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  1. AU="Aziz Belkadi"
  2. AU="Weiying, Lu"
  3. AU="Hiroki Ishikawa"
  4. AU=Fischer Lorenz
  5. AU="Hooberman, B H"
  6. AU="Vaid, Nidhi"
  7. AU="Xiao Han"
  8. AU="Stuart G. Tangye"
  9. AU="Yao-Zhong Zhao"
  10. AU="Chern, Chang-Ming"
  11. AU="Floeter, Jens"
  12. AU="Wijnen, Petal"
  13. AU="Saravanamuthu, Pira"
  14. AU="Kalpana Deepa Priya Dorayappan"
  15. AU="Xiao, Hongkui"
  16. AU="Lali, Arvind M"
  17. AU="Kim, Hyojeong"
  18. AU="Nasseri, Saeed"
  19. AU="Kluge"
  20. AU="Bierbaumer, Lisa"
  21. AU="Rashid, Muhammad"
  22. AU="Huang, Chiun-Sheng"
  23. AU="Shevchuk, O O"
  24. AU="Mulvihill, Emily"
  25. AU="Gandhi, Adarsh"
  26. AU="Zhao, Chuanrui"
  27. AU="Shelley Wiart"
  28. AU="Lydia E. Wroblewski" AU="Lydia E. Wroblewski"
  29. AU="Paterson, Ross"
  30. AU="Alexander Marx"
  31. AU="Robinson, Jill"
  32. AU="Mitchell, Adam W M"
  33. AU="Ingham, Jesse R"

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  1. Artikel ; Online: Deep sequencing of DNA from urine of kidney allograft recipients to estimate donor/recipient-specific DNA fractions.

    Aziz Belkadi / Gaurav Thareja / Darshana Dadhania / John R Lee / Thangamani Muthukumar / Catherine Snopkowski / Carol Li / Anna Halama / Sara Abdelkader / Silvana Abdulla / Yasmin Mahmoud / Joel Malek / Manikkam Suthanthiran / Karsten Suhre

    PLoS ONE, Vol 16, Iss 4, p e

    2021  Band 0249930

    Abstract: Kidney transplantation is the treatment of choice for patients with end-stage kidney failure, but transplanted allograft could be affected by viral and bacterial infections and by immune rejection. The standard test for the diagnosis of acute pathologies ...

    Abstract Kidney transplantation is the treatment of choice for patients with end-stage kidney failure, but transplanted allograft could be affected by viral and bacterial infections and by immune rejection. The standard test for the diagnosis of acute pathologies in kidney transplants is kidney biopsy. However, noninvasive tests would be desirable. Various methods using different techniques have been developed by the transplantation community. But these methods require improvements. We present here a cost-effective method for kidney rejection diagnosis that estimates donor/recipient-specific DNA fraction in recipient urine by sequencing urinary cell DNA. We hypothesized that in the no-pathology stage, the largest tissue types present in recipient urine are donor kidney cells, and in case of rejection, a larger number of recipient immune cells would be observed. Extensive in-silico simulation was used to tune the sequencing parameters: number of variants and depth of coverage. Sequencing of DNA mixture from 2 healthy individuals showed the method is highly predictive (maximum error < 0.04). We then demonstrated the insignificant impact of familial relationship and ethnicity using an in-house and public database. Lastly, we performed deep DNA sequencing of urinary cell pellets from 32 biopsy-matched samples representing two pathology groups: acute rejection (AR, 11 samples) and acute tubular injury (ATI, 12 samples) and 9 samples with no pathology. We found a significant association between the donor/recipient-specific DNA fraction in the two pathology groups compared to no pathology (P = 0.0064 for AR and P = 0.026 for ATI). We conclude that deep DNA sequencing of urinary cells from kidney allograft recipients offers a noninvasive means of diagnosing acute pathologies in the human kidney allograft.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2021-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Whole genome sequencing in the Middle Eastern Qatari population identifies genetic associations with 45 clinically relevant traits

    Gaurav Thareja / Yasser Al-Sarraj / Aziz Belkadi / Maryam Almotawa / The Qatar Genome Program Research (QGPR) Consortium / Karsten Suhre / Omar M. E. Albagha

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Band 10

    Abstract: The genetic basis for traits can vary between populations. Here the authors report a genome wide association study with 45 clinically-relevant traits in individuals from Qatar, replicating many known loci and identifying new Qatari-predominant signals. ...

    Abstract The genetic basis for traits can vary between populations. Here the authors report a genome wide association study with 45 clinically-relevant traits in individuals from Qatar, replicating many known loci and identifying new Qatari-predominant signals.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2021-02-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Detection of infiltrating fibroblasts by single-cell transcriptomics in human kidney allografts

    Hemant Suryawanshi / Hua Yang / Michelle Lubetzky / Pavel Morozov / Mila Lagman / Gaurav Thareja / Alicia Alonso / Carol Li / Catherine Snopkowski / Aziz Belkadi / Franco B. Mueller / John R. Lee / Darshana M. Dadhania / Steven P. Salvatore / Surya V. Seshan / Vijay K. Sharma / Karsten Suhre / Manikkam Suthanthiran / Thomas Tuschl /
    Thangamani Muthukumar

    PLoS ONE, Vol 17, Iss

    2022  Band 6

    Abstract: We tested the hypothesis that single-cell RNA-sequencing (scRNA-seq) analysis of human kidney allograft biopsies will reveal distinct cell types and states and yield insights to decipher the complex heterogeneity of alloimmune injury. We selected 3 ... ...

    Abstract We tested the hypothesis that single-cell RNA-sequencing (scRNA-seq) analysis of human kidney allograft biopsies will reveal distinct cell types and states and yield insights to decipher the complex heterogeneity of alloimmune injury. We selected 3 biopsies of kidney cortex from 3 individuals for scRNA-seq and processed them fresh using an identical protocol on the 10x Chromium platform; (i) HK: native kidney biopsy from a living donor, (ii) AK1: allograft kidney with transplant glomerulopathy, tubulointerstitial fibrosis, and worsening graft function, and (iii) AK2: allograft kidney after successful treatment of active antibody-mediated rejection. We did not study T-cell-mediated rejections. We generated 7217 high-quality single cell transcriptomes. Taking advantage of the recipient-donor sex mismatches revealed by X and Y chromosome autosomal gene expression, we determined that in AK1 with fibrosis, 42 months after transplantation, more than half of the kidney allograft fibroblasts were recipient-derived and therefore likely migratory and graft infiltrative, whereas in AK2 without fibrosis, 84 months after transplantation, most fibroblasts were donor-organ-derived. Furthermore, AK1 was enriched for tubular progenitor cells overexpressing profibrotic extracellular matrix genes. AK2, eight months after successful treatment of rejection, contained plasmablast cells with high expression of immunoglobulins, endothelial cell elaboration of T cell chemoattractant cytokines, and persistent presence of cytotoxic T cells. In addition to these key findings, our analysis revealed unique cell types and states in the kidney. Altogether, single-cell transcriptomics yielded novel mechanistic insights, which could pave the way for individualizing the care of transplant recipients.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2022-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Microdeletion on chromosome 8p23.1 in a familial form of severe Buruli ulcer.

    Quentin B Vincent / Aziz Belkadi / Cindy Fayard / Estelle Marion / Ambroise Adeye / Marie-Françoise Ardant / Christian R Johnson / Didier Agossadou / Lazaro Lorenzo / Julien Guergnon / Christine Bole-Feysot / Jeremy Manry / Patrick Nitschké / Ioannis Theodorou / Jean-Laurent Casanova / Laurent Marsollier / Annick Chauty / Laurent Abel / Alexandre Alcaïs /
    Franco-Beninese Buruli Research Group

    PLoS Neglected Tropical Diseases, Vol 12, Iss 4, p e

    2018  Band 0006429

    Abstract: Buruli ulcer (BU), the third most frequent mycobacteriosis worldwide, is a neglected tropical disease caused by Mycobacterium ulcerans. We report the clinical description and extensive genetic analysis of a consanguineous family from Benin comprising two ...

    Abstract Buruli ulcer (BU), the third most frequent mycobacteriosis worldwide, is a neglected tropical disease caused by Mycobacterium ulcerans. We report the clinical description and extensive genetic analysis of a consanguineous family from Benin comprising two cases of unusually severe non-ulcerative BU. The index case was the most severe of over 2,000 BU cases treated at the Centre de Dépistage et de Traitement de la Lèpre et de l'Ulcère de Buruli, Pobe, Benin, since its opening in 2003. The infection spread to all limbs with PCR-confirmed skin, bone and joint infections. Genome-wide linkage analysis of seven family members was performed and whole-exome sequencing of both patients was obtained. A 37 kilobases homozygous deletion confirmed by targeted resequencing and located within a linkage region on chromosome 8 was identified in both patients but was absent from unaffected siblings. We further assessed the presence of this deletion on genotyping data from 803 independent local individuals (402 BU cases and 401 BU-free controls). Two BU cases were predicted to be homozygous carriers while none was identified in the control group. The deleted region is located close to a cluster of beta-defensin coding genes and contains a long non-coding (linc) RNA gene previously shown to display highest expression values in the skin. This first report of a microdeletion co-segregating with severe BU in a large family supports the view of a key role of human genetics in the natural history of the disease.
    Schlagwörter Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2018-04-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel: Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity

    Israel, Laura / Andrew Moran / Anne Puel / Avinash Abhyankar / Aziz Belkadi / Bruce Beutler / Capucine Picard / Carolina Prando / Damien Chaussabel / Elisabeth Israelsson / Erika Della Mina / François Vandenesch / Frederic Batteux / Jean-Laurent Casanova / Jethro Herberg / Katarzyna Bulek / Laurent Abel / Lazaro Lorenzo / Leonard E. Weisman /
    Ling Yun / Marc Descatoire / Maya Chrabieh / Michael Levin / Nicole A. Lemmens / Peter D. Arkwright / Sandra Weller / Théo Lasseau / Vanessa Sancho-Shimizu / Vincent Pedergnana / Willem J.B. van Wamel / Xiaoxia Li / Ying Wang / Yuval Itan / Zhao Zhang

    Cell. 2017 Feb. 23, v. 168, no. 5

    2017  

    Abstract: The molecular basis of the incomplete penetrance of monogenic disorders is unclear. We describe here eight related individuals with autosomal recessive TIRAP deficiency. Life-threatening staphylococcal disease occurred during childhood in the proband, ... ...

    Abstract The molecular basis of the incomplete penetrance of monogenic disorders is unclear. We describe here eight related individuals with autosomal recessive TIRAP deficiency. Life-threatening staphylococcal disease occurred during childhood in the proband, but not in the other seven homozygotes. Responses to all Toll-like receptor 1/2 (TLR1/2), TLR2/6, and TLR4 agonists were impaired in the fibroblasts and leukocytes of all TIRAP-deficient individuals. However, the whole-blood response to the TLR2/6 agonist staphylococcal lipoteichoic acid (LTA) was abolished only in the index case individual, the only family member lacking LTA-specific antibodies (Abs). This defective response was reversed in the patient, but not in interleukin-1 receptor-associated kinase 4 (IRAK-4)-deficient individuals, by anti-LTA monoclonal antibody (mAb). Anti-LTA mAb also rescued the macrophage response in mice lacking TIRAP, but not TLR2 or MyD88. Thus, acquired anti-LTA Abs rescue TLR2-dependent immunity to staphylococcal LTA in individuals with inherited TIRAP deficiency, accounting for incomplete penetrance. Combined TIRAP and anti-LTA Ab deficiencies underlie staphylococcal disease in this patient.
    Schlagwörter adaptive immunity ; agonists ; childhood ; fibroblasts ; homozygosity ; humans ; innate immunity ; interleukin-1 ; leukocytes ; lipoteichoic acids ; macrophages ; mice ; monoclonal antibodies ; patients ; penetrance ; Toll-like receptor 2 ; Toll-like receptor 4
    Sprache Englisch
    Erscheinungsverlauf 2017-0223
    Umfang p. 789-800.e10.
    Erscheinungsort Elsevier Inc.
    Dokumenttyp Artikel
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2017.01.039
    Datenquelle NAL Katalog (AGRICOLA)

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