Project description:This study aims to investigate a wheat recombination hotspot (H1) in comparison with a “regular” recombination site (Rec7) on the sequence and epigenetic level in conditions with functional and non-functional Ph1 locus.
Project description:To investigate a Florida manatee (Trichechus manatus latirostris) mortality event following a red tide bloom in Southwest Florida, a RNA-Seq experiment was conducted. Cell processes such as immune response, cell proliferation and differentiation and apoptosis were among the most affected by red tide. These were involved in potential diseases such as neoplasms, inflammation, and wounds and injuries, among others. There were both up-regulated and down-regulated genes, but the highest fold changes relative to controls were for genes that were down-regulated. Piccolo presynaptic cytomatrix protein (PCLO) gene, the one most down-regulated (fold change -9.93; p-value 0.0009) is associated with neurotransmitter release, cognitive functioning, neuronal loss, and neuronal synapse function. Another gene that has a similar function, ankyrin 2, neuronal, transcript variant 1 (ANK2) was also down-regulated (fold change -8.66; p-value 0.0023). ANK2 is associated with the stability of neuron synapses. Two immune genes, interleukin 6 (interferon, beta 2) (IL6) and zinc finger protein 804B (ZNF804B), were down-regulated (fold change -9.31; p-value 0.000003 and fold change -8.90; p-value 0.0164, respectively). Interleukin 6 encodes proteins involved in acute phase response, inflammation, and autoimmune response. ZNF804B is associated with neuronal chemokine and cytokine regulation, autoimmune response, and immune activation. The family with sequence similarity 186, member A (FAM186A) gene was down-regulated (fold change -8.79; p-value 0.0143). FAM186A gene mutation is associated with tumor metastasis in colorectal cancer tumors. Among the most up-regulated genes, CCAAT/enhancer binding protein (C/EBP) is involved in granulocytic differentiation and also involved with the immune system. Determining the differentially expressed genes associated with red tide enhances our understanding of manatee immune response to red tide toxins and aids in the development of red tide biomarkers. This information will better assist clinicians and researchers in diagnosing and treating future illnesses.
Project description:Hepatocytes-like cells (HLC) derived from human induced pluripotent stem cells show great promise for cell-based liver therapies and disease modelling. However, their application is currently hindered by the low production yields of existing protocols. We aim to develop a bioprocess able to generate high numbers of HLC. We used stirred-tank bioreactors with a rational control of dissolved oxygen concentration (DO) for the optimization of HLC production as 3D aggregates. We evaluated the impact of controlling DO at physiological levels (4%O2) during hepatic progenitors’ stage on cell proliferation and differentiation efficiency. Whole transcriptome analysis and biochemical assays were performed to provide a detailed characterization of HLC quality attributes. When DO was controlled at 4%O2 during the hepatic progenitors’ stage, cells presented an upregulation of genes associated with hypoxia-inducible factor pathway and a downregulation of oxidative stress genes. This condition promoted higher HLC production (maximum cell concentration: 2×106 cell/mL) and improved differentiation efficiencies (80% Albumin-positive cells) when compared to the bioreactor operated under atmospheric oxygen levels (21%O2, 0.6×106 cell/mL, 43% Albumin positive cells). These HLC exhibited functional characteristics of hepatocytes: capacity to metabolize drugs, ability to synthesize hepatic metabolites, and inducible cytochrome P450 activity. Bioprocess robustness was confirmed with HLC derived from different donors, including a primary hyperoxaluria type 1 (PH1) patient. The generated PH1.HLC showed metabolic features of PH1 disease with higher secretion of oxalate compared with HLC generated from healthy individuals. This work reports a reproducible bioprocess, that shows the importance of controlling DO at physiological levels to increase HLC production, and the HLC capability to display PH1 disease features.
Project description:The 29th International Conference on Antiviral Research (ICAR) was held in La Jolla, CA, USA from April 17 to 21, 2016. This report opens with a tribute to the late Chris McGuigan, a Past-President of ISAR, then continues with summaries of the principal invited lectures. Doug Richman (Elion Award) investigated HIV resistance, Bob Vince (Holý Award) showed how carbocyclic nucleoside analogs led to abacavir and Jerome Deval (Prusoff Award) explained how his group chose to seek a nucleoside analog to treat RSV. ALS-8176 was active in a human RSV-challenge study and is being evaluated in children. The first keynote address, by Richard H. Scheuermann, reported on the remarkable progress made in viral genomics. The second keynote address, by Heinz Feldmann, gave an overview of Ebola virus disease. There were four mini-symposia, Structural Biology, Diagnostic Technologies, DNA viruses and Zika virus. Diagnostic assays are approaching an ideal aim, a compact instrument, simple to use with any type of sample, no sample preparation and a result within an hour. The diversity of HCMV is far greater than for other herpesviruses, typically, an individual having >20,000 single nucleotide polymorphisms (SNPs). During antiviral treatment, there is rapid CMV evolution which is presumed to be due to preferential selection of already present variants rather than by the creation of new variants. A selection of contributor presentations includes oral prodrugs for nucleoside triphosphate analogs, a new method for the synthesis of phosphoramidate prodrugs and the clinical evaluation of brincidofovir for treating transplant recipients with adenovirus infections.