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Article: TAOK3 limits age-associated inflammation by negatively modulating macrophage differentiation and their production of TNFα.

Poirier, Alexandre / Wu, Chenyue / Hincapie, Ana Maria / Martinez-Cordova, Zuzet / Abidin, Belma Melda / Tremblay, Michel L

Immunity & ageing : I & A

2023 Volume 20, Issue 1, Page(s) 31

Abstract: Background: Human aging is characterized by a state of chronic inflammation, termed inflammaging, for which the causes are incompletely understood. It is known, however, that macrophages play a driving role in establishing inflammaging by promoting pro- ... ...

Abstract	Background: Human aging is characterized by a state of chronic inflammation, termed inflammaging, for which the causes are incompletely understood. It is known, however, that macrophages play a driving role in establishing inflammaging by promoting pro-inflammatory rather than anti-inflammatory responses. Numerous genetic and environmental risk factors have been implicated with inflammaging, most of which are directly linked to pro-inflammatory mediators IL-6, IL1Ra, and TNFα. Genes involved in the signaling and production of those molecules have also been highlighted as essential contributors. TAOK3 is a serine/threonine kinase of the STE-20 kinase family that has been associated with an increased risk of developing auto-immune conditions in several genome-wide association studies (GWAS). Yet, the functional role of TAOK3 in inflammation has remained unexplored. Results: We found that mice deficient in the serine/Threonine kinase Taok3 developed severe inflammatory disorders with age, which was more pronounced in female animals. Further analyses revealed a drastic shift from lymphoid to myeloid cells in the spleens of those aged mice. This shift was accompanied by hematopoietic progenitor cells skewing in Taok3 Conclusions: Essentially, Taok3 deficiency promotes the accumulation of monocytes in the periphery and their adoption of a pro-inflammatory phenotype. These findings illustrate the role of Taok3 in age-related inflammation and highlight the importance of genetic risk factors in this condition.
Language	English
Publishing date	2023-07-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2168941-6
ISSN	1742-4933
ISSN	1742-4933
DOI	10.1186/s12979-023-00350-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The induction of SHP-1 degradation by TAOK3 ensures the responsiveness of T cells to TCR stimulation.

Poirier, Alexandre / Ormonde, João Vitor Silva / Aubry, Isabelle / Abidin, Belma Melda / Feng, Chu-Han / Martinez-Cordova, Zuzet / Hincapie, Ana Maria / Wu, Chenyue / Pérez-Quintero, Luis Alberto / Wang, Chia-Lin / Gingras, Anne Claude / Madrenas, Joaquín / Tremblay, Michel L

Science signaling

2024 Volume 17, Issue 817, Page(s) eadg4422

Abstract: Thousand-and-one-amino acid kinase 3 (TAOK3) is a serine and threonine kinase that belongs to the STE-20 family of kinases. Its absence reduces T cell receptor (TCR) signaling and increases the interaction of the tyrosine phosphatase SHP-1, a major ... ...

Abstract	Thousand-and-one-amino acid kinase 3 (TAOK3) is a serine and threonine kinase that belongs to the STE-20 family of kinases. Its absence reduces T cell receptor (TCR) signaling and increases the interaction of the tyrosine phosphatase SHP-1, a major negative regulator of proximal TCR signaling, with the kinase LCK, a component of the core TCR signaling complex. Here, we used mouse models and human cell lines to investigate the mechanism by which TAOK3 limits the interaction of SHP-1 with LCK. The loss of TAOK3 decreased the survival of naïve CD4
MeSH term(s)	Animals ; Humans ; Mice ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck) ; Phosphorylation ; Protein Serine-Threonine Kinases/metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; T-Lymphocytes/metabolism ; Threonine/metabolism
Chemical Substances	Lymphocyte Specific Protein Tyrosine Kinase p56(lck) (EC 2.7.10.2) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 (EC 3.1.3.48) ; Protein Tyrosine Phosphatase, Non-Receptor Type 6 (EC 3.1.3.48) ; Receptors, Antigen, T-Cell ; Threonine (2ZD004190S) ; TAOK3 protein, human (EC 2.7.11.1) ; Taok3 protein, mouse (EC 2.7.11.1)
Language	English
Publishing date	2024-01-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2417226-1
ISSN	1937-9145 ; 1945-0877
ISSN (online)	1937-9145
ISSN	1945-0877
DOI	10.1126/scisignal.adg4422
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Article ; Online: Base genética de la enfermedad celiaca en el diagnóstico

Sylvia Torres Odio / Zuzet Martínez Córdova

Revista Cubana de Medicina, Vol 51, Iss 2, Pp 170-

2012 Volume 182

Abstract: La enfermedad celiaca es un síndrome de malabsorción caracterizado por intolerancia a las proteínas del gluten en individuos genéticamente predispuestos con los alelos HLA-DQ2/DQ8. Su causa es multifactorial y los factores dietéticos, ambientales y ... ...

Abstract	La enfermedad celiaca es un síndrome de malabsorción caracterizado por intolerancia a las proteínas del gluten en individuos genéticamente predispuestos con los alelos HLA-DQ2/DQ8. Su causa es multifactorial y los factores dietéticos, ambientales y genéticos tienen una significación importante en su aparición. El diagnóstico temprano posibilita prevenir complicaciones como la osteopenia, las enfermedades malignas y la infertilidad. El objetivo de este estudio fue compilar información actualizada sobre la base genética de esta enfermedad y su papel en el diagnóstico.
Keywords	enfermedad celiaca ; alelos HLA-DQ2/DQ8 ; genotipaje HLA ; Medicine ; R
Language	Spanish
Publishing date	2012-06-01T00:00:00Z
Publisher	Editorial Ciencias Médicas
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Base genética de la enfermedad celiaca en el diagnóstico Genetic base of celiac diseases in diagnosis

Sylvia Torres Odio / Zuzet Martínez Córdova

Revista Cubana de Medicina, Vol 51, Iss 2, Pp 170-

2012 Volume 182

Abstract	La enfermedad celiaca es un síndrome de malabsorción caracterizado por intolerancia a las proteínas del gluten en individuos genéticamente predispuestos con los alelos HLA-DQ2/DQ8. Su causa es multifactorial y los factores dietéticos, ambientales y genéticos tienen una significación importante en su aparición. El diagnóstico temprano posibilita prevenir complicaciones como la osteopenia, las enfermedades malignas y la infertilidad. El objetivo de este estudio fue compilar información actualizada sobre la base genética de esta enfermedad y su papel en el diagnóstico. The celiac disease is syndrome of malabsorption characterized by intolerance fo gluten proteins in subjects with genetic predisposition with the HLA-DQ2/DQ8 alleles. Its cause is multifactor and the dietetic, environmental and genetic factors have a great significance in its appearance. The early diagnosis allows the prevention of complications including osteopenia, malignant diseases and infertility. The aim of present paper was to collect updated information on the genetic base of this disease and its role in the diagnosis.
Keywords	enfermedad celiaca ; alelos HLA-DQ2/DQ8 ; genotipaje HLA ; celiac disease ; JLA-DQ2/DQ8 alleles ; HLA genotyping ; Medicine ; R
Language	Spanish
Publishing date	2012-06-01T00:00:00Z
Publisher	Editorial Ciencias Médicas
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Factores genéticos, inmunológicos y ambientales asociados a la autoinmunidad Genetic, immunologic and environmental factors associated with autoimmunity

Sylvia Torres Odio / Zuzet Martínez Córdova

Revista Cubana de Investigaciones Biomédicas, Vol 30, Iss 4, Pp 501-

2011 Volume 510

Abstract: La autoinmunidad se caracteriza por una pérdida de la tolerancia inmunológica que produce la destrucción de células y tejidos propios. El sistema del complejo mayor de histocompatibilidad posee una fuerte asociación con las enfermedades autoinmunes ... ...

Abstract	La autoinmunidad se caracteriza por una pérdida de la tolerancia inmunológica que produce la destrucción de células y tejidos propios. El sistema del complejo mayor de histocompatibilidad posee una fuerte asociación con las enfermedades autoinmunes aunque determinados genes que codifican para citoquinas y moléculas coestimuladoras incrementan la susceptibilidad genética. Estudios de concordancia entre gemelos monocigóticos demuestran el papel de los factores ambientales en la aparición de las enfermedades autoinmunes. A pesar de los avances científicos producidos en esta área de investigación, los mecanismos subyacentes de estas afecciones son desconocidos. El objetivo deeste trabajo es exponer de forma sintetizada el papel de los factores genéticos, inmunológicos y ambientales en la autoinmunidad. The autoimmunity is characterized by a loss of immunologic tolerance producing the destruction of cells and own tissues. The major complex system of histocompatibility has a close association with the autoimmune diseases although determined genes codifying for cytokines and co-stimulators molecules increase the genetic susceptibility. Concordance studies among monozygotic twins demonstrate the role of environmental factors in appearance of autoimmune diseases. Despite the scientific advances achieved in this research field, the underlying mechanisms of these affections are unknown. The objective of present paper is to expose in a summarized way the role of the genetic, immunologic and environmental factors in autoimmunity.
Keywords	Enfermedades autoinmunes ; sistema HLA ; tolerancia central y periférica ; Autoimmune diseases ; HLA system ; central and peripheral tolerance ; Medicine (General) ; R5-920
Language	Spanish
Publishing date	2011-12-01T00:00:00Z
Publisher	Centro Nacional de Información de Ciencias Médicas. Editorial de Ciencias Médicas (ECIMED)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Furin deficiency in myeloid cells leads to attenuated revascularization in a mouse-model of oxygen-induced retinopathy.

Vähätupa, Maria / Cordova, Zuzet Martinez / Barker, Harlan / Aittomäki, Saara / Uusitalo, Hannu / Järvinen, Tero A H / Pesu, Marko / Uusitalo-Järvinen, Hannele

Experimental eye research

2017 Volume 166, Page(s) 160–167

Abstract: Ischemic retinopathy is a vision-threatening disease associated with chronic retinal inflammation and hypoxia leading to abnormal angiogenesis. Furin, a member of the proprotein convertase family of proteins, has been implicated in the regulation of ... ...

Abstract	Ischemic retinopathy is a vision-threatening disease associated with chronic retinal inflammation and hypoxia leading to abnormal angiogenesis. Furin, a member of the proprotein convertase family of proteins, has been implicated in the regulation of angiogenesis due to its essential role in the activation of several angiogenic growth factors, including vascular endothelial growth factor-C (VEGF-C), VEGF-D and transforming growth factor - β (TGF- β). In the present study, we evaluated expression of furin in the retina and its role in retinal angiogenesis. As both inflammation and hypoxia contribute to angiogenesis, the role of furin was evaluated using myeloid-cell specific furin knockout (KO) mice (designated LysMCre-fur
MeSH term(s)	Animals ; Disease Models, Animal ; Endothelial Cells/metabolism ; Furin/deficiency ; Furin/metabolism ; Furin/physiology ; Macrophages/metabolism ; Mice ; Mice, Knockout ; Microglia/metabolism ; Myeloid Cells/metabolism ; Retina/metabolism ; Retinal Neovascularization/metabolism ; Retinal Neurons/metabolism
Chemical Substances	Furin (EC 3.4.21.75)
Language	English
Publishing date	2017-10-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80122-7
ISSN	1096-0007 ; 0014-4835
ISSN (online)	1096-0007
ISSN	0014-4835
DOI	10.1016/j.exer.2017.10.013
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Article ; Online: Prevalencia de anticuerpos anti-VHC y del antígeno de superficie de la hepatitis B en pacientes tratados con hemodiálisis Prevalence of anti-HCV antibodies and of the hepatitis B surface antigen in patients treated with hemodialysis

Zuzet Martínez Córdova / Natacha Peña Fresneda

Revista Cubana de Medicina, Vol 47, Iss 1, p

2008

Abstract: Se estudiaron 108 pacientes con tratamiento de hemodiálisis para determinar la prevalencia de anticuerpos contra el virus de la hepatitis C (anti-VHC) y del antígeno de superficie de la hepatitis B (HBsAg) empleando la tecnología SUMA. Se obtuvo elevada ... ...

Abstract	Se estudiaron 108 pacientes con tratamiento de hemodiálisis para determinar la prevalencia de anticuerpos contra el virus de la hepatitis C (anti-VHC) y del antígeno de superficie de la hepatitis B (HBsAg) empleando la tecnología SUMA. Se obtuvo elevada prevalencia de anticuerpos contra el virus de la hepatitis C (90 %) y menor prevalencia del HBsAg (4 %). Se hallaron títulos protectores de anticuerpos anti-HBsAg en el 91 % de los pacientes. Se observó que los pacientes con niveles de anticuerpos de 10 UI/L resultaron protegidos lo que se corresponde con una respuesta efectiva a nuestro esquema de vacunación y con mejores resultados que lo normalmente reportado para este tipo de paciente (100 UI/L). Se presentaron valores persistentemente normales de actividad enzimática de la enzima glutámico-pirúvica (TGP) en el 65 % de los pacientes, lo que podría indicar una enfermedad crónica y corrobora la frecuente disminución que se observa en la actividad enzimática de la TGP. 108 hemodialysis patients were studied to determine the prevalence of antibodies against hepatitis C virus (anti-HCV) and of the hepatitis B surface antigen (HBsAg) by using the SUMA technology. It was obtained an elevated prevalence of antibodies against the hepatitis C virus (90 %) and a lower prevalence of of HBsAg (4 %). Titres protecting anti-HBsAg antibodies were found in 91 % of the patients. It was observed that the patients with antibody levels of 10 UI/L were protected, which corresponds to an effective response to our vaccination scheme and to better results than the ones normally reported for this type of patient (100 UI/L). Persistently normal values of the enzymatic activity of the glutamic piruvic enzyme (GPT) were present in 65 % of the patients, which could indicate a chronic disease and corroborate the frequent decrease observed in the enzymatic activity of GPT.
Keywords	Hemodializados ; anti-VHC ; HBsAg ; anti-HBsAg ; TGP ; Hemodialysis patients ; anti-HCV ; GPT ; Medicine ; R
Language	Spanish
Publishing date	2008-03-01T00:00:00Z
Publisher	Editorial Ciencias Médicas
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: T-cell-expressed proprotein convertase FURIN inhibits DMBA/TPA-induced skin cancer development.

Vähätupa, Maria / Aittomäki, Saara / Martinez Cordova, Zuzet / May, Ulrike / Prince, Stuart / Uusitalo-Järvinen, Hannele / Järvinen, Tero A / Pesu, Marko

Oncoimmunology

2016 Volume 5, Issue 12, Page(s) e1245266

Abstract: Proprotein convertases (PCSK) have a critical role in the body homeostasis as enzymes responsible for processing precursor proteins into their mature forms. FURIN, the first characterized member of the mammalian PCSK family, is overexpressed in multiple ... ...

Abstract	Proprotein convertases (PCSK) have a critical role in the body homeostasis as enzymes responsible for processing precursor proteins into their mature forms. FURIN, the first characterized member of the mammalian PCSK family, is overexpressed in multiple malignancies and the inhibition of its activity has been considered potential cancer treatment. FURIN has also an important function in the adaptive immunity, since its deficiency in T cells causes an impaired peripheral immune tolerance and accelerates immune responses. We addressed whether deleting FURIN from the immune cells would strengthen anticancer responses by subjecting mouse strains lacking FURIN from either T cells or macrophages and granulocytes to the DMBA/TPA two-stage skin carcinogenesis protocol. Unexpectedly, deficiency of FURIN in T cells resulted in enhanced and accelerated development of tumors, whereas FURIN deletion in macrophages and granulocytes had no effect. The epidermises of T-cell-specific FURIN deficient mice were significantly thicker with more proliferating Ki67+ cells. In contrast, there were no differences in the numbers of the T cells. The flow cytometric analyses of T-cell populations in skin draining lymph nodes showed that FURIN T-cell KO mice have an inherent upregulation of early activation marker CD69 as well as more CD4
Language	English
Publishing date	2016-10-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-4011
ISSN (online)	2162-402X
ISSN	2162-4011
DOI	10.1080/2162402X.2016.1245266
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Article ; Online: Prevalencia del virus de la hepatitis C en las unidades de hemodiálisis de la región occidental cubana Hepatitis C virus present in hemodialysis units from Cuban western region

Rita Rosa Santana Hernández / Zuzet Martínez Córdova / María Teresa Martínez Echeverría / Jorge Mato Luis

Revista Cubana de Medicina, Vol 48, Iss 3, Pp 28-

2009 Volume 35

Abstract: La población de hemodiálisis constituye un grupo de alto riesgo en el caso de la infección por el virus de la hepatitis C. Se realizó un análisis multicéntrico de la prevalencia de la infección por el virus de la hepatitis C en las unidades de diálisis ... ...

Abstract	La población de hemodiálisis constituye un grupo de alto riesgo en el caso de la infección por el virus de la hepatitis C. Se realizó un análisis multicéntrico de la prevalencia de la infección por el virus de la hepatitis C en las unidades de diálisis de la región occidental aplicando las técnicas serológicas y moleculares, y se observó si existían diferencias significativas en cuanto a la aplicación de ambas técnicas. Se obtuvieron valores elevados de prevalencia de anticuerpos anti-VHC en todas las unidades de diálisis (76 %), así como la calculada aplicando la detección del ARN viral (55 %). No se hallaron diferencias significativas (k) en cuanto a la aplicación de ambas técnicas en la mayoría de las unidades de diálisis analizadas. La elevada prevalencia viral se asocia a la transmisión nosocomial provocada por el incumplimiento de las normas de precaución universal establecidas. Hemodialysis population is a high risk group related to hepatitis C virus infection. Authors made a multicenter analysis on infection prevalence of hepatitis C virus in dialysis units of western region applying serologic and molecular techniques observing if there significant differences as regards the application of both techniques. We achieved high values of anti-CHV antibody prevalence in all dialysis units (76 %) as well as the estimated prevalence applying viral RNA detection (55 %). There were not significant differences (k) as regards application of both techniques in most of analyzed dialysis units. Viral high prevalence is associated with nosocomial transmission caused by no-fulfillment of established universal precaution standards.
Keywords	Hepatitis C ; hemodiálisis ; prevalencia ; diagnóstico molecular ; C hepatitis ; hemodialysis ; prevalence ; molecular diagnosis ; Medicine ; R
Language	Spanish
Publishing date	2009-09-01T00:00:00Z
Publisher	Editorial Ciencias Médicas
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Papel de los polimorfismos genéticos del receptor de reconocimiento de patrones "Toll" en el trasplante Role of polymorphisms of recognition receptor from Toll patterns in case of transplant

Zuzet Martínez Córdova / Flora Calzadilla Lugo / Igrid García González / Dalila del Valle Calzadilla

Revista Cubana de Medicina, Vol 48, Iss 3, Pp 88-

2009 Volume 100

Abstract: La inmunidad innata es fundamental en la respuesta del hospedero ante agentes infecciosos y los receptores de reconocimiento de patrones "Toll" (TLRs) son clave en la activación y regulación de esta respuesta inmune. La función de los receptores Toll ha ... ...

Abstract	La inmunidad innata es fundamental en la respuesta del hospedero ante agentes infecciosos y los receptores de reconocimiento de patrones "Toll" (TLRs) son clave en la activación y regulación de esta respuesta inmune. La función de los receptores Toll ha sido investigada en numerosas enfermedades, comparando su incidencia entre individuos con diferentes polimorfismos genéticos, lo que sugiere que esas variaciones podrían estar asociadas con la susceptibilidad a determinadas enfermedades. En este trabajo se hace referencia a varios estudios relacionados con determinados polimorfismos en los receptores Toll y su posible efecto en el rechazo del trasplante y en la enfermedad del injerto versus hospedero. Estas investigaciones permitirán profundizar en la patogénesis de muchas enfermedades, la cascada de cambios implicados en el rechazo del trasplante, en la enfermedad injerto versus hospedero, el desarrollo de nuevos productos terapéuticos y la individualización del tratamiento. The pure immunity is essential in host response to infectious agents and the receptors of "Toll" patterns recognition (TLRs) are a key element in activation and regulation of this immune response. Toll receptors function has been researched in many diseases compared to its incidence among subjects with different genetic polymorphisms suggesting that these variations could be associated with some studies related to determined polymorphisms in Toll receptors and its possible effect on transplant rejection and in graft versus host disease. Theses researches will allow us to deepen in pathogenesis of many diseases, the cascade of changes involved in transplant rejection, in graft versus host disease, the development of new therapeutical products, and the treatment individualization.
Keywords	Receptores "Toll" ; receptores de reconocimiento de patógenos ; enfermedad del injerto versus hospedero ; Toll receptors ; pathogens recognition receptors ; graft versus host disease ; Medicine ; R
Language	Spanish
Publishing date	2009-09-01T00:00:00Z
Publisher	Editorial Ciencias Médicas
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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