Comparative Genomic Analysis of six Glossina Genomes, Vectors of African Trypanosomes

Background: Tsetse flies (Glossina sp.) are the vectors of human and animal trypanosomiasis throughout subSaharan Africa. Tsetse flies are distinguished from other Diptera by unique adaptations, including lactation and the birthing of live young (obligate viviparity), a vertebrate blood-specific diet by both sexes, and obligate bacterial symbiosis. This work describes the comparative analysis of six Glossina genomes representing three sub-genera: Morsitans (G. morsitans morsitans, G. pallidipes, G. austeni), Palpalis (G. palpalis, G. fuscipes), and Fusca (G. brevipalpis) which represent different habitats, host preferences, and vectorial capacity. Results: Genomic analyses validate established evolutionary relationships and sub-genera. Syntenic analysis of Glossina relative to Drosophila melanogaster shows reduced structural conservation across the sex-linked X chromosome. Sex-linked scaffolds show increased rates of female-specific gene expression and lower evolutionary rates relative to autosome associated genes. Tsetse-specific genes are enriched in protease, odorant-binding, and helicase activities. Lactation-associated genes are conserved across all Glossina species while male seminal proteins are rapidly evolving. Olfactory and gustatory genes are reduced across the genus relative to other insects. Visionassociated Rhodopsin genes show conservation of motion detection/tracking functions and variance in the Rhodopsin detecting colors in the blue wavelength ranges. Conclusions: Expanded genomic discoveries reveal the genetics underlying Glossina biology and provide a rich body of knowledge for basic science and disease control. They also provide insight into the evolutionary biology underlying novel adaptations and are relevant to applied aspects of vector control such as trap design and discovery of novel pest and disease control strategies

Comparative genomic analysis of six Glossina genomes, vectors of African trypanosomes

BACKGROUND Tsetse flies (Glossina sp.) are the vectors of human and animal trypanosomiasis throughout sub-Saharan Africa. Tsetse flies are distinguished from other Diptera by unique adaptations, including lactation and the birthing of live young (obligate viviparity), a vertebrate blood-specific diet by both sexes, and obligate bacterial symbiosis. This work describes the comparative analysis of six Glossina genomes representing three sub-genera: Morsitans (G. morsitans morsitans, G. pallidipes, G. austeni), Palpalis (G. palpalis, G. fuscipes), and Fusca (G. brevipalpis) which represent different habitats, host preferences, and vectorial capacity. RESULTS Genomic analyses validate established evolutionary relationships and sub-genera. Syntenic analysis of Glossina relative to Drosophila melanogaster shows reduced structural conservation across the sex-linked X chromosome. Sex-linked scaffolds show increased rates of female-specific gene expression and lower evolutionary rates relative to autosome associated genes. Tsetse-specific genes are enriched in protease, odorant-binding, and helicase activities. Lactation-associated genes are conserved across all Glossina species while male seminal proteins are rapidly evolving. Olfactory and gustatory genes are reduced across the genus relative to other insects. Vision-associated Rhodopsin genes show conservation of motion detection/tracking functions and variance in the Rhodopsin detecting colors in the blue wavelength ranges. CONCLUSIONS Expanded genomic discoveries reveal the genetics underlying Glossina biology and provide a rich body of knowledge for basic science and disease control. They also provide insight into the evolutionary biology underlying novel adaptations and are relevant to applied aspects of vector control such as trap design and discovery of novel pest and disease control strategies

PDIA6 and Maspin in Prostate Cancer

BACKGROUND/AIM: PDIA6 is a disulphide isomerase of the PDI family, known to mediate disulphide bond formation in the endoplasmic reticulum. However, PDI-related proteins also function in other parts of the cell and PDIA6 has been shown to be involved in many types of cancers. We previously identified PDIA6 as a putative Maspin interactor. Maspin has itself been implicated in prostate cancer progression. Our aim was to further explore the roles of Maspin in prostate cancer and establish whether PDIA6 is also involved in prostate cancer.MATERIALS AND METHODS: RNA levels of PDIA6 and Maspin in prostate cell lines were measured using RT-PCR. Bioinformatics analysis of the TCGA database was used to find RNA levels of PDIA6 and Maspin in prostate cancer. siRNAs were used to knock-down PDIA6, and proliferation and migration assays were conducted on those cells.RESULTS: PDIA6 and Maspin RNA were shown to be expressed at varying levels in prostate cell lines. RNAseq data showed that PDIA6 expression was significantly increased in prostate adenocarcinoma samples, while Maspin RNA expression was decreased. When PDIA6 expression was knocked-down using siRNA in prostate cell lines, proliferation was decreased substantially in the two prostate cancer cell lines (DU145 and PC3) and also decreased in the normal prostate cell line (PNT1a), though less strongly.CONCLUSION: PDIA6 expression is higher in prostate cancer cells compared to normal prostate cells. Decreasing PDIA6 expression decreases proliferation. Thus, PDIA6 is a promising target for prostate cancer therapeutics.</p

Uncovering potential diagnostic and pathophysiological roles of α-synuclein and DJ-1 in melanoma

BACKGROUND: Melanoma, the most lethal skin cancer type, occurs more frequently in Parkinson's disease (PD), and PD is more frequent in melanoma patients, suggesting disease mechanisms overlap. α-synuclein, a protein that accumulates in PD brain, and the oncogene DJ-1, which is associated with PD autosomal recessive forms, are both elevated in melanoma cells. Whether this indicates melanoma progression or constitutes a protective response remains unclear. We hereby investigated the molecular mechanisms through which α-synuclein and DJ-1 interact, suggesting novel biomarkers and targets in melanoma.METHODS: The Cancer Genome Atlas (TCGA) expression profiles derived from UCSC Xena were used to obtain α-synuclein and DJ-1 expression and correlated with survival in skin cutaneous melanoma (SKCM). Immunohistochemistry determined the expression in metastatic melanoma lymph nodes. Protein-protein interactions (PPIs) and molecular docking assessed protein binding and affinity with chemotherapeutic drugs. Further validation was performed using in vitro cellular models and ELISA immunoassays.RESULTS: α-synuclein and DJ-1 were upregulated in primary and metastatic SKCM. Aggregated α-synuclein was selectively detected in metastatic melanoma lymph nodes. α-synuclein overexpression in SK-MEL-28 cells induced the expression of DJ-1, supporting PPI and a positive correlation in melanoma patients. Molecular docking revealed a stable protein complex, with differential binding to chemotherapy drugs such as temozolomide, dacarbazine, and doxorubicin. Parallel reduction of both proteins in temozolomide-treated SK-MEL-28 spheroids suggests drug binding may affect protein interaction and/or stability.CONCLUSION: α-synuclein, together with DJ-1, may play a role in melanoma progression and chemosensitivity, constituting novel targets for therapeutic intervention, and possible biomarkers for melanoma.</p