA, similar to M protein, could induce protein-specific high IgG titer in BALB/c mice. Furthermore, following GAS challenge, the mice immunized with FbaA showed the same protective rate as those with M protein. These results indicate that FbaA is similar in ability to M protein in inducing protective immunity against GAS challenge in mice.

  16. Group A rotavirus and norovirus display sharply distinct seasonal profiles in Belém, northern Brazil

    Directory of Open Access Journals (Sweden)

    Jones Anderson Monteiro Siqueira

    2013-08-01

    Full Text Available Several viruses have been associated with acute gastroenteritis (AGE, and group A rotavirus (RVA and nor-ovirus (NoV are the most prevalent. This study aimed to assess their prevalence among children hospitalised for diarrhoea during a three-year surveillance study. From May 2008-April 2011, overall positivity rates of 21.6% (628/2904 and 35.4% (171/483 were observed for RVA and NoV, respectively. The seasonality observed indicated distinct patterns when both viruses were compared. This finding may explain why hospitalisation for AGE remains constant throughout the year. Continuous AGE monitoring is needed to better assess the patterns of infection.

  17. Conserved patterns hidden within group A Streptococcus M protein hypervariability recognize human C4b-binding protein

    Energy Technology Data Exchange (ETDEWEB)

    Buffalo, Cosmo Z.; Bahn-Suh, Adrian J.; Hirakis, Sophia P.; Biswas, Tapan; Amaro, Rommie E.; Nizet, Victor; Ghosh, Partho

    2016-09-05

    No vaccine exists against group A Streptococcus (GAS), a leading cause of worldwide morbidity and mortality. A severe hurdle is the hypervariability of its major antigen, the M protein, with >200 different M types known. Neutralizing antibodies typically recognize M protein hypervariable regions (HVRs) and confer narrow protection. In stark contrast, human C4b-binding protein (C4BP), which is recruited to the GAS surface to block phagocytic killing, interacts with a remarkably large number of M protein HVRs (apparently ∼90%). Such broad recognition is rare, and we discovered a unique mechanism for this through the structure determination of four sequence-diverse M proteins in complexes with C4BP. The structures revealed a uniform and tolerant ‘reading head’ in C4BP, which detected conserved sequence patterns hidden within hypervariability. Our results open up possibilities for rational therapies that target the M–C4BP interaction, and also inform a path towards vaccine design.

  18. 人A组轮状病毒疫苗研究进展%Progress of human group A rotavirus vaccine

    Institute of Scientific and Technical Information of China (English)

    段招军

    2012-01-01

    Group A rotavirus( RV) is the leading cause of severe diarrhea disease in infants and young children worldwide, which causes a high desease burden. Studies have indicated that further improvements in hygiene are unlikely to prevent the disease. Rotavirus vaccines are the most effective public health interventions for controlling rotavirus diarrhea. Currently there are 3 different brands of rotavirus vaccines put into use globally in more than 100 countries and regions, and have been included in some countries'childhood vaccination programs. This review briefly introduces the development status of Group A rotavirus vaccines, providing a reference for application and further promotion of rotavirus vaccines in our country.%A组轮状病毒是导致全球婴幼儿重症腹泻的最主要病因,其疾病负担巨大.已有研究证实,卫生状况的改善对轮状病毒腹泻的控制效果甚微,疫苗则是控制轮状病毒腹泻最有效的公共卫生干预措施.目前3种轮状病毒疫苗已在全球100多个国家及地区投入使用,并纳入部分国家的儿童计划免疫程序.本文简要综述人A组轮状病毒疫苗的研究进展,以期对我国轮状病毒疫苗的使用和推广提供借鉴.

  19. NCBI nr-aa BLAST: CBRC-RNOR-05-0198 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-RNOR-05-0198 ref|XP_001163354.1| PREDICTED: T-cell acute lymphocytic leukemia ...1 isoform 1 [Pan troglodytes] ref|XP_001163426.1| PREDICTED: T-cell acute lymphocytic leukemia 1 isoform 2 [...Pan troglodytes] ref|XP_513389.2| PREDICTED: T-cell acute lymphocytic leukemia 1 isoform 3 [Pan troglodytes] XP_001163354.1 1e-174 91% ...

  20. Increased expression of high-mobility group A2: A novel independent indicator of poor prognosis in patients with esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Rongna Wei

    2016-01-01

    Conclusions: High HMGA2 expression was related to lymph node metastasis and poor prognosis in ESCC. Our results indicated that HMGA2 could act as a potential biomarker for prognosis evaluation of ESCC patients.

  1. From solution to in-cell study of the chemical reactivity of acid sensitive functional groups: a rational approach towards improved cleavable linkers for biospecific endosomal release.

    Science.gov (United States)

    Jacques, Sylvain A; Leriche, Geoffray; Mosser, Michel; Nothisen, Marc; Muller, Christian D; Remy, Jean-Serge; Wagner, Alain

    2016-06-07

    pH-Sensitive linkers designed to undergo selective hydrolysis at acidic pH compared to physiological pH can be used for the selective release of therapeutics at their site of action. In this paper, the hydrolytic cleavage of a wide variety of molecular structures that have been reported for their use in pH-sensitive delivery systems was examined. A wide variety of hydrolytic stability profiles were found among the panel of tested chemical functionalities. Even within a structural family, a slight modification of the substitution pattern has an unsuspected outcome on the hydrolysis stability. This work led us to establish a first classification of these groups based on their reactivities at pH 5.5 and their relative hydrolysis at pH 5.5 vs. pH 7.4. From this classification, four representative chemical functions were selected and studied in-vitro. The results revealed that only the most reactive functions underwent significant lysosomal cleavage, according to flow cytometry measurements. These last results question the acid-based mechanism of action of known drug release systems and advocate for the importance of an in-depth structure-reactivity study, using a tailored methodology, for the rational design and development of bio-responsive linkers.

  2. A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells

    DEFF Research Database (Denmark)

    Claessens, Antoine; Adams, Yvonne; Ghumra, Ashfaq

    2012-01-01

    of these variants. The clinical in vivo relevance of the HBEC-selected parasites was supported by significantly higher surface recognition of HBEC-selected parasites compared with unselected parasites by antibodies from young African children suffering cerebral malaria (Mann-Whitney test, P = 0...

  3. IgG protease Mac/IdeS is not essential for phagocyte resistance or mouse virulence of M1T1 group A Streptococcus.

    Science.gov (United States)

    Okumura, Cheryl Y M; Anderson, Ericka L; Döhrmann, Simon; Tran, Dan N; Olson, Joshua; von Pawel-Rammingen, Ulrich; Nizet, Victor

    2013-07-30

    The Mac/IdeS protein of group A Streptococcus (GAS) is a secreted cysteine protease with cleavage specificity for IgG and is highly expressed in the GAS serotype M1T1 clone, which is the serotype most frequently isolated from patients with life-threatening invasive infections. While studies of Mac/IdeS with recombinant protein have shown that the protein can potentially prevent opsonophagocytosis of GAS by neutrophils, the role of the protein in immune evasion as physiologically produced by the living organism has not been studied. Here we examined the contribution of Mac/IdeS to invasive GAS disease by generating a mutant lacking Mac/IdeS in the hyperinvasive M1T1 background. While Mac/IdeS was highly expressed and proteolytically active in the hyperinvasive strain, elimination of the bacterial protease did not significantly influence GAS phagocytic uptake, oxidative-burst induction, cathelicidin sensitivity, resistance to neutrophil or macrophage killing, or pathogenicity in pre- or postimmune mouse infectious challenges. We conclude that in the highly virulent M1T1 background, Mac/IdeS is not essential for either phagocyte resistance or virulence. Given the conservation of Mac/IdeS and homologues across GAS strains, it is possible that Mac/IdeS serves another important function in GAS ecology or contributes to virulence in other strain backgrounds. Group A Streptococcus (GAS) causes human infections ranging from strep throat to life-threatening conditions such as flesh-eating disease and toxic shock syndrome. Common disease-associated clones of GAS can cause both mild and severe infections because of a characteristic mutation and subsequent change in the expression of several genes that develops under host immune selection. One of these genes encodes Mac/IdeS, a protease that has been shown to cleave antibodies important to the immune defense system. In this study, we found that while Mac/IdeS is highly expressed in hypervirulent GAS, it does not significantly

  4. Increased β-haemolytic group A streptococcal M6 serotype and streptodornase B-specific cellular immune responses in Swedish narcolepsy cases.

    Science.gov (United States)

    Ambati, A; Poiret, T; Svahn, B-M; Valentini, D; Khademi, M; Kockum, I; Lima, I; Arnheim-Dahlström, L; Lamb, F; Fink, K; Meng, Q; Kumar, A; Rane, L; Olsson, T; Maeurer, M

    2015-09-01

    Type 1 narcolepsy is a neurological disorder characterized by excessive daytime sleepiness and cataplexy associated with the HLA allele DQB1*06:02. Genetic predisposition along with external triggering factors may drive autoimmune responses, ultimately leading to the selective loss of hypocretin-positive neurons. The aim of this study was to investigate potential aetiological factors in Swedish cases of postvaccination (Pandemrix) narcolepsy defined by interferon-gamma (IFNγ) production from immune cells in response to molecularly defined targets. Cellular reactivity defined by IFNγ production was examined in blood from 38 (HLA-DQB1*06:02(+) ) Pandemrix-vaccinated narcolepsy cases and 76 (23 HLA-DQB1*06:02(+) and 53 HLA-DQB1*06:02(-) ) control subjects, matched for age, sex and exposure, using a variety of different antigens: β-haemolytic group A streptococcal (GAS) antigens (M5, M6 and streptodornase B), influenza (the pandemic A/H1N1/California/7/09 NYMC X-179A and A/H1N1/California/7/09 NYMC X-181 vaccine antigens, previous Flu-A and -B vaccine targets, A/H1N1/Brisbane/59/2007, A/H1N1/Solomon Islands/3/2006, A/H3N2/Uruguay/716/2007, A/H3N2/Wisconsin/67/2005, A/H5N1/Vietnam/1203/2004 and B/Malaysia/2506/2004), noninfluenza viral targets (CMVpp65, EBNA-1 and EBNA-3) and auto-antigens (hypocretin peptide, Tribbles homolog 2 peptide cocktail and extract from rat hypothalamus tissue). IFN-γ production was significantly increased in whole blood from narcolepsy cases in response to streptococcus serotype M6 (P = 0.0065) and streptodornase B protein (P = 0.0050). T-cell recognition of M6 and streptodornase B was confirmed at the single-cell level by intracellular cytokine (IL-2, IFNγ, tumour necrosis factor-alpha and IL-17) production after stimulation with synthetic M6 or streptodornase B peptides. Significantly, higher (P = 0.02) titres of serum antistreptolysin O were observed in narcolepsy cases, compared to vaccinated controls. β-haemolytic GAS may be

  5. Whole genome sequencing of group A Streptococcus: development and evaluation of an automated pipeline for emmgene typing

    Directory of Open Access Journals (Sweden)

    Georgia Kapatai

    2017-04-01

    Full Text Available Streptococcus pyogenes group A Streptococcus (GAS is the most common cause of bacterial throat infections, and can cause mild to severe skin and soft tissue infections, including impetigo, erysipelas, necrotizing fasciitis, as well as systemic and fatal infections including septicaemia and meningitis. Estimated annual incidence for invasive group A streptococcal infection (iGAS in industrialised countries is approximately three per 100,000 per year. Typing is currently used in England and Wales to monitor bacterial strains of S. pyogenes causing invasive infections and those isolated from patients and healthcare/care workers in cluster and outbreak situations. Sequence analysis of the emm gene is the currently accepted gold standard methodology for GAS typing. A comprehensive database of emm types observed from superficial and invasive GAS strains from England and Wales informs outbreak control teams during investigations. Each year the Bacterial Reference Department, Public Health England (PHE receives approximately 3,000 GAS isolates from England and Wales. In April 2014 the Bacterial Reference Department, PHE began genomic sequencing of referred S. pyogenes isolates and those pertaining to selected elderly/nursing care or maternity clusters from 2010 to inform future reference services and outbreak analysis (n = 3, 047. In line with the modernizing strategy of PHE, we developed a novel bioinformatics pipeline that can predict emmtypes using whole genome sequence (WGS data. The efficiency of this method was measured by comparing the emmtype assigned by this method against the result from the current gold standard methodology; concordance to emmsubtype level was observed in 93.8% (2,852/3,040 of our cases, whereas in 2.4% (n = 72 of our cases concordance was observed to emm type level. The remaining 3.8% (n = 117 of our cases corresponded to novel types/subtypes, contamination, laboratory sample transcription errors or problems arising

  6. Defence against methylglyoxal in Group A Streptococcus: a role for Glyoxylase I in bacterial virulence and survival in neutrophils?

    Science.gov (United States)

    Zhang, May M; Ong, Cheryl-lynn Y; Walker, Mark J; McEwan, Alastair G

    2016-03-01

    Methylglyoxal is a dicarbonyl compound that acts as a toxic electrophile in biological systems. Methylglyoxal is produced in certain bacteria as a byproduct of glycolysis through methylglyoxal synthase. Like many bacteria, Group A Streptococcus (GAS), a Gram-positive human pathogen responsible for a wide spectrum of diseases, uses a two-step glyoxalase system to remove methylglyoxal. However, bioinformatic analysis revealed that no homologue of methylglyoxal synthase is present in GAS, suggesting that the role of the glyoxalase system is to detoxify methylglyoxal produced by the host. In this study, we investigated the role of methylglyoxal detoxification in the pathogenesis of GAS. A mutant (5448ΔgloA), deficient in glyoxylase I (S-lactoylglutathione lyase), was constructed and tested for susceptibility to methylglyoxal, human neutrophil survival and virulence in a murine model of infection. 5448ΔgloA was more sensitive to methylglyoxal and was also more susceptible to human neutrophil killing. Inhibition of neutrophil myeloperoxidase rescued the gloA-deficient mutant indicating that this enzyme was required for methylglyoxal production. Furthermore, the 5448ΔgloA mutant was slower at disseminating into the blood in the murine model. These data suggest that neutrophils produce methylglyoxal as an antimicrobial agent during bacterial infection, and the glyoxalase system is part of the GAS defence against the innate immune system during pathogenesis.

  7. RocA Truncation Underpins Hyper-Encapsulation, Carriage Longevity and Transmissibility of Serotype M18 Group A Streptococci

    Science.gov (United States)

    Lynskey, Nicola N.; Goulding, David; Gierula, Magdalena; Turner, Claire E.; Dougan, Gordon; Edwards, Robert J.; Sriskandan, Shiranee

    2013-01-01

    Group A streptococcal isolates of serotype M18 are historically associated with epidemic waves of pharyngitis and the non-suppurative immune sequela rheumatic fever. The serotype is defined by a unique, highly encapsulated phenotype, yet the molecular basis for this unusual colony morphology is unknown. Here we identify a truncation in the regulatory protein RocA, unique to and conserved within our serotype M18 GAS collection, and demonstrate that it underlies the characteristic M18 capsule phenotype. Reciprocal allelic exchange mutagenesis of rocA between M18 GAS and M89 GAS demonstrated that truncation of RocA was both necessary and sufficient for hyper-encapsulation via up-regulation of both precursors required for hyaluronic acid synthesis. Although RocA was shown to positively enhance covR transcription, quantitative proteomics revealed RocA to be a metabolic regulator with activity beyond the CovR/S regulon. M18 GAS demonstrated a uniquely protuberant chain formation following culture on agar that was dependent on excess capsule and the RocA mutation. Correction of the M18 rocA mutation reduced GAS survival in human blood, and in vivo naso-pharyngeal carriage longevity in a murine model, with an associated drop in bacterial airborne transmission during infection. In summary, a naturally occurring truncation in a regulator explains the encapsulation phenotype, carriage longevity and transmissibility of M18 GAS, highlighting the close interrelation of metabolism, capsule and virulence. PMID:24367267

  8. MalE of Group A Streptococcus Participates in the Rapid Transport of Maltotriose and Longer Maltodextrins▿ †

    Science.gov (United States)

    Shelburne, Samuel A.; Fang, Han; Okorafor, Nnaja; Sumby, Paul; Sitkiewicz, Izabela; Keith, David; Patel, Payal; Austin, Celest; Graviss, Edward A.; Musser, James M.; Chow, Dar-Chone

    2007-01-01

    Study of the maltose/maltodextrin binding protein MalE in Escherichia coli has resulted in fundamental insights into the molecular mechanisms of microbial transport. Whether gram-positive bacteria employ a similar pathway for maltodextrin transport is unclear. The maltodextrin binding protein MalE has previously been shown to be key to the ability of group A Streptococcus (GAS) to colonize the oropharynx, the major site of GAS infection in humans. Here we used a multifaceted approach to elucidate the function and binding characteristics of GAS MalE. We found that GAS MalE is a central part of a highly efficient maltodextrin transport system capable of transporting linear maltodextrins that are up to at least seven glucose molecules long. Of the carbohydrates tested, GAS MalE had the highest affinity for maltotriose, a major breakdown product of starch in the human oropharynx. The thermodynamics and fluorescence changes induced by GAS MalE-maltodextrin binding were essentially opposite those reported for E. coli MalE. Moreover, unlike E. coli MalE, GAS MalE exhibited no specific binding of maltose or cyclic maltodextrins. Our data show that GAS developed a transport system optimized for linear maltodextrins longer than two glucose molecules that has several key differences from its well-studied E. coli counterpart. PMID:17259319

  9. Sensitivity for Diagnosing Group A Streptococcal Pharyngitis from Manufacturers is 10% Higher than Reported in Peer-Reviewed Publications.

    Science.gov (United States)

    Vachhani, Raj; Patel, Toral; Centor, Robert M; Estrada, Carlos A

    2017-01-01

    Meta-analyses based on peer-reviewed publications report a sensitivity of approximately 85% for rapid antigen streptococcus tests to diagnose group A streptococcal (GAS) pharyngitis. Because these meta-analyses excluded package inserts, we examined the test characteristics of rapid antigen streptococcal tests and molecular methods that manufacturers report in their package inserts. We included tests available in the US market (Food and Drug Administration, period searched 1993-2015) and used package insert data to calculate pooled sensitivity and specificity. To examine quality, we used the Quality Assessment of Diagnostic Accuracy Studies-2. We excluded 26 tests having different trade names but identical methods and data. The study design was prospective in 41.7% (10 of 24). The pooled sensitivity of the most commonly used method, lateral flow/immunochromatographic, was 95% (95% confidence interval [CI] 94-96) and the pooled specificity was 98% (96-98); 7108 patients. The pooled sensitivity of the polymerase chain reaction or molecular methods was 98% (95% CI 96-98) and the pooled specificity was 96% (95% CI 95-97); 5685 patients. Package inserts include sponsored studies that overestimate the sensitivity of rapid tests to diagnose GAS pharyngitis by approximately 10%. Physicians should understand that package inserts overestimate diagnostic test utility; a negative test cannot be used to exclude GAS pharyngitis.

  10. Differences in SpeB protease activity among group A streptococci associated with superficial, invasive, and autoimmune disease.

    Science.gov (United States)

    Ly, Anhphan T; Noto, John P; Walwyn, Odaelys L; Tanz, Robert R; Shulman, Stanford T; Kabat, William; Bessen, Debra E

    2017-01-01

    The secreted cysteine proteinase SpeB is an important virulence factor of group A streptococci (GAS), whereby SpeB activity varies widely among strains. To establish the degree to which SpeB activity correlates with disease, GAS organisms were recovered from patients with pharyngitis, impetigo, invasive disease or acute rheumatic fever (ARF), and selected for analysis using rigorous sampling criteria; >300 GAS isolates were tested for SpeB activity by casein digestion assays, and each GAS isolate was scored as a SpeB-producer or non-producer. Highly significant statistical differences (p < 0.01) in SpeB production are observed between GAS recovered from patients with ARF (41.5% SpeB-non-producers) compared to pharyngitis (20.5%), invasive disease (16.7%), and impetigo (5.5%). SpeB activity differences between pharyngitis and impetigo isolates are also significant, whereas pharyngitis versus invasive isolates show no significant difference. The disproportionately greater number of SpeB-non-producers among ARF-associated isolates may indicate an altered transcriptional program for many rheumatogenic strains and/or a protective role for SpeB in GAS-triggered autoimmunity.

  11. Alone against the group: A unanimously disagreeing group leads to conformity, but cardiovascular threat depends on one's goals.

    Science.gov (United States)

    Seery, Mark D; Gabriel, Shira; Lupien, Shannon P; Shimizu, Mitsuru

    2016-08-01

    A long history of research in psychology has studied the consequences of when individuals face a group that unanimously disagrees with them. However, relatively little research has attempted to understand individuals' internal reactions to such disagreement while it is experienced. Psychophysiological measures are particularly well suited for this purpose. We used the perspective of the biopsychosocial model of challenge/threat to test whether and under what circumstances expressing one's political opinion to a disagreeing group led to a cardiovascular threat response (high total peripheral resistance, low cardiac output). We hypothesized that, when participants were provided with a goal to fit in with the group, a disagreeing group would elicit cardiovascular responses consistent with greater threat than an agreeing group, but that this effect would disappear if not reverse when participants were provided with a goal to express their individuality. Results supported hypotheses and further revealed a divergence between cardiovascular responses and conformity behavior, such that a disagreeing group fostered conformity regardless of goal condition. These findings suggest that (a) facing the prospect of a disagreeing group need not necessarily result in the negative experience of threat (reflecting evaluating low resources/high demands), and (b) conformity behavior can mask a range of internal states.

  12. Highly frequent mutations in negative regulators of multiple virulence genes in group A streptococcal toxic shock syndrome isolates.

    Science.gov (United States)

    Ikebe, Tadayoshi; Ato, Manabu; Matsumura, Takayuki; Hasegawa, Hideki; Sata, Tetsutaro; Kobayashi, Kazuo; Watanabe, Haruo

    2010-04-01

    Streptococcal toxic shock syndrome (STSS) is a severe invasive infection characterized by the sudden onset of shock and multiorgan failure; it has a high mortality rate. Although a number of studies have attempted to determine the crucial factors behind the onset of STSS, the responsible genes in group A Streptococcus have not been clarified. We previously reported that mutations of csrS/csrR genes, a two-component negative regulator system for multiple virulence genes of Streptococcus pyogenes, are found among the isolates from STSS patients. In the present study, mutations of another negative regulator, rgg, were also found in clinical isolates of STSS patients. The rgg mutants from STSS clinical isolates enhanced lethality and impaired various organs in the mouse models, similar to the csrS mutants, and precluded their being killed by human neutrophils, mainly due to an overproduction of SLO. When we assessed the mutation frequency of csrS, csrR, and rgg genes among S. pyogenes isolates from STSS (164 isolates) and non-invasive infections (59 isolates), 57.3% of the STSS isolates had mutations of one or more genes among three genes, while isolates from patients with non-invasive disease had significantly fewer mutations in these genes (1.7%). The results of the present study suggest that mutations in the negative regulators csrS/csrR and rgg of S. pyogenes are crucial factors in the pathogenesis of STSS, as they lead to the overproduction of multiple virulence factors.

  13. Successful Treatment of Both Mother and Infant in Pregnancy-Associated Group A Streptococcal Toxic Shock Syndrome

    Directory of Open Access Journals (Sweden)

    Takayuki Tanaka

    2007-01-01

    Full Text Available All perinatal cases of group A streptococcal toxic shock syndrome (STSS previously documented in English literature have been fatal for the mother, the fetus or both. We present the first report of successful treatment of a mother-infant pair with perinatal STSS. A pregnant woman developed STSS at 34 weeks’ gestation 3 h after delivery, following a 25-h history of fever and sore throat. The patient received intravenous penicillin, clindamycin and immnoglobulins and continuous hemodialysis, along with numerous supportive agents during early clinical course. The newborn infant was born with mild asphyxia and developed transient tachypnea. Both mother and infant survived without any sequelae. Streptococcus pyogenes was isolated from the patient’s blood, nasopharynx of the infant and throat of two family members. These strains were identically type T1M1 (emm1 and produced streptococcal pyrogenic exotoxins A (SPEA and B. SPEA was remarkably elevated in the maternal blood, but not in the infant’s blood. Extremely low serum anti-SPEA antibody levels might have predisposed the mother to severe invasive infection. This case highlights the importance of early recognition, prompt and intensive multimodal therapy and rapid delivery before a transfer of pathogen and its toxin to the fetus.

  14. Clustered Regularly Interspaced Short Palindromic Repeats Are emm Type-Specific in Highly Prevalent Group A Streptococci.

    Science.gov (United States)

    Zheng, Po-Xing; Chan, Yuen-Chi; Chiou, Chien-Shun; Chiang-Ni, Chuan; Wang, Shu-Ying; Tsai, Pei-Jane; Chuang, Woei-Jer; Lin, Yee-Shin; Liu, Ching-Chuan; Wu, Jiunn-Jong

    2015-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) are the bacterial adaptive immune system against foreign nucleic acids. Given the variable nature of CRISPR, it could be a good marker for molecular epidemiology. Group A streptococcus is one of the major human pathogens. It has two CRISPR loci, including CRISPR01 and CRISPR02. The aim of this study was to analyze the distribution of CRISPR-associated gene cassettes (cas) and CRISPR arrays in highly prevalent emm types. The cas cassette and CRISPR array in two CRISPR loci were analyzed in a total of 332 strains, including emm1, emm3, emm4, emm12, and emm28 strains. The CRISPR type was defined by the spacer content of each CRISPR array. All strains had at least one cas cassette or CRISPR array. More than 90% of the spacers were found in one emm type, specifically. Comparing the consistency between emm and CRISPR types by Simpson's index of diversity and the adjusted Wallace coefficient, CRISPR01 type was concordant to emm type, and CRISPR02 showed unidirectional congruence to emm type, suggesting that at least for the majority of isolates causing infection in high income countries, the emm type can be inferred from CRISPR analysis, which can further discriminate isolates sharing the same emm type.

  15. The IL-8 Protease SpyCEP/ScpC of Group A Streptococcus Promotes Resistance to Neutrophil Killing

    Science.gov (United States)

    Zinkernagel, Annelies S.; Timmer, Anjuli M.; Pence, Morgan A.; Locke, Jeffrey B.; Buchanan, John T.; Turner, Claire E.; Mishalian, Inbal; Sriskandan, Shiranee; Hanski, Emanuel; Nizet, Victor

    2009-01-01

    SUMMARY Interleukin-8 (IL-8) promotes neutrophil-mediated host defense through its chemoattractant and immunostimulatory activities. The Group A Streptococcus (GAS) protease SpyCEP (also called ScpC) cleaves IL-8, and SpyCEP expression is strongly upregulated in vivo in the M1T1 GAS strains associated with life-threatening systemic disease including necrotizing fasciitis. Coupling allelic replacement with heterologous gene expression, we show that SpyCEP is necessary and sufficient for IL-8 degradation. SpyCEP decreased IL-8-dependent neutrophil endothelial transmigration and bacterial killing, the latter by reducing neutrophil extracellular trap formation. The knockout mutant lacking SpyCEP was attenuated for virulence in murine infection models, and SpyCEP expression conferred protection to coinfecting bacteria. We also show that the zoonotic pathogen Streptococcus iniae possesses a functional homolog of SpyCEP (Cepl) that cleaves IL-8, promotes neutrophil resistance, and contributes to virulence. By inactivating the multifunctional host defense peptide IL-8, the SpyCEP protease impairs neutrophil clearance mechanisms, contributing to the pathogenesis of invasive streptococcal infection. PMID:18692776

  16. Clustered Regularly Interspaced Short Palindromic Repeats Are emm Type-Specific in Highly Prevalent Group A Streptococci.

    Directory of Open Access Journals (Sweden)

    Po-Xing Zheng

    Full Text Available Clustered regularly interspaced short palindromic repeats (CRISPR are the bacterial adaptive immune system against foreign nucleic acids. Given the variable nature of CRISPR, it could be a good marker for molecular epidemiology. Group A streptococcus is one of the major human pathogens. It has two CRISPR loci, including CRISPR01 and CRISPR02. The aim of this study was to analyze the distribution of CRISPR-associated gene cassettes (cas and CRISPR arrays in highly prevalent emm types. The cas cassette and CRISPR array in two CRISPR loci were analyzed in a total of 332 strains, including emm1, emm3, emm4, emm12, and emm28 strains. The CRISPR type was defined by the spacer content of each CRISPR array. All strains had at least one cas cassette or CRISPR array. More than 90% of the spacers were found in one emm type, specifically. Comparing the consistency between emm and CRISPR types by Simpson's index of diversity and the adjusted Wallace coefficient, CRISPR01 type was concordant to emm type, and CRISPR02 showed unidirectional congruence to emm type, suggesting that at least for the majority of isolates causing infection in high income countries, the emm type can be inferred from CRISPR analysis, which can further discriminate isolates sharing the same emm type.

  17. Successful unintentional ABO-incompatible renal transplantation: Blood group A1B donor into an A2B recipient.

    Science.gov (United States)

    Fadeyi, Emmanuel A; Stratta, Robert J; Farney, Alan C; Pomper, Gregory J

    2014-05-01

    To report a successful unintentional transplantation of a deceased donor kidney from an "incompatible" A1B donor into a recipient who was blood group A2B with unsuspected preformed anti-A1 antibodies. The donor and recipient were both typed for ABO antigens. The recipient was tested for ABO and non-ABO antibodies. The recipient was typed for HLA class I and class II antigens, including HLA antibody screen. The T-and B-flow cytometry crossmatch test was performed using standard protocol. The donor-recipient pair was a complete six-antigen human leukocyte antigen mismatch, but final T- and B-flow cytometry cross-match tests were compatible. The recipient was a 65-year-old woman with a medical history of end-stage renal disease secondary to diabetic nephropathy who underwent kidney transplantation from a 46-year-old brain-dead standard criteria donor. The recipient's RBCs were negative with A1 lectin, and the recipient was thus typed as an A2 subgroup. Anti-A1 could be demonstrated in the recipient's plasma. The donor's RBCs were positive with A1 lectin, thereby conferring an A1 blood type. It is safe to transplant across the A1/A2 blood group barrier provided that the preformed antibodies are not reactive at 37°C and with anti-human globulin.

  18. Late-onset Rash in Patients with Group A Beta-hemolytic Streptococcal Pharyngitis Treated with Amoxicillin

    Science.gov (United States)

    2015-01-01

    We observed late-onset rashes in patients with group A beta-hemolytic streptococcal (GAS) pharyngitis. Of 1028 patients with GAS pharyngitis, which was principally treated with amoxicillin, we evaluated those who developed a late-onset rash and excluded those with scarlet fever alone. Twenty-one patients developed a rash (2.0%, 95% confidence interval, 1.3-3.1%), 7 to 20 days (median, 8 days) after GAS pharyngitis onset. The rashes were characterized by maculopapules, which increased in size with coalescence and some developing into plaques, with a symmetrical distribution with a propensity for the extremities, including the palms and soles. The clinical courses of the patients were good, and the rashes subsided within 14 days. A non-immediate reaction to β-lactams, which usually manifests as a maculopapular rash, is a possible cause in our patients, however, repeated courses of amoxicillin in 3 patients did not induce the rash. The underlying mechanism of the late-onset rash after GAS pharyngitis with amoxicillin treatment remains unclear. PMID:26734124

  19. Late-onset rash in patients with group A beta-hemolytic streptococcal pharyngitis treated with amoxicillin

    Directory of Open Access Journals (Sweden)

    Masahiko Kimura

    2015-12-01

    Full Text Available We observed late-onset rashes in patients with group A beta-hemolytic streptococcal (GAS pharyngitis. Of 1028 patients with GAS pharyngitis, which was principally treated with amoxicillin, we evaluated those who developed a late-onset rash and excluded those with scarlet fever alone. Twenty-one patients developed a rash (2.0%, 95% confidence interval, 1.3- 3.1%, 7 to 20 days (median, 8 days after GAS pharyngitis onset. The rashes were characterized by maculopapules, which increased in size with coalescence and some developing into plaques, with a symmetrical distribution with a propensity for the extremities, including the palms and soles. The clinical courses of the patients were good, and the rashes subsided within 14 days. A non-immediate reaction to β-lactams, which usually manifests as a maculopapular rash, is a possible cause in our patients, however, repeated courses of amoxicillin in 3 patients did not induce the rash. The underlying mechanism of the late-onset rash after GAS pharyngitis with amoxicillin treatment remains unclear.

  20. Inference of antibiotic resistance and virulence among diverse group A Streptococcus strains using emm sequencing and multilocus genotyping methods.

    Directory of Open Access Journals (Sweden)

    David Metzgar

    Full Text Available BACKGROUND: Group A Streptococcus pyogenes (GAS exhibits a high degree of clinically relevant phenotypic diversity. Strains vary widely in terms of antibiotic resistance (AbR, clinical severity, and transmission rate. Currently, strain identification is achieved by emm typing (direct sequencing of the genomic segment coding for the antigenic portion of the M protein or by multilocus genotyping methods. Phenotype analysis, including critical AbR typing, is generally achieved by much slower and more laborious direct culture-based methods. METHODOLOGY/PRINCIPAL FINDINGS: We compare genotype identification (by emm typing and PCR/ESI-MS with directly measured phenotypes (AbR and outbreak associations for 802 clinical isolates of GAS collected from symptomatic patients over a period of 6 years at 10 military facilities in the United States. All independent strain characterization methods are highly correlated. This shows that recombination, horizontal transfer, and other forms of reassortment are rare in GAS insofar as housekeeping genes, primary virulence and antibiotic resistance determinants, and the emm gene are concerned. Therefore, genotyping methods offer an efficient way to predict emm type and the associated AbR and virulence phenotypes. CONCLUSIONS/SIGNIFICANCE: The data presented here, combined with much historical data, suggest that emm typing assays and faster molecular methods that infer emm type from genomic signatures could be used to efficiently infer critical phenotypic characteristics based on robust genotype: phenotype correlations. This, in turn, would enable faster and better-targeted responses during identified outbreaks of constitutively resistant or particularly virulent emm types.

  1. The change of macrolide resistance rates in group A Streptococcus isolates from children between 2002 and 2013 in Asahikawa city.

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    Sakata, Hiroshi

    2015-05-01

    This study targeted patients in the Department of Pediatrics, Asahikawa Kosei Hospital, between January 2002 and December 2013. In patients suspected of having hemolytic streptococcal infection, Group A Streptococcus (GAS) strains isolated from a throat swab were examined for antimicrobial susceptibility testing. The MICs were measured by the broth microdilution method. The annual number of GAS strains examined for antimicrobial susceptibility testing ranged from 28 to 65 strains, for a total of 574 strains. Some of the isolates obtained from 2006 to 2009 and from 2011 to 2013 were analyzed to determine their emm types. An erythromycin (EM) resistant strain was not detected until 2004, but one EM-resistant strain appeared in 2005. Subsequently, EM-resistant strains rapidly increased, and 48 of 65 strains (73.8%) examined in 2009 were resistant. In 2010, the number of EM-resistant strains decreased to 12 of 36 strains (33.3%). However, it gradually increased afterwards, and 37 of 60 strains (61.7%) were resistant in 2013. Out of 574 strains examined, 184 exhibited EM-resistance, and the overall resistance rate was 31.9%. Partitioning the 124 strains examined between 2006 and 2008 according to emm types, only emm28 strains, which exhibited a high resistance rate, and emm12 strains demonstrated resistance. For the 142 strains examined between 2011 and 2013, the resistance rate of emm28 strains was similarly high; the resistance of emm12 strains significantly increased, and emm1 strains exhibited a high resistance rate. The number of emm types associated with the resistant strains increased. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. Evidence of natural transmission of group A rotavirus between domestic pigs and wild boars (Sus scrofa) in Japan.

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    Okadera, Kota; Abe, Masako; Ito, Naoto; Morikawa, Shigeki; Yamasaki, Ari; Masatani, Tatsunori; Nakagawa, Keisuke; Yamaoka, Satoko; Sugiyama, Makoto

    2013-12-01

    Group A rotaviruses (RVAs) are a major cause of acute dehydrating diarrhea in infants and young animals worldwide. RVAs have also been detected in several wild and zoo animals, indicating wide susceptibility of wild animals. However, the role of wild animals in the infection cycle of RVAs is unclear. Wild boars are indigenous in many countries in the world. Japanese wild boars (Sus scrofa leucomystax) have been migrating close to human habitats in Japan, indicating the possibility of natural transmission between domestic animals or humans and wild boars. We investigated infection of RVAs in wild boars in Japan to identify types of RVAs infecting wild animals. We obtained stool samples from 90 wild boars and detected a VP4 gene of RVAs by RT-semi-nested PCR. RVAs were detected in samples from four of the 90 wild boars. Nucleotide analyses of VP7 and VP4 genes revealed that the four strains belong to G9P[23], G4P[23], G9P[13] and G4P[6], suggesting a relation to porcine and human RVAs. We therefore characterized RVAs circulating among domestic pigs living in the same area as the wild boars. We collected stool samples from 82 domestic pigs. RVAs were detected in samples from 49 of the 82 domestic pigs. Phylogenetic and similarity analyses provided evidence for natural transmission between domestic pigs and wild boars. The results also suggested that natural reassortment events occurred before or after transmission between domestic pigs and wild boars. Our findings indicate the possibility that RVAs circulate among wild animals, humans and domestic animals in nature. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Co-Activation of Th17 and Antibody Responses Provides Efficient Protection against Mucosal Infection by Group A Streptococcus

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    Chen, Xianyang; Li, Ning; Bi, Shuai; Wang, Xiaoguang; Wang, Beinan

    2016-01-01

    Conserved protein antigens among serotypes of group A Streptococcus pyogenes (GAS) have been focused for vaccine development because of the diversity of GAS serotypes and risks of autoimmunity post-GAS infection. Precise delineation of protective immune response to each of GAS antigens is critical for vaccine efficacy and safety. We recently reported that immunization with SrtA of GAS provides Th17-dependent clearance of heterologous serotypes of GAS in NALT. SCPA is a surface virulence molecule of GAS and known to induce antibody-mediated protection against GAS. We hypothesized that co-immunization with SrtA and SCPA would provide more efficient protection by eliciting combined Th17 and antibody responses. The present study showed that mice that were intranasally co-immunized with SrtA/SCPA cleared GAS more efficiently than the mice that were immunized with either SrtA or SCPA individually, and as efficient as the mice that experienced repeated GAS infections. The co-immunization induced Th17 and robust SCPA antibody responses, accompanied by a rapid influx of neutrophils and high myeloperoxidase activity in NALT, suggesting that simultaneous induction of mucosal Th17 and neutralizing antibody responses offers more effective GAS elimination through rapid infiltration and activation of neutrophils. Moreover, Th17 response was strongly induced in mice that experienced repeated GAS-infection and maintained at a high level even after the bacteria were cleared; whereas, it was moderately induced and promptly returned to baseline following bacterial elimination in SrtA/SCPA co-immunized mice. Additional results showed that the survival rate of systemic challenge was significantly higher in infection experienced than in co-immunized mice, indicating that more immune elements are required for protection against systemic than mucosal GAS infection. PMID:28030629

  4. Genomic characterisation, chromosomal assignment and in vivo localisation of the canine High Mobility Group A1 (HMGA1 gene

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    Reimann-Berg Nicola

    2008-07-01

    Full Text Available Abstract Background The high mobility group A1 proteins (HMGA1a/HMGA1b are highly conserved between mammalian species and widely described as participating in various cellular processes. By inducing DNA conformation changes the HMGA1 proteins indirectly influence the binding of various transcription factors and therefore effect the transcription regulation. In humans chromosomal aberrations affecting the HMGA1 gene locus on HSA 6p21 were described to be the cause for various benign mesenchymal tumours while high titres of HMGA1 proteins were shown to be associated with the neoplastic potential of various types of cancer. Interestingly, the absence of HMGA1 proteins was shown to cause insulin resistance and diabetes in humans and mice. Due to the various similarities in biology and presentation of human and canine cancers the dog has joined the common rodent animal model for therapeutic and preclinical studies. Accordingly, the canine genome was sequenced completely twice but unfortunately this could not solve the structure of canine HMGA1 gene. Results Herein we report the characterisation of the genomic structure of the canine HMGA1 gene consisting of 7 exons and 6 introns spanning in total 9524 bp, the in vivo localisation of the HMGA1 protein to the nucleus, and a chromosomal assignment of the gene by FISH to CFA12q11. Additionally, we evaluated a described canine HMGA1 exon 6 SNP in 55 Dachshunds. Conclusion The performed characterisations will make comparative analyses of aberrations affecting the human and canine gene and proteins possible, thereby providing a basis for revealing mechanisms involved in HMGA1 related pathogenesis in both species.

  5. Highly frequent mutations in negative regulators of multiple virulence genes in group A streptococcal toxic shock syndrome isolates.

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    Tadayoshi Ikebe

    2010-04-01

    Full Text Available Streptococcal toxic shock syndrome (STSS is a severe invasive infection characterized by the sudden onset of shock and multiorgan failure; it has a high mortality rate. Although a number of studies have attempted to determine the crucial factors behind the onset of STSS, the responsible genes in group A Streptococcus have not been clarified. We previously reported that mutations of csrS/csrR genes, a two-component negative regulator system for multiple virulence genes of Streptococcus pyogenes, are found among the isolates from STSS patients. In the present study, mutations of another negative regulator, rgg, were also found in clinical isolates of STSS patients. The rgg mutants from STSS clinical isolates enhanced lethality and impaired various organs in the mouse models, similar to the csrS mutants, and precluded their being killed by human neutrophils, mainly due to an overproduction of SLO. When we assessed the mutation frequency of csrS, csrR, and rgg genes among S. pyogenes isolates from STSS (164 isolates and non-invasive infections (59 isolates, 57.3% of the STSS isolates had mutations of one or more genes among three genes, while isolates from patients with non-invasive disease had significantly fewer mutations in these genes (1.7%. The results of the present study suggest that mutations in the negative regulators csrS/csrR and rgg of S. pyogenes are crucial factors in the pathogenesis of STSS, as they lead to the overproduction of multiple virulence factors.

  6. Spectrum and inoculum size effect of a rapid antigen detection test for group A streptococcus in children with pharyngitis.

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    Jérémie F Cohen

    Full Text Available BACKGROUND: The stability of the accuracy of a diagnostic test is critical to whether clinicians can rely on its result. We aimed to assess whether the performance of a rapid antigen detection test (RADT for group A streptococcus (GAS is affected by the clinical spectrum and/or bacterial inoculum size. METHODS: Throat swabs were collected from 785 children with pharyngitis in an office-based, prospective, multicenter study (2009-2010. We analysed the effect of clinical spectrum (i.e., the McIsaac score and its components and inoculum size (light or heavy GAS growth on the accuracy (sensitivity, specificity, likelihood ratios and predictive values of a RADT, with laboratory throat culture as the reference test. We also evaluated the accuracy of a McIsaac-score-based decision rule. RESULTS: GAS prevalence was 36% (95CI: 33%-40%. The inoculum was heavy for 85% of cases (81%-89%. We found a significant spectrum effect on sensitivity, specificity, likelihood ratios and positive predictive value (p<0.05 but not negative predictive value, which was stable at about 92%. RADT sensitivity was greater for children with heavy than light inoculum (95% vs. 40%, p<0.001. After stratification by inoculum size, the spectrum effect on RADT sensitivity was significant only in patients with light inoculum, on univariate and multivariate analysis. The McIsaac-score-based decision rule had 99% (97%-100% sensitivity and 52% (48%-57% specificity. CONCLUSIONS: Variations in RADT sensitivity only occur in patients with light inocula. Because the spectrum effect does not affect the negative predictive value of the test, clinicians who want to rule out GAS can rely on negative RADT results regardless of clinical features if they accept that about 10% of children with negative RADT results will have a positive throat culture. However, such a policy is more acceptable in populations with very low incidence of complications of GAS infection.

  7. Phylogeographical footprint of colonial history in the global dispersal of human immunodeficiency virus type 2 group A.

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    Faria, Nuno R; Hodges-Mameletzis, Ioannis; Silva, Joana C; Rodés, Berta; Erasmus, Smit; Paolucci, Stefania; Ruelle, Jean; Pieniazek, Danuta; Taveira, Nuno; Treviño, Ana; Gonçalves, Maria F; Jallow, Sabelle; Xu, Li; Camacho, Ricardo J; Soriano, Vincent; Goubau, Patrick; de Sousa, João D; Vandamme, Anne-Mieke; Suchard, Marc A; Lemey, Philippe

    2012-04-01

    Human immunodeficiency virus type 2 (HIV-2) emerged in West Africa and has spread further to countries that share socio-historical ties with this region. However, viral origins and dispersal patterns at a global scale remain poorly understood. Here, we adopt a Bayesian phylogeographic approach to investigate the spatial dynamics of HIV-2 group A (HIV-2A) using a collection of 320 partial pol and 248 partial env sequences sampled throughout 19 countries worldwide. We extend phylogenetic diffusion models that simultaneously draw information from multiple loci to estimate location states throughout distinct phylogenies and explicitly attempt to incorporate human migratory fluxes. Our study highlights that Guinea-Bissau, together with Côte d'Ivoire and Senegal, have acted as the main viral sources in the early stages of the epidemic. We show that convenience sampling can obfuscate the estimation of the spatial root of HIV-2A. We explicitly attempt to circumvent this by incorporating rate priors that reflect the ratio of human flow from and to West Africa. We recover four main routes of HIV-2A dispersal that are laid out along colonial ties: Guinea-Bissau and Cape Verde to Portugal, Côte d'Ivoire and Senegal to France. Within Europe, we find strong support for epidemiological linkage from Portugal to Luxembourg and to the UK. We demonstrate that probabilistic models can uncover global patterns of HIV-2A dispersal providing sampling bias is taken into account and we provide a scenario for the international spread of this virus.

  8. Awareness, knowledge, perceptions, and attitudes towards genetic testing for cancer risk among ethnic minority groups: a systematic review.

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    Hann, Katie E J; Freeman, Madeleine; Fraser, Lindsay; Waller, Jo; Sanderson, Saskia C; Rahman, Belinda; Side, Lucy; Gessler, Sue; Lanceley, Anne

    2017-05-25

    Genetic testing for risk of hereditary cancer can help patients to make important decisions about prevention or early detection. US and UK studies show that people from ethnic minority groups are less likely to receive genetic testing. It is important to understand various groups' awareness of genetic testing and its acceptability to avoid further disparities in health care. This review aims to identify and detail awareness, knowledge, perceptions, and attitudes towards genetic counselling/testing for cancer risk prediction in ethnic minority groups. A search was carried out in PsycInfo, CINAHL, Embase and MEDLINE. Search terms referred to ethnicity, genetic testing/counselling, cancer, awareness, knowledge, attitudes, and perceptions. Quantitative and qualitative studies, written in English, and published between 2000 and 2015, were included. Forty-one studies were selected for review: 39 from the US, and two from Australia. Results revealed low awareness and knowledge of genetic counselling/testing for cancer susceptibility amongst ethnic minority groups including African Americans, Asian Americans, and Hispanics. Attitudes towards genetic testing were generally positive; perceived benefits included positive implications for personal health and being able to inform family. However, negative attitudes were also evident, particularly the anticipated emotional impact of test results, and concerns about confidentiality, stigma, and discrimination. Chinese Australian groups were less studied, but of interest was a finding from qualitative research indicating that different views of who close family members are could impact on reported family history of cancer, which could in turn impact a risk assessment. Interventions are needed to increase awareness and knowledge of genetic testing for cancer risk and to reduce the perceived stigma and taboo surrounding the topic of cancer in ethnic minority groups. More detailed research is needed in countries other than the US and

  9. M protein typing of Thai group A streptococcal isolates by PCR-Restriction fragment length polymorphism analysis

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    Good Michael F

    2005-10-01

    Full Text Available Abstract Background Group A streptococcal (GAS infections can lead to the development of severe post-infectious sequelae, such as rheumatic fever (RF and rheumatic heart disease (RHD. RF and RHD are a major health concern in developing countries, and in indigenous populations of developed nations. The majority of GAS isolates are M protein-nontypeable (MNT by standard serotyping. However, GAS typing is a necessary tool in the epidemiologically analysis of GAS and provides useful information for vaccine development. Although DNA sequencing is the most conclusive method for M protein typing, this is not a feasible approach especially in developing countries. To overcome this problem, we have developed a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP-based assay for molecular typing the M protein gene (emm of GAS. Results Using one pair of primers, 13 known GAS M types showed one to four bands of PCR products and after digestion with Alu I, they gave different RFLP patterns. Of 106 GAS isolates examined from the normal Thai population and from patients with GAS-associated complications including RHD, 95 isolates gave RFLP patterns that corresponded to the 13 known M types. Only 11 isolates gave RFLP patterns that differed from the 13 known M types. These were then analyzed by DNA sequencing and six additional M types were identified. In addition, we found that M93 GAS was the most common M type in the population studied, and is consistent with a previous study of Thai GAS isolates. Conclusion PCR-RFLP analysis has the potential for the rapid screening of different GAS M types and is therefore considerably advantageous as an alternative M typing approach in developing countries in which GAS is endemic.

  10. Use of intravenous immunoglobulin therapy in the treatment of septic shock, in particular severe invasive group A streptococcal disease

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    Ajay H Raithatha

    2012-01-01

    Full Text Available Group A streptococcus (GAS is a β-hemolytic bacterium often found in the throat and skin. The two most severe clinical manifestations of GAS are streptococcal toxic shock syndrome and necrotizing fasciitis. Intravenous immunoglobulin (IVIg is a gamma globulin made from purified pooled plasma of thousands of donors, consisting mainly of IgG. We report the case of a 40-year-old man admitted after 2 days of vomiting and severe right-sided chest pain. He was hypotensive with a sinus tachycardia, pyrexial, and vasodilated. The only other positive finding was a swollen and erythematous chest wall. Muscle layer biopsies and blood cultures soon grew extensive GAS, and an initial diagnosis of necrotizing fasciitis was made. The clinical syndrome was of severe septic shock secondary to invasive GAS. The patient quickly deteriorated with a worsening metabolic acidosis. Despite maximal intensive care therapy including fluids, vasoactive agents, and also activated protein C, the patient continued to remain profoundly hypotensive. A decision was made to commence IVIg, with the aim of immunomodulation of the inflammatory cascade seen in sepsis. Over the next 24 hours the patient improved, was extubated 3 days later, and subsequently discharged from hospital after 2 weeks. Although the evidence for the use of IVIg in severe invasive GAS disease is limited, we feel that on reviewing the available literature its use in this case was justified. The limited worldwide supply and high costs, together with a limited evidence base, warrant restricting its use to cases in which conventional therapy has failed. The literature for use of intravenous immunoglobulin in invasive GAS infection will be reviewed in this article.

  11. Molecular Epidemiological Traits of Group A Rotaviruses in Japanese Children During Transitional Period of Rotavirus Vaccine Implementation, 2011 - 2014.

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    Takanashi, Sayaka; Thongprachum, Aksara; Okitsu, Shoko; Nishimura, Shuichi; Kobayashi, Masaaki; Kikuta, Hideaki; Yamamoto, Atsuko; Sugita, Kumiko; Baba, Tsuneyoshi; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

    2017-05-01

    Group A rotavirus (RVA) vaccines have been introduced in Japan since 2011. To investigate the molecular epidemiological traits of RVA during the transitional period of rotavirus vaccine implementation in Japan, this study was undertaken by following up three-decade long surveillance conducted in the same regions. RVA were screened and genotyped by RT-PCR from diarrheal samples collected from non-hospitalized patients in six localities (Hokkaido, Tokyo, Shizuoka, Osaka, Kyoto, and Saga) during 2011 - 2014. Selected samples were sequenced to elucidate the evolutionary trend. Among 1858 specimens, the detection rate of RVA declined to 4.0% in 2013 - 2014 from 17.9% in 2011 - 2012 and 22.1% in 2012 - 2013. G1P[8] was the most predominant genotype in the first two years accounting for more than half, and G9P[8] showed the highest detection rate as 35.0% in the last year. Interestingly, the proportional rate of G2 strains in the studied period increased from 0% to 25%. VP6 genotyping revealed that DS-1 like reassortant G1P[8] strains were detected all over Japan and their prevalence fluctuated greatly from 35.0% to 89.5%. Sequence analysis of VP6 showed that strains in the current strains were closely related but distinct from the original reference strains, namely Wa and DS-1. The detection rates of RVA, their GP combinations, prevalence of reassortant strains varied greatly after the introduction of rotavirus vaccines in Japan. Continuous monitoring is warranted to refine future vaccine strategy.

  12. Group a rotavirus and norovirus genotypes circulating in the northeastern Brazil in the post-monovalent vaccination era.

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    Sá, Ana Caroline C; Gómez, Mariela M; Lima, Ila Fernanda N; Quetz, Josiane S; Havt, Alexandre; Oriá, Reinaldo B; Lima, Aldo A; Leite, José Paulo G

    2015-09-01

    Group A rotaviruses (RVA) and noroviruses (NoV) are the leading cause of acute gastroenteritis (AGE) worldwide. Childhood diarrhea deaths and hospital admissions have declined since the introduction of the monovalent (G1P[8]) vaccine (Rotarix(®) [RV1]) in the National Immunization Program in Brazil in 2006. This study aims to investigate the epidemiological profile of NoV and RVA infections from children with AGE in the Northeastern region of Brazil in the post vaccine season. Two-hundred fecal samples collected from children up to 10 years old in Fortaleza, Ceará between 2008-2009 were screened for the presence of RVA and NoV. Positive samples were genotyped and sequenced. The RVA screening revealed 12% prevalence and all RVA strains belonged to G2P[4] genotype. Phylogenetic analysis based on the 11 RVA genome segments sequenced from eight samples revealed a DS-1-like genotype constellation: I2-R2-C2-M2-A2-N2-T2-E2-H2. For NoV screening, the prevalence observed was 17% and the following genotypes were detected: GII.4 (59%), GII.12 (17%), GII.6 (9%), GII.3 (6%), and GII.? (9%). At least four different NoVs genotypes and two RVA G2P[4] variants were identified circulating in the Northeastern region of Brazil. RVA phylogenetic analysis suggests that the RVA G2P[4] strains might have originated from intragenogroup reassortment events. Whether the genetic modifications observed in these contemporary G2P[4] RVA strains may impact the long-term effectiveness of the current vaccination programs remains to be explored. These data reinforce the importance of surveillance for monitoring the emergence of new strains of RVA and NoV and their impact on cases of acute gastroenteritis.

  13. Diversity of group A rotavirus genes detected in the Triângulo Mineiro region, Minas Gerais, Brazil.

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    Dulgheroff, Ana Carolina Bernardes; Silva, George Allan Villarouco da; Naveca, Felipe Gomes; Oliveira, Adriana Gonçalves de; Domingues, André Luiz da Silva

    2016-01-01

    Group A rotaviruses are the main causative agent of infantile gastroenteritis. The segmented nature of the viral genome allows reassortment of genome segments, which can generate genetic variants. In this study, we characterized the diversity of the VP7, VP4 (VP8*), VP6, NSP4, and NSP5 genes of the rotaviruses that circulated from 2005 to 2011 in the Triângulo Mineiro (TM) region of Brazil. Samples with genotypes G2 (sublineages IVa-1 and IVa-3), G1 (sublineage I-A), G9 (lineage III), G12 (lineages II and III), G8 (lineage II), G3 (lineage III), P[4] (sublineages IVa and IVb), P[8] (sublineages P[8]-3.6, P[8]-3.3, and P[8]-3.1), I2 (lineage VII), E2 (lineages VI, XII, and X), and H2 (lineage III) were identified. The associations found in the samples were G1, G9, or G12 with P[8]-I1-E1-H1; G2 or G8 with P[4]-I2-E2-H2; G12 with I3-E3-H6; and G3 with P[4]-I2-E3-H3 (previously unreported combination). Reassortment events in G2P[4] strains and an apparent pattern of temporal segregation within the lineages were observed. Five TM samples contained genes that exhibited high nucleotide and amino acid identities with strains of animal origin. The present study includes a period of pre- and post-introduction of rotavirus vaccination in all Brazilian territories, thereby serving as a basis for monitoring changes in the genetic constitution of rotaviruses. The results also contribute to the understanding of the diversity and evolution of rotaviruses in a global context.

  14. Diversity of group A rotavirus genes detected in the Triângulo Mineiro region, Minas Gerais, Brazil

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    Ana Carolina Bernardes Dulgheroff

    Full Text Available ABSTRACT Group A rotaviruses are the main causative agent of infantile gastroenteritis. The segmented nature of the viral genome allows reassortment of genome segments, which can generate genetic variants. In this study, we characterized the diversity of the VP7, VP4 (VP8*, VP6, NSP4, and NSP5 genes of the rotaviruses that circulated from 2005 to 2011 in the Triângulo Mineiro (TM region of Brazil. Samples with genotypes G2 (sublineages IVa-1 and IVa-3, G1 (sublineage I-A, G9 (lineage III, G12 (lineages II and III, G8 (lineage II, G3 (lineage III, P[4] (sublineages IVa and IVb, P[8] (sublineages P[8]-3.6, P[8]-3.3, and P[8]-3.1, I2 (lineage VII, E2 (lineages VI, XII, and X, and H2 (lineage III were identified. The associations found in the samples were G1, G9, or G12 with P[8]-I1-E1-H1; G2 or G8 with P[4]-I2-E2-H2; G12 with I3-E3-H6; and G3 with P[4]-I2-E3-H3 (previously unreported combination. Reassortment events in G2P[4] strains and an apparent pattern of temporal segregation within the lineages were observed. Five TM samples contained genes that exhibited high nucleotide and amino acid identities with strains of animal origin. The present study includes a period of pre- and post-introduction of rotavirus vaccination in all Brazilian territories, thereby serving as a basis for monitoring changes in the genetic constitution of rotaviruses. The results also contribute to the understanding of the diversity and evolution of rotaviruses in a global context.

  15. A Quantitative Study on the in-vitro and in-vivo Acetylation of High Mobility Group A1 Proteins

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    Zhang, Qingchun; Zhang, Kangling; Zou, Yan; Perna, Avi; Wang, Yinsheng

    2007-01-01

    High mobility group (HMG) A1 proteins are subject to a number of post-translational modifications, which may regulate their function in gene transcription and other cellular processes. We examined, by using mass spectrometry, the acetylation of HMGA1a and HMGA1b proteins induced by histone acetyltransferases p300 and PCAF in vitro and in PC-3 human prostate cancer cells in vivo. It turned out that five lysine residues in HMGA1a, i.e., Lys-14, Lys-64, Lys-66, Lys-70, and Lys-73, could be acety...

  16. The relevance of testing the efficacy of anti-angiogenesis treatments on cells derived from primary tumors: a new method for the personalized treatment of renal cell carcinoma.

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    Renaud Grépin

    Full Text Available Despite the numerous available drugs, the most appropriate treatments for patients affected by common or rare renal cell carcinomas (RCC, like those associated with the Xp11.2 translocation/transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3 gene fusion (TFE3 RCC, are not clearly defined. We aimed to make a parallel between the sensitivity to targeted therapies on living patients and on cells derived from the initial tumor. Three patients diagnosed with a metastatic RCC (one clear cell RCC [ccRCC], two TFE3 RCC were treated with anti-angiogenesis drugs. The concentrations of the different drugs giving 50% inhibition of cell proliferation (IC50 were determined with the Thiazolyl Blue Tetrazolium Bromide (MTT assay on cells from the primary tumors and a reference sensitive RCC cell line (786-O. We considered the cells to be sensitive if the IC50 was lower or equal to that in 786-O cells, and insensitive if the IC50 was higher to that in 786-O cells (IC 50 of 6 ± 1 µM for sunitinib, 10 ± 1 µM for everolimus and 6 ± 1 µM for sorafenib. Based on this standard, the response in patients and in cells was equivalent. The efficacy of anti-angiogenesis therapies was also tested in cells obtained from five patients with non-metastatic ccRCC, and untreated as recommended by clinical practice in order to determine the best treatment in case of progression toward a metastatic grade. In vitro experiments may represent a method for evaluating the best first-line treatment for personalized management of ccRCC during the period following surgery.

  17. Shedding light on proteins, nucleic acids, cells, humans and fish

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    Setlow, Richard B.

    2002-01-01

    I was trained as a physicist in graduate school. Hence, when I decided to go into the field of biophysics, it was natural that I concentrated on the effects of light on relatively simple biological systems, such as proteins. The wavelengths absorbed by the amino acid subunits of proteins are in the ultraviolet (UV). The wavelengths that affect the biological activities, the action spectra, also are in the UV, but are not necessarily parallel to the absorption spectra. Understanding these differences led me to investigate the action spectra for affecting nucleic acids, and the effects of UV on viruses and cells. The latter studies led me to the discovery of the important molecular nature of the damages affecting DNA (cyclobutane pyrimidine dimers) and to the discovery of nucleotide excision repair. Individuals with the genetic disease xeroderma pigmentosum (XP) are extraordinarily sensitive to sunlight-induced skin cancer. The finding, by James Cleaver, that their skin cells were defective in DNA repair strongly suggested that DNA damage was a key step in carcinogenesis. Such information was important for estimating the wavelengths in sunlight responsible for human skin cancer and for predicting the effects of ozone depletion on the incidence of non-melanoma skin cancer. It took experiments with backcross hybrid fish to call attention to the probable role of the longer UV wavelengths not absorbed by DNA in the induction of melanoma. These reflections trace the biophysicist's path from molecules to melanoma.

  18. On the viability of cyclometalated Ru(II) complexes as dyes in DSSC regulated by COOH group, a DFT study.

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    Wang, Jian; Bai, Fu-Quan; Xia, Bao-Hui; Feng, Lu; Zhang, Hong-Xing; Pan, Qing-Jiang

    2011-02-14

    The Ru(II) complexes [Ru(bpp)(dcbpy)Cl](+) (1), [Ru(tcbpp)(bpy)Cl](+) (2), and [Ru(tc'bpp)(bpy)Cl](+) (3) (bpp = 2,6-bis(N-pyrazolyl)pyridine, dcbpy = 4,4'-dicarboxyl-bipyridine, bpy = bipyridine, tcbpp = 4-carboxyl-2,6-bis(2-carboxyl-N-pyrazolyl)pyridine, tc'bpp = 4-carboxyl-2,6-bis(4-carboxyl-N-pyrazolyl)pyridine) are studied theoretically using density functional theory (DFT) techniques to explore their properties as dye in a solar cell. The calculated geometry structure and absorption spectrum of 1 are consistent with its experimental results. The calculation results indicate which sites the COOH groups attach to can significantly influence the electronic structure of the complex. By migrating the COOH groups from the bpy ligand in 1 to bpp ligand in 2 and 3, the nature of LUMO changes from bpy-localized to bpp dominated. The calculated low-lying absorptions at λ > 370 nm of the three complexes are categorized as metal-to-ligand charge-transfer (MLCT) transitions and the transition terminates at the orbital populated by the COOH appended ligand. The atomic spin density analysis also indicates that the ligand which is modified by the COOH groups is the ideal spot for the captured electron to situate. It can be predicted that the performance of 2 and 3 in the dye-sensitized solar cell can be enhanced as compared with 1.

  19. Tetracarboxylatoplatinum(IV) complexes featuring monodentate leaving groups - A rational approach toward exploiting the platinum(IV) prodrug strategy.

    Science.gov (United States)

    Höfer, Doris; Varbanov, Hristo P; Legin, Anton; Jakupec, Michael A; Roller, Alexander; Galanski, Markus; Keppler, Bernhard K

    2015-12-01

    A series of novel symmetrically and unsymmetrically coordinated platinum(IV) complexes with monodentate carboxylato ligands was synthesized. The compounds exhibit a general coordination sphere of [Pt(en)(OCOR)2(OCOR')(OCOR″)], where the carboxylato ligands are represented by acetato and succinic acid monoester ligands. Dicarboxylatoplatinum(II) complexes were synthesized and oxidized symmetrically or unsymmetrically to obtain platinum(IV) complexes, which were subsequently carboxylated with noncyclic anhydrides. The compounds were investigated in detail by elemental analysis, mass spectrometry, infrared and multinuclear ((1)H, (13)C, (15)N, (195)Pt) NMR spectroscopy as well as by X-ray diffraction in some cases. The reduction behavior was followed by NMR spectroscopy, while stability and lipophilicity were examined by analytical reversed phase HPLC measurements. Cytotoxic properties were studied in three human cancer cell lines derived from cisplatin sensitive ovarian teratocarcinoma (CH1/PA-1), cisplatin insensitive colon carcinoma (SW480) and non-small cell lung cancer (A549). Thereby, the most lipophilic (yet water soluble) platinum(IV) complexes showed promising IC50 values in the low micromolar and even nanomolar range, demonstrating the significant advantage of using equatorially coordinated monodentate carboxylato ligands. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Cytotoxic Effect of Ethanol Extract of Microalga, Chaetoceros calcitrans, and Its Mechanisms in Inducing Apoptosis in Human Breast Cancer Cell Line

    Science.gov (United States)

    Ebrahimi Nigjeh, Siyamak; Yusoff, Fatimah Md; Mohamed Alitheen, Noorjahan Banu; Rasoli, Mehdi; Keong, Yeap Swee; Omar, Abdul Rahman bin

    2013-01-01

    Marine microalgae have been prominently featured in cancer research. Here, we examined cytotoxic effect and apoptosis mechanism of crude ethanol extracts of an indigenous microalga, Chaetoceros calcitrans (UPMAAHU10) on human breast cell lines. MCF-7 was more sensitive than MCF-10A with IC50 value of 3.00 ± 0.65, whilst the IC50 value of Tamoxifen against MCF-7 was 12.00 ± 0.52 μg/mL after 24 hour incubation. Based on Annexin V/Propidium iodide and cell cycle flow cytometry analysis, it was found that inhibition of cell growth by EEC on MCF-7 cells was through the induction of apoptosis without cell cycle arrest. The apoptotic cells at subG0/G1 phase in treated MCF-7 cells at 48 and 72 hours showed 34 and 16 folds increased compared to extract treated MCF-10A cells which showed only 6 and 7 folds increased at the same time points, respectively. Based on GeXP study, EEC induced apoptosis on MCF-7 cells via modulation of CDK2, MDM2, p21Cip1, Cyclin A2, Bax and Bcl-2. The EEC treated MCF-7 cells also showed an increase in Bax/Bcl-2 ratio that in turn activated the caspase-dependent pathways by activating caspase 7. Thus, marine microalga, Chaetoceros calcitrans may be considered a good candidate to be developed as a new anti-breast cancer drug. PMID:23509778

  1. A族β溶血性链球菌耐药%Resistance of Group A β-hemolytic streptococcus

    Institute of Scientific and Technical Information of China (English)

    梁云梅; 李苗; 呙芳; 张金; 任思其

    2016-01-01

    A 族β溶血性链球菌(GAS)即酿脓链球菌,是人类最重要的病原体之一,可导致皮肤、黏膜浅表感染性疾病,危及生命的侵袭性疾病,毒素介导性疾病及免疫相关性疾病。抗生素是控制 GAS 菌感染的有效手段,β-内酰胺类抗生素是治疗 GAS 感染的首选药物,大环内酯类抗生素常作为阻断 GAS 外毒素产物的手段或对β-内酰胺类抗生素过敏患者替代治疗药物而被推荐。但随着大环内酯类抗生素的广泛使用,大环内酯类抗生素耐药 GAS 在全球范围内播散,成为全球关注的问题。现将对 GAS 对大环内酯类抗生素耐药情况进行阐述。%Group A β-hemolytic streptococcus (GAS),namely Streptococcus pyogenes,is one of the most im-portant human pathogen.GAS can cause skin and mucous membrane superficial infectious diseases,life -threatening invasive disease,toxin -mediated diseases and immune -related diseases.Antibiotic is an effective mean to control GAS infection.The β-lactam antibiotics remain the first -choice treatment for GAS infection and the macrolides are often recommended as a replacement therapy for β-lactam antibiotics allergic patients or a means to blocking GAS exotoxin product.But with the widespread use of macrolides autibiotics,macrolide -resistant GAS spread in the world. This paper will elaborate the situation of macrolide -resistant clones.

  2. Seven-year surveillance of emm types of pediatric Group A streptococcal pharyngitis isolates in Western Greece.

    Directory of Open Access Journals (Sweden)

    George A Syrogiannopoulos

    Full Text Available BACKGROUND: An experimental 26-valent M protein Group A streptococcal (GAS vaccine has entered clinical studies. Pharyngeal GAS emm type surveillances in different areas and time-periods enhance the understanding of the epidemiology of GAS pharyngitis. Moreover, these surveillances, combined with the data on GAS invasive disease, can play a significant role in the formulation of multivalent type-specific vaccines. METHODS: During a 7-year period (1999-2005, 2408 GAS isolates were recovered from consecutive children with pharyngitis in Western Greece. The overall macrolide resistance rate was 22.8%. Along the study period we noted a tendency towards significantly decreased rates of resistance, with the lowest rates occurring in 2002 (15.3%, 2003 (15% and 2004 (16.7%. A random sample of isolates from each year, 338 (61.7% of the 548 macrolide-resistant and 205 (11% of the macrolide-susceptible, underwent molecular analysis, including emm typing. RESULTS: The 543 typed isolates had 28 different emm types. A statistically significant association was found between macrolide resistance and emm4, emm22 and emm77, whereas emm1, emm3, emm6, emm12, emm87 and emm89 were associated with macrolide susceptibility. A significant yearly fluctuation was observed in emm4, emm28 and emm77. The most common macrolide-resistant GAS were emm77 isolates harboring erm(A, either alone or in combination with mef(A, emm4 carrying mef(A, emm28 possessing erm(B, emm75 carrying mef(A, emm12 harboring mef(A and emm22 carrying erm(A. We estimated that 82.8% of the isolates belonged to emm types included in the novel 26-valent M protein vaccine. The vaccine coverage rate was determined mainly by the increased frequency of nonvaccine emm4 isolates. CONCLUSIONS: A limited number of emm types dominated among macrolide-susceptible and macrolide-resistant GAS isolates. We observed seasonal fluctuations, which were significant for emm4, emm28 and emm77. This type of data can serve as

  3. [Serotypes and antimicrobial susceptibilities of invasive group A streptococci identified in eastern Black Sea region of Turkey].

    Science.gov (United States)

    Bayramoğlu, Gülçin; Topkaya, Aynur E; Balıkcı, Ahmet; Aydın, Faruk

    2011-07-01

    Frequency of invasive group A streptococcus (GAS) infections is increasing worldwide in recent 20 years. Serotypes responsible for these clinical manifestations and their antibiotic susceptibilities should be known in order to establish preventive measures and initiate appropriate treatment. This study was aimed to determine the serotypes, antibiotic susceptibilities and inducible clindamycin resistance among invasive GAS isolated between 2006-2009 period. A total of 22 GAS strains isolated from clinical samples [sterile body fluids (peritoneal, pleural, pericardial, joint and cerebrospinal fluids), blood, tissue biopsy] of the patients (14 male, 8 female; age range: 3-82 years, median age: 59) who admitted to Karadeniz Technical University Faculty of Medicine, Farabi Hospital located in Trabzon province (Eastern Black Sea Region of Turkey), between March 2006 and March 2009 were included in the study. GAS serotypes were determined by the investigation of serum opacity factors (SOF), T proteins and M proteins. SOF production was investigated by microplate method using human serum and SOF types were determined by SOF-inhibition test using specific antisera. T protein types were detected by agglutination method using polyvalent anti-T sera, and M serotypes were detected by capillary precipitation method using M antisera. Antimicrobial susceptibility tests were performed by disk-diffusion method according to CLSI recommendations. SOF were positive in 9 (41%) samples. Use of T antiserum yielded T (n= 8) and U (n= 7) types and M antiserum M1 (n= 4) and M2 (n= 3) types. The overall antibiotic susceptibility rate of the isolates was 68% (15/22) and overall resistance rate was 32% (7/22). All of the GAS strains were found susceptible to benzylpenicillin, ceftriaxone, vancomycin, levofloxacine and linezolid, however 9 (41%) were intermediate susceptible to tetracycline and 1 (4.5%) was intermediate susceptible to erythromycin. Four (18%) strains were found resistant to

  4. Dual-site phosphorylation of the control of virulence regulator impacts group a streptococcal global gene expression and pathogenesis.

    Directory of Open Access Journals (Sweden)

    Nicola Horstmann

    2014-05-01

    Full Text Available Phosphorylation relays are a major mechanism by which bacteria alter transcription in response to environmental signals, but understanding of the functional consequences of bacterial response regulator phosphorylation is limited. We sought to characterize how phosphorylation of the control of virulence regulator (CovR protein from the major human pathogen group A Streptococcus (GAS influences GAS global gene expression and pathogenesis. CovR mainly serves to repress GAS virulence factor-encoding genes and has been shown to homodimerize following phosphorylation on aspartate-53 (D53 in vitro. We discovered that CovR is phosphorylated in vivo and that such phosphorylation is partially heat-stable, suggesting additional phosphorylation at non-aspartate residues. Using mass spectroscopy along with targeted mutagenesis, we identified threonine-65 (T65 as an additional CovR phosphorylation site under control of the serine/threonine kinase (Stk. Phosphorylation on T65, as mimicked by the recombinant CovR T65E variant, abolished in vitro CovR D53 phosphorylation. Similarly, isoallelic GAS strains that were either unable to be phosphorylated at D53 (CovR-D53A or had functional constitutive phosphorylation at T65 (CovR-T65E had essentially an identical gene repression profile to each other and to a CovR-inactivated strain. However, the CovR-D53A and CovR-T65E isoallelic strains retained the ability to positively influence gene expression that was abolished in the CovR-inactivated strain. Consistent with these observations, the CovR-D53A and CovR-T65E strains were hypervirulent compared to the CovR-inactivated strain in a mouse model of invasive GAS disease. Surprisingly, an isoalleic strain unable to be phosphorylated at CovR T65 (CovR-T65A was hypervirulent compared to the wild-type strain, as auto-regulation of covR gene expression resulted in lower covR gene transcript and CovR protein levels in the CovR-T65A strain. Taken together, these data

  5. Complement-mediated opsonization of invasive group A Streptococcus pyogenes strain AP53 is regulated by the bacterial two-component cluster of virulence responder/sensor (CovRS) system.

    Science.gov (United States)

    Agrahari, Garima; Liang, Zhong; Mayfield, Jeffrey A; Balsara, Rashna D; Ploplis, Victoria A; Castellino, Francis J

    2013-09-20

    Group A Streptococcus pyogenes (GAS) strain AP53 is a primary isolate from a patient with necrotizing fasciitis. These AP53 cells contain an inactivating mutation in the sensor component of the cluster of virulence (cov) responder (R)/sensor (S) two-component gene regulatory system (covRS), which enhances the virulence of the primary strain, AP53/covR(+)S(-). However, specific mechanisms by which the covRS system regulates the survival of GAS in humans are incomplete. Here, we show a key role for covRS in the regulation of opsonophagocytosis of AP53 by human neutrophils. AP53/covR(+)S(-) cells displayed potent binding of host complement inhibitors of C3 convertase, viz. Factor H (FH) and C4-binding protein (C4BP), which concomitantly led to minimal C3b deposition on AP53 cells, further showing that these plasma protein inhibitors are active on GAS cells. This resulted in weak killing of the bacteria by human neutrophils and a corresponding high death rate of mice after injection of these cells. After targeted allelic alteration of covS(-) to wild-type covS (covS(+)), a dramatic loss of FH and C4BP binding to the AP53/covR(+)S(+) cells was observed. This resulted in elevated C3b deposition on AP53/covR(+)S(+) cells, a high level of opsonophagocytosis by human neutrophils, and a very low death rate of mice infected with AP53/covR(+)S(+). We show that covRS is a critical transcriptional regulator of genes directing AP53 killing by neutrophils and regulates the levels of the receptors for FH and C4BP, which we identify as the products of the fba and enn genes, respectively.

  6. Genome-Wide Uniparental Disomy and Copy Number Variations in Renal Cell Carcinomas Associated with Birt-Hogg-Dubé Syndrome.

    Science.gov (United States)

    Iribe, Yasuhiro; Yao, Masahiro; Tanaka, Reiko; Kuroda, Naoto; Nagashima, Yoji; Nakatani, Yukio; Furuya, Mitsuko

    2016-02-01

    Birt-Hogg-Dubé syndrome is an inherited disorder caused by germline mutations of the folliculin gene (FLCN). The affected patients are prone to developing renal cell carcinomas (RCCs). Most mutant FLCN-associated RCCs (mFLCN-RCCs) are histologically chromophobe RCCs and hybrid oncocytic/chromophobe tumors. It is incompletely understood whether mFLCN-RCCs have different chromosomal abnormalities compared with their sporadic histological counterparts. Herein, we describe somatic mutations of FLCN and DNA-copy number abnormalities using a high-density, whole-genome, single-nucleotide polymorphism array. The histological types included chromophobe RCC (n = 12), hybrid oncocytic/chromophobe tumor (n = 5), and clear-cell RCC (n = 2). Of 19 tumors, 8 had pathological somatic mutations of FLCN. Among 11 mFLCN-RCCs investigated by single-nucleotide polymorphism array, 8 showed balanced genomic profiles, 2 had gains in chromosome 3q, and 1 had gains in chromosomes 1q and 7. All had copious numbers of loss of heterozygosity in a wide range of chromosomes. The common loss-of-heterozygosity regions were chromosomes 3p24, 8q11, 16q11, Xp22-21, Xp11, Xq11, Xq13, and Xq23. Most of the loss of heterozygosity was because of uniparental disomy. Common uniparental disomy patterns in chromophobe RCCs and hybrid oncocytic/chromophobe tumors indicated that these types were relatively similar in cytogenetic events. Two clear-cell RCCs also shared several uniparental disomy regions with chromophobe RCCs and hybrid oncocytic/chromophobe tumors. mFLCN-RCCs may have common therapeutic targets among different histological types.

  7. Stem Cells

    Science.gov (United States)

    Stem cells are cells with the potential to develop into many different types of cells in the body. ... the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  8. Ovarian tumors in pediatric age group - A clinicopathologic study of 10 years′ cases in West Bengal, India

    Directory of Open Access Journals (Sweden)

    Bhattacharyya Nirmal

    2010-01-01

    Full Text Available Background and objectives: Objective in this retrospective study is to find out the incidence of different ovarian tumors of girls up to 20 years of age observed in last ten years in North Bengal Medical College and to correlate clinical and gross findings with histopathologic findings and to compare the incidence with other studies and follow-up of patients with malignant ovarian tumors. Materials and Methods: Findings were retrieved from records of different pathological reports and clinical reports. Results: Total 151 cases of ovarian tumors were received in pathology department in which 34 cases were malignant (22.6%. Amongst malignant cases, 66% are of germ-cell origin-dysgerminoma being the commonest. Strikingly we got 9 cases of malignant surface epithelial tumor. As per follow-up records most of the dysgerminoma came in stage IA and recovered fully following chemotherapy and radiotherapy. Amongst other malignant tumors, few lost the follow-up management and others expired due to metastasis. Conclusions: Patients from hilly areas of North Bengal and low socio-economic status led to lower detection rate of ovarian tumors in early stage which are absolutely necessary for proper guidelines of management to reduce mortality.

  9. Genetic diversity in the G protein gene of group A human respiratory syncytial viruses circulating in Riyadh, Saudi Arabia.

    Science.gov (United States)

    Almajhdi, Fahad N; Farrag, Mohamed A; Amer, Haitham M

    2014-01-01

    Human respiratory syncytial virus (HRSV) is a frequent cause of hospitalization and mortality in children worldwide. The molecular epidemiology and circulation pattern of HRSV in Saudi Arabia is mostly uncharted. In the current study, the genetic variability and phylogenetic relationships of HRSV type A strains circulating in Riyadh Province were explored. Nasopharyngeal aspirates were collected from hospitalized children with acute respiratory symptoms during the winter-spring seasons of 2007/08 and 2008/09. Among 175 samples analyzed, 39 (22.3 %) were positive for HRSV by one-step RT-PCR (59 % type A and 41 % type B). Propagation of positive samples in HEp-2 cells permitted the recovery of the first Saudi HRSV isolates. Genetic variability among Saudi HRSV-A strains was evaluated by sequence analysis of the complete attachment (G) protein gene. The nucleotide sequence was compared to representatives of the previously identified HRSV-A genotypes. Sequence and phylogenetic analysis showed that the strains examined in this study were very closely related at both the nucleotide and amino acid level, and all of them are clustered in the GA2 genotype (and mostly belonged to the NA-1 subtype). A total of 23 mutation sites, 14 of which resulted in an amino acid change, were recorded only in Saudi strains. This is the first report on genetic diversity of HRSV-A strains in Saudi Arabia. Further analysis of strains on a geographical and temporal basis is needed to fully understand HRSV-A circulation patterns in Saudi Arabia.

  10. Sinorhizobium meliloti CpdR1 is critical for co-ordinating cell cycle progression and the symbiotic chronic infection.

    Science.gov (United States)

    Kobayashi, Hajime; De Nisco, Nicole J; Chien, Peter; Simmons, Lyle A; Walker, Graham C

    2009-08-01

    ATP-driven proteolysis plays a major role in regulating the bacterial cell cycle, development and stress responses. In the nitro -fixing symbiosis with host plants, Sinorhizobium meliloti undergoes a profound cellular differentiation, including endoreduplication of the ome. The regulatory mechanisms governing the alterations of the S. meliloti cell cycle in planta are largely unknown. Here, we report the characterization of two cpdR homologues, cpdR1 and cpdR2, of S. meliloti that encode single-domain response regulators. In Caulobacter crescentus, CpdR controls the polar localization of the ClpXP protease, thereby mediating the regulated proteolysis of key protein(s), such as CtrA, involved in cell cycle progression. The S. meliloti cpdR1-null mutant can invade the host cytoplasm, however, the intracellular bacteria are unable to differentiate into bacteroids. We show that S. meliloti CpdR1 has a polar localization pattern and a role in ClpX positioning similar to C. crescentus CpdR, suggesting a conserved function of CpdR proteins among alpha-proteobacteria. However, in S. meliloti, free-living cells of the cpdR1-null mutant show a striking morphology of irregular coccoids and aberrant DNA replication. Thus, we demonstrate that CpdR1 mediates the co-ordination of cell cycle events, which are critical for both the free-living cell division and the differentiation required for the chronic intracellular infection.

  11. Mechanisms by which Human Cells Bypass Damaged Bases during DNA Replication after Ultraviolet Irradiation

    Directory of Open Access Journals (Sweden)

    James E. Cleaver

    2002-01-01

    Full Text Available The replication of damaged DNA involves cascading mechanisms of increasing complexity but decreasing accuracy. The most accurate mechanism uses low-fidelity DNA polymerases, Pol H and Pol I, which have active sites sufficiently large to accommodate a pyrimidine dimer. Replicative bypass of DNA damage by these polymerases produces an accurately replicated, newly synthesized strand. Pol H negative cells (XP-V cell lines either adopt a proposed secondary bypass mechanism or a recombinational mode. The mechanism of the secondary bypass is unclear, but a number of experiments suggests roles for excision repair to remove damage ahead of replication forks, hRad6/18 proteolysis to clear the blocked forks, and the Rad17-RFC and 9-1-1 complexes to establish a new replication apparatus. This alternative pathway requires functional p53. In Pol H negative cells in which p53 is also inactive, the arrested fork fragments into DNA double strand breaks. Foci containing PCNA, Mre11/Rad50/Nbs1, and gamma-H2Ax can then be detected, along with chromosomal rearrangement and high frequencies of sister chromatid exchanges. The recruitment of recombination components to the arrested forks represents the ultimate failure of replication machinery to relieve the arrested state and bypass the damage. The resulting chromosomal instability in surviving cells will contribute to malignant transformation.

  12. Cells, cells, and more cells.

    Science.gov (United States)

    Bhatti, M Tariq; Gres, Katherine E; Petitto, Virginia B; Cross, Shelley Ann

    2007-01-01

    A 64-year-old woman presented with bilateral optic nerve swelling, vitreous cells, and cerebrospinal fluid monocytic pleocytosis. A chest radiograph and computed tomography demonstrated a lesion in the left lung, which histologically was confirmed to be a small-cell lung carcinoma. The serum was positive for the anti-CV2 (anti-CRMP-5) antibody. Following treatment with chemoradiation the optic nerve swelling and vitritis resolved. The differential diagnosis of uveal-meningeal diseases is discussed and the pathophysiology and clinical manifestations of paraneoplastic syndromes reviewed.

  13. Yeast RAD2, a homolog of human XPG, plays a key role in the regulation of the cell cycle and actin dynamics

    Directory of Open Access Journals (Sweden)

    Mi-Sun Kang

    2013-12-01

    Mutations in the human XPG gene cause Cockayne syndrome (CS and xeroderma pigmentosum (XP. Transcription defects have been suggested as the fundamental cause of CS; however, defining CS as a transcription syndrome is inconclusive. In particular, the function of XPG in transcription has not been clearly demonstrated. Here, we provide evidence for the involvement of RAD2, the Saccharomyces cerevisiae counterpart of XPG, in cell cycle regulation and efficient actin assembly following ultraviolet irradiation. RAD2 C-terminal deletion, which resembles the XPG mutation found in XPG/CS cells, caused cell growth arrest, the cell cycle stalling, a defective α-factor response, shortened lifespan, cell polarity defect, and misregulated actin-dynamics after DNA damage. Overexpression of the C-terminal 65 amino acids of Rad2p was sufficient to induce hyper-cell polarization. In addition, RAD2 genetically interacts with TPM1 during cell polarization. These results provide insights into the role of RAD2 in post-UV irradiation cell cycle regulation and actin assembly, which may be an underlying cause of XPG/CS.

  14. Comparison of Serum Zinc Levels among Children with Simple Febrile Seizure and Control Group: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Mohammad Mehdi NASEHI

    2015-01-01

    Full Text Available How to Cite This Article: Nasehi MM, Sakhaei R, Moosazadeh M, Aliramzany M. Comparison of Serum Zinc Levels among Children with Simple Febrile Seizure and Control Group: A Systematic Review. Iran J Child Neurol. 2015 Winter;9(1:17-24 .AbstractObjectiveSeveral factors are involved in the etiology of febrile seizure (FS, among themis zinc (Zn, which has been discussed in various studies. The present systematic review compares Zn levels in children with FS and a control group.Materials & MethodsWe searched keywords of febrile seizure, febrile convulsion, children, childhood,fever, trace elements, risk factor, predisposing, zinc, Zn, and epilepsy in thefollowing databases: SCOPUS, PubMed, and Google Scholar. The quality ofresearch papers was assessed using a checklist. Data was extracted from primarystudies based on demographic variables and amounts of Zn in case and controlgroups.ResultsTwenty primary studies were entered in the present study. Of which, eighteenstudies, reported that Zn serum levels were significantly lower in the case group(patients with FS than the control group.ConclusionThe present systematic review indicated that Zn is one factor for predicting FS.A low level of this element among children can be regarded as a contributingfactor for FS, a conclusion with a high consensus among different studies carriedout in different parts of the world. ReferencesHeydarian F, Ashrafzadeh F, Ghasemian A. Serum ZINC level in Patients with simple febrile seizure. Iran J Child Neurology 2010; 14(2:41-44.Mahyar A, Pahlavan AA, Varasteh-Nejad A. Serum zinc level in children with febrile seizure. Acta Medica Iranica 2008; 46(6: 477-80.Kunda GK, Rabin F, Nandi ER, Sheikh N, Akhter S. Etiology and Risk Factors of Febrile Seizure – An Update. Bangladesh J Child Health 2010; 34 (3:103-112.Abbaskhaniyan A, Shokrzadeh M, Rafati MR, Mashhadiakabr M, Arab A, Yazdani J. Survey and Relation of Serum Magnesium Level in Children with Seizure. J Mazand Univ

  15. Group a Pfemp1 functional domains bind icam1 and induce cross-reactive and adhesion inhibitory antibodies during malaria infections

    DEFF Research Database (Denmark)

    Bengtsson, A.; Jørgensen, L.; Rask, Thomas Salhøj

    2012-01-01

    The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) plays an important role in antigenic variation and pathogenesis of malaria. PfEMP1 proteins encoded by group A var genes appear to be involved in the pathogenesis of severe disease and have been suggested as attractive candidates f...

  16. A Conserved UDP-Glucose Dehydrogenase Encoded outside the hasABC Operon Contributes to Capsule Biogenesis in Group A Streptococcus

    NARCIS (Netherlands)

    Cole, Jason N.; Aziz, Ramy K.; Kuipers, Kirsten; Timmer, Anjuli M.; Nizet, Victor; van Sorge, Nina M.

    2012-01-01

    Group A Streptococcus (GAS) is a human-specific bacterial pathogen responsible for serious morbidity and mortality worldwide. The hyaluronic acid (HA) capsule of GAS is a major virulence factor, contributing to bloodstream survival through resistance to neutrophil and antimicrobial peptide killing a

  17. Determination of the relationship between group A streptococcal genome content, M type, and toxic shock syndrome by a mixed genome microarray

    NARCIS (Netherlands)

    Vlaminckx, B.J.M.; Schuren, F.H.J.; Montijn, R.C.; Caspers, M.P.M.; Fluit, A.C.; Wannet, W.J.B.; Schouls, L.M.; Verhoef, J.; Jansen, W.T.M.

    2007-01-01

    Group A streptococci (GAS), or Streptococcus pyogenes, are associated with a remarkable variety of diseases, ranging from superficial infections to life-threatening diseases such as toxic-shock-like syndrome (TSS). GAS strains belonging to M types M1 and M3 are associated with TSS. This study aims t

  18. Cloning and analysis of the mouse Fanconi anemia group a cDNA and an overlapping penta zinc finger cDNA

    NARCIS (Netherlands)

    Wong, JCY; Alon, N; Norga, K; Kruyt, FAE; Youssoufian, H; Buchwald, M

    2000-01-01

    Despite the cloning of four disease-associated genes for Fanconi anemia (FA), the molecular pathogenesis of FA remains largely unknown. To study FA complementation group A using the mouse as a mode I system, we cloned and characterized the mouse homolog of the human FANCA cDNA, The mouse cDNA

  19. Antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and group A beta-haemolytic streptococci in 2002-2003. Results of the multinational GRASP Surveillance Program

    DEFF Research Database (Denmark)

    Beekmann, Susan E; Heilmann, Kris P; Richter, Sandra S

    2005-01-01

    A multinational surveillance study, GRASP, was conducted between November 2002 and April 2003 with the aim of assessing rates of antimicrobial resistance among 2656 isolates of Streptococcus pneumoniae, 2486 isolates of group A beta-haemolytic streptococci, 1358 isolates of Haemophilus influenzae...... and 1047 of Moraxella catarrhalis from 20 countries in Europe, eastern Asia and southern Africa. Conspicuous differences between various countries were noted in the S. pneumoniae resistance rates observed for penicillin (0-79.2%) and erythromycin (4-66%), along with other antimicrobials. The percentage...... of MDR strains was above 25% in 8 of the 20 countries studied. Group A streptococcal macrolide resistance rates ranged from 0% to 35% by country, while rates of beta-lactamase production ranged from 0% to 39% for H. influenzae and 80-100% for M. catarrhalis. Antibiotic resistance in S. pneumoniae remains...

  20. New advance of group A human rotavirus epidemiology and vaccine development%A组人轮状病毒流行病学及疫苗研究进展

    Institute of Scientific and Technical Information of China (English)

    童志礼; 方肇寅

    2002-01-01

    A组人轮状病毒(group A human rotavirus, HRV)是世界范围内婴幼儿重症腹泻的主要病因.本文在介绍HRV结构和特性的基础上,对世界范围内HRV血清型流行病学特征以及HRV疫苗研究现状和趋势分别作了综述.