scholarly journals Perturbations in the gene regulatory pathways controlling mitochondrial energy production in the failing heart

2013 ◽  
Vol 1833 (4) ◽  
pp. 840-847 ◽  
Author(s):  
Gregory Aubert ◽  
Rick B. Vega ◽  
Daniel P. Kelly
Author(s):  
Majd AlGhatrif ◽  
Ariel Zane ◽  
Matt Oberdier ◽  
Marco Canepa ◽  
Stephanie Studenski ◽  
...  

2006 ◽  
Vol 44 (6) ◽  
pp. 519-525 ◽  
Author(s):  
S. Prabhu ◽  
Mallika Jainu ◽  
K.E. Sabitha ◽  
C.S. Shyamala Devi

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Katchen Julliany Pereira Silva ◽  
Jugpreet Singh ◽  
Ryland Bednarek ◽  
Zhangjun Fei ◽  
Awais Khan

2019 ◽  
Author(s):  
Jennifer K. Forsyth ◽  
Daniel Nachun ◽  
Michael J. Gandal ◽  
Daniel H. Geschwind ◽  
Ariana E. Anderson ◽  
...  

AbstractBackground22q11.2 copy number variants (CNVs) are among the most highly penetrant genetic risk variants for developmental neuropsychiatric disorders such as schizophrenia (SCZ) and autism spectrum disorder (ASD). However, the specific mechanisms through which they confer risk remain unclear.MethodsUsing a functional genomics approach, we integrated transcriptomic data from the developing human brain, genome-wide association findings for SCZ and ASD, protein interaction data, and pathophysiological signatures of SCZ and ASD to: 1) organize genes into the developmental cellular and molecular systems within which they operate; 2) identify neurodevelopmental processes associated with polygenic risk for SCZ and ASD across the allelic frequency spectrum; and 3) elucidate pathways and individual genes through which 22q11.2 CNVs may confer risk for each disorder.ResultsPolygenic risk for SCZ and ASD converged on partially overlapping gene networks involved in synaptic function and transcriptional regulation, with ASD risk variants additionally enriched for networks involved in neuronal differentiation during fetal development. The 22q11.2 locus formed a large protein network that disproportionately affected SCZ- and ASD-associated neurodevelopmental networks, including loading highly onto synaptic and gene regulatory pathways. SEPT5, PI4KA, and SNAP29 genes are candidate drivers of 22q11.2 synaptic pathology relevant to SCZ and ASD, and DGCR8 and HIRA are candidate drivers of disease-relevant alterations in gene regulation.ConclusionsThe current approach provides a powerful framework to identify neurodevelopmental processes affected by diverse risk variants for SCZ and ASD, and elucidate the mechanisms through which highly penetrant multi-gene CNVs contribute to disease risk.


Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2876
Author(s):  
Poh-Shiow Yeh ◽  
Jui-Tai Chen ◽  
Yih-Giun Cherng ◽  
Shun-Tai Yang ◽  
Yu-Ting Tai ◽  
...  

An estrogen deficiency is the main cause of osteoporosis in postmenopausal women. In bone remodeling, estrogen receptors (ERs) can mediate estrogen-transducing signals. Methylpiperidinopyrazole (MPP) is a highly specific antagonist of ER-alpha (ERα). This study was designed to evaluate the effects of MPP on estrogen-induced energy production, subsequent osteoblast maturation, and the possible mechanisms. Exposure of primary osteoblasts isolated from neonatal rat calvarias to MPP did not affect cell morphology or survival. Estradiol can induce translocation of ERα into mitochondria from the cytoplasm. Interestingly, pretreatment of rat calvarial osteoblasts with MPP lowered estrogen-induced ERα translocation. Sequentially, estrogen-triggered expressions of mitochondrial energy production-linked cytochrome c oxidase (COX) I and COX II messenger (m)RNAs were inhibited following pretreatment with MPP. Consequently, MPP caused decreases in estrogen-triggered augmentation of the activities of mitochondrial respiratory complex enzymes and levels of cellular adenosine phosphate (ATP). During progression of osteoblast maturation, estrogen induced bone morphogenetic protein (BMP)-6 and type I collagen mRNA expressions, but MPP treatment inhibited such induction. Consequently, estrogen-induced osteoblast activation and mineralization were attenuated after exposure to MPP. Taken together, MPP suppressed estrogen-induced osteoblast maturation through decreasing chromosomal osteogenesis-related BMP-6 and type I collagen mRNA expressions and mitochondrial ATP synthesis due to inhibiting energy production-linked COX I and II mRNA expressions. MPP can appropriately be applied to evaluate estrogen-involved bioenergetics and osteoblast maturation.


2020 ◽  
Vol 18 (01) ◽  
pp. 2040003 ◽  
Author(s):  
Nazmus Salehin ◽  
Patrick P. L. Tam ◽  
Pierre Osteil

Assays for transposase-accessible chromatin sequencing (ATAC-seq) provides an innovative approach to study chromatin status in multiple cell types. Moreover, it is also possible to efficiently extract differentially accessible chromatin (DACs) regions by using state-of-the-art algorithms (e.g. DESeq2) to predict gene activity in specific samples. Furthermore, it has recently been shown that small dips in sequencing peaks can be attributed to the binding of transcription factors. These dips, also known as footprints, can be used to identify trans-regulating interactions leading to gene expression. Current protocols used to identify footprints (e.g. pyDNAse and HINT-ATAC) have shown limitations resulting in the discovery of many false positive footprints. We generated a novel approach to identify genuine footprints within any given ATAC-seq dataset. Herein, we developed a new pipeline embedding DACs together with bona fide footprints resulting in the generation of a Predictive gene regulatory Network (PreNet) simply from ATAC-seq data. We further demonstrated that PreNet can be used to unveil meaningful molecular regulatory pathways in a given cell type.


Author(s):  
Patrick Ritz ◽  
Jean-François Dumas ◽  
Pierre-Henri Ducluzeau ◽  
Gilles Simard

2014 ◽  
Vol 16 (6) ◽  
pp. 511-511 ◽  
Author(s):  
Christina Karlsson Rosenthal

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