Gene Expression Regulation, Enzymologic

Publication Title: 
PLoS biology

An increasing number of genes required for mitochondrial biogenesis, dynamics, or function have been found to be mutated in metabolic disorders and neurological diseases such as Leigh Syndrome. In a forward genetic screen to identify genes required for neuronal function and survival in Drosophila photoreceptor neurons, we have identified mutations in the mitochondrial methionyl-tRNA synthetase, Aats-met, the homologue of human MARS2. The fly mutants exhibit age-dependent degeneration of photoreceptors, shortened lifespan, and reduced cell proliferation in epithelial tissues.

Bayat, Vafa
Thiffault, Isabelle
Jaiswal, Manish
TÈtreault, Martine
Donti, Taraka
Sasarman, Florin
Bernard, GeneviËve
Demers-Lamarche, Julie
Dicaire, Marie-JosÈe
Mathieu, Jean
Vanasse, Michel
Bouchard, Jean-Pierre
Rioux, Marie-France
Lourenco, Charles M.
Li, Zhihong
Haueter, Claire
Shoubridge, Eric A.
Graham, Brett H.
Brais, Bernard
Bellen, Hugo J.
Publication Title: 
Cell Metabolism

Excess adipose tissue is associated with metabolic disease and reduced life span, whereas caloric restriction decreases these risks. Here we show that as mice age, there is downregulation of Dicer and miRNA processing in adipose tissue resulting in decreases of multiple miRNAs. A similar decline of Dicer with age is observed in C.†elegans. This is prevented in both species by caloric restriction. Decreased Dicer expression also occurs in preadipocytes from elderly humans and can be produced in cells by exposure to oxidative stress or UV radiation.

Mori, Marcelo A.
Raghavan, Prashant
Thomou, Thomas
Boucher, Jeremie
Robida-Stubbs, Stacey
Macotela, Yazmin
Russell, Steven J.
Kirkland, James L.
Blackwell, T. Keith
Kahn, C. Ronald
Publication Title: 
The EMBO journal

Lifespan of C. elegans is affected by the nervous system; however, the underlying neural integration still remains unclear. In this work, we targeted an antagonistic neural system consisting of low-oxygen sensing BAG neurons and high-oxygen sensing URX neurons. While ablation of BAG neurons increases lifespan of C. elegans, ablation of URX neurons decreases lifespan. Genetic analysis revealed that BAG and URX neurons counterbalance each other via different guanylate cyclases (GCYs) to control lifespan balance.

Liu, Tiewen
Cai, Dongsheng
Publication Title: 
Journal of Neurochemistry

The human tyrosine hydroxylase (hTH) gene has a 42†bp evolutionarily conserved region designated (CR) II at -7.24†kb, which bears 93% homology to the region we earlier identified as containing the glucocorticoid response element, a 7†bp activator protein-1 (AP-1)-like motif in the rat TH gene. We cloned this hTH-CRII region upstream of minimal basal hTH promoter in luciferase (Luc) reporter vector, and tested glucocorticoid responsiveness in human cell lines.

Sheela Rani, C. S.
Soto-Pina, Alexandra
Iacovitti, Lorraine
Strong, Randy
Publication Title: 
Brain Research

Diet restriction of rodents during adult life is known to cause an increased life span. It has been hypothesised that this increase may be related to effects on the anti-oxidant defence systems. However, it has been suggested that undernutrition during the gestation and pre-weaning may reduce their life span as it is known to have other deleterious effects on a rodent's growth and development.

Partadiredja, G.
Worrall, S.
Bedi, K. S.
Publication Title: 
The Journal of Clinical Investigation

Children conceived by assisted reproductive technologies (ART) display a level of vascular dysfunction similar to that seen in children of mothers with preeclamspia. The long-term consequences of ART-associated vascular disorders are unknown and difficult to investigate in healthy children. Here, we found that vasculature from mice generated by ART display endothelial dysfunction and increased stiffness, which translated into arterial hypertension in vivo. Progeny of male ART mice also exhibited vascular dysfunction, suggesting underlying epigenetic modifications.

Rexhaj, Emrush
Paoloni-Giacobino, Ariane
Rimoldi, Stefano F.
Fuster, Daniel G.
Anderegg, Manuel
Somm, Emmanuel
Bouillet, Elisa
Allemann, Yves
Sartori, Claudio
Scherrer, Urs
Publication Title: 

In this review, we discuss changes in the regulation of gene expression in the central nervous system (CNS) associated with DNA (cytosine-5) methylation, chromatin remodeling and post-translational covalent modifications of histones. During brain development, abnormal intrinsic or extrinsic cues may compromise epigenetic processes regulating neural stem cell proliferation and differentiation and thus directly or indirectly could contribute to altered epiphenotypes leading to psychiatric disorders.

Costa, Erminio
Dong, Erbo
Grayson, Dennis R.
Guidotti, Alessandro
Ruzicka, William
Veldic, Marin
Publication Title: 
Current Drug Abuse Reviews

Addiction research focusing on homocysteine metabolism and its association with aspects of alcohol dependence has revealed important findings. Recent literature on this topic has been taken into account for the review provided. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the homocysteine metabolism. Plasma homocysteine levels are influenced by the single-nucleotide polymorphism (SNP) MTHFR C677T. Besides genetic factors, environmental factors have an impact on homocysteine plasma levels too.

Lutz, Ulrich C.
Publication Title: 
Progress in Neurobiology

Alterations in the epigenetic modulation of gene expression have been implicated in several developmental disorders, cancer, and recently, in a variety of mental retardation and complex psychiatric disorders. A great deal of effort is now being focused on why the nervous system may be susceptible to shifts in activity of epigenetic modifiers.

MacDonald, Jessica L.
Roskams, A. Jane
Publication Title: 
European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology

We aimed to get a comprehensive insight into the genetic evidence supporting the role of GSK3beta in bipolar disorder (BD). Using broad searches in NCBI's PubMed and the Genetic Association Database we looked for association, whole-genome linkage, genome-wide association, gene expression, pharmocogenomic, epigenetic, cytogenetic, and mouse model studies performed for BD until July 2009. Per gene, we rated the degree of converging evidence across these types of genetic studies.

Luykx, J. J.
Boks, M. P. M.
Terwindt, A. P. R.
Bakker, S.
Kahn, R. S.
Ophoff, R. A.


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