Project description:Recently, we reported an emerging pathology named Brown Muscle Disease (BMD) affecting Asari clams inhabiting the most productive area for this species in France, the Arcachon Bay. The main macroscopic feature of the pathology relies on the atrophy of the posterior adductor muscle, affecting the ability of clams to burry. The research of the etiological agent of BMD privileged a viral infection. Contrary to healthy clams, infected animals are always found at the surface of the sediment and exhibit 30 nm virus-like particles in muscle, granulocytic and rectal cells. In order to get more insights on the etiology and impacts of the BMD on clams, we took advantage in the present study of next generation sequencing technologies. An RNA-Seq approach was used (i) to test whether viral RNA sequences can be specifically found in the transcriptome of diseased animals and (ii) to identify the genes that are differentially regulated between diseased and healthy clams. Contrary to healthy buried animals, in diseased clams one sequence showing extensive homologies with retroviridae-related genes was detected. Among the biological processes that were affected in diseased clams, the synaptic transmission process was the most represented. To deepen this result, a new sampling was carried out and the transcription level of genes involved in synaptic transmission was determined in healthy and diseased clams but also in clams with no visible sign of pathology but located at the surface of the sediment. Our findings suggest that muscle atrophy is a latter sign of the pathology and that nervous system could be instead a primary target of the BMD agent.
Project description:Polypoidal choroidal vasculopathy (PCV) is characterized by polyp-like dilatation of blood vessels and turbulent blood flow in the choroid of the eye. Here, we cultivated blood outgrowth endothelial cells (BOECs) from PCV patients and normal controls. When BOECs were exposed to heterogeneous flow, single-cell analysis revealed that PCV BOECs preferentially adopted migratory-angiogenic cell state, while normal BOECs undertook proinflammatory cell state. PCV BOECs also had a repressed protective response to flow stress by demonstrating lower mitochondrial functions. We uncovered that elevated hyaluronidase-1 in PCV BOECs led to increased degradation of hyaluronan, a major component of endothelial glycocalyx. Hyaluronidase-1 was correspondingly detected in PCV patient vitreous humor and plasma samples. Notably, knockdown of hyaluronidase-1 in PCV BOECs modulated their abnormal cell migration and barrier permeability due to glycocalyx impairment. Therefore, hyaluronidase-1 inhibition could be a potential therapeutic modality in preserving glycocalyx integrity and endothelial stability in ocular diseases with vascular origin.
Project description:Males are 50% more likely to develop end stage kidney failure compared to women. As a model of the human condition we analyzed gene expression changes in healthy and diseased mouse kidneys. Interestingly, the set of gender biased genes in healthy kidneys were different from those in diseased kidneys indicating not only baseline gene expression differences but also that the male and female kidney respond differently to disease condition. Keywords: Gender difference We used AffymetrixM430A2.0 microarrays to determine global gene expression differences in kidneys of 10-week old healthy Balb/c male and female mice. In order to identify gene expression differences under disease conditions, animals were injected with doxorubicin, a substance that is known to induce albuminuria and glomerulosclerosis in Balb/c mice as it is directly toxic to podocytes.
Project description:The Flavivirus genus contains some of the most prevalent vector-borne viruses such as dengue, Zika and yellow fever viruses that cause devastating diseases in humans. However, the insect-specific clade of flaviviruses is restricted to mosquito hosts; albeit they have retained the general features of the genus such as genome structure and replication. The interaction between insect-specific flaviviruses (ISFs) and their mosquito hosts are largely unknown. Pathogenic flaviviruses are known to modulate host-derived microRNAs (miRNAs), a class of non-coding RNAs that are important in controlling gene expression. Alteration in miRNAs may represent changes in host gene expression and provide understanding of virus-host interactions. The role of miRNAs in ISF-mosquito interactions is largely unknown. A recently discovered Australian ISF, Palm Creek virus (PCV), has the ability to suppress medically relevant flaviviruses. Here, we investigated the potential involvement of miRNAs in PCV infection using the model mosquito Aedes aegypti. By combining small RNA sequencing and bioinformatics analysis, differentially expressed miRNAs were determined. Our results indicated that PCV infection hardly affects host miRNAs. Out of 101 reported miRNAs of Ae. aegypti, only aae-miR-2940-5p had significant altered expression over the course of infection. However, further analysis of aae-miR-2940-5p revealed that this miRNA does not have any direct impact on PCV replication in vitro. Thus, the results overall suggest that PCV infection has a limited effect on the mosquito miRNA profile and therefore, they may not play a significant role the PCV- Ae. aegypti interaction.
2017-07-08 | GSE100917 | GEO
Project description:Biological Soil Crust Healthy and Diseased