Search results for "Pathway"
showing 10 items of 1685 documents
D2R striatopallidal neurons inhibit both locomotor and drug reward processes.
2009
The specific functions of dopamine D(2) receptor-positive (D(2)R) striatopallidal neurons remain poorly understood. Using a genetic mouse model, we found that ablation of D(2)R neurons in the entire striatum induced hyperlocomotion, whereas ablation in the ventral striatum increased amphetamine conditioned place preference. Thus D(2)R striatopallidal neurons limit both locomotion and, unexpectedly, drug reinforcement.
Methylthioacetaldehyde, a possible intermediate metabolite for the production of volatile sulphur compounds from L-methionine by Lactococcus lactis
2004
Volatile sulphur compounds (VSCs) production from L-methionine was studied in Lactococcus lactis. In vitro studies with radiolabelled L-methionine and resting cells of L. lactis revealed that L-methionine was initially converted to alpha-keto-gamma-methylthiobutyrate (KMBA) by a transamination reaction. A part of KMBA was subsequently chemically converted to methylthioacetaldehyde, methanethiol and dimethylsulphides. Chemical conversion of KMBA to methylthioacetaldehyde was dependent on pH, Mn(II) and oxygen. Since methanethiol and dimethylsulphide production was highly related to that of methylthioacetaldehyde, the latter compound was proposed as being an intermediate in VSCs production by…
High miR-196a levels promote the oncogenic phenotype of colorectal cancer cells.
2009
AIM: To analyze the relevance of the microRNA miR-196a for colorectal oncogenesis. METHODS: The impact of miR-196a on the restriction targets HoxA7, HoxB8, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction (RT-PCR) after transient transfection of SW480 cancer cells. The miR-196a transcription profile in colorectal cancer samples, mucosa samples and diverse cancer cell lines was quantified by RT-PCR. Transiently miR-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in vivo. RESULTS: HoxA7, HoxB8, HoxC8 and HoxD8 were restricted by miR-196a in a dose-dependent and gene-specific mann…
mTOR Driven Gene Transcription Is Required for Cholesterol Production in Neurons of the Developing Cerebral Cortex
2021
AbstractDysregulated mammalian target of rapamycin (mTOR) activity is associated with various neurodevelopmental disorders ranging from idiopathic autism spectrum disorders to syndromes caused by single gene defects. This suggests that maintaining mTOR activity levels in a physiological range is essential for brain development and functioning. Upon activation, mTOR regulates a variety of cellular processes such as cell growth, autophagy and metabolism. On a molecular level, however, the consequences of mTOR activation in the brain are not well understood.Low levels of cholesterol are associated with a wide variety of neurodevelopmental disorders. We here describe numerous genes of the stero…
A compound-based proteomic approach discloses 15-ketoatractyligenin methyl ester as a new PPARγ partial agonist with anti-proliferative ability
2017
AbstractProteomics based approaches are emerging as useful tools to identify the targets of bioactive compounds and elucidate their molecular mechanisms of action. Here, we applied a chemical proteomic strategy to identify the peroxisome proliferator-activated receptor γ (PPARγ) as a molecular target of the pro-apoptotic agent 15-ketoatractyligenin methyl ester (compound 1). We demonstrated that compound 1 interacts with PPARγ, forms a covalent bond with the thiol group of C285 and occupies the sub-pocket between helix H3 and the β-sheet of the ligand-binding domain (LBD) of the receptor by Surface Plasmon Resonance (SPR), mass spectrometry-based studies and docking experiments. 1 displayed…
Hypoxia-inducible factor 1Α may regulate the commitment of mesenchymal stromal cells toward angio-osteogenesis by mirna-675-5P
2017
Abstract Background aims During bone formation, angiogenesis and osteogenesis are regulated by hypoxia, which is able to induce blood vessel formation, as well as recruit and differentiate human mesenchymal stromal cells (hMSCs). The molecular mechanisms involved in HIF-1α response and hMSC differentiation during bone formation are still unclear. This study aimed to investigate the synergistic role of hypoxia and hypoxia-mimetic microRNA miR-675-5p in angiogenesis response and osteo-chondroblast commitment of hMSCs. Methods By using a suitable in vitro cell model of hMSCs (maintained in hypoxia or normoxia), the role of HIF-1α and miR-675-5p in angiogenesis and osteogenesis coupling was inv…
Impairing Otp homeodomain function in oral ectoderm cells affects skeletogenesis in sea urchin embryos
2003
AbstractIn the sea urchin embryo skeletogenesis is the result of a complex series of molecular and cellular events that coordinate the morphogenetic process. Past and recent evidence strongly indicate that skeletal initiation and growth are strictly dependent on signals emanating from the oral ectodermal wall. As previously suggested, Orthopedia (Otp), a homeodomain-containing transcription factor specifically expressed in a small subset of oral ectoderm cells, might be implicated in this signalling pathway. In this study, we utilize three different strategies to address the issue of whether Otp is an upstream regulator of sketelogenesis. We describe the effects of microinjection of Otp mor…
Major orchestration of shikimate, early phenylpropanoid and stilbenoid pathways by Subgroup 2 R2R3-MYBs in grapevine
2021
AbstractThe stilbenoid pathway is responsible for the production of resveratrol and its derivatives in grapevine. A few transcription factors (TFs) have been previously identified as regulators of this pathway but the extent of this control is yet to be fully understood. Here we demonstrate how DNA affinity purification sequencing (DAP-Seq) allows for genome-wide TF binding site interrogation in a non-model species. We obtained 5,190 and 4,443 binding events assigned to 4,041 and 3,626 genes for MYB14 and MYB15, respectively (around 40% of peaks being located within -10kb of transcription start sites). DAP-Seq of MYB14 and MYB15 was combined with aggregate gene centred co-expression network…
Suppression of intestinal microbiota-dependent production of pro-atherogenic trimethylamine N-oxide by shifting L-carnitine microbial degradation.
2014
Abstract Aims Trimethylamine-N-oxide (TMAO) is produced in host liver from trimethylamine (TMA). TMAO and TMA share common dietary quaternary amine precursors, carnitine and choline, which are metabolized by the intestinal microbiota. TMAO recently has been linked to the pathogenesis of atherosclerosis and severity of cardiovascular diseases. We examined the effects of anti-atherosclerotic compound meldonium, an aza-analogue of carnitine bioprecursor gamma-butyrobetaine (GBB), on the availability of TMA and TMAO. Main methods Wistar rats received L-carnitine, GBB or choline alone or in combination with meldonium. Plasma, urine and rat small intestine perfusate samples were assayed for L-car…
A helicopter perspective on TB biomarkers: pathway and process based analysis of gene expression data provides new insight into TB pathogenesis.
2013
Biomarker host genetic signatures are considered key tools for improved early diagnosis of tuberculosis (TB) disease (development). The analysis of gene expression changes based on a limited number of genes or single study designs, however, may not be sufficient for the identification of universal diagnostic biomarker profiles. Here we propose that biological pathway and process based analyses from multiple data sets may be more relevant for identification of key pathways in TB pathogenesis, and may reveal novel candidate diagnostic TB biomarkers. A number of independent genome-wide gene expression studies have recently been performed to study expression of biomarkers for TB disease. We hav…