ErbB3 Signaling and its Effect on Spheroid Formation in Ovarian Cancer

ErbB3 is a receptor tyrosine kinase in the epidermal growth factor receptor (EGFR) family. Like other family members, it has an extracellular ligand-binding domain, a transmembrane domain, and an intracellular kinase domain. ErbB3 requires interactions with other receptors and dimerizes with ErbB2 and MET, to activate downstream signaling pathways. Mutations in the ErbB3 gene within the extracellular and kinase domains have been identified in many cancer types. To understand the impact of ErbB3 on cancer growth and metastasis, the human ovarian cancer cell line, OVCAR8, was used as a model. Parental OVCAR8 cells that express ErbB2 and ErbB3 were compared to a CRISPR-edited ErbB3 knockout cell line (ErbB3 KO) and ErbB3 KO lines stably expressing ErbB3 mutants (V104L, T355I, V855A, and E928G). To understand how the mutant ErbB3 receptors interact with other receptor tyrosine kinases, cells were stimulated with the ErbB3 ligand, heregulin (HRG), and the phosphorylation of receptors was quantified by fluorescent western blotting. Data shows that expression of ErbB3 V104L or V855A rescues ligand-dependent phosphorylation of ErbB3 and ErbB2. Interestingly, expression of these mutants also leads to ligand-independent activation of MET, but not ErbB2, suggesting that mutations in ErbB3 may enhance interactions with MET. Spheroid formation and spheroid attachment assays were performed to observe how loss or mutation of ErbB3 affects spheroid characteristics. Spheroid area and circumference were measured after 24 and 48 hours of spheroid formation and circularity was calculated. Data shows that loss of ErbB3 compromises spheroid formation resulting in larger, less compact spheroids. Surprisingly, ErbB3 KO has the opposite effect compared to ErbB2 KO, which produces tighter and more circular spheroids. A double ErbB2/ErbB3 KO shows a similar spheroid phenotype to the ErbB3 KO. ErbB3 mutants V104L and V855A partially rescue spheroid formation in this assay. Thus, we suggest ErbB3 may play an important role in spheroid formation and metastasis in ovarian cancer

Sleep Quality: A Mediator in the Pathway of Stress and Cold Symptom Severity

Stress is a known contributor to immune system suppression associated with higher illness susceptibility, including acute infectious respiratory illness or the common cold. Sleep quality is an additional mechanism that may underlie the association between stress and cold symptomatology. Although the associations between stress and sleep and cold symptomatology have been examined separately, little is known about the mechanistic role of sleep in these associations. The present study fills that void by examining archival data from the Common Cold Project (Pittsburgh Cold Study 3). The results indicate sleep quality surfaced as an indirect pathway linking stress to changes in cold severity. Additionally, better sleep was associated with greater changes in cold severity above perceived stress. These findings suggest that better sleep may be associated with less severe symptomatology. Future research should address mechanisms underlying the associations between stress, sleep, and cold symptomatology

Effects of SARS-CoV-2 B1.1.7 Spike Mutations on Vaccine Efficacy

This is a literature review on the effects of spike mutations in the B1.1.7 SARS-CoV-2 variant and its effect on vaccine efficacy. This paper has organized the pertinent literature on the researched effects of vaccine efficacy and explores a number of mutations in the spike protein. The search was conducted on PubMed and the criteria for inclusion was based on relevance to specifically mutations in the B1.1.7 variant, being a primary source, conducted after January of 2021, and its reproducibility and pertinence to the research topic. There are 16 fully extracted studies discussed in the results, with a brief overview of the conducted experiment in relation to the papers’ conclusions. The strengths of this paper are distilling the molecular methods of these individual papers and being able to compare and contrast diverse experiments on the same mutations. However, due to the diversity of experiments discussed in this paper, the landscape of SARS-CoV-2 mutations and vaccine efficacy are difficult to distill. The discussed papers were evaluated on the possible threats of the mutations and the comparable effect of known mutations. This is an important step for evaluating transmissibility and virulence. This literature review further shows the need to have a standard set of experiments that can be used to evaluate the effect of mutations in SARS-CoV-2 variants and its effect on vaccine efficacy in order to mak