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Article ; Online: Dietary Supplementation of Inulin Contributes to the Prevention of Estrogen Receptor-Negative Mammary Cancer by Alteration of Gut Microbial Communities and Epigenetic Regulations.

Wu, Huixin / Van Der Pol, William J / Dubois, Laura G / Morrow, Casey D / Tollefsbol, Trygve O

International journal of molecular sciences

2023 Volume 24, Issue 10

Abstract: Breast cancer (BC) is among the most frequently diagnosed malignant cancers in women in the United States. Diet and nutrition supplementation are closely related to BC onset and progression, and inulin is commercially available as a health supplement to ... ...

Abstract	Breast cancer (BC) is among the most frequently diagnosed malignant cancers in women in the United States. Diet and nutrition supplementation are closely related to BC onset and progression, and inulin is commercially available as a health supplement to improve gut health. However, little is known with respect to inulin intake for BC prevention. We investigated the effect of an inulin-supplemented diet on the prevention of estrogen receptor-negative mammary carcinoma in a transgenic mouse model. Plasma short-chain fatty acids were measured, the gut microbial composition was analyzed, and the expression of proteins related to cell cycle and epigenetics-related genes was measured. Inulin supplementation greatly inhibited tumor growth and significantly delayed tumor latency. The mice that consumed inulin had a distinct microbiome and higher diversity of gut microbial composition compared to the control. The concentration of propionic acid in plasma was significantly higher in the inulin-supplemented group. The protein expression of epigenetic-modulating histone deacetylase 2 (Hdac2), Hdac8, and DNA methyltransferase 3b decreased. The protein expression of factors related to tumor cell proliferation and survival, such as Akt, phospho-PI3K, and NF-kB, also decreased with inulin administration. Furthermore, sodium propionate showed BC prevention effect in vivo through epigenetic regulations. These studies suggest that modulating microbial composition through inulin consumption may be a promising strategy for BC prevention.
MeSH term(s)	Female ; Animals ; Mice ; Inulin/pharmacology ; Inulin/metabolism ; Receptors, Estrogen/metabolism ; Epigenesis, Genetic ; Gastrointestinal Microbiome ; Microbiota ; Dietary Supplements ; Prebiotics/analysis ; Neoplasms
Chemical Substances	Inulin (9005-80-5) ; Receptors, Estrogen ; Prebiotics
Language	English
Publishing date	2023-05-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24109015
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A ketogenic diet enhances fluconazole efficacy in murine models of systemic fungal infection.

Palmucci, Julia R / Sells, Blake E / Giamberardino, Charles D / Toffaletti, Dena L / Dai, Baodi / Asfaw, Yohannes G / Dubois, Laura G / Li, Zhong / Theriot, Barbara / Schell, Wiley A / Hope, William / Tenor, Jennifer L / Perfect, John R

mBio

2024 Volume 15, Issue 5, Page(s) e0064924

Abstract: Invasive fungal infections are a significant public health concern, with mortality rates ranging from 20% to 85% despite current treatments. Therefore, we examined whether a ketogenic diet could serve as a successful treatment intervention in murine ... ...

Abstract	Invasive fungal infections are a significant public health concern, with mortality rates ranging from 20% to 85% despite current treatments. Therefore, we examined whether a ketogenic diet could serve as a successful treatment intervention in murine models of
MeSH term(s)	Animals ; Diet, Ketogenic ; Fluconazole/pharmacology ; Fluconazole/administration & dosage ; Mice ; Antifungal Agents/administration & dosage ; Antifungal Agents/pharmacology ; Disease Models, Animal ; Candidiasis/drug therapy ; Candidiasis/diet therapy ; Candidiasis/microbiology ; Candida albicans/drug effects ; Cryptococcus neoformans/drug effects ; Cryptococcosis/drug therapy ; Cryptococcosis/microbiology ; Cryptococcosis/diet therapy ; Cryptococcosis/prevention & control ; Female ; Brain/metabolism ; Brain/drug effects ; Lung/microbiology ; Lung/drug effects
Chemical Substances	Fluconazole (8VZV102JFY) ; Antifungal Agents
Language	English
Publishing date	2024-04-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.00649-24
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Article ; Online: Efficacy of APX2039 in a Rabbit Model of Cryptococcal Meningitis.

Giamberardino, Charles D / Schell, Wiley A / Tenor, Jennifer L / Toffaletti, Dena L / Palmucci, Julia R / Marius, Choiselle / Boua, Jane-Valeriane K / Soltow, Quinlyn / Mansbach, Robert / Moseley, M Arthur / Thompson, J Will / Dubois, Laura G / Hope, William / Perfect, John R / Shaw, Karen Joy

mBio

2022 Volume 13, Issue 6, Page(s) e0234722

Abstract: Cryptococcal Meningitis (CM) is uniformly fatal if not treated, and treatment options are limited. We previously reported on the activity of APX2096, the prodrug of the novel Gwt1 inhibitor APX2039, in a mouse model of CM. Here, we investigated the ... ...

Abstract	Cryptococcal Meningitis (CM) is uniformly fatal if not treated, and treatment options are limited. We previously reported on the activity of APX2096, the prodrug of the novel Gwt1 inhibitor APX2039, in a mouse model of CM. Here, we investigated the efficacy of APX2039 in mouse and rabbit models of CM. In the mouse model, the controls had a mean lung fungal burden of 5.95 log
MeSH term(s)	Animals ; Humans ; Mice ; Rabbits ; Amphotericin B/therapeutic use ; Antifungal Agents/pharmacology ; Drug Therapy, Combination ; Fluconazole/therapeutic use ; Meningitis, Cryptococcal/microbiology
Chemical Substances	Amphotericin B (7XU7A7DROE) ; Antifungal Agents ; Fluconazole (8VZV102JFY) ; APX2039
Language	English
Publishing date	2022-10-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.02347-22
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Article ; Online: Author Correction: Neuroprotective pentapeptide CN-105 improves functional and histological outcomes in a murine model of intracerebral hemorrhage.

Lei, Beilei / James, Michael L / Liu, Ji / Zhou, Guanen / Venkatraman, Talaignair N / Lascola, Christopher D / Acheson, Shawn K / Dubois, Laura G / Laskowitz, Daniel T / Wang, Haichen

Scientific reports

2020 Volume 10, Issue 1, Page(s) 6898

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Language	English
Publishing date	2020-04-20
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-63178-2
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Article ; Online: Influence of Sex on Platelet Reactivity in Response to Aspirin.

Friede, Kevin A / Infeld, Margaret M / Tan, Ru San / Knickerbocker, Holly J / Myers, Rachel A / Dubois, Laura G / Thompson, J Will / Kaddurah-Daouk, Rima / Ginsburg, Geoffrey S / Ortel, Thomas L / Voora, Deepak

Journal of the American Heart Association

2020 Volume 9, Issue 14, Page(s) e014726

Abstract: Background There are sex differences in the efficacy and safety of aspirin for the prevention of myocardial infarction and stroke. Whether this is explained by underlying differences in platelet reactivity and aspirin response remains poorly understood. ... ...

Abstract	Background There are sex differences in the efficacy and safety of aspirin for the prevention of myocardial infarction and stroke. Whether this is explained by underlying differences in platelet reactivity and aspirin response remains poorly understood. Methods and Results Healthy volunteers (n=378 208 women) and patients with coronary artery disease or coronary artery disease risk factors (n=217 112 women) took aspirin for 4 weeks. Light transmittance aggregometry using platelet-rich plasma was used to measure platelet reactivity in response to epinephrine, collagen, and ADP at baseline, 3 hours after the first aspirin dose, and after 4 weeks of daily aspirin therapy. A subset of patients underwent pharmacokinetic and pharmacodynamic assessment with levels of salicylate and cyclooxygenase-1-derived prostaglandin metabolites and light transmittance aggregometry in response to arachidonic acid and after ex vivo exposure to aspirin. At baseline, women had increased platelet aggregation in response to ADP and collagen. Innate platelet response to aspirin, assessed with ex vivo aspirin exposure of baseline platelets, did not differ by sex. Three hours after the first oral aspirin dose, platelet aggregation was inhibited in women to a greater degree in response to epinephrine and to a lesser degree with collagen. After 4 weeks of daily therapy, despite higher salicylate concentrations and greater cyclooxygenase-1 inhibition, women exhibited an attenuation of platelet inhibition in response to epinephrine and ADP. Conclusions We observed agonist-dependent sex differences in platelet responses to aspirin. Despite higher cyclooxygenase-1 inhibition, daily aspirin exposure resulted in a paradoxical attenuation of platelet inhibition in response to epinephrine and ADP over time in women but not in men.
MeSH term(s)	Adult ; Aged ; Aspirin/pharmacology ; Case-Control Studies ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation/drug effects ; Platelet Aggregation Inhibitors/pharmacology ; Sex Characteristics ; Young Adult
Chemical Substances	Platelet Aggregation Inhibitors ; Aspirin (R16CO5Y76E)
Language	English
Publishing date	2020-07-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.119.014726
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Article: Proteomic Analysis of an Unculturable Bacterial Endosymbiont (Blochmannia) Reveals High Abundance of Chaperonins and Biosynthetic Enzymes

Fan, Yongliang / Thompson, J. Will / Dubois, Laura G / Moseley, M. Arthur / Wernegreen, Jennifer J

Journal of Proteome Research. 2013 Feb. 01, v. 12, no. 2

2013

Abstract: Many insect groups have coevolved with bacterial endosymbionts that live within specialized host cells. As a salient example, ants in the tribe Camponotini rely on Blochmannia, an intracellular bacterial mutualist that synthesizes amino acids and ... ...

Abstract	Many insect groups have coevolved with bacterial endosymbionts that live within specialized host cells. As a salient example, ants in the tribe Camponotini rely on Blochmannia, an intracellular bacterial mutualist that synthesizes amino acids and recycles nitrogen for the host. We performed a shotgun, label-free, LC/MS/MS quantitative proteomic analysis to investigate the proteome of Blochmannia associated with Camponotus chromaiodes. We identified more than 330 Blochmannia proteins, or 54% coverage of the predicted proteome, as well as 244 Camponotus proteins. Using the average intensity of the top 3 “best flier” peptides along with spiking of a surrogate standard at a known concentration, we estimated the concentration (fmol/μg) of those proteins with confident identification. The estimated dynamic range of Blochmannia protein abundance spanned 3 orders of magnitude and covered diverse functional categories, with particularly high representation of metabolism, information transfer, and chaperones. GroEL, the most abundant protein, totaled 6% of Blochmannia protein abundance. Biosynthesis of essential amino acids, fatty acids, and nucleotides, and sulfate assimilation had disproportionately high coverage in the proteome, further supporting a nutritional role of the symbiosis. This first quantitative proteomic analysis of an ant endosymbiont illustrates a promising approach to study the functional basis of intimate symbioses.
Keywords	Camponotus chromaiodes ; biosynthesis ; chaperonins ; coevolution ; endosymbionts ; enzymes ; essential amino acids ; fatty acids ; insects ; microsymbionts ; mutualism ; nitrogen ; nucleotides ; peptides ; proteome ; proteomics ; sulfates
Language	English
Dates of publication	2013-0201
Size	p. 704-718.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021%2Fpr3007842
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Proteomic differences between male and female anterior cruciate ligament and patellar tendon.

Little, Dianne / Thompson, J Will / Dubois, Laura G / Ruch, David S / Moseley, M Arthur / Guilak, Farshid

PloS one

2014 Volume 9, Issue 5, Page(s) e96526

Abstract: The risk of anterior cruciate ligament (ACL) injury and re-injury is greater for women than men. Among other factors, compositional differences may play a role in this differential risk. Patellar tendon (PT) autografts are commonly used during ... ...

Abstract	The risk of anterior cruciate ligament (ACL) injury and re-injury is greater for women than men. Among other factors, compositional differences may play a role in this differential risk. Patellar tendon (PT) autografts are commonly used during reconstruction. The aim of the study was to compare protein expression in male and female ACL and PT. We hypothesized that there would be differences in key structural components between PT and ACL, and that components of the proteome critical for response to mechanical loading and response to injury would demonstrate significant differences between male and female. Two-dimensional liquid chromatography-tandem mass spectrometry and a label-free quantitative approach was used to identify proteomic differences between male and female PT and ACL. ACL contained less type I and more type III collagen than PT. There were tissue-specific differences in expression of proteoglycans, and ACL was enriched in elastin, tenascin C and X, cartilage oligomeric matrix protein, thrombospondin 4 and periostin. Between male and female donors, alcohol dehydrogenase 1B and complement component 9 were enriched in female compared to male. Myocilin was the major protein enriched in males compared to females. Important compositional differences between PT and ACL were identified, and we identified differences in pathways related to extracellular matrix regulation, complement, apoptosis, metabolism of advanced glycation end-products and response to mechanical loading between males and females. Identification of proteomic differences between male and female PT and ACL has identified novel pathways which may lead to improved understanding of differential ACL injury and re-injury risk between males and females.
MeSH term(s)	Anterior Cruciate Ligament/metabolism ; Chromatography, Liquid ; Female ; Humans ; Male ; Middle Aged ; Patellar Ligament/metabolism ; Tandem Mass Spectrometry ; Tendons/metabolism
Language	English
Publishing date	2014-05-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0096526
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Article ; Online: Skyline for Small Molecules: A Unifying Software Package for Quantitative Metabolomics.

Adams, Kendra J / Pratt, Brian / Bose, Neelanjan / Dubois, Laura G / St John-Williams, Lisa / Perrott, Kevin M / Ky, Karina / Kapahi, Pankaj / Sharma, Vagisha / MacCoss, Michael J / Moseley, M Arthur / Colton, Carol A / MacLean, Brendan X / Schilling, Birgit / Thompson, J Will

Journal of proteome research

2020 Volume 19, Issue 4, Page(s) 1447–1458

Abstract: Vendor-independent software tools for quantification of small molecules and metabolites are lacking, especially for targeted analysis workflows. Skyline is a freely available, open-source software tool for targeted quantitative mass spectrometry method ... ...

Abstract	Vendor-independent software tools for quantification of small molecules and metabolites are lacking, especially for targeted analysis workflows. Skyline is a freely available, open-source software tool for targeted quantitative mass spectrometry method development and data processing with a 10 year history supporting six major instrument vendors. Designed initially for proteomics analysis, we describe the expansion of Skyline to data for small molecule analysis, including selected reaction monitoring, high-resolution mass spectrometry, and calibrated quantification. This fundamental expansion of Skyline from a peptide-sequence-centric tool to a molecule-centric tool makes it agnostic to the source of the molecule while retaining Skyline features critical for workflows in both peptide and more general biomolecular research. The data visualization and interrogation features already available in Skyline, such as peak picking, chromatographic alignment, and transition selection, have been adapted to support small molecule data, including metabolomics. Herein, we explain the conceptual workflow for small molecule analysis using Skyline, demonstrate Skyline performance benchmarked against a comparable instrument vendor software tool, and present additional real-world applications. Further, we include step-by-step instructions on using Skyline for small molecule quantitative method development and data analysis on data acquired with a variety of mass spectrometers from multiple instrument vendors.
MeSH term(s)	Amino Acid Sequence ; Mass Spectrometry ; Metabolomics ; Proteomics ; Software
Language	English
Publishing date	2020-03-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/acs.jproteome.9b00640
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Article ; Online: Proteomic analysis of ERK1/2-mediated human sickle red blood cell membrane protein phosphorylation

Soderblom Erik J / Thompson J Will / Schwartz Evan A / Chiou Edward / Dubois Laura G / Moseley M Arthur / Zennadi Rahima

Clinical Proteomics, Vol 10, Iss 1, p

2013 Volume 1

Abstract: Abstract Background In sickle cell disease (SCD), the mitogen-activated protein kinase (MAPK) ERK1/2 is constitutively active and can be inducible by agonist-stimulation only in sickle but not in normal human red blood cells (RBCs). ERK1/2 is involved in ...

Abstract	Abstract Background In sickle cell disease (SCD), the mitogen-activated protein kinase (MAPK) ERK1/2 is constitutively active and can be inducible by agonist-stimulation only in sickle but not in normal human red blood cells (RBCs). ERK1/2 is involved in activation of ICAM-4-mediated sickle RBC adhesion to the endothelium. However, other effects of the ERK1/2 activation in sickle RBCs leading to the complex SCD pathophysiology, such as alteration of RBC hemorheology are unknown. Results To further characterize global ERK1/2-induced changes in membrane protein phosphorylation within human RBCs, a label-free quantitative phosphoproteomic analysis was applied to sickle and normal RBC membrane ghosts pre-treated with U0126, a specific inhibitor of MEK1/2, the upstream kinase of ERK1/2, in the presence or absence of recombinant active ERK2. Across eight unique treatment groups, 375 phosphopeptides from 155 phosphoproteins were quantified with an average technical coefficient of variation in peak intensity of 19.8%. Sickle RBC treatment with U0126 decreased thirty-six phosphopeptides from twenty-one phosphoproteins involved in regulation of not only RBC shape, flexibility, cell morphology maintenance and adhesion, but also glucose and glutamate transport, cAMP production, degradation of misfolded proteins and receptor ubiquitination. Glycophorin A was the most affected protein in sickle RBCs by this ERK1/2 pathway, which contained 12 unique phosphorylated peptides, suggesting that in addition to its effect on sickle RBC adhesion, increased glycophorin A phosphorylation via the ERK1/2 pathway may also affect glycophorin A interactions with band 3, which could result in decreases in both anion transport by band 3 and band 3 trafficking. The abundance of twelve of the thirty-six phosphopeptides were subsequently increased in normal RBCs co-incubated with recombinant ERK2 and therefore represent specific MEK1/2 phospho-inhibitory targets mediated via ERK2. Conclusions These findings expand upon the current model for the ...
Keywords	Sickle cell disease ; Mitogen-activated protein kinase ERK1/2 ; Red blood cell membrane ; Label-free quantitation ; Phosphoproteomics ; Glycophorin A ; Hemorheology ; Medicine ; R
Subject code	571
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Chlamydia trachomatis Infection Leads to Defined Alterations to the Lipid Droplet Proteome in Epithelial Cells.

Saka, Hector Alex / Thompson, J Will / Chen, Yi-Shan / Dubois, Laura G / Haas, Joel T / Moseley, Arthur / Valdivia, Raphael H

PloS one

2015 Volume 10, Issue 4, Page(s) e0124630

Abstract: The obligate intracellular bacterium Chlamydia trachomatis is a major human pathogen and a main cause of genital and ocular diseases. During its intracellular cycle, C. trachomatis replicates inside a membrane-bound vacuole termed an "inclusion". ... ...

Abstract	The obligate intracellular bacterium Chlamydia trachomatis is a major human pathogen and a main cause of genital and ocular diseases. During its intracellular cycle, C. trachomatis replicates inside a membrane-bound vacuole termed an "inclusion". Acquisition of lipids (and other nutrients) from the host cell is a critical step in chlamydial replication. Lipid droplets (LD) are ubiquitous, ER-derived neutral lipid-rich storage organelles surrounded by a phospholipids monolayer and associated proteins. Previous studies have shown that LDs accumulate at the periphery of, and eventually translocate into, the chlamydial inclusion. These observations point out to Chlamydia-mediated manipulation of LDs in infected cells, which may impact the function and thereby the protein composition of these organelles. By means of a label-free quantitative mass spectrometry approach we found that the LD proteome is modified in the context of C. trachomatis infection. We determined that LDs isolated from C. trachomatis-infected cells were enriched in proteins related to lipid metabolism, biosynthesis and LD-specific functions. Interestingly, consistent with the observation that LDs intimately associate with the inclusion, a subset of inclusion membrane proteins co-purified with LD protein extracts. Finally, genetic ablation of LDs negatively affected generation of C. trachomatis infectious progeny, consistent with a role for LD biogenesis in optimal chlamydial growth.
MeSH term(s)	Animals ; Cell Line ; Chlamydia Infections/metabolism ; Chlamydia Infections/microbiology ; Chlamydia trachomatis ; Epithelial Cells/metabolism ; HeLa Cells ; Humans ; Lipid Droplets/metabolism ; Lipid Metabolism ; Mice ; Proteome ; Proteomics/methods
Chemical Substances	Proteome
Language	English
Publishing date	2015-04-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0124630
Database	MEDical Literature Analysis and Retrieval System OnLINE

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