Calcium handling genes are regulated by promoter DNA methylation in colorectal cancer cells.

Calcium signaling regulates various cellular processes, including proliferation and cell death. DNA methylation of gene promoters is an epigenetic modification that facilitates transcriptional suppression. Disruption of calcium homeostasis and DNA methylation in cancer are each linked to tumor development and progression.

Development and assessment of a nationwide, cross-discipline women faculty mentoring program.

Introduction: Professional health care associations present a unique opportunity for formal mentorship programs, with membership often spanning a variety of experiences, professional ranks, and institutions. However, scarce literature describes the role of professional associations in the development and assessment of mentoring programs. This paper describes development of the American Association of Colleges of Pharmacy Women Faculty Special Interest Group (SIG) mentoring program and characterizes the impact of the program.

Development of a laboratory-based pharmacogenomics independent study and advanced pharmacy practice experience: Connecting basic science to clinical application.

Background And Purpose: The role of pharmacists in pharmacogenomics (PGx) use clinically is expanding, leading to increased pharmacy education requirements. Current reports indicate that PGx is primarily taught through didactic courses, indicating a need for applied coursework in pharmacy curricula, including laboratory exercises and clinical experiences. Such courses are instrumental in helping students connect the science of PGx to patient care.

Student and faculty perceptions of integrated therapeutics courses in a doctor of pharmacy program.

Introduction: There has been a movement in clinical education towards integrating foundational and applied course content. It remains unclear what best practices are for integration or how meaningful integration is for improving learning. We assessed the impact and perceptions of different degrees of integration in Integrated Pharmacy Care and Patient Management (IPC) courses.

Pharmacogenomics Education Improves Pharmacy Student Perceptions of Their Abilities and Roles in Its Use.

To assess whether a required first-year course, Principles in Genetics and Pharmacogenomics, and integration into subsequent courses affected pharmacy students' perceptions of pharmacogenomics. A survey was distributed to Professional Year (PY) 1 students during the first and last weeks of the course from 2014 to 2016. A follow-up survey was distributed to PY2, PY3, and PY4 students.

Epigenetic Regulation via Altered Histone Acetylation Results in Suppression of Mast Cell Function and Mast Cell-Mediated Food Allergic Responses.

Mast cells are highly versatile cells that perform a variety of functions depending on the immune trigger, context of activation, and cytokine stimulus. Antigen-mediated mast cell responses are regulated by transcriptional processes that result in the induction of numerous genes contributing to mast cell function. Recently, we also showed that exposure to dietary agents with known epigenetic actions such as curcumin can suppress mast cell-mediated food allergy, suggesting that mast cell responses may be epigenetically regulated.

IL-10 Enhances IgE-Mediated Mast Cell Responses and Is Essential for the Development of Experimental Food Allergy in IL-10-Deficient Mice.

IL-10 is a key pleiotropic cytokine that can both promote and curb Th2-dependent allergic responses. In this study, we demonstrate a novel role for IL-10 in promoting mast cell expansion and the development of IgE-mediated food allergy. Oral OVA challenge in sensitized BALB/c mice resulted in a robust intestinal mast cell response accompanied by allergic diarrhea, mast cell activation, and a predominance of Th2 cytokines, including enhanced IL-10 expression.

Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy.

IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, the active ingredient of the curry spice turmeric, has anti-inflammatory properties, and thus may have the capacity to regulate Th2 cells and mucosal mast cell function during allergic responses. We assessed whether curcumin ingestion during oral allergen exposure can modulate the development of food allergy using a murine model of ovalbumin (OVA)-induced intestinal anaphylaxis.

Nanopores suggest a negligible influence of CpG methylation on nucleosome packaging and stability.

Nucleosomes are the fundamental repeating units of chromatin, and dynamic regulation of their positioning along DNA governs gene accessibility in eukaryotes. Although epigenetic factors have been shown to influence nucleosome structure and dynamics, the impact of DNA methylation on nucleosome packaging remains controversial. Further, all measurements to date have been carried out under zero-force conditions.

Fast, label-free force spectroscopy of histone-DNA interactions in individual nucleosomes using nanopores.

Herein we report a novel approach for fast, label-free probing of DNA-histone interactions in individual nucleosomes. We use solid-state nanopores to unravel individual DNA/histone complexes for the first time and find that the unraveling time depends on the applied electrophoretic force, and our results are in line with previous studies that employ optical tweezers. Our approach for studying nucleosomal interactions can greatly accelerate the understanding of fundamental mechanisms by which transcription, replication, and repair processes in a cell are modulated through DNA-histone interactions, as well as in diagnosis of diseases with abnormal patterns of DNA and histone modifications.

Ten eleven translocation enzymes and 5-hydroxymethylation in mammalian development and cancer.

5-Hydroxymethylcytosine (5hmC) is an oxidative product of 5-methylcytosine (5mC), catalyzed by the ten eleven translocation (TET) family of enzymes. Although 5hmC was discovered several decades ago, it was only after its recent identification in murine brain and stem cell DNA that it has become a major focus of epigenomic research. Part of the reason for this delay is due to the difficulty in detecting both global and locus-specific 5hmC levels.

The MspJI family of modification-dependent restriction endonucleases for epigenetic studies.

MspJI is a novel modification-dependent restriction endonuclease that cleaves at a fixed distance away from the modification site. Here, we present the biochemical characterization of several MspJI homologs, including FspEI, LpnPI, AspBHI, RlaI, and SgrTI. All of the enzymes specifically recognize cytosine C5 modification (methylation or hydroxymethylation) in DNA and cleave at a constant distance (N(12)/N(16)) away from the modified cytosine.

Regulation of expression and activity of DNA (cytosine-5) methyltransferases in mammalian cells.

Three active DNA (cytosine-5) methyltransferases (DNMTs) have been identified in mammalian cells, Dnmt1, Dnmt3a, and Dnmt3b. DNMT1 is primarily a maintenance methyltransferase, as it prefers to methylate hemimethylated DNA during DNA replication and in vitro. DNMT3A and DNMT3B are de novo methyltransferases and show similar activity on unmethylated and hemimethylated DNA.

Opposing roles of Dnmt1 in early- and late-stage murine prostate cancer.

Previous studies have shown that tumor progression in the transgenic adenocarcinoma of mouse prostate (TRAMP) model is characterized by global DNA hypomethylation initiated during early-stage disease and locus-specific DNA hypermethylation occurring predominantly in late-stage disease. Here, we utilized Dnmt1 hypomorphic alleles to examine the role of Dnmt1 in normal prostate development and in prostate cancer in TRAMP. Prostate tissue morphology and differentiation status was normal in Dnmt1 hypomorphic mice, despite global DNA hypomethylation.