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Article: Editorial: Molecular basis of stem cells underlying plant vitality.

Chen, Chunli / Cruz-Ramirez, Alfredo / Zhang, Yonghong / Ishikawa, Masaki

2024 Volume 15, Page(s) 1371814

Language	English
Publishing date	2024-02-07
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2613694-6
ISSN	1664-462X
ISSN	1664-462X
DOI	10.3389/fpls.2024.1371814
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Article ; Online: Step by step: towards a better understanding of the genetic architecture of Alzheimer's disease.

Lambert, Jean-Charles / Ramirez, Alfredo / Grenier-Boley, Benjamin / Bellenguez, Céline

Molecular psychiatry

2023 Volume 28, Issue 7, Page(s) 2716–2727

Abstract: Alzheimer's disease (AD) is considered to have a large genetic component. Our knowledge of this component has progressed over the last 10 years, thanks notably to the advent of genome-wide association studies and the establishment of large consortia that ...

Abstract	Alzheimer's disease (AD) is considered to have a large genetic component. Our knowledge of this component has progressed over the last 10 years, thanks notably to the advent of genome-wide association studies and the establishment of large consortia that make it possible to analyze hundreds of thousands of cases and controls. The characterization of dozens of chromosomal regions associated with the risk of developing AD and (in some loci) the causal genes responsible for the observed disease signal has confirmed the involvement of major pathophysiological pathways (such as amyloid precursor protein metabolism) and opened up new perspectives (such as the central role of microglia and inflammation). Furthermore, large-scale sequencing projects are starting to reveal the major impact of rare variants - even in genes like APOE - on the AD risk. This increasingly comprehensive knowledge is now being disseminated through translational research; in particular, the development of genetic risk/polygenic risk scores is helping to identify the subpopulations more at risk or less at risk of developing AD. Although it is difficult to assess the efforts still needed to comprehensively characterize the genetic component of AD, several lines of research can be improved or initiated. Ultimately, genetics (in combination with other biomarkers) might help to redefine the boundaries and relationships between various neurodegenerative diseases.
MeSH term(s)	Humans ; Alzheimer Disease/genetics ; Genome-Wide Association Study ; Risk Factors ; Biomarkers ; Apolipoproteins E/genetics
Chemical Substances	Biomarkers ; Apolipoproteins E
Language	English
Publishing date	2023-05-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/s41380-023-02076-1
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Article ; Online: Predicted landscape of RETINOBLASTOMA-RELATED LxCxE-mediated interactions across the Chloroplastida.

León-Ruiz, Jesús A / Cruz Ramírez, Alfredo

The Plant journal : for cell and molecular biology

2022 Volume 112, Issue 6, Page(s) 1507–1524

Abstract: The colonization of land by a single streptophyte algae lineage some 450 million years ago has been linked to multiple key innovations such as three-dimensional growth, alternation of generations, the presence of stomata, as well as innovations inherent ... ...

Abstract	The colonization of land by a single streptophyte algae lineage some 450 million years ago has been linked to multiple key innovations such as three-dimensional growth, alternation of generations, the presence of stomata, as well as innovations inherent to the birth of major plant lineages, such as the origins of vascular tissues, roots, seeds and flowers. Multicellularity, which evolved multiple times in the Chloroplastida coupled with precise spatiotemporal control of proliferation and differentiation were instrumental for the evolution of these traits. RETINOBLASTOMA-RELATED (RBR), the plant homolog of the metazoan Retinoblastoma protein (pRB), is a highly conserved and multifunctional core cell cycle regulator that has been implicated in the evolution of multicellularity in the green lineage as well as in plant multicellularity-related processes such as proliferation, differentiation, stem cell regulation and asymmetric cell division. RBR fulfills these roles through context-specific protein-protein interactions with proteins containing the Leu-x-Cys-x-Glu (LxCxE) short-linear motif (SLiM); however, how RBR-LxCxE interactions have changed throughout major innovations in the Viridiplantae kingdom is a question that remains unexplored. Here, we employ an in silico evo-devo approach to predict and analyze potential RBR-LxCxE interactions in different representative species of key Chloroplastida lineages, providing a valuable resource for deciphering RBR-LxCxE multiple functions. Furthermore, our analyses suggest that RBR-LxCxE interactions are an important component of RBR functions and that interactions with chromatin modifiers/remodelers, DNA replication and repair machinery are highly conserved throughout the Viridiplantae, while LxCxE interactions with transcriptional regulators likely diversified throughout the water-to-land transition.
MeSH term(s)	Animals ; Retinoblastoma ; Retinoblastoma Protein/metabolism ; Cell Differentiation ; Retinal Neoplasms
Chemical Substances	Retinoblastoma Protein
Language	English
Publishing date	2022-12-02
Publishing country	England
Document type	Journal Article
ZDB-ID	1088037-9
ISSN	1365-313X ; 0960-7412
ISSN (online)	1365-313X
ISSN	0960-7412
DOI	10.1111/tpj.16012
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Article ; Online: Population-Based Genetic Studies: The Search for Causative Variants in Parkinson's Disease.

Ramirez, Alfredo

Movement disorders : official journal of the Movement Disorder Society

2015 Volume 30, Issue 10, Page(s) 1297–1300

MeSH term(s)	Asian Continental Ancestry Group/genetics ; European Continental Ancestry Group/genetics ; Genetic Association Studies ; Humans ; Linkage Disequilibrium/genetics ; Parkinson Disease/genetics ; Polymorphism, Single Nucleotide/genetics
Language	English
Publishing date	2015-09
Publishing country	United States
Document type	Comment ; Editorial
ZDB-ID	607633-6
ISSN	1531-8257 ; 0885-3185
ISSN (online)	1531-8257
ISSN	0885-3185
DOI	10.1002/mds.26341
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Article ; Online: Predicted landscape of RETINOBLASTOMA‐RELATED LxCxE‐mediated interactions across the Chloroplastida

León‐Ruiz, Jesús A. / Cruz-Ramírez, Alfredo

The Plant Journal. 2022 Dec., v. 112, no. 6 p.1507-1524

2022

Abstract: The colonization of land by a single streptophyte algae lineage some 450 million years ago has been linked to multiple key innovations such as three‐dimensional growth, alternation of generations, the presence of stomata, as well as innovations inherent ... ...

Abstract	The colonization of land by a single streptophyte algae lineage some 450 million years ago has been linked to multiple key innovations such as three‐dimensional growth, alternation of generations, the presence of stomata, as well as innovations inherent to the birth of major plant lineages, such as the origins of vascular tissues, roots, seeds and flowers. Multicellularity, which evolved multiple times in the Chloroplastida coupled with precise spatiotemporal control of proliferation and differentiation were instrumental for the evolution of these traits. RETINOBLASTOMA‐RELATED (RBR), the plant homolog of the metazoan Retinoblastoma protein (pRB), is a highly conserved and multifunctional core cell cycle regulator that has been implicated in the evolution of multicellularity in the green lineage as well as in plant multicellularity‐related processes such as proliferation, differentiation, stem cell regulation and asymmetric cell division. RBR fulfills these roles through context‐specific protein–protein interactions with proteins containing the Leu‐x‐Cys‐x‐Glu (LxCxE) short‐linear motif (SLiM); however, how RBR‐LxCxE interactions have changed throughout major innovations in the Viridiplantae kingdom is a question that remains unexplored. Here, we employ an in silico evo‐devo approach to predict and analyze potential RBR‐LxCxE interactions in different representative species of key Chloroplastida lineages, providing a valuable resource for deciphering RBR‐LxCxE multiple functions. Furthermore, our analyses suggest that RBR‐LxCxE interactions are an important component of RBR functions and that interactions with chromatin modifiers/remodelers, DNA replication and repair machinery are highly conserved throughout the Viridiplantae, while LxCxE interactions with transcriptional regulators likely diversified throughout the water‐to‐land transition.
Keywords	Animalia ; DNA replication ; Viridiplantae ; cell division ; chromatin ; computer simulation ; evolution ; landscapes ; stem cells ; transcription (genetics)
Language	English
Dates of publication	2022-12
Size	p. 1507-1524.
Publishing place	John Wiley & Sons, Ltd
Document type	Article ; Online
Note	JOURNAL ARTICLE
ZDB-ID	1088037-9
ISSN	1365-313X ; 0960-7412
ISSN (online)	1365-313X
ISSN	0960-7412
DOI	10.1111/tpj.16012
Database	NAL-Catalogue (AGRICOLA)

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Article: Transcriptional analysis of

Aragón-Raygoza, Alejandro / Herrera-Estrella, Luis / Cruz-Ramírez, Alfredo

Frontiers in plant science

2022 Volume 13, Page(s) 924660

Abstract: Gene expression in roots has been assessed in different plant species in studies ranging from complete organs to specific cell layers, and more recently at the single cell level. While certain genes or functional categories are expressed in the root of ... ...

Abstract	Gene expression in roots has been assessed in different plant species in studies ranging from complete organs to specific cell layers, and more recently at the single cell level. While certain genes or functional categories are expressed in the root of all or most plant species, lineage-specific genes have also been discovered. An increasing amount of transcriptomic data is available for angiosperms, while a limited amount of data is available for ferns, and few studies have focused on fern roots. Here, we present a
Language	English
Publishing date	2022-08-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2613694-6
ISSN	1664-462X
ISSN	1664-462X
DOI	10.3389/fpls.2022.924660
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Article ; Online: Cancer in Amphibia, a rare phenomenon?

Torres-Dimas, Esteban / Cruz-Ramírez, Alfredo / Bermúdez-Cruz, Rosa María

Cell biology international

2022 Volume 46, Issue 12, Page(s) 1992–1998

Abstract: Compared to other animals, the spontaneous occurrence of tumors in wild amphibians is relatively rare, generally limited to specific populations or species. The number of reports of spontaneous tumors in amphibians known up to 1986 was 491 cases in ... ...

Abstract	Compared to other animals, the spontaneous occurrence of tumors in wild amphibians is relatively rare, generally limited to specific populations or species. The number of reports of spontaneous tumors in amphibians known up to 1986 was 491 cases in anurans and about 253 cases in urodeles. Similarly, there have been many, unsuccessful attempts to chemically or biologically induce tumors in amphibians. With these considerations, it is inevitable to wonder: do urodeles and anurans have an inherent resistance to cancer? Here, we review the spontaneous and induced occurrence of tumors in amphibians in a timeline, as well as failed attempts to induce tumors in these amphibians. Indeed, recent studies seem to indicate that there is a relationship between regeneration and cancer because regenerating tissues seem to resist tumorigenesis, as opposed to nonregenerative tissues of the same amphibian models. Although the mechanisms that allow regenerating tissues to resist tumorigenesis have not been elucidated, it is worth to note that, in addition to the apparent relationship between regeneration and cancer, amphibians possess characteristics that could contribute to their ability to resist the development of neoplastic events. The implications of these features in cancer susceptibility are discussed.
MeSH term(s)	Animals ; Amphibians ; Neoplasms/veterinary ; Neoplasms/pathology ; Cell Transformation, Neoplastic
Language	English
Publishing date	2022-08-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1143453-3
ISSN	1095-8355 ; 1065-6995
ISSN (online)	1095-8355
ISSN	1065-6995
DOI	10.1002/cbin.11888
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Article ; Online: Polygenic Effect on Tau Pathology Progression in Alzheimer's Disease.

Rubinski, Anna / Frerich, Simon / Malik, Rainer / Franzmeier, Nicolai / Ramirez, Alfredo / Dichgans, Martin / Ewers, Michael

Annals of neurology

2023 Volume 93, Issue 4, Page(s) 819–829

Abstract: Objective: Polygenic variation accounts for a substantial portion of the risk of Alzheimer's disease (AD), but its effect on the rate of fibrillar-tau accumulation as a key driver of dementia symptoms is unclear.: Methods: We combined the to-date ... ...

Abstract	Objective: Polygenic variation accounts for a substantial portion of the risk of Alzheimer's disease (AD), but its effect on the rate of fibrillar-tau accumulation as a key driver of dementia symptoms is unclear. Methods: We combined the to-date largest number of genetic risk variants of AD (n = 85 lead single-nucleotide polymorphisms [SNPs]) from recent genome-wide association studies (GWAS) to generate a polygenic score (PGS). We assessed longitudinal tau-positron emission tomography (PET), amyloid-PET, and cognition in 231 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Using the PGS, together with global amyloid-PET, we predicted the rate of tau-PET increases in Braak-stage regions-of-interest and cognitive decline. We also assessed PGS-risk enrichment effects on the required sample size in clinical trials targeting tau pathology. Results: We found that a higher PGS was associated with higher rates of tau-PET accumulation, in particular at elevated amyloid-PET levels. The tau-PET increases mediated the association between PGS and faster cognitive decline. Risk enrichment through high PGS afforded sample size savings by 34%. Interpretation: Our results demonstrate that the PGS predicts faster tau progression and thus cognitive decline, showing utility to enhance statistical power in clinical trials. ANN NEUROL 2023;93:819-829.
MeSH term(s)	Humans ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/genetics ; tau Proteins/genetics ; tau Proteins/metabolism ; Genome-Wide Association Study ; Brain/pathology ; Biomarkers ; Cognitive Dysfunction/diagnosis ; Positron-Emission Tomography/methods ; Amyloid ; Amyloid beta-Peptides/genetics
Chemical Substances	tau Proteins ; Biomarkers ; Amyloid ; Amyloid beta-Peptides
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80362-5
ISSN	1531-8249 ; 0364-5134
ISSN (online)	1531-8249
ISSN	0364-5134
DOI	10.1002/ana.26588
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Article ; Online: RETINOBLASTOMA-RELATED interactions with key factors of the RNA-directed DNA methylation (RdDM) pathway and its influence on root development.

León-Ruiz, Jesús / Espinal-Centeno, Annie / Blilou, Ikram / Scheres, Ben / Arteaga-Vázquez, Mario / Cruz-Ramírez, Alfredo

Planta

2023 Volume 257, Issue 6, Page(s) 105

Abstract: Main conclusion: Our study presents evidence for a novel mechanism for RBR function in transcriptional gene silencing by interacting with key players of the RdDM pathway in Arabidopsis and several plant clades. Transposable elements and other repetitive ...

Abstract	Main conclusion: Our study presents evidence for a novel mechanism for RBR function in transcriptional gene silencing by interacting with key players of the RdDM pathway in Arabidopsis and several plant clades. Transposable elements and other repetitive elements are silenced by the RNA-directed DNA methylation pathway (RdDM). In RdDM, POLIV-derived transcripts are converted into double-stranded RNA (dsRNA) by the activity of RDR2 and subsequently processed into 24 nucleotide short interfering RNAs (24-nt siRNAs) by DCL3. 24-nt siRNAs serve as guides to direct AGO4-siRNA complexes to chromatin-bound POLV-derived transcripts generated from the template/target DNA. The interaction between POLV, AGO4, DMS3, DRD1, RDM1 and DRM2 promotes DRM2-mediated de novo DNA methylation. The Arabidopsis Retinoblastoma protein homolog (RBR) is a master regulator of the cell cycle, stem cell maintenance, and development. We in silico predicted and explored experimentally the protein-protein interactions (PPIs) between RBR and members of the RdDM pathway. We found that the largest subunits of POLIV and POLV (NRPD1 and NRPE1), the shared second largest subunit of POLIV and POLV (NRPD/E2), RDR1, RDR2, DCL3, DRM2, and SUVR2 contain canonical and non-canonical RBR binding motifs and several of them are conserved since algae and bryophytes. We validated experimentally PPIs between Arabidopsis RBR and several of the RdDM pathway proteins. Moreover, seedlings from loss-of-function mutants in RdDM and RBR show similar phenotypes in the root apical meristem. We show that RdDM and SUVR2 targets are up-regulated in the 35S:AmiGO-RBR background.
MeSH term(s)	Arabidopsis/genetics ; Arabidopsis/metabolism ; DNA Methylation/genetics ; Arabidopsis Proteins/genetics ; Arabidopsis Proteins/metabolism ; DNA-Directed RNA Polymerases/genetics ; Retinoblastoma/genetics ; RNA, Small Interfering/genetics ; RNA, Double-Stranded/metabolism ; RNA, Plant/genetics ; RNA, Plant/metabolism ; Retinal Neoplasms/genetics ; Gene Expression Regulation, Plant ; Ribonuclease III/genetics
Chemical Substances	Arabidopsis Proteins ; DNA-Directed RNA Polymerases (EC 2.7.7.6) ; RNA, Small Interfering ; RNA, Double-Stranded ; RNA, Plant ; DCL3 protein, Arabidopsis (EC 3.1.26.3) ; Ribonuclease III (EC 3.1.26.3)
Language	English
Publishing date	2023-04-30
Publishing country	Germany
Document type	Journal Article
ZDB-ID	208909-9
ISSN	1432-2048 ; 0032-0935 ; 1866-2749
ISSN (online)	1432-2048
ISSN	0032-0935 ; 1866-2749
DOI	10.1007/s00425-023-04135-x
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Article ; Online: Brain Health Services: Erfassung des individuellen Demenzrisikos am Kölner Alzheimer Präventionszentrum.

Zeyen, Philip / Sannemann, Lena / Bohr, Lara / Escher, Claus / Müller, Theresa / Ramírez, Alfredo / Rostamzadeh, Ayda / Jessen, Frank

Der Nervenarzt

2023 Volume 94, Issue 5, Page(s) 392–399

Abstract: Background: According to current knowledge approximately 30-40% of all cases of dementia can be attributed to modifiable risk factors. As a result, dementia prevention and the concept of brain health are becoming increasingly relevant.: Research ... ...

Title translation	Brain health services: individual dementia risk profiling at the Cologne Alzheimer Prevention Center.
Abstract	Background: According to current knowledge approximately 30-40% of all cases of dementia can be attributed to modifiable risk factors. As a result, dementia prevention and the concept of brain health are becoming increasingly relevant. Research question: The requirements for brain health services and their implementation are discussed and the Cologne Alzheimer Prevention Center (KAP) of the University Hospital Cologne is described as an example. Material and methods: In addition to a report on international brain health initiatives, the main activities of the KAP are presented. A program for individual risk profiling and risk communication is provided, which was piloted in the KAP in the context of the "Individual risk profiling for Alzheimer's disease and dementia prevention (INSPIRATION)" study. The prevalence of risk factors in a cognitively healthy sample aged 50-86 years (n = 162) with interest in dementia prevention is presented. Results: The most common risk factors were non-Mediterranean diet, obesity, subjective poor sleep quality and increased stress. Based on these results, preventive interventions can be developed that are adapted to the individual risk profile as a personalized medicine approach. Discussion: Structures such as the KAP can provide individual risk factor assessment and personalized dementia prevention. The efficacy of this approach on dementia risk reduction needs to be evaluated.
MeSH term(s)	Humans ; Alzheimer Disease/diagnosis ; Alzheimer Disease/epidemiology ; Alzheimer Disease/prevention & control ; Dementia/diagnosis ; Dementia/epidemiology ; Dementia/prevention & control ; Brain ; Risk Factors ; Health Services
Language	German
Publishing date	2023-03-07
Publishing country	Germany
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	123291-5
ISSN	1433-0407 ; 0028-2804
ISSN (online)	1433-0407
ISSN	0028-2804
DOI	10.1007/s00115-023-01451-1
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