Here, recognizing that the immune response to cancer results in biomarkers that can be used to assess the immune status of cancer patients, the authors investigated the concentrations of key cytokines (TH1 and TH2 cytokines) in healthy controls and cancer patients. They identified significant changes in resting and activated cytokine profiles, suggesting that data of biomarkers such as these could serve as a starting point for further treatment with regard to a patient's specific immune profile.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are allosteric inhibitors that bind to the HIV reverse transcriptase and prevent replication. Indolyl aryl sulfones (IAS) and IAS derivatives have been found to be highly effective against mutant strains of HIV-1 reverse transcriptase. Here, we analyzed molecules designed using aryl sulfone scaffolds paired to cyclic compounds as potential NNRTIs through the computational design and docking of 100 novel NNRTI candidates. Moreover, we explored the specific combinations of functional groups and aryl sulfones that resulted in the NNRTI candidates with the strongest binding affinity while testing all compounds for carcinogenicity. We hypothesized that the combination of an IAS scaffold and pyrimidine would produce the compounds with the best binding affinity. Our hypothesis was correct as the series of molecules with an IAS scaffold and pyrimidine exhibited the best average binding affinity. Additionally, this study found 32 molecules designed in this procedure with higher or equal binding affinities to the previously successful IAS derivative 5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]indole-2-carboxyamide when docked to HIV-1 reverse transcriptase.
In this study, the authors use high-throughput virtual screening to design and evaluate a set of non-nucleoside reverse transcriptase inhibitors for binding affinity to the protein reverse transcriptase. These studies have important applications toward HIV therapies.
In healthy ecosystems, organisms interact in a relationship that helps maintain one another's existence. Stress can disrupt this interaction, compromising the survival of some of the members of such relationships. Here, the authors investigate the effect of stress on the interaction between anemones and their microbiome. Their study suggests that stress changes the composition of the surface microbiome of the anemone D. lineata, which is accompanied by an increase in mucus secretion. Future research into the composition of this stress-induced mucus might reveal useful antimicrobial properties.
Alcohol is known to cause various developmental diseases including Fetal Alcohol Syndrome. Here the authors investigate the effect of ethanol on the development of zebrafish beta cells, the part of the pancreas associated with Type 1 Diabetes. They find that exposure to ethanol does adversely affect beta-cell development, suggesting that alcohol ingestion during pregnancy may be linked to diabetes in newborns.
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.
Engineered bacteria that degrade oil are currently being considered as a safe option for the treatment of oil spills. For this approach to be successful, the bacteria must effectively express oil-degrading genes they uptake as part of an external genoming vehicle called a "plasmid". Using a computational approach, the authors investigate plasmid-bacterium compatibility to find pairs that ensure high levels of gene expression.
The Human Immunodeficiency Virus (HIV) infects approximately 40 million people globally, and one million people die every year from Acquired Immune Deficiency Syndrome (AIDS)-related illnesses. This study examined the interactions between the HIV-1 envelope glycoprotein gp120 and the human lymphocyte receptor integrin α4β7, the putative first long-range receptor for the envelope glycoprotein of the virus in mucosal tissues. Presented data support the claim that the V1 loop is involved in the binding between α4β7 and the HIV-1 envelope glycoprotein through molecular dockings.
DegS is an integral inner membrane protein in E. coli that helps break down misfolded proteins. When it is mutated, there is a large increase in the production of outer membrane vesicles (OMVs), which are thought to play a role in pathogenesis. This study used mutant strains of uropathogenic E. coli (UPEC) to characterize the role of DegS and OMVs on UPEC virulence.
