Mechanisms of Drug Resistance in Ovarian Cancer and Associated Gene Targets.

In the United States, over 100,000 women are diagnosed with a gynecologic malignancy every year, with ovarian cancer being the most lethal. One of the hallmark characteristics of ovarian cancer is the development of resistance to chemotherapeutics. While the exact mechanisms of chemoresistance are poorly understood, it is known that changes at the cellular and molecular level make chemoresistance challenging to treat.

Methods to evaluate the impact of SARS-CoV-2 nucleocapsid mutations on antigen detection by rapid diagnostic tests.

Mutations in the nucleocapsid of SARS-CoV-2 may interfere with antigen detection by diagnostic tests. We used several methods to evaluate the effect of various SARS-CoV-2 nucleocapsid mutations on the performance of the Panbio™ and BinaxNOW™ lateral flow rapid antigen tests and a prototype high-throughput immunoassay that utilizes Panbio antibodies. Variant detection was also evaluated by immunoblot and BIAcore™ assay.

At the Front Lines: Effectively Training Community Stakeholders to Recognize and Report Child Abuse and Neglect.

In states with universal mandatory reporting of child abuse and neglect (CAN), it is essential that people who work with children and youth in a community be appropriately trained to recognize and report CAN. The primary goal of CAN training is early detection and intervention with a secondary purpose of impacting rates of violence, disease, drug use, and teen pregnancies in the community. The purpose of this project was to implement a standardized, community-tailored CAN training for laypersons and a train-the-trainer program in a rural Oklahoma community.

Comprehensive quantitative analysis of fatty-acyl-Coenzyme A species in biological samples by ultra-high performance liquid chromatography-tandem mass spectrometry harmonizing hydrophilic interaction and reversed phase chromatography.

Fatty acyl-Coenzyme A species (acyl-CoAs) are key biomarkers in studies focusing on cellular energy metabolism. Existing analytical approaches are unable to simultaneously detect the full range of short-, medium-, and long-chain acyl-CoAs, while chromatographic limitations encountered in the analysis of limited amounts of biological samples are an often overlooked problem. We report the systematic development of a UHPLC-ESI-MS/MS method which incorporates reversed phase (RP) and hydrophilic interaction liquid chromatography (HILIC) separations in series, in an automated mode.

Separating myoblast differentiation from muscle cell fusion using IGF-I and the p38 MAP kinase inhibitor SB202190.

The p38 MAP kinases play critical roles in skeletal muscle biology, but the specific processes regulated by these kinases remain poorly defined. Here we find that activity of p38α/β is important not only in early phases of myoblast differentiation, but also in later stages of myocyte fusion and myofibrillogenesis. By treatment of C2 myoblasts with the promyogenic growth factor insulin-like growth factor (IGF)-I, the early block in differentiation imposed by the p38 chemical inhibitor SB202190 could be overcome.

Defining Akt actions in muscle differentiation.

Muscle development in childhood and muscle regeneration in adults are highly regulated processes that are necessary for reaching and maintaining optimal muscle mass and strength throughout life. Muscle repair after injury relies on stem cells, termed satellite cells, whose activity is controlled by complex signals mediated by cell-cell contact, by growth factors, and by hormones, which interact with genetic programs controlled by myogenic transcription factors. Insulin-like growth factors (IGFs) play key roles in muscle development and help coordinate muscle repair after injury, primarily by stimulating the phosphatidylinositol 3-kinase-Akt signaling pathway, and both in vitro and in vivo studies have shown that Akt kinase activity is critical for optimal muscle growth and regeneration.

TGF-β inhibits muscle differentiation by blocking autocrine signaling pathways initiated by IGF-II.

Skeletal muscle differentiation and regeneration are regulated by interactions between exogenous hormone- and growth factor-activated signaling cascades and endogenous muscle-specific transcriptional programs. IGF-I and IGF-II can promote muscle differentiation in vitro and can enhance muscle maintenance and repair in vivo. In contrast, members of the TGF-β superfamily prominently inhibit muscle differentiation and regeneration.

Targeting mediators of Wnt signalling pathways by GnRH in gonadotropes.

The binding of GnRH to its receptor on pituitary gonadotropes leads to the targeting of a diverse array of signalling mediators. These mediators drive multiple signal transduction pathways, which in turn regulate a variety of cellular processes, including the biosynthesis and secretion of the gonadotropins LH and FSH. Advances in our understanding of the mechanisms and signalling pathways that are recruited to regulate gonadotrope function are continually being made.

Emerging targets of the GnRH receptor: novel interactions with Wnt signalling mediators.

The diversity of signalling pathways that gonadotropin-releasing hormone (GnRH) receptors can target has been extended markedly in recent years, ranging from classical heterotrimeric G-protein-coupled second-messenger mobilisation to MAPK cascade activation and epidermal growth factor receptor transactivation. More recently, the targeting of non-classical signalling pathways has been demonstrated, including the activation of monomeric G-proteins and integrin/focal adhesion complexes to mediate cytoskeletal remodelling, androgen receptor nuclear translocation, and luteinising hormone beta-subunit gene transcription. These have been further extended to include c-Src-mediated activation of diacylglycerol kinase, and a novel mechanism of cross-talk to prostaglandin receptor signalling.

Nuclear stabilization of beta-catenin and inactivation of glycogen synthase kinase-3beta by gonadotropin-releasing hormone: targeting Wnt signaling in the pituitary gonadotrope.

The GnRH receptor is a G protein-coupled receptor (GPCR), and its ligand GnRH is the central regulator of the reproductive system. GnRH receptors are known to target a wide variety of signal transduction pathways. Several recent studies have shown that activation of GPCRs can impact on beta-catenin signaling.