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  1. AU="Emily Locke"
  2. AU="Arets, E.J.M.M."
  3. AU="Bruce Brew"
  4. AU="Ensinger, Carol L"
  5. AU="Li, Yibo"
  6. AU="DiCicco-Bloom, Emanuel"
  7. AU="Rossi, Ugo"
  8. AU="Iancu, Marieta"
  9. AU="Jia, Jianping"
  10. AU="Kuhlman, Kate R"
  11. AU="Brufsky, A"
  12. AU="SU Xian-feng"
  13. AU="Toledo, Maximiliano A"
  14. AU="Yushun Wan"
  15. AU="Jahangir, Muhammad"
  16. AU="Kannan, Shankar"
  17. AU="Andreyev, H Jervoise N"
  18. AU="O'Sullivan, Fionnuala"
  19. AU="Chaudhary, Sibgha Gull"
  20. AU="Höger, Brigitta"
  21. AU="Sai, Victor"
  22. AU="Ghasemi, H M"
  23. AU="Ruliang Li"
  24. AU="Gilchriese, M G D"
  25. AU="Rist, Andreas"
  26. AU="Katznelson, Andrew" AU="Katznelson, Andrew"
  27. AU="Solís-Martínez, Obed"
  28. AU="Dumitrescu, Florentina"
  29. AU="Hodge, Sarah"
  30. AU="Piasek, Joanna"

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  1. Artikel ; Online: Multiplex serological assay for establishing serological profiles of polymorphic, closely related peptide antigens

    Jessica Bolton / Sidhartha Chaudhury / Randall S. MacGill / Angela M. Early / C. Richter King / Emily Locke / Daniel E. Neafsey / Elke S. Bergmann-Leitner

    MethodsX, Vol 8, Iss , Pp 101345- (2021)

    2021  

    Abstract: Profiling of serological responses to establish the landscape of antibody specificities in individuals exposed to pathogens or vaccines is crucial for (a) revealing humoral immune correlates of protection; (b) uncovering markers of pathogen exposure; and ...

    Abstract Profiling of serological responses to establish the landscape of antibody specificities in individuals exposed to pathogens or vaccines is crucial for (a) revealing humoral immune correlates of protection; (b) uncovering markers of pathogen exposure; and (c) identifying antigens and epitopes associated with disease vs. protection. Establishing the antigenic profile of serological responses requires either expensive microarrays or labor- and time-intensive ELISA assays. Multiplex assay platforms are increasingly being evaluated for their usefulness for high-throughput testing of sera or plasma. The methodology described here utilizes a plate-based assay that allows the simultaneous detection of up to ten antigens per well in a 96 well format using an electrochemiluminescence immunoassay (ECLIA). • The newly developed protocol outlines high-throughput profiling of serological responses using a multiplex testing platform with subsequent computational analysis. • The protocol is a modification of the basic assay development manual from the manufacturer of the MESO QuickPlex SQ 120 instrument (MSD, Gaithersburg, MD) and can be used for synthetic peptides as well as full length proteins. • The protocol can be applied to map serological responses to pathogens or pathogen-derived antigens to establish serological profiles in search for biomarkers or immune correlates.
    Schlagwörter Sero-surveillance multiplex assay ; Science ; Q
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2021-01-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
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  2. Artikel ; Online: Structural and biophysical correlation of anti-NANP antibodies with in vivo protection against P. falciparum

    Tossapol Pholcharee / David Oyen / Yevel Flores-Garcia / Gonzalo Gonzalez-Paez / Zhen Han / Katherine L. Williams / Wayne Volkmuth / Daniel Emerling / Emily Locke / C. Richter King / Fidel Zavala / Ian A. Wilson

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

    2021  Band 14

    Abstract: The most advanced P. falciparum circumsporozoite protein (PfCSP)-based malaria vaccine confers partial protection. Here, Pholcharee et al. present crystal structures, binding affinities/kinetics, and in vivo protection of 8 anti-NANP antibodies to ... ...

    Abstract The most advanced P. falciparum circumsporozoite protein (PfCSP)-based malaria vaccine confers partial protection. Here, Pholcharee et al. present crystal structures, binding affinities/kinetics, and in vivo protection of 8 anti-NANP antibodies to understand in vivo protection of PfCSP-targeting antibodies.
    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: Characterization of two in vivo challenge models to measure functional activity of monoclonal antibodies to Plasmodium falciparum circumsporozoite protein

    Rama Raghunandan / Bryan T. Mayer / Yevel Flores-Garcia / Monica W. Gerber / Raphael Gottardo / Hugo Jhun / Sonia M. Herrera / Daniel W. Perez-Ramos / Emily Locke / C. Richter King / Fidel Zavala

    Malaria Journal, Vol 19, Iss 1, Pp 1-

    2020  Band 15

    Abstract: Abstract Background New strategies are needed to reduce the incidence of malaria, and promising approaches include the development of vaccines and monoclonal antibodies (mAbs) that target the circumsporozoite protein (CSP). To select the best candidates ... ...

    Abstract Abstract Background New strategies are needed to reduce the incidence of malaria, and promising approaches include the development of vaccines and monoclonal antibodies (mAbs) that target the circumsporozoite protein (CSP). To select the best candidates and speed development, it is essential to standardize preclinical assays to measure the potency of such interventions in animal models. Methods Two assay configurations were studied using transgenic Plasmodium berghei expressing Plasmodium falciparum full-length circumsporozoite protein. The assays measured (1) reduction in parasite infection of the liver (liver burden) following an intravenous (i.v) administration of sporozoites and (2) protection from parasitaemia following mosquito bite challenge. Two human CSP mAbs, AB311 and AB317, were compared for their ability to inhibit infection. Multiple independent experiments were conducted to define assay variability and resultant impact on the ability to discriminate differences in mAb functional activity. Results Overall, the assays produced highly consistent results in that all individual experiments showed greater functional activity for AB317 compared to AB311 as calculated by the dose required for 50% inhibition (ID50) as well as the serum concentration required for 50% inhibition (IC50). The data were then used to model experimental designs with adequate statistical power to rigorously screen, compare, and rank order novel anti-CSP mAbs. Conclusion The results indicate that in vivo assays described here can provide reliable information for comparing the functional activity of mAbs. The results also provide guidance regarding selection of the appropriate experimental design, dose selection, and group sizes.
    Schlagwörter Malaria ; Transgenic parasite ; Bioluminescence ; Monoclonal antibodies ; Functional activity ; Circumsporozoite protein (CSP) ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
    Sprache Englisch
    Erscheinungsdatum 2020-03-01T00:00:00Z
    Verlag BMC
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: A novel CSP C-terminal epitope targeted by an antibody with protective activity against Plasmodium falciparum.

    Nathan Beutler / Tossapol Pholcharee / David Oyen / Yevel Flores-Garcia / Randall S MacGill / Elijah Garcia / Jaeson Calla / Mara Parren / Linlin Yang / Wayne Volkmuth / Emily Locke / Jason A Regules / Sheetij Dutta / Daniel Emerling / Angela M Early / Daniel E Neafsey / Elizabeth A Winzeler / C Richter King / Fidel Zavala /
    Dennis R Burton / Ian A Wilson / Thomas F Rogers

    PLoS Pathogens, Vol 18, Iss 3, p e

    2022  Band 1010409

    Abstract: Potent and durable vaccine responses will be required for control of malaria caused by Plasmodium falciparum (Pf). RTS,S/AS01 is the first, and to date, the only vaccine that has demonstrated significant reduction of clinical and severe malaria in ... ...

    Abstract Potent and durable vaccine responses will be required for control of malaria caused by Plasmodium falciparum (Pf). RTS,S/AS01 is the first, and to date, the only vaccine that has demonstrated significant reduction of clinical and severe malaria in endemic cohorts in Phase 3 trials. Although the vaccine is protective, efficacy declines over time with kinetics paralleling the decline in antibody responses to the Pf circumsporozoite protein (PfCSP). Although most attention has focused on antibodies to repeat motifs on PfCSP, antibodies to other regions may play a role in protection. Here, we expressed and characterized seven monoclonal antibodies to the C-terminal domain of CSP (ctCSP) from volunteers immunized with RTS,S/AS01. Competition and crystal structure studies indicated that the antibodies target two different sites on opposite faces of ctCSP. One site contains a polymorphic region (denoted α-ctCSP) and has been previously characterized, whereas the second is a previously undescribed site on the conserved β-sheet face of the ctCSP (denoted β-ctCSP). Antibodies to the β-ctCSP site exhibited broad reactivity with a diverse panel of ctCSP peptides whose sequences were derived from field isolates of P. falciparum whereas antibodies to the α-ctCSP site showed very limited cross reactivity. Importantly, an antibody to the β-site demonstrated inhibition activity against malaria infection in a murine model. This study identifies a previously unidentified conserved epitope on CSP that could be targeted by prophylactic antibodies and exploited in structure-based vaccine design.
    Schlagwörter Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2022-03-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
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  5. Artikel ; Online: Vaccine co-display of CSP and Pfs230 on liposomes targeting two Plasmodium falciparum differentiation stages

    Wei-Chiao Huang / Moustafa T. Mabrouk / Luwen Zhou / Minami Baba / Mayumi Tachibana / Motomi Torii / Eizo Takashima / Emily Locke / Jordan Plieskatt / C. Richter King / Camila H. Coelho / Patrick E. Duffy / Carole Long / Takafumi Tsuboi / Kazutoyo Miura / Yimin Wu / Tomoko Ishino / Jonathan F. Lovell

    Communications Biology, Vol 5, Iss 1, Pp 1-

    2022  Band 13

    Abstract: Co-display of two P. falciparum malaria vaccine antigens (Pfs230D1+ and CSP) on the surface of immunogenic liposomes results in functional immune responses upon immunization of mice and rabbits. Combining both antigens produces immune responses that both ...

    Abstract Co-display of two P. falciparum malaria vaccine antigens (Pfs230D1+ and CSP) on the surface of immunogenic liposomes results in functional immune responses upon immunization of mice and rabbits. Combining both antigens produces immune responses that both block transmission and prevent infection.
    Schlagwörter Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2022-08-01T00:00:00Z
    Verlag Nature Portfolio
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    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: A no film slot blot for the detection of developing P. falciparum oocysts in mosquitoes.

    Bryan Grabias / Nitin Verma / Hong Zheng / Abhai K Tripathi / Godfree Mlambo / Merribeth J Morin / Emily Locke / Sanjai Kumar

    PLoS ONE, Vol 12, Iss 4, p e

    2017  Band 0174229

    Abstract: Non-microscopy-based assays for sensitive and rapid detection of Plasmodium infection in mosquitoes are needed to allow rapid and high throughput measurement of transmission intensity and malaria control program effectiveness. Here, we report on a ... ...

    Abstract Non-microscopy-based assays for sensitive and rapid detection of Plasmodium infection in mosquitoes are needed to allow rapid and high throughput measurement of transmission intensity and malaria control program effectiveness. Here, we report on a modified enhanced chemiluminescence-based slot blot assay for detection of Plasmodium falciparum (Pf) circumsporozite protein (PfCSP) expressed on parasite oocysts developing inside the mosquito midgut. This modified assay has several novel features that include eliminating the need for exposure to autoradiography (AR) film, as well as utilizing a novel high affinity anti-CSP antibody, and optimizing assay procedures resulting in significant reduction in the time required to perform the assay. The chemiluminescent signal for the detection of PfCSP in mosquito samples was captured digitally utilizing the C-Digit blot scanner that, allowed the detection of 0.01 pg of recombinant P. falciparum CSP and as few as 0.02 P. falciparum oocysts in a little over two hours. The earlier ECL-SB detected rCSP and oocysts and took approximately 5 h to perform. Whole mosquito lysates from both high and low prevalence-infected mosquito populations were prepared and evaluated for PfCSP detection on the ECL-SB by both AR film and digital data capture and analysis. There was a 100% agreement between the AR film and the C-Digit scanner methods for PfCSP detection in randomly sampled mosquitoes. This novel "No Film" Slot Blot assay obviates the need for AR film exposure and development and significantly reduces the assay time enabling widespread use in field settings.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 500
    Sprache Englisch
    Erscheinungsdatum 2017-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Optimization of an in vivo model to study immunity to Plasmodium falciparum pre-erythrocytic stages

    Yevel Flores-Garcia / Sonia M. Herrera / Hugo Jhun / Daniel W. Pérez-Ramos / C. Richter King / Emily Locke / Ramadevi Raghunandan / Fidel Zavala

    Malaria Journal, Vol 18, Iss 1, Pp 1-

    2019  Band 9

    Abstract: Abstract Background The circumsporozoite protein (CSP) of Plasmodium is a key surface antigen that induces antibodies and T-cells, conferring immune protection in animal models and humans. However, much of the work on CSP and immunity has been developed ... ...

    Abstract Abstract Background The circumsporozoite protein (CSP) of Plasmodium is a key surface antigen that induces antibodies and T-cells, conferring immune protection in animal models and humans. However, much of the work on CSP and immunity has been developed based on studies using rodent or non-human primate CSP antigens, which may not be entirely translatable to CSP expressed by human malaria parasites, especially considering the host specificity of the different species. Methods Using a genetically engineered strain of Plasmodium berghei that expresses luciferase, GFP and the Plasmodium falciparum orthologue of CSP, the effect of laboratory preparation, mosquito treatment and mouse factors on sporozoite infectivity was assessed using an in vivo bioluminescence assay on mice. This assay was compared with a PCR-based protection assay using an already described monoclonal antibody that can provide sterile protection against sporozoite challenge. Results Bioluminescence assay demonstrated similar detection levels of the quantity and kinetics of liver-stage infection, compared to PCR-based detection. This assay was used to evaluate treatment of sporozoite and delivery method on mouse infectivity, as well as the effects of age, sex and strain of mice. Finally, this assay was used to test the protective capacity of monoclonal antibody AB317; results strongly recapitulate the findings of previous work on this antibody. Conclusions The PbGFP-Luc line and in vivo bioluminescence imaging provide highly sensitive read-outs of liver-stage infection in mice, and this method can be useful to reliably evaluate potency of pre-erythrocytic interventions.
    Schlagwörter Malaria ; Transgenic parasite ; Bioluminescence ; Vaccine ; Plasmodium falciparum ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2019-12-01T00:00:00Z
    Verlag BMC
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Transcriptome analysis based detection of Plasmodium falciparum development in Anopheles stephensi mosquitoes

    Miranda S. Oakley / Nitin Verma / Timothy G. Myers / Hong Zheng / Emily Locke / Merribeth J. Morin / Abhai K. Tripathi / Godfree Mlambo / Sanjai Kumar

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Band 12

    Abstract: Abstract The Plasmodium life cycle within the mosquito involves the gamete, zygote, motile ookinete, and the oocyst stage that supports sporogony and sporozoite formation. We mapped the P. falciparum transcriptome as the parasite progresses through the ... ...

    Abstract Abstract The Plasmodium life cycle within the mosquito involves the gamete, zygote, motile ookinete, and the oocyst stage that supports sporogony and sporozoite formation. We mapped the P. falciparum transcriptome as the parasite progresses through the oocyst stage of development on days 2, 4, 6, and 8 post-P. falciparum infectious blood meal. Through these genomic studies, we identified 212 novel transmission stage biomarkers including genes that are developmentally expressed at a single time point and genes that are pan-developmentally expressed at all four time points in P. falciparum oocysts. Validation of a small subset of genes at the transcriptional and translational level resulted in identification of a signature of genes/proteins that can detect parasites within the mosquito as early as day 2 post-infectious blood meal and can be used to distinguish early versus late stage P. falciparum oocyst development in the mosquito. Currently, circumsporozoite protein (CSP), which is detectable only after day 7 post-infection, is the only marker used for detection of P. falciparum infection in mosquitoes. Our results open the prospect to develop a non-CSP based detection assay for assessment of P. falciparum infection in mosquitoes and evaluate the effect of intervention measures on malaria transmission in an endemic setting.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 572
    Sprache Englisch
    Erscheinungsdatum 2018-08-01T00:00:00Z
    Verlag Nature Publishing Group
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel ; Online: Reductions in HIV Stigma as Measured by Social Distance

    Emily Locke / Angela Meshack / Ruth Githumbi / Glenn Urbach / Beau Miller / Ron Peters / Michael W. Ross

    International Journal of Social Science Studies, Vol 2, Iss 3, Pp 117-

    Impact of a Stigma Reduction Campaign in a Historically Black University

    2014  Band 122

    Abstract: We evaluated the effectiveness of a small media campaign intervention on a historically African American college campus aimed to lower social distance (willingness to interact) for people with HIV. A modified version of the Bogardus Social scale was used ...

    Abstract We evaluated the effectiveness of a small media campaign intervention on a historically African American college campus aimed to lower social distance (willingness to interact) for people with HIV. A modified version of the Bogardus Social scale was used to measure social distance. The survey included questions regarding HIV transmission knowledge and sympathy felt towards those with HIV. Time between pre-test (n= 207) and post-test (n=210) was 1 month. There was significant change in social distance from pre- to post-test only among women (p<.001). In a regression analysis transmission knowledge (p=.027), sympathy towards those with HIV (p=.000) and gender (p=.000) were significantly related to social distance. There was a significance difference between men and women for transmission knowledge (p=.001) and sympathy (p=.001). Small media campaigns can be effective at lowering social distance among female African American students but may need to be modified to be effective among males.
    Schlagwörter Social Sciences ; H
    Sprache Englisch
    Erscheinungsdatum 2014-07-01T00:00:00Z
    Verlag Redfame Publishing
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  10. Artikel ; Online: Structure and mechanism of monoclonal antibody binding to the junctional epitope of Plasmodium falciparum circumsporozoite protein.

    David Oyen / Jonathan L Torres / Phillip C Aoto / Yevel Flores-Garcia / Špela Binter / Tossapol Pholcharee / Sean Carroll / Sini Reponen / Rachael Wash / Qi Liang / Franck Lemiale / Emily Locke / Allan Bradley / C Richter King / Daniel Emerling / Paul Kellam / Fidel Zavala / Andrew B Ward / Ian A Wilson

    PLoS Pathogens, Vol 16, Iss 3, p e

    2020  Band 1008373

    Abstract: Lasting protection has long been a goal for malaria vaccines. The major surface antigen on Plasmodium falciparum sporozoites, the circumsporozoite protein (PfCSP), has been an attractive target for vaccine development and most protective antibodies ... ...

    Abstract Lasting protection has long been a goal for malaria vaccines. The major surface antigen on Plasmodium falciparum sporozoites, the circumsporozoite protein (PfCSP), has been an attractive target for vaccine development and most protective antibodies studied to date interact with the central NANP repeat region of PfCSP. However, it remains unclear what structural and functional characteristics correlate with better protection by one antibody over another. Binding to the junctional region between the N-terminal domain and central NANP repeats has been proposed to result in superior protection: this region initiates with the only NPDP sequence followed immediately by NANP. Here, we isolated antibodies in Kymab mice immunized with full-length recombinant PfCSP and two protective antibodies were selected for further study with reactivity against the junctional region. X-ray and EM structures of two monoclonal antibodies, mAb667 and mAb668, shed light on their differential affinity and specificity for the junctional region. Importantly, these antibodies also bind to the NANP repeat region with equal or better affinity. A comparison with an NANP-only binding antibody (mAb317) revealed roughly similar but statistically distinct levels of protection against sporozoite challenge in mouse liver burden models, suggesting that junctional antibody protection might relate to the ability to also cross-react with the NANP repeat region. Our findings indicate that additional efforts are necessary to isolate a true junctional antibody with no or much reduced affinity to the NANP region to elucidate the role of the junctional epitope in protection.
    Schlagwörter Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Thema/Rubrik (Code) 570
    Sprache Englisch
    Erscheinungsdatum 2020-03-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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