ABSTRACT: RNA expression across 6 strains of mice in relation to prepulse inhibition testing, as described in: Pdxdc1 (pyridoxal-dependent decarboxylase domain containing 1) modulates pre-pulse inhibition of acoustic startle in the mouse
Project description:C3H/HeJ, BalbC/J, C57BL/6J, C57BL10/J, C57BLKS/J, C57L/J strains were tested for variability in gene expression in hippocampus, striatal, and brainstem tissues to affiliate findings with behavioural prepulse inhibition scores Abstract: Current antipsychotic medications used to treat schizophrenia all target the dopamine D2 receptor. Although these drugs have serious side effects and limited efficacy, no novel molecular targets for schizophrenia treatment have been successfully translated into new medications. To identify novel potential treatment targets for schizophrenia, we searched for previously unknown molecular modulators of acoustic pre-pulse inhibition (PPI), a schizophrenia endophenotype, in the mouse. We examined six inbred mouse strains that have a range of PPI, and used microarrays to determine which mRNA levels correlated with PPI across these mouse strains. We examined several brain regions involved in PPI and schizophrenia: hippocampus, striatum and brainstem, and found transcripts that had good correlation with PPI level, and confirmed this with real-time quantitative PCR. We then selected one candidate gene for further study, Pdxdc1 (pyridoxal-dependent decarboxylase domain containing 1), because it is a putative enzyme that could metabolize catecholamine neurotransmitters, and thus might be a feasible target for new medications. We determined that Pdxdc1 mRNA and protein are both strongly expressed in the hippocampus and levels of Pdxdc1 are inversely correlated with PPI across the six mouse strains. Using shRNA packaged in a lentiviral vector, we suppressed Pdxdc1 protein levels in the hippocampus and increased PPI by at least 16%. Our results suggest that Pdxdc1 may regulate PPI and could be investigated further as a potential treatment target for schizophrenia.
Project description:Primary objectives: The main objective is to determine the feasibility and safety of adoptive cell therapy in combination with checkpoint inhibition across different metastatic solid cancers.
Primary endpoints: Toxicity: Registration of all AEs and unexpected events in relation to the treatment will be done in accordance with the common terminology criteria for adverse events (CTCAE) criteria as described in appendix 3.
| 2537065 | ecrin-mdr-crc
Project description:UBE3A modulates Angelman syndrome transcriptome via retrovirus like GAG domain containing protein PEG10
Project description:A study that is blinded to the patient and the investigator where the combination of Arfolitixorin + 5-FU is compared to Calciumfolinate + 5-FU. The patients will be randomised and will receive the above described combination as IV bolus injections, peroperatively in conjuction with collection of the first tissue sample.
A low dose (30 mg) and a high dose (120) mg of Arfolitixorin will be used in order to investigate the relation between dose of Arfolitixorin and TS-inhibition.
Project description:whole embryo (all tissues) measurement of mRNA decay by 4-thiouridine pulse-chase These TU-Decay microarrays analyze mRNA levels at three timepoints: a one hour pulse, one hour chase, and three hour chase. Measurements with or without transcription inhibition by actinomycin D (ActD) were compared.
Project description:<p>Transcriptome sequencing of solitary fibrous tumors / hemangiopericytomas from a variety of anatomic sites revealed recurrent gene fusions between two genes, NAB2 and STAT6. All SFTs examined exhibited an in-frame fusion transcript encoding a fusion protein containing the EGR1 interaction domain of NAB2 with the transcriptional activation domain of STAT6. Functional testing of the fusion alleles confirmed the conversion of the wt NAB2 repressor into a transcriptional activator. A range of individual fusion junctions can be detected by next-generation sequencing acro the sample set, highlighting the suitability of this method in the diagnostic characterization of SFTs. This study indentified the pathognomonic alteration in solitary fibrous tumors and illuminates a pathway towards targeted therapeutics for this cancer.</p>
Project description:Puf4 is a pumilio/fbf domain containing RNA binding protein. Our previous work revelated that Puf4 modulates ER stress and anrifungal resistance in C. neoformans. Our recent work showed that Puf4 is targeted by arginine methyltransferases. We investigated the RNA binding network of wildtype Puf4 as well as two mutants that have methyl-deficient (arginine to lysine) mutations.
Project description:Nascent RNA was tagged with EU, via EC feeding, in targeted cells (neuroblasts or neurons) then purified after the initial pulse labeling or after a chase using media containing excess unmodified uridine
Project description:ChIP-chip analyses of pulse-expressed H3-T7 in clr3-CDx2 and wild type cells Chromodomain-mediated HDAC loading suppresses histone turnover at self-templated heterochromatin domain. Chromodomain-mediated loading targets Clr3-CDx2 to heterochromatin domains.
