The long-term impact of receiving incidental findings on parents undergoing genome-wide sequencing.

Genome-wide (exome or genome) sequencing (GWS) has the potential to detect incidental findings (IFs): variants unrelated to the primary indication for testing that may be of medical or personal utility. As GWS becomes increasingly common in clinical practice, it is important to understand the impact of IFs on the individuals and their families. Our goal was to explore the immediate and long-term lived experience of individuals who received IFs as part of diagnostic GWS. We interviewed parents who received an IF as part of the CAUSES translational research study at Children's and Women's Health Centre of British Columbia. Five hundred families were offered trio-based GWS for their child with a suspected, undiagnosed genetic condition. Nine hundred and one of the 1000 parents chose to find out about IFs and 21 parents received an IF for themselves. Twelve of these parents participated in this study. They were interviewed an average of 2.3 years after the IFs were returned. Thematic analysis of transcribed interviews revealed that the participants' decisions and motivations to receive IFs were influenced by personal values and beliefs and by having a child with a suspected genetic condition. Participants' experiences were also influenced by the type of IF received, having a personal or family history of a related condition, their personal interpretation and perceived utility of the information, and the impact of the IF on other family members. Participants expressed either no regret or mild decisional regret on the Decisional Regret Scale. Two years post results, most participants reported little negative impact from receiving the IF. The utility of the information varied: some reported lifestyle changes and proactive screening, while others felt the information may be more relevant in the future. Understanding the immediate and longer term impact of receiving IFs from GWS can inform both pre- and post-test genetic counseling.

The Wdr1-LIMK-Cofilin Axis Controls B Cell Antigen Receptor-Induced Actin Remodeling and Signaling at the Immune Synapse.

When B cells encounter membrane-bound antigens, the formation and coalescence of B cell antigen receptor (BCR) microclusters amplifies BCR signaling. The ability of B cells to probe the surface of antigen-presenting cells (APCs) and respond to APC-bound antigens requires remodeling of the actin cytoskeleton. Initial BCR signaling stimulates actin-related protein (Arp) 2/3 complex-dependent actin polymerization, which drives B cell spreading as well as the centripetal movement and coalescence of BCR microclusters at the B cell-APC synapse. Sustained actin polymerization depends on concomitant actin filament depolymerization, which enables the recycling of actin monomers and Arp2/3 complexes. Cofilin-mediated severing of actin filaments is a rate-limiting step in the morphological changes that occur during immune synapse formation. Hence, regulators of cofilin activity such as WD repeat-containing protein 1 (Wdr1), LIM domain kinase (LIMK), and coactosin-like 1 (Cotl1) may also be essential for actin-dependent processes in B cells. Wdr1 enhances cofilin-mediated actin disassembly. Conversely, Cotl1 competes with cofilin for binding to actin and LIMK phosphorylates cofilin and prevents it from binding to actin filaments. We now show that Wdr1 and LIMK have distinct roles in BCR-induced assembly of the peripheral actin structures that drive B cell spreading, and that cofilin, Wdr1, and LIMK all contribute to the actin-dependent amplification of BCR signaling at the immune synapse. Depleting Cotl1 had no effect on these processes. Thus, the Wdr1-LIMK-cofilin axis is critical for BCR-induced actin remodeling and for B cell responses to APC-bound antigens.

Engineering of new graphene-based materials as potential materials to assist near-infrared photothermal therapy cancer treatment.

Photothermal therapy is an emerging method of cancer treatment in which tumors are ablated by heating agents using near-infrared light (700-1000 nm). A semiconductor with a band gap between 0.3-0.7 eV would therefore efficiently emit near-infrared light. The new "magic" material graphene has a band gap of zero, which is advantageous with regard to designing a new material with a suitable band gap for the emission of near infrared light. In our investigations, using the first principles density functional theory calculation method, we aimed to and successfully designed graphene-based materials with a direct band gap of 0.68 eV. They have the potential to be optimal and efficient near-infrared light sources, due to their narrow yet fitting band gap. The present results open up a new avenue for the application of graphene-based materials to assist in photothermal therapy.