Integrative analysis of angiogenic signaling in obesity: capillary features and VEGF binding kinetics.

Obesity is a global health crisis, with its prevalence particularly severe in the United States, where over 42% of adults are classified as obese. Obesity is driven by complex molecular and tissue-level mechanisms that remain poorly understood. Among these, angiogenesis-primarily mediated by vascular endothelial growth factor (VEGF-A)-is critical for adipose tissue expansion but presents unique challenges for therapeutic targeting due to its intricate regulation.

Understanding the effects of oxytocin receptor variants on OXT-OXT receptor binding: A mathematical model.

Approximately half of U.S. women giving birth annually receive Pitocin, the synthetic form of oxytocin (OXT), yet its effective dose can vary significantly.

Quantification of surface-localized and total oxytocin receptor in myometrial smooth muscle cells.

Oxytocin acts through the oxytocin receptor (OXTR) to modulate uterine contractility. We previously identified OXTR genetic variants and showed that, in HEK293T cells, two of the OXTR protein variants localized to the cell surface less than wild-type OXTR. Here, we sought to measure OXTR in the more native human myometrial smooth muscle cell (HMSMC) line on both the cell-surface and across the whole cell, and used CRISPR editing to add an HA tag to the endogenous OXTR gene for anti-HA measurement.

Incorporating Diversity, Equity, and Inclusion Content Into Bioengineering Curricula: A Program-Level Approach.

Diversity, equity, and inclusion (DEI) are interconnected with bioengineering, yet have historically been absent from accreditation standards and curricula. Toward educating DEI-competent bioengineers and meeting evolving accreditation requirements, we took a program-level approach to incorporate, catalog, and assess DEI content through the bioengineering undergraduate program. To support instructors in adding DEI content and inclusive pedagogy, our team developed a DEI planning worksheet and surveyed instructors pre- and post-course.

Innovation and Entrepreneurship in Promotion and Tenure in Biomedical Engineering: Communication from the Biomedical Engineering Society Long Range Planning Committee.

Promotion and tenure (P&T) remain the central tenets of academia. The criteria for P&T both create and reflect the mission of an institution. The discipline of biomedical engineering is built upon the invention and translation of tools to address unmet clinical needs.

Correction: Innovation and Entrepreneurship in Promotion and Tenure in Biomedical Engineering.

[This corrects the article DOI: 10.1007/s12195-023-00767-x.].

Axl and Vascular Endothelial Growth Factor Receptors Exhibit Variations in Membrane Localization and Heterogeneity Across Monolayer and Spheroid High-Grade Serous Ovarian Cancer Models.

Vascular endothelial growth factor receptors (VEGFRs) and Axl are receptor tyrosine kinases (RTK) that are targeted in ovarian cancer therapy. Two-dimensional monolayer culture and three-dimensional spheroids are common models for RTK-targeted drug screening: monolayers are simple and economical while spheroids include several genetic and histological tumor features. RTK membrane localization dictates RTK signaling and drug response, however, it is not characterized in these models.

Pharmacological chaperones for the oxytocin receptor increase oxytocin responsiveness in myometrial cells.

Oxytocin is a potent uterotonic agent administered to nearly all patients during childbirth in the United States. Inadequate oxytocin response can necessitate Cesarean delivery or lead to uterine atony and postpartum hemorrhage. Thus, it may be clinically useful to identify patients at risk for poor oxytocin response and develop strategies to sensitize the uterus to oxytocin.

Naturally Occurring Genetic Variants in the Oxytocin Receptor Alter Receptor Signaling Profiles.

The hormone oxytocin is commonly administered during childbirth to initiate and strengthen uterine contractions and prevent postpartum hemorrhage. However, patients have wide variation in the oxytocin dose required for a clinical response. To begin to uncover the mechanisms underlying this variability, we screened the 11 most prevalent missense genetic variants in the oxytocin receptor () gene.

Sex differences in cancer mechanisms.

We now know that cancer is many different diseases, with great variation even within a single histological subtype. With the current emphasis on developing personalized approaches to cancer treatment, it is astonishing that we have not yet systematically incorporated the biology of sex differences into our paradigms for laboratory and clinical cancer research. While some sex differences in cancer arise through the actions of circulating sex hormones, other sex differences are independent of estrogen, testosterone, or progesterone levels.

Synthesis, Chemical Characterization and Multiscale Biological Evaluation of a Dimeric-cRGD Peptide for Targeted Imaging of α β Integrin Activity.

Cyclic peptides containing the Arg-Gly-Asp (RGD) sequence have been shown to specifically bind the angiogenesis biomarker α β integrin. We report the synthesis, chemical characterization, and biological evaluation of two novel dimeric cyclic RGD-based molecular probes for the targeted imaging of α β activity (a radiolabeled version, Cu-NOTA-PEG-cRGD, for PET imaging, and a fluorescent version, FITC-PEG-cRGD, for in vitro work). We investigated the performance of this probe at the receptor, cell, organ, and whole-body levels, including its use to detect diabetes associated impairment of ischemia-induced myocardial angiogenesis.

Integrative meta-modeling identifies endocytic vesicles, late endosome and the nucleus as the cellular compartments primarily directing RTK signaling.

Recently, intracellular receptor signaling has been identified as a key component mediating cell responses for various receptor tyrosine kinases (RTKs). However, the extent each endocytic compartment (endocytic vesicle, early endosome, recycling endosome, late endosome, lysosome and nucleus) contributes to receptor signaling has not been quantified. Furthermore, our understanding of endocytosis and receptor signaling is complicated by cell- or receptor-specific endocytosis mechanisms.

qFlow Cytometry-Based Receptoromic Screening: A High-Throughput Quantification Approach Informing Biomarker Selection and Nanosensor Development.

Nanosensor-based detection of biomarkers can improve medical diagnosis; however, a critical factor in nanosensor development is deciding which biomarker to target, as most diseases present several biomarkers. Biomarker-targeting decisions can be informed via an understanding of biomarker expression. Currently, immunohistochemistry (IHC) is the accepted standard for profiling biomarker expression.

Inhibition of Caspase-1 Activation in Endothelial Cells Improves Angiogenesis: A NOVEL THERAPEUTIC POTENTIAL FOR ISCHEMIA.

Deficient angiogenesis may contribute to worsen the prognosis of myocardial ischemia, peripheral arterial disease, ischemic stroke, etc. Dyslipidemic and inflammatory environments attenuate endothelial cell (EC) proliferation and angiogenesis, worsening the prognosis of ischemia. Under these dyslipidemic and inflammatory environments, EC-caspase-1 becomes activated and induces inflammatory cell death that is defined as pyroptosis.

Plasmonic optical trapping in biologically relevant media.

We present plasmonic optical trapping of micron-sized particles in biologically relevant buffer media with varying ionic strength. The media consist of 3 cell-growth solutions and 2 buffers and are specifically chosen due to their widespread use and applicability to breast-cancer and angiogenesis studies. High-precision rheological measurements on the buffer media reveal that, in all cases excluding the 8.

Quantitative fluorescent profiling of VEGFRs reveals tumor cell and endothelial cell heterogeneity in breast cancer xenografts.

Plasma membrane-localized vascular endothelial growth factor receptors (VEGFR) play a critical role in transducing VEGF signaling toward pro and antiangiogenic outcomes and quantitative characterization of these receptors is critical toward identifying biomarkers for antiangiogenic therapies, understanding mechanisms of action of antiangiogenic drugs, and advancing predictive computational models. While in vitro analysis of cell surface-VEGFRs has been performed, little is known about the levels of cell surface-VEGFR on tumor cells. Therefore, we inoculate nude mice with the human triple-negative breast cancer, MDA-MB-231, cell line; isolate human tumor cells and mouse tumor endothelial cells from xenografts; and quantitatively characterize the VEGFR localization on these cells.

Expression of VEGF receptors on endothelial cells in mouse skeletal muscle.

VEGFR surface localization plays a critical role in converting extracellular VEGF signaling towards angiogenic outcomes, and the quantitative characterization of these parameters is critical for advancing computational models; however the levels of these receptors on blood vessels is currently unknown. Therefore our aim is to quantitatively determine the VEGFR localization on endothelial cells from mouse hindlimb skeletal muscles. We contextualize this VEGFR quantification through comparison to VEGFR-levels on cells in vitro.

Subcellular trafficking, pentameric assembly, and subunit stoichiometry of neuronal nicotinic acetylcholine receptors containing fluorescently labeled alpha6 and beta3 subunits.

Neuronal nicotinic acetylcholine (ACh) receptors are ligand-gated, cation-selective ion channels. Nicotinic receptors containing alpha4, alpha6, beta2, and beta3 subunits are expressed in midbrain dopaminergic neurons, and they are implicated in the response to smoked nicotine. Here, we have studied the cell biological and biophysical properties of receptors containing alpha6 and beta3 subunits by using fluorescent proteins fused within the M3-M4 intracellular loop.