LIVIVO - Search results -

Search results

Result 1 - 10 of total 17

Search options

Article ; Online: High-affinity Anticalins with aggregation-blocking activity directed against the Alzheimer β-amyloid peptide.

Rauth, Sabine / Hinz, Dominik / Börger, Michael / Uhrig, Markus / Mayhaus, Manuel / Riemenschneider, Matthias / Skerra, Arne

The Biochemical journal

2016 Volume 473, Issue 11, Page(s) 1563–1578

Abstract: Amyloid beta (Aβ) peptides, in particular Aβ42 and Aβ40, exert neurotoxic effects and their overproduction leads to amyloid deposits in the brain, thus constituting an important biomolecular target for treatments of Alzheimer's disease (AD). We describe ... ...

Abstract	Amyloid beta (Aβ) peptides, in particular Aβ42 and Aβ40, exert neurotoxic effects and their overproduction leads to amyloid deposits in the brain, thus constituting an important biomolecular target for treatments of Alzheimer's disease (AD). We describe the engineering of cognate Anticalins as a novel type of neutralizing protein reagent based on the human lipocalin scaffold. Phage display selection from a genetic random library comprising variants of the human lipocalin 2 (Lcn2) with mutations targeted at 20 exposed amino acid positions in the four loops that form the natural binding site was performed using both recombinant and synthetic target peptides and resulted in three different Anticalins. Biochemical characterization of the purified proteins produced by periplasmic secretion in Escherichia coli revealed high folding stability in a monomeric state, with Tm values ranging from 53.4°C to 74.5°C, as well as high affinities for Aβ40, between 95 pM and 563 pM, as measured by real-time surface plasmon resonance analysis. The central linear VFFAED epitope within the Aβ sequence was mapped using a synthetic peptide array on membranes and was shared by all three Anticalins, despite up to 13 mutual amino acid differences in their binding sites. All Anticalins had the ability-with varying extent-to inhibit Aβ aggregation in vitro according to the thioflavin-T fluorescence assay and, furthermore, they abolished Aβ42-mediated toxicity in neuronal cell culture. Thus, these Anticalins provide not only useful protein reagents to study the molecular pathology of AD but they also show potential as alternative drug candidates compared with antibodies.
MeSH term(s)	Alzheimer Disease/drug therapy ; Alzheimer Disease/metabolism ; Amino Acid Sequence ; Amyloid beta-Peptides/antagonists & inhibitors ; Binding Sites ; Humans ; Lipocalins/chemistry ; Lipocalins/pharmacology ; Lipocalins/therapeutic use ; Molecular Sequence Data ; Peptide Library ; Protein Binding ; Protein Conformation ; Protein Engineering/methods
Chemical Substances	Amyloid beta-Peptides ; Lipocalins ; Peptide Library
Language	English
Publishing date	2016-06-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2969-5
ISSN	1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
ISSN (online)	1470-8728
ISSN	0006-2936 ; 0306-3275 ; 0264-6021
DOI	10.1042/BCJ20160114
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

In stock of ZB MED Cologne/Königswinter

Uc I Zs.110: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Book ; Thesis: Identifizierung und Charakterisierung von gig-2, einem neuen durch Aktivität des muskarinischen Azetylcholinrezeptors, induzierten humanen Gen

Mayhaus, Manuel

2000

Author's details	von Manuel Mayhaus
Language	German
Size	72 S, Ill., graph. Darst
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Univ., Diss.--Hamburg, 2000
Database	Former special subject collection: coastal and deep sea fishing

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Book ; Thesis: Identifizierung und Charakterisierung von gig-2, einem neuen durch Aktivität des muskarinischen Azetylcholinrezeptors, induzierten humanen Gen

Mayhaus, Manuel

2000

Author's details	von Manuel Mayhaus
Language	German
Size	72 S, Ill., graph. Darst
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Univ., Diss.--Hamburg, 2000
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: Amyloid-β Protein Precursor Cleavage Products in Postmortem Ventricular Cerebrospinal Fluid of Alzheimer's Disease Patients.

Hartl, Daniela / Gu, Wei / Mayhaus, Manuel / Pichler, Sabrina / Schöpe, Jakob / Wagenpfeil, Stefan / Riemenschneider, Matthias

Journal of Alzheimer's disease : JAD

2015 Volume 47, Issue 2, Page(s) 365–372

Abstract: Accumulation and aggregation of amyloid-β (Aβ) are considered etiologic processes in Alzheimer's disease (AD). However, the roles of other AβPP cleavage products in disease pathology remain elusive. Here, we measured levels of the major secreted AβPP ... ...

Abstract	Accumulation and aggregation of amyloid-β (Aβ) are considered etiologic processes in Alzheimer's disease (AD). However, the roles of other AβPP cleavage products in disease pathology remain elusive. Here, we measured levels of the major secreted AβPP processing products sAβPPα, sAβPPβ, and Aβ species in postmortem collected ventricular CSF of 196 AD patients and 74 controls. In AD we identified Aβ₄₂ to decrease continuously with progressing Braak stages, whereas Aβ₄₀ was upregulated in early stages of the disease (Braak stage 4) and down-regulated with progressing pathology. Interestingly, both sAβPPα and sAβPPβ were upregulated in AD as compared to controls (sAβPPα, p = 0.02; sAβPPβ, p = 0.01). Moreover, we observed a strong positive correlation of both alternative AβPP processing products, sAβPPα and sAβPPβ (r²= 0.781; p < 0.0001). Together, our results argue for generally enhanced AβPP processing in AD patients and emphasize the necessity of analyzing the roles of all AβPP processing products in AD pathology.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/cerebrospinal fluid ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/cerebrospinal fluid ; Amyloid beta-Protein Precursor/cerebrospinal fluid ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Peptide Fragments/cerebrospinal fluid
Chemical Substances	APP protein, human ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Peptide Fragments ; amyloid beta-protein (1-40) ; amyloid beta-protein (1-42)
Language	English
Publishing date	2015
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-150191
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6084: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The miRNome of Alzheimer's disease: consistent downregulation of the miR-132/212 cluster.

Pichler, Sabrina / Gu, Wei / Hartl, Daniela / Gasparoni, Gilles / Leidinger, Petra / Keller, Andreas / Meese, Eckart / Mayhaus, Manuel / Hampel, Harald / Riemenschneider, Matthias

Neurobiology of aging

2017 Volume 50, Page(s) 167.e1–167.e10

Abstract: MicroRNAs (miRNAs) are small noncoding RNA molecules, with essential functions in RNA silencing and post-transcriptional regulation of gene expression. miRNAs appear to regulate the development and function of the nervous system. Alterations of miRNA ... ...

Abstract	MicroRNAs (miRNAs) are small noncoding RNA molecules, with essential functions in RNA silencing and post-transcriptional regulation of gene expression. miRNAs appear to regulate the development and function of the nervous system. Alterations of miRNA expression have been associated with Alzheimer's disease (AD). To characterize the AD miRNA signature, we examined genome-wide miRNA and mRNA expression patterns in the temporal cortex of AD and control samples. We validated our miRNA results by semiquantitative real-time polymerase chain reaction (PCR) in independent prefrontal cortex. Furthermore, we separated gray and white matter brain sections to identify the cellular origin of the altered miRNA expression. We observed genome-wide downregulation of hsa-miR-132-3p and hsa-miR-212-3p in AD with a stronger decrease in gray matter AD samples. We further identified 10 differently expressed transcripts achieving genome-wide levels of significance. Significantly deregulated miRNAs and mRNAs were correlated and examined for potential binding sites (in silico). This miRNome-wide study in AD provides supportive evidence and corroborates an important contribution of miR-132/212 and corresponding target mRNAs to the pathogenesis of AD.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/genetics ; Binding Sites ; Down-Regulation ; Female ; Gene Expression ; Genome-Wide Association Study ; Gray Matter/metabolism ; Humans ; Male ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Multigene Family/genetics
Chemical Substances	MIRN132 microRNA, human ; MIRN212 microRNA, human ; MicroRNAs
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2016.09.019
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1685: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 10: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Rare

May, Patrick / Pichler, Sabrina / Hartl, Daniela / Bobbili, Dheeraj R / Mayhaus, Manuel / Spaniol, Christian / Kurz, Alexander / Balling, Rudi / Schneider, Jochen G / Riemenschneider, Matthias

Neurology. Genetics

2018 Volume 4, Issue 2, Page(s) e224

Abstract: Objective: The aim of this study was to identify variants associated with familial late-onset Alzheimer disease (AD) using whole-genome sequencing.: Methods: Several families with an autosomal dominant inheritance pattern of AD were analyzed by whole- ...

Abstract	Objective: The aim of this study was to identify variants associated with familial late-onset Alzheimer disease (AD) using whole-genome sequencing. Methods: Several families with an autosomal dominant inheritance pattern of AD were analyzed by whole-genome sequencing. Variants were prioritized for rare, likely pathogenic variants in genes already known to be associated with AD and confirmed by Sanger sequencing using standard protocols. Results: We identified 2 rare Conclusions: We conclude that both SNVs might contribute to the development of AD in the examined family members. Together with previous findings, our data confirm
Language	English
Publishing date	2018-03-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2818607-2
ISSN	2376-7839
ISSN	2376-7839
DOI	10.1212/NXG.0000000000000224
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease.

Molecular psychiatry

2018 Volume 25, Issue 3, Page(s) 629–639

Abstract: Common variants of about 20 genes contributing to AD risk have so far been identified through genome-wide association studies (GWAS). However, there is still a large proportion of heritability that might be explained by rare but functionally important ... ...

Abstract	Common variants of about 20 genes contributing to AD risk have so far been identified through genome-wide association studies (GWAS). However, there is still a large proportion of heritability that might be explained by rare but functionally important variants. One of the so far identified genes with rare AD causing variants is ADAM10. Using whole-genome sequencing we now identified a single rare nonsynonymous variant (SNV) rs142946965 [p.R215I] in ADAM17 co-segregating with an autosomal-dominant pattern of late-onset AD in one family. Subsequent genotyping and analysis of available whole-exome sequencing data of additional case/control samples from Germany, UK, and USA identified five variant carriers among AD patients only. The mutation inhibits pro-protein cleavage and the formation of the active enzyme, thus leading to loss-of-function of ADAM17 alpha-secretase. Further, we identified a strong negative correlation between ADAM17 and APP gene expression in human brain and present in vitro evidence that ADAM17 negatively controls the expression of APP. As a consequence, p.R215I mutation of ADAM17 leads to elevated Aß formation in vitro. Together our data supports a causative association of the identified ADAM17 variant in the pathogenesis of AD.
MeSH term(s)	ADAM17 Protein/genetics ; ADAM17 Protein/metabolism ; Aged ; Alzheimer Disease/genetics ; Amyloid Precursor Protein Secretases/metabolism ; Amyloid beta-Protein Precursor/genetics ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Germany ; Humans ; Loss of Function Mutation/genetics ; Male ; Middle Aged ; Mutation ; Whole Exome Sequencing
Chemical Substances	Amyloid beta-Protein Precursor ; Amyloid Precursor Protein Secretases (EC 3.4.-) ; ADAM17 Protein (EC 3.4.24.86) ; ADAM17 protein, human (EC 3.4.24.86)
Language	English
Publishing date	2018-07-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/s41380-018-0091-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4812: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Temporal gene expression profile of the hippocampus following trace fear conditioning.

Sirri, Alessandra / Bianchi, Veronica / Pelizzola, Mattia / Mayhaus, Manuel / Ricciardi-Castagnoli, Paola / Toniolo, Daniela / D'Adamo, Patrizia

Brain research

2009 Volume 1308, Page(s) 14–23

Abstract: In this paper we report the results of gene expression profiling of C57Bl/6N mice hippocampus after trace fear conditioning (TFC), and the identification of genes regulated at early and late steps after conditioning. Several of the genes regulated at ... ...

Abstract	In this paper we report the results of gene expression profiling of C57Bl/6N mice hippocampus after trace fear conditioning (TFC), and the identification of genes regulated at early and late steps after conditioning. Several of the genes regulated at early steps following TFC appeared common to many training protocols. At later stages (2 and 6 h), most of the genes identified were different from those identified following other learning paradigms resulting in memory consolidation. At 6 h after training, few genes were upregulated in respect to the naïve condition, suggesting that many gene products have eventually to be downregulated to achieve stable synapses modification and memory formation. In conclusion, the results presented highlight a number of genes whose expression is specifically modified in the mouse hippocampus following TFC and demonstrate the specificity associated to different forms of conditioning.
MeSH term(s)	Animals ; Conditioning, Classical/physiology ; Fear ; Gene Expression/genetics ; Gene Expression Profiling ; Hippocampus/metabolism ; Male ; Memory/physiology ; Mice ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors ; Up-Regulation/genetics
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2009-10-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2009.10.049
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 161: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The Genopolis Microarray Database

Splendiani Andrea / Brandizi Marco / Even Gael / Beretta Ottavio / Pavelka Norman / Pelizzola Mattia / Mayhaus Manuel / Foti Maria / Mauri Giancarlo / Ricciardi-Castagnoli Paola

BMC Bioinformatics, Vol 8, Iss Suppl 1, p S

2007 Volume 21

Abstract: Abstract Background Gene expression databases are key resources for microarray data management and analysis and the importance of a proper annotation of their content is well understood. Public repositories as well as microarray database systems that can ...

Abstract	Abstract Background Gene expression databases are key resources for microarray data management and analysis and the importance of a proper annotation of their content is well understood. Public repositories as well as microarray database systems that can be implemented by single laboratories exist. However, there is not yet a tool that can easily support a collaborative environment where different users with different rights of access to data can interact to define a common highly coherent content. The scope of the Genopolis database is to provide a resource that allows different groups performing microarray experiments related to a common subject to create a common coherent knowledge base and to analyse it. The Genopolis database has been implemented as a dedicated system for the scientific community studying dendritic and macrophage cells functions and host-parasite interactions. Results The Genopolis Database system allows the community to build an object based MIAME compliant annotation of their experiments and to store images, raw and processed data from the Affymetrix GeneChip ® platform. It supports dynamical definition of controlled vocabularies and provides automated and supervised steps to control the coherence of data and annotations. It allows a precise control of the visibility of the database content to different sub groups in the community and facilitates exports of its content to public repositories. It provides an interactive users interface for data analysis: this allows users to visualize data matrices based on functional lists and sample characterization, and to navigate to other data matrices defined by similarity of expression values as well as functional characterizations of genes involved. A collaborative environment is also provided for the definition and sharing of functional annotation by users. Conclusion The Genopolis Database supports a community in building a common coherent knowledge base and analyse it. This fills a gap between a local database and a public repository, where the ...
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7 ; Biology (General) ; QH301-705.5
Subject code	004
Language	English
Publishing date	2007-03-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Pharmacogenomics in Alzheimer's disease: a genome-wide association study of response to cholinesterase inhibitors.

Martinelli-Boneschi, Filippo / Giacalone, Giacomo / Magnani, Giuseppe / Biella, Gloria / Coppi, Elisabetta / Santangelo, Roberto / Brambilla, Paola / Esposito, Federica / Lupoli, Sara / Clerici, Francesca / Benussi, Luisa / Ghidoni, Roberta / Galimberti, Daniela / Squitti, Rosanna / Confaloni, Annamaria / Bruno, Giuseppe / Pichler, Sabrina / Mayhaus, Manuel / Riemenschneider, Matthias /

Mariani, Claudio / Comi, Giancarlo / Scarpini, Elio / Binetti, Giuliano / Forloni, Gianluigi / Franceschi, Massimo / Albani, Diego

Neurobiology of aging

2013 Volume 34, Issue 6, Page(s) 1711.e7–13

Abstract: We conducted a genome-wide association study in a cohort of 176 Italian Alzheimer's disease (AD) patients with extreme phenotype of response to cholinesterase inhibitors. Patients were classified into responders in case of positive, stable, or ≤1 ... ...

Abstract	We conducted a genome-wide association study in a cohort of 176 Italian Alzheimer's disease (AD) patients with extreme phenotype of response to cholinesterase inhibitors. Patients were classified into responders in case of positive, stable, or ≤1 worsening of mini-mental state examination score and into nonresponders if >3 points worsening during a median follow-up of 0.85 years of treatment. Forty-eight single-nucleotide polymorphisms were selected for replication in 198 additional AD-treated patients. By using the dichotomous response trait and a quantitative trait approach (change of mini-mental state examination), a nominal replication and evidence of association when combining data were achieved for 2 single-nucleotide polymorphisms associated with response to treatment: rs6720975A (pcombined = 2.9 × 10(-5), beta regression coefficient: 1.61) and rs17798800A (pcombined = 6.8 × 10(-6), odds ratio = 0.38, 95% confidence interval = 0.25-0.58). Rs6720975 maps in the intronic region of PRKCE, a protein kinase involved in several cellular functions, whereas rs17798800 is intergenic and, according to expression quantitative trait locus (eQTL) analysis, it acts as a cis-regulator of NBEA, an A kinase-anchoring protein playing a substantial role in the maturation of the nervous system. Despite its limitations, this project paves the way for the application of personalized medicine in AD patients and for collaborative efforts in this field.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis ; Alzheimer Disease/drug therapy ; Alzheimer Disease/genetics ; Cholinesterase Inhibitors/therapeutic use ; Cohort Studies ; Female ; Follow-Up Studies ; Genome-Wide Association Study/methods ; Humans ; Male ; Pharmacogenetics ; Polymorphism, Single Nucleotide/genetics
Chemical Substances	Cholinesterase Inhibitors
Language	English
Publishing date	2013-06
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2012.12.008
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1685: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 10: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito