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Antagonism Between Bone Morphogenetic Protein and Activin Signaling Pathways in Osteoprogenitor Cells
Get PDFOsteoporosis is a disease characterized by low bone mineral density due to the rate of bone resorption exceeding that of bone formation. Evidence indicates the Bone Morphogenetic Protein (BMP) pathway promotes bone formation through action of effectors SMAD1/5/8 while the Activin pathway negatively influences bone mass through effectors SMAD2/3. Studies suggest that BMPs and Activins regulate bone mass in a see-saw-like mechanism. We seek to test this hypothesis in vitro via signaling responsiveness assays using pathway-specific western blot analyses in the osteogenic murine bone marrow stromal cell line W-20-17. We first confirmed that W-20-17 cells exhibit basal activation of SMAD1/5/8 and SMAD2/3 under serum-restricted conditions. Treatment with Follistatin, which sequesters Activin ligands in the extracellular environment, leads to an increase in BMP pathway activation. To determine the mechanism allowing for this, we treated W-20-17 cells with SB431542, an intracellular inhibitor of Activin signaling that functions downstream of receptor engagement, and found no effect on BMP pathway activation. In contrast, treatment with BMP pathway inhibitor Noggin had no effect on Activin pathway activation despite robust inhibition of BMP signaling. Our results suggest Activin-mediated repression of BMP signaling in these cells is ligand-dependent but occurs upstream of SMAD2/3 activation. Gene expression analyses indicate that W-20-17 cells express Activin A and its receptors ALK4, ACVR2A, and ACVR2B. Given that ACVR2A and ACVR2B also have high affinity for BMP ligands, this raises the possibility that Activin-mediated repression of BMP signaling may occur via competition for a shared pool of receptors. Over-expression studies and osteoblast activity assays are underway to examine this hypothesis. Our work seeks to elucidate the mechanism(s) that regulate antagonism of BMP and Activin signaling pathways to identify novel opportunities for treating low bone mass in humans
Ministry to Transgender Teenagers (Part Two): Providing Pastoral Care, Support, and Advocacy to Trans Youth
Get PDFThis article considers the ministry and pastoral care to transgender teenagers. It begins by offering a brief introduction and then concentrates on the ways or methods for providing pastoral care, support, and advocacy to transgender teenagers. The article suggests a pastoral framework for those in pastoral positions who work with adolescents to minister appropriately and competently to this overlooked sexual minority group and motivate them with a sense of urgency to serve this population more effectively
The Effect that Docosahexaenoic Omega-3 Fatty Acid Has on Intestinal Microbiome and its Relationship to Age-Related Macular Degeneration
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Experience with and Perception of Research Among First Year Osteopathic Medical Students at Marian University
Get PDFThere are limited data regarding research experience and/or interest among osteopathic medical students despite a rapidly increasing enrollment and expansion of the number of osteopathic medical schools. A 2016 study of first-year osteopathic medical students at WesternU/COMP and WesternU/COMP-NW indicated that 81% of respondents had prior research experience and 75% were either currently doing research or were interested in doing research during medical school. Here, we extended that survey to Marian University College of Osteopathic Medicine to determine the research experience and interest among first-year osteopathic medical students. Based on a response rate of 32%, a majority of respondents reported prior research experience (79.7%), with 13% of those students having garnered peer-reviewed publication(s). This is consistent with a strong perception of research being valuable, with 96.43% indicating some level of importance and 41.07% indicating very or extremely important. Interestingly, fewer respondents (56.6%) are either currently participating in research or affirmed interest in performing research during medical school, with the highest level of interest in clinical research (32%) followed by basic science (22.67%). Regarding incentives that might encourage participation in research, respondents prefer monetary compensation (37.38%) and/or extra credit in courses (36.45%). Reported barriers to performing research include possible negative impact on coursework (59.04%) and preference for other extracurricular activities (18.07%). Most students (78.57%) reported awareness that research opportunities are available, but fewer (46.43%) were aware of whether opportunities exist in their specific field of interest. Our findings indicate a strong positive perception of research among MU-COM students and highlight opportunities for improved communication and enhancement of the research environment through incentivization and/or removal of perceived barriers
Multi Drug Resistant Plasmid Transfer Between Salmonella and Two E. Coli Strains
Get PDFMultiple drug resistance is becoming increasingly problematic in the U.S., where antibiotics are overused both in agriculture and healthcare. One way bacteria can develop this resistance is through acquisition of antibiotic resistance genes, either on their chromosomes or on plasmids. A plasmid is an autonomous extrachromosomal DNA structure that replicates independently of the bacterial chromosome. Plasmids can be horizontally spread across different bacterial species through conjugation, transformation, or transduction, allowing multiple bacteria the ability to select for a resistant, advantageous phenotype. Salmonella infects around 400,000 people a year. Children, elderly, and the immunocompromised are the most at risk. Recent Salmonella and Escherichia coli clinical isolates have been found to carry antibiotic resistance plasmids. This limits treatment options even for healthy individuals. Salmonella, like other members of the Enterobacteriaceae family, have been found to carry more than one type of beta-lactamase genes, such as the blaCMY2 gene or blaCTX-M gene. To determine if horizontal transfer of these plasmids is possible, two different E. coli lab isolates were transformed with plasmids from Salmonella clinical isolates. The goal of the current project is to isolate these plasmids and analyze them for their incompatibility groups and their antibiotic resistance profiles. Using an extraction kit specifically designed for larger plasmids, isolates were analyzed in order to form a more complete picture of the Inc plasmids found in the E. coli strains. Moving forward these plasmids can now be further analyzed to determine what specific antibiotic resistance each plasmid carries. This study will advance our knowledge concerning the development and dissemination of multiple antimicrobial resistance among Salmonella spp. and other enteric bacteria in nature
Role of Protein Kinase-C and Rho Kinase in the Cytotoxic Effects of Bitter Melon Extract on Metastatic Breast Cancer Cells
Get PDFIntroduction: Bitter melon extract (BME) is known to inhibit breast cancer cells (MCF-7) proliferation. The PKC and ROK play critical roles in cell division, migration, and survival. However, the roles of protein kinase-c (PKC) and rho kinase (ROK) inhibition on MCF-7 cells have not been established. Moreover, whether potential effects of BME’s effects on MCF-7 cells are mediated by PKC and ROK are unknown. Aims: We aimed to investigate if BME exerts cytotoxic effects on breast cancer cells (MCF-7 cells) and if PKC and ROCK mediate BME’s effects. We hypothesized that BME inhibits proliferation of MCF-7 cells by decreasing PKC activity and increasing ROK activity. Methods: Fresh bitter melons were purchased from an Asian grocery store and the extract (BME) was extracted, centrifuged, and filter sterilized. The MCF-7 cells were cultured in DMEM medium with different amounts of BME [0%, 0.5%, 1%, 2%, 5%, and 10% of BME (v/v)], and in the presence of absence of PKC inhibitor (GF109203x; 0.5µM) and ROK inhibitor (H-1152; 1 µM). After culturing cells for 6 days (for the dose-response study) and 2 days (for the inhibitor studies), pictures of cultures were taken, cell viability was determined using Trypan blue dye, and change in protein expression was determined using western blotting. Repeated t-test was used to determine statistical significance. Results & Discussion: BME dose-dependently inhibited viability of MCF-cells (N=3) and MYPT1 (Myosin phosphatase targeting subunit-1) expression (N=1, duplicate). The PKC inhibitor alone did not have significant effect on cell viability (N=4) but the ROK inhibitor decreased cell viability (N=5) and MYPT1 expression. In the future, we will be studying phosphorylation of ROK’s target proteins to examine how ROK mediates BME’s cytotoxic effects
