Project description:The mesencephalic dopaminergic (mDA) cell system is composed by two major groups of projecting cells in the Substantia Nigra (A9 neurons) and the Ventral Tegmental Area (A10 cells). A9 neurons form the nigrostriatal pathway and are involved in regulating voluntary movements and postural reflexes. Their selective degeneration leads to Parkinsons disease (PD). We used cDNA microarrays and nanoCAGE technology coupled with Laser Capture Microdissection (LCM) to characterize the intrinsic physiological properties of A9 DA neurons. Surprisingly, we found that these cells express alpha- and beta- chains of haemoglobin. Here we report that globin-immunoreactivity decorates the majority of A9 DA neurons, a subpopulation of cortical and hippocampal astrocytes as well as mature oligodendrocytes. This pattern of expression was confirmed in different mouse strains, in rat and human. This is the first report showing that haemoglobin is expressed in the Substantia Nigra of human post mortem brain. Our data suggest that the most famed oxygen-carrying globin is not exclusively restricted to the blood, but it may play a role in the normal physiology of the brain as well as in neurodegenerative disorders. To investigate the biological effects of globin expression, alpha- and beta- chains of mouse hemoglobin were overexpressed in MN9D dopaminergic neuroblastoma cell lines. RNA from 4 replicates each of over-expressing cells and of control samples, for a total of 8 samples, were hybridized on Affymetrix GeneChip Mouse Genome 430A 2.0 Arrays. Hybridization of one of the control samples did not pass quality assessment and the sample was therefore excluded from further analysis.

2010-02-25 | E-GEOD-16192 | biostudies-arrayexpress

Direct correction of haemoglobin E / beta-thalassaemia using base editors

Project description:Haemoglobin E (HbE)/β-thalassaemia causes approximately 50% of all severe thalassaemia worldwide; equating to around 30,000 births per year. HbE/β-thalassaemia is due to a point mutation in codon 26 of the human HBB gene on one allele (GAG; glutamate → GAA; lysine, E26K), and any mutation causing severe β-thalassaemia on the other. When inherited together in compound heterozygosity these mutations can cause a severe thalassaemic phenotype. However, if only one allele is mutated individuals are carriers for the respective mutation and have an asymptomatic phenotype (β-thalassaemia trait). Here we describe a base editing strategy which corrects the HbE mutation either to wildtype (WT) or a normal variant haemoglobin (E26G) known as Hb Aubenas and thereby recreates the asymptomatic trait phenotype. We have achieved editing efficiencies in excess of 85% in primary human CD34+ cells. We demonstrate editing of long-term repopulating haematopoietic stem cells (LT-HSCs) using serial xenotransplantation in NSG mice. We have profiled the off-target effects using a combination of CIRCLE-seq and deep targeted capture and have developed machine-learning based methods to predict functional effects of candidate off-target mutations.

2023-01-25 | GSE206098 | GEO

Effect of beta-hydroxy-beta-methylbutyrate (HMB) enriched oral nutrition supplement on surgical outcomes and physical performance in colorectal cancer patients: a randomized Controlled Trial

Project description:Interventions: The patient receives standard oral supplement (Ensure),The patient receives beta-hydroxy-beta-methylbutyrate (HMB) enriched oral supplement;Treatment,Treatment;Group 1 ,Group 2 Primary outcome(s): physical performance 1 month Short Physical Performance Battery (SPPB),physical performance 1 month Handgrip strength test ,Bioelectrical Impedance Analysis (BIA) 1 month Bioelectrical Impedance Analysis (BIA)

| 2738383 | ecrin-mdr-crc

Identification and control for the effects of bioinformatic globin depletion on human RNA- seq differential expression analysis

Project description:To compare the impact of haemoglobin depletion by hybridisation-based removal or bioinformatic removal of reads on the outcome of differential gene expression analysis. This comparisons was performed using RNA-seq data from 58 human tuberculosis (TB) patient whole blood samples – 29 globin kit-depleted and 29 matched non-depleted – a subset of which were taken at TB diagnosis and at six months post-TB treatment from the same patient

2022-10-17 | GSE215456 | GEO

Generation of matched patient-derived xenograft in vitro-in vivo models using 3D macroporous hydrogels for the study of liver cancer [WES]

Project description:Whole exome sequencing of matched patient-derived xenograft in vitro-in vivo models.

2018-01-31 | GSE109954 | GEO

Transcription profiling time series of human estrogen-responsive human breast cancer cells treated with 17 beta-estradiol

Project description:Human estrogen-responsive breast cancer cell line ZR-75-1 was treated with 10nM of 17 beta-estradiol. Gene expression was analyzed on total RNA extracted before or after 1, 2, 4, 6, 8, 12, 16, 20, 24, 28 and 32 hours hormonal stimulation. For each condition 2 technical replicates were performed, except the reference sample (before stimulation - 0h) which was in quadruplicate and the 4h sample in triplicate.

2009-02-03 | E-TABM-631 | biostudies-arrayexpress

Ribosome profiling of CLL patient samples

Project description:Ribosome profiling of CLL patient samples

| PRJEB23398 | ENA