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Article ; Online: Interplay between cardiac transcription factors and non-coding RNAs in predisposing to atrial fibrillation.

Mikhailov, Alexander T / Torrado, Mario

Journal of molecular medicine (Berlin, Germany)

2018 Volume 96, Issue 7, Page(s) 601–610

Abstract: There is growing evidence that putative gene regulatory networks including cardio-enriched transcription factors, such as PITX2, TBX5, ZFHX3, and SHOX2, and their effector/target genes along with downstream non-coding RNAs can play a potentially ... ...

Abstract	There is growing evidence that putative gene regulatory networks including cardio-enriched transcription factors, such as PITX2, TBX5, ZFHX3, and SHOX2, and their effector/target genes along with downstream non-coding RNAs can play a potentially important role in the process of adaptive and maladaptive atrial rhythm remodeling. In turn, expression of atrial fibrillation-associated transcription factors is under the control of upstream regulatory non-coding RNAs. This review broadly explores gene regulatory mechanisms associated with susceptibility to atrial fibrillation-with key examples from both animal models and patients-within the context of both cardiac transcription factors and non-coding RNAs. These two systems appear to have multiple levels of cross-regulation and act coordinately to achieve effective control of atrial rhythm effector gene expression. Perturbations of a dynamic expression balance between transcription factors and corresponding non-coding RNAs can provoke the development or promote the progression of atrial fibrillation. We also outline deficiencies in current models and discuss ongoing studies to clarify remaining mechanistic questions. An understanding of the function of transcription factors and non-coding RNAs in gene regulatory networks associated with atrial fibrillation risk will enable the development of innovative therapeutic strategies.
MeSH term(s)	Animals ; Atrial Fibrillation/genetics ; Atrial Fibrillation/metabolism ; Atrial Fibrillation/physiopathology ; Biomarkers ; Disease Susceptibility ; Gene Expression Regulation ; Humans ; MicroRNAs/genetics ; Models, Biological ; Myocardium/metabolism ; RNA, Untranslated/genetics ; Transcription Factors/metabolism
Chemical Substances	Biomarkers ; MicroRNAs ; RNA, Untranslated ; Transcription Factors
Language	English
Publishing date	2018-05-12
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1223802-8
ISSN	1432-1440 ; 0946-2716
ISSN (online)	1432-1440
ISSN	0946-2716
DOI	10.1007/s00109-018-1647-4
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Article ; Online: Russian comparative embryology takes form: a conceptual metamorphosis toward "evo-devo".

Mikhailov, Alexander T

Evolution & development

2012 Volume 14, Issue 1, Page(s) 9–19

Abstract: This essay recapitulates major paths followed by the Russian tradition of what we refer to today as evolutionary developmental biology ("evo-devo"). The article addresses several questions regarding the conceptual history of evolutionary embryological ... ...

Abstract	This essay recapitulates major paths followed by the Russian tradition of what we refer to today as evolutionary developmental biology ("evo-devo"). The article addresses several questions regarding the conceptual history of evolutionary embryological thought in its particularly Russian perspective: (1) the assertion by the St. Petersburg academician Wolff regarding the possible connections between environmental modifications during morphogenesis and the "transformation" of species, (2) the discovery of shared "principles" underlying animal development by von Baer, (3) the experimental expression of Baer's principles by Kowalevsky and Mechnikoff, (4) Severtsov's theory of phylembryogenesis, (5) Filatov's approach to the study of evolution using comparative "developmental mechanics", and (6) Shmalgausen's concept of "stabilizing" selection as an attempt to elucidate the evolution of developmental mechanisms. The focus on comparative evolutionary embryology, which was established by Kowalevsky and Mechnikoff, still continues to be popular in present-day "evo-devo" research in Russia.
MeSH term(s)	Anatomy, Comparative/history ; Biological Evolution ; Embryology/history ; History, 18th Century ; History, 19th Century ; History, 20th Century ; Natural History/history ; Russia ; Russia (Pre-1917) ; Zoology/history
Language	English
Publishing date	2012-01
Publishing country	United States
Document type	Historical Article ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2020288-X
ISSN	1525-142X ; 1520-541X
ISSN (online)	1525-142X
ISSN	1520-541X
DOI	10.1111/j.1525-142X.2011.00518.x
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Article ; Online: Myocardial transcription factors in diastolic dysfunction: clues for model systems and disease.

Mikhailov, Alexander T / Torrado, Mario

Heart failure reviews

2016 Volume 21, Issue 6, Page(s) 783–794

Abstract: There are multiple intrinsic mechanisms for diastolic dysfunction ranging from molecular to structural derangements in ventricular myocardium. The molecular mechanisms regulating the progression from normal diastolic function to severe dysfunction still ... ...

Abstract	There are multiple intrinsic mechanisms for diastolic dysfunction ranging from molecular to structural derangements in ventricular myocardium. The molecular mechanisms regulating the progression from normal diastolic function to severe dysfunction still remain poorly understood. Recent studies suggest a potentially important role of core cardio-enriched transcription factors (TFs) in the control of cardiac diastolic function in health and disease through their ability to regulate the expression of target genes involved in the process of adaptive and maladaptive cardiac remodeling. The current relevant findings on the role of a variety of such TFs (TBX5, GATA-4/6, SRF, MYOCD, NRF2, and PITX2) in cardiac diastolic dysfunction and failure are updated, emphasizing their potential as promising targets for novel treatment strategies. In turn, the new animal models described here will be key tools in determining the underlying molecular mechanisms of disease. Since diastolic dysfunction is regulated by various TFs, which are also involved in cross talk with each other, there is a need for more in-depth research from a biomedical perspective in order to establish efficient therapeutic strategies.
Language	English
Publishing date	2016-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	1336499-6
ISSN	1573-7322 ; 1382-4147
ISSN (online)	1573-7322
ISSN	1382-4147
DOI	10.1007/s10741-016-9569-0
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Article ; Online: In search of novel targets for heart disease: myocardin and myocardin-related transcriptional cofactors.

Mikhailov, Alexander T / Torrado, Mario

Biochemistry research international

2012 Volume 2012, Page(s) 973723

Abstract: Growing evidence suggests that gene-regulatory networks, which are responsible for directing cardiovascular development, are altered under stress conditions in the adult heart. The cardiac gene regulatory network is controlled by cardioenriched ... ...

Abstract	Growing evidence suggests that gene-regulatory networks, which are responsible for directing cardiovascular development, are altered under stress conditions in the adult heart. The cardiac gene regulatory network is controlled by cardioenriched transcription factors and multiple-cell-signaling inputs. Transcriptional coactivators also participate in gene-regulatory circuits as the primary targets of both physiological and pathological signals. Here, we focus on the recently discovered myocardin-(MYOCD) related family of transcriptional cofactors (MRTF-A and MRTF-B) which associate with the serum response transcription factor and activate the expression of a variety of target genes involved in cardiac growth and adaptation to stress via overlapping but distinct mechanisms. We discuss the involvement of MYOCD, MRTF-A, and MRTF-B in the development of cardiac dysfunction and to what extent modulation of the expression of these factors in vivo can correlate with cardiac disease outcomes. A close examination of the findings identifies the MYOCD-related transcriptional cofactors as putative therapeutic targets to improve cardiac function in heart failure conditions through distinct context-dependent mechanisms. Nevertheless, we are in support of further research to better understand the precise role of individual MYOCD-related factors in cardiac function and disease, before any therapeutic intervention is to be entertained in preclinical trials.
Language	English
Publishing date	2012-05-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2566725-7
ISSN	2090-2255 ; 2090-2255
ISSN (online)	2090-2255
ISSN	2090-2255
DOI	10.1155/2012/973723
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Article ; Online: A Novel Heterozygous Intronic Mutation in the

Torrado, Mario / Maneiro, Emilia / Trujillo-Quintero, Juan Pablo / Evangelista, Arturo / Mikhailov, Alexander T / Monserrat, Lorenzo

BioMed research international

2018 Volume 2018, Page(s) 3536495

Abstract: Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder, mostly caused by mutations in the fibrillin-1 ( ...

Abstract	Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder, mostly caused by mutations in the fibrillin-1 (
MeSH term(s)	Adult ; Aorta/pathology ; Dilatation, Pathologic ; Fibrillin-1/genetics ; Heterozygote ; Humans ; Introns/genetics ; Male ; Marfan Syndrome/genetics ; Microfilament Proteins ; Mutation
Chemical Substances	FBN1 protein, human ; Fibrillin-1 ; Microfilament Proteins
Language	English
Publishing date	2018-05-29
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2018/3536495
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Article: The enigmatic role of the ankyrin repeat domain 1 gene in heart development and disease.

Mikhailov, Alexander T / Torrado, Mario

The International journal of developmental biology

2008 Volume 52, Issue 7, Page(s) 811–821

Abstract: It has been proposed that the ankyrin repeat domain 1 (ANKRD1) factor (also known as CARP) plays a critical role in transcriptional regulation, myofibrillar assembly and stretch sensing during heart development and cardiac insults. ANKRD1/CARP has also ... ...

Abstract	It has been proposed that the ankyrin repeat domain 1 (ANKRD1) factor (also known as CARP) plays a critical role in transcriptional regulation, myofibrillar assembly and stretch sensing during heart development and cardiac insults. ANKRD1/CARP has also been reported to negatively regulate cardiac gene expression in cell-based promoter-reporter assays. Consequently, rapid up-regulation of the ankrd1 gene in myocardium in response to developmental stimuli or pathological insults has tended to be interpreted in the context of the inhibitory effects of ANKRD1 on cardiomyocyte gene expression. Surprisingly, a total ankrd1 knockout resulted in a complete lack of phenotype, suggesting that ANKRD1/CARP is not crucial for regulation of cardiac gene expression in vivo. In this essay, we summarize (1) the accumulated evidence for the apparent multifunctional properties of this enigmatic protein, (2) the distinct chamber-dependent regulation of ankrd1 expression patterns in the heart, both during development and cardiac injury, and (3) ANKRD1 involvement in networks regulating adaptation of the myocardium to stress. Whenever feasible, we present the results obtained in patients together with those obtained in the relevant animal and cellular models. A close examination of the findings still fails to define ANKRD1 as a negative regulator of cardiac gene expression in vivo, but rather indicates that its augmented expression can represent an adaptive response of the myocardium to stress both during development and various heart insults.
MeSH term(s)	Ankyrin Repeat/genetics ; Gene Expression Regulation, Developmental ; Heart/embryology ; Heart Defects, Congenital/genetics ; Heart Defects, Congenital/metabolism ; Humans ; Muscle Proteins/genetics ; Muscle Proteins/metabolism ; Myocardium/metabolism ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Organogenesis/genetics ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription, Genetic
Chemical Substances	ANKRD1 protein, human ; Muscle Proteins ; Nuclear Proteins ; Repressor Proteins ; Transcription Factors
Language	English
Publishing date	2008
Publishing country	Spain
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1036070-0
ISSN	1696-3547 ; 0214-6282
ISSN (online)	1696-3547
ISSN	0214-6282
DOI	10.1387/ijdb.082655am
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Article: The cardiac ankyrin repeat domain 1 protein: do you know enough about its dimerization properties?

Mikhailov, Alexander T / Torrado, Mario

Journal of muscle research and cell motility

2006 Volume 27, Issue 3-4, Page(s) 203–4; author reply 251–2

MeSH term(s)	Animals ; Ankyrin Repeat ; Dimerization ; Muscle Proteins/chemistry ; Muscle Proteins/metabolism ; Myocardium/metabolism ; Protein Folding
Chemical Substances	Muscle Proteins
Language	English
Publishing date	2006
Publishing country	Netherlands
Document type	Comment ; Journal Article
ZDB-ID	283053-x
ISSN	1573-2657 ; 0142-4319
ISSN (online)	1573-2657
ISSN	0142-4319
DOI	10.1007/s10974-006-9061-x
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Zs.B 2376: 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)
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Article: Detection of protein interactions based on GFP fragment complementation by fluorescence microscopy and spectrofluorometry.

Torrado, Mario / Iglesias, Raquel / Mikhailov, Alexander T

BioTechniques

2008 Volume 44, Issue 1, Page(s) 70, 72, 74

Abstract: We have developed a set of simple modifications of the green fluorescent protein (GFP)fragment reassembly assay in bacteria that permits: (i)fluorescent microscopy visualization of GFP reassembly only 1-2 h after induction of protein expression, thus ... ...

Abstract	We have developed a set of simple modifications of the green fluorescent protein (GFP)fragment reassembly assay in bacteria that permits: (i)fluorescent microscopy visualization of GFP reassembly only 1-2 h after induction of protein expression, thus approximating the detection of GFP reassembly to the real-time dynamics of protein complex formation in living cells; (ii) spectrofluorometric detection of reassembled GFP fluorescent signals directly in lysates from cell suspension thereby avoiding, in many cases, the need for tag-affinity isolation of protein complexes; and (iii) comparative quantification of signal intensity in numerous cell-sample lysates using a Bio-Rad IQ5 spectrofluorometric detection system (Bio-Rad Laboratories, Madrid, Spain). Collectively, the results demonstrate that the combination of microscopic and spectrofluorometric detection provides a time-saving and sensitive alternative to existing methods of fluorescence complementation analysis.
MeSH term(s)	Escherichia coli/cytology ; Genetic Complementation Test ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Microscopy, Fluorescence/methods ; Peptide Fragments/metabolism ; Protein Binding ; Protein Interaction Mapping ; Spectrometry, Fluorescence/methods
Chemical Substances	Peptide Fragments ; Green Fluorescent Proteins (147336-22-9)
Language	English
Publishing date	2008-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	48453-2
ISSN	1940-9818 ; 0736-6205
ISSN (online)	1940-9818
ISSN	0736-6205
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Article: From development to evolution: the re-establishment of the "Alexander Kowalevsky Medal".

Mikhailov, Alexander T / Gilbert, Scott F

The International journal of developmental biology

2002 Volume 46, Issue 5, Page(s) 693–698

Abstract: The Saint Petersburg Society of Naturalists has reinstated the Alexander O. Kowalevsky Medal. This article announces the winners of the first medals and briefly reviews the achievements of A.O. Kowalevsky, the Russian comparative embryologist whose ... ...

Abstract	The Saint Petersburg Society of Naturalists has reinstated the Alexander O. Kowalevsky Medal. This article announces the winners of the first medals and briefly reviews the achievements of A.O. Kowalevsky, the Russian comparative embryologist whose studies on amphioxus, tunicates and germ layer homologies pioneered evolutionary embryology and confirmed the evolutionary continuity between invertebrates and vertebrates. In re-establishing this international award, the Society is pleased to recognize both the present awardees and the memory of Kowalevsky, whose work pointed to that we now call evolutionary developmental biology.
MeSH term(s)	Animals ; Awards and Prizes ; Embryology/history ; History, 19th Century ; History, 20th Century ; Humans ; Invertebrates/embryology ; Russia (Pre-1917)
Language	English
Publishing date	2002-08-01
Publishing country	Spain
Document type	Biography ; Historical Article ; Journal Article ; Portrait
ZDB-ID	1036070-0
ISSN	1696-3547 ; 0214-6282
ISSN (online)	1696-3547
ISSN	0214-6282
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Article ; Online: Identification of candidate genes potentially relevant to chamber-specific remodeling in postnatal ventricular myocardium.

Torrado, Mario / Iglesias, Raquel / Nespereira, Beatriz / Mikhailov, Alexander T

Journal of biomedicine & biotechnology

2010 Volume 2010, Page(s) 603159

Abstract: Molecular predisposition of postnatal ventricular myocardium to chamber-dependent (concentric or eccentric) remodeling remains largely elusive. To this end, we compared gene expression in the left (LV) versus right ventricle (RV) in newborn piglets, ... ...

Abstract	Molecular predisposition of postnatal ventricular myocardium to chamber-dependent (concentric or eccentric) remodeling remains largely elusive. To this end, we compared gene expression in the left (LV) versus right ventricle (RV) in newborn piglets, using a differential display reverse transcription-PCR (DDRT-PCR) technique. Out of more than 5600 DDRT-PCR bands, a total of 153 bands were identified as being differentially displayed. Of these, 96 bands were enriched in the LV, whereas the remaining 57 bands were predominant in the RV. The transcripts, displaying over twofold LV-RV expression differences, were sequenced and identified by BLAST comparison to known mRNA sequences. Among the genes, whose expression was not previously recognized as being chamber-dependent, we identified a small cohort of key regulators of muscle cell growth/proliferation (MAP3K7IP2, MSTN, PHB2, APOBEC3F) and gene expression (PTPLAD1, JMJD1C, CEP290), which may be relevant to the chamber-dependent predisposition of ventricular myocardium to respond differentially to pressure (LV) and volume (RV) overloads after birth. In addition, our data demonstrate chamber-dependent alterations in expression of as yet uncharacterized novel genes, which may also be suitable candidates for association studies in animal models of LV/RV hypertrophy.
MeSH term(s)	Animals ; Animals, Newborn ; Gene Expression Profiling/methods ; Gene Expression Regulation, Developmental ; Heart/anatomy & histology ; Heart Ventricles/metabolism ; Heart Ventricles/pathology ; Myocardium/metabolism ; Myocardium/pathology ; Myostatin/genetics ; Myostatin/metabolism ; Polymerase Chain Reaction ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Swine ; Ventricular Remodeling/genetics
Chemical Substances	Myostatin ; RNA, Messenger
Language	English
Publishing date	2010-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2052552-7
ISSN	1110-7251 ; 1110-7243
ISSN (online)	1110-7251
ISSN	1110-7243
DOI	10.1155/2010/603159
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