Insights Gained into the Use of Individual Development Plans as a Framework for Mentoring NIH Postbaccalaureate Research Education Program (PREP) Trainees.

This study examines the use of individual development plans (IDPs) in a structured mentoring program as an effective mechanism for reducing identity-related anxiety for underrepresented trainees and increasing their learner agency. Social cognitive theory served to provide the theoretical framework for our implementation of IDPs and our investigation of the effects of completing IDPs on trainees attaining academic goals and subsequent success in enrolling in competitive PhD programs. Results suggest that IDPs are also an effective tool that can allow faculty mentors to provide the social support necessary for trainees to persist in accomplishing their short- and long-term learning goals.

Incorporating Identity Safety into the Laboratory Safety Culture.

Chemistry practitioners, particularly in educational settings, often associate building strong safety cultures with compliance or regulatory requirements around laboratory glass-ware, equipment, flammable and incompatible materials, signage, container labels, and safety data sheets. Other fields of science also emphasize biohazardous materials, animal handling, human subject, and ergonomics. However, little attention in the literature has gone toward describing the interpersonal interactions and behaviors affecting the physical and emotional safety and wellbeing of laboratory trainees and personnel from marginalized backgrounds.

A Model for Crafting Diversity, Inclusion, Respect, and Equity (DIRE) Policy Statements Toward Catalyzing Organizational Change.

We present a model for STEM organizations to write catalytic diversity, inclusion, respect, and equity (DIRE) policy statements as structured steps for sustained action.

Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer.

Studies have suggested that type 2 diabetes (T2D) is associated with a higher incidence of breast cancer and related mortality rates. T2D postmenopausal women have an ~20% increased chance of developing breast cancer, and women with T2D and breast cancer have a 50% increase in mortality compared to breast cancer patients without diabetes. This correlation has been attributed to the general activation of insulin receptor signaling, glucose metabolism, phosphatidylinositol (PI) kinases, and growth pathways.

Identification of Specific Lysines and Arginines That Mediate Angiomotin Membrane Association.

The family of Angiomotin (Amot) proteins regulate several biological pathways associated with cellular differentiation, proliferation, and migration. These adaptor proteins target proteins to the apical membrane, actin fibers, or the nucleus. A major function of the Amot coiled-coil homology (ACCH) domain is to initiate protein interactions with the cellular membrane, particularly those containing phosphatidylinositol lipids.

Reorganization of Ternary Lipid Mixtures of Nonphosphorylated Phosphatidylinositol Interacting with Angiomotin.

Phosphatidylinositol (PI) lipids are necessary for many cellular signaling pathways of membrane associated proteins, such as angiomotin (Amot). The Amot family regulates cellular polarity, growth, and migration. Given the low concentration of PI lipids in these membranes, it is likely that such protein-membrane interactions are stabilized by lipid domains or small lipid clusters.

Using the Predicted Structure of the Amot Coiled Coil Homology Domain to Understand Lipid Binding.

Angiomotins (Amots) are a family of adapter proteins that modulate cellular polarity, differentiation, proliferation, and migration. Amot family members have a characteristic lipid-binding domain, the coiled coil homology (ACCH) domain that selectively targets the protein to membranes, which has been directly linked to its regulatory role in the cell. Several spot blot assays were used to validate the regions of the domain that participate in its membrane association, deformation, and vesicle fusion activity, which indicated the need for a structure to define the mechanism.

Systematic Survey of the Role of IGF in the Link Between Diabetes and Cancer.

Epidemiological studies have proposed a link between type II diabetes and cancer via the IGF/insulin signaling pathway, which includes insulin-like peptides (IGF1, IGF2, and insulin), insulin receptors (IR-A, IR-B, IGF1R, and hybrids), and insulin substrate proteins (IRS1-6). In this study, up- and down-regulation of various components in the IGF/insulin signaling pathway are compared to clinical outcomes for cancer patients; the components include diagnosis age, overall survival, tumor invasion and vascularization, and body mass index. It was found that the up-regulation of insulin growth Factor (IGF)/insulin components was associated with overall survival and tumor invasion and vascularization, while the down-regulation of equivalent components was not associated with clinical outcomes assessed in this study.

Phase coexistence in single-lipid membranes induced by buffering agents.

Recent literature has shown that buffers affect the interaction between lipid bilayers through a mechanism that involves van der Waals forces, electrostatics, hydration forces and membrane bending rigidity. This letter shows an additional peculiar effect of buffers on the mixed chain 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers, namely phase coexistence similar to what was reported by Rappolt et al. for alkali chlorides.

Development of selective inhibitors for aldehyde dehydrogenases based on substituted indole-2,3-diones.

Aldehyde dehydrogenases (ALDH) participate in multiple metabolic pathways and have been indicated to play a role in several cancerous disease states. Our laboratory is interested in developing novel and selective ALDH inhibitors. We looked to further work recently published by developing a class of isoenzyme-selective inhibitors using similar indole-2,3-diones that exhibit differential inhibition of ALDH1A1, ALDH2, and ALDH3A1.

Iterative layer-by-layer assembly of polymer-tethered multi-bilayers using maleimide–thiol coupling chemistry.

The current study reports on the layer-by-layer assembly of a polymer-tethered lipid multi-bilayer stack using the iterative addition and roll out of giant unilamellar vesicles (GUVs) containing constituents with thiol and maleimide functional groups, respectively. Confocal microscopy and photobleaching experiments confirm stack integrity and stability over time, as well as the lateral fluidity of individual bilayers within the stacks. Complementary wide-field single molecule fluorescence microscopy and atomic force microscopy experiments show that increasing bilayer-substrate distances are associated with changes in lipid lateral mobility and bilayer morphology.

Discovery of a novel class of covalent inhibitor for aldehyde dehydrogenases.

Human aldehyde dehydrogenases (ALDHs) comprise a family of 17 homologous enzymes that metabolize different biogenic and exogenic aldehydes. To date, there are relatively few general ALDH inhibitors that can be used to probe the contribution of this class of enzymes to particular metabolic pathways. Here, we report the discovery of a general class of ALDH inhibitors with a common mechanism of action.

Native ligands change integrin sequestering but not oligomerization in raft-mimicking lipid mixtures.

Distinct lipid environments, including lipid rafts, are increasingly recognized as a crucial factor affecting membrane protein function in plasma membranes. Unfortunately, an understanding of their role in membrane protein activation and oligomerization has remained elusive due to the challenge of characterizing these often small and transient plasma membrane heterogeneities in live cells. To address this difficulty, we present an experimental model membrane platform based on polymer-supported lipid bilayers containing stable raft-mimicking domains (type I) and homogeneous cholesterol-lipid mixtures (type II) into which transmembrane proteins are incorporated (α(v)β(3) and α(5)β(1) integrins).

Discovery of novel regulators of aldehyde dehydrogenase isoenzymes.

Over the past three years we have been involved in high-throughput screening in an effort to discover novel small molecular modulators of aldehyde dehydrogenase (ALDH) activity. In particular, we have been interested in both the activation and inhibition of the three commonly studied isoenzymes, ALDH1A1, ALDH2 and ALDH3A1, as their distinct, yet overlapping substrate specificities, present a particularly difficult challenge for inhibitor discovery and design. Activation of ALDH2 has been shown to benefit cardiovascular outcome following periods of ischemia and renewed interest in specific inhibition of ALDH2 has application for alcohol aversion therapy, and more recently, in cocaine addiction.