PDE8, a type of phosphodiesterase (PDE), is proven to be crucial in various cellular activities and physiological activities by influencing second messenger systems. It is involved in a wide range of diseases, including Alzheimer’s disease and various heart diseases. However, there is limited information about PDE8 selective inhibitors. This work aimed to improve the solubility and yield of PDE8 in the supernatant by exploring suitable culture conditions, including temperatures and different additives.
Cystic fibrosis is a genetic disease caused by mutations in the CFTR gene. In this paper, the authors attempt to identify variations in stretches of up to 8 nucleotides in the protein-coding portions of the CFTR gene that are associated with disease development. This would allow screening of newborns or even fetuses in utero to determine the likelihood they develop cystic fibrosis.
Human cytomegalovirus (HCMV) causes serious infections in immunocompromised patients and therapies to inhibit latent HCMV are not developed. Using CRISPR/Cas9, the authors were able to delete an important promoter region in HCMV.
Major depressive disorder (MDD) is a prevalent mood disorder. The direct causes and biological mechanisms of depression still elude understanding, though genetic factors have been implicated. This study looked to identify the mechanism behind the aberrant response to the dexamethasone suppression test (DST) displayed by MDD patients, in which they display a lack of cortisol suppression. Analysis revealed several pro-inflammatory genes that were significant and differentially expressed between affected and non-affected groups in response to the DST. Looking at ways to decrease the inflammatory response could have implications for treatment and may explain why some people treated for depression still display symptoms or may lead researchers to different classes of drugs for treatment.
Here, seeking to identify a possible explanation for the more frequent diagnosis of autism spectrum disorder (ASD) in males than females, they sought to investigate a potential sex bias in the expression of ASD-associated genes. Based on their analysis, they identified 17 ASD-associated candidate genes that showed stronger collective sex-dependent expression.
Tertiary lymphoid structures (TLS) are lymph node-like structures that form at sites of inflammation, and their presence in cancer patients is predictive of a better clinical outcome. One significant obstacle to TLS formation is reduced immune cell infiltration into the tumor microenvironment (TME). Recent studies have shown that vasculature normalizing (VN) agents may override this defect to improve tissue perfusion and increased immune cell entry into the TME. However, their effects on immune cell and tumor cell phenotype remain understudied. Here the authors investigate whether treating tumor cells with VN would reduce their immunosuppressive phenotype and promote production of chemokine that recruit immune cells and foster TLS formation.
Recent declines in the brook trout population of the Lake Champlain Basin have made the genetic screening of this and other trout species of utmost importance. In this study, the authors collected and analyzed 21 DNA samples from Lake Champlain Basin trout populations and performed a phylogenetic analysis on these samples using the cytochrome b gene. The findings presented in this study may influence future habitat decisions in this region.
Glioblastoma Multiforme (GBM) is the most malignant brain tumor with the highest fraction of genome alterations (FGA), manifesting poor disease-free status (DFS) and overall survival (OS). We explored The Cancer Genome Atlas (TCGA) and cBioportal public dataset- Firehose legacy GBM to study DNA repair genes Activating Signal Cointegrator 1 Complex Subunit 3 (ASCC3) and Alpha-Ketoglutarate-Dependent Dioxygenase AlkB Homolog 3 (ALKBH3). To test our hypothesis that these genes have correlations with FGA and can better determine prognosis and survival, we sorted the dataset to arrive at 254 patients. Analyzing using RStudio, both ASCC3 and ALKBH3 demonstrated hypomethylation in 82.3% and 61.8% of patients, respectively. Interestingly, low mRNA expression was observed in both these genes. We further conducted correlation tests between both methylation and mRNA expression of these genes with FGA. ASCC3 was found to be negatively correlated, while ALKBH3 was found to be positively correlated, potentially indicating contrasting dysregulation of these two genes. Prognostic analysis showed the following: ASCC3 hypomethylation is significant with DFS and high ASCC3 mRNA expression to be significant with OS, demonstrating ASCC3’s potential as disease prediction marker.