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Mice Lacking the a2d1 Auxiliary Voltage Sensitive Calcium Channel Subunit Have Impaired Bone Quantity and Decreased Lean Mass
No full textMechanical loading is critical for bone remodeling. Voltage sensitive calcium channels (VSCCs) influence bone development and responses to loading. The α2δ1 VSCC subunit regulates osteocyte mechanosensation. Here we used α2δ1 knockout mice to determine the role of this subunit in bone development. Dual energy x-ray absorptiometry (DEXA) analyses (n=6/genotype) included male and female mice. Cacna2d1 KO mice had reduced body weight, compared to control mice, by an average of 17.85% (p\u3c0.01) over the ages examined (6, 9, 12, 15, and 18 weeks). Absolute lean mass was reduced in KO mice by an average of 20.68% (p\u3c0.0001). When normalized to body weight, lean mass was reduced in Cacna2d1 KO mice by 7.62% (p\u3c0.01). Whole body bone mineral density (BMD) and bone mineral content (BMC) were reduced by 8.95% (p\u3c0.001) and 26.04% (p\u3c0.0001) respectively. BMD and BMC of the femur was reduced in KO mice by an average of 15.01% (p\u3c0.0001) and 28.62% (p\u3c0.0001) respectively. BMD and BMC of L3-L5 vertebrae were reduced by an average of 11.67% and 23.53% respectively (p\u3c0.0001). μCT analysis of the cancellous compartment of distal femoral metaphyses (n=3 per genotype) revealed that KO mice had decreased trabecular BV/TV (40.43%), decreased trabecular connectivity (77.89%), decreased trabecular number (17.17%), and increased trabecular spacing (22.4%) (p\u3c0.05). Total BMC was decreased in Cacna2d1 KO mice by 18.54%, while cortical BMC was reduced by 13.75% (p=0.0525). Here we show that deletion of α2δ1 in C57BL/6 mice decreased whole body BMC and BMD prominently in trabecular bone, while lean mass was also reduced. We have previously shown that the α2δ1 subunit supports osteocyte responses to force in vitro, thus this subunit may regulate load-induced bone formation. Additionally, as the α2δ1 subunit is the receptor for the antiepileptic drug gabapentin, future work seeks to reveal the mechanisms underlying gabapentin-associated bone loss
The Prole and the Prelate
Get PDFThe chapter opens with a discussion of the Great Railroad Strike of 1877 in which questions regarding the social order, class, equity, and like matters arise. The coincidental arrival in Indianapolis of Denis Kearney and the new bishop of the diocese, Francis Silas Chatard, on 17 August 1878, extends the discussion and the role that the Catholic Church and its laity would and should play. Kearney, an immigrant Irishman, at the time was notorious as an agitator for the working class, while the Chatard was a scion of a prominent Baltimore family. The contrast in their biographies and in the reception in the city each received in the next few days illustrates the alternatives at stake. What each thought the laity owed the hierarchy as well as their convictions about the social order were miles apart. Chatard’s family and educational history is discussed, especially the influence that a papal representative to the United States in the 1850s, Gaetano Bedini, had on his thinking. The attention given to the Irish is justified on the ground that during the Gilded Age and later, their numbers led to the habit of conflating “Irish” with “Catholic,” ordinarily to the benefit of neither. Their prominence in the trade union movement and in the secret societies working for Ireland’s independence (to be taken up in the next chapter), and the problems they caused Chatard, are other reasons
Empowerment Through Education: A Comparative Study of Gender Equality in Schools in Brazil and The United States
Get PDFWith a grant and a fun group of feminist scholars who were interested in studying cultural and legal Brazilian equality, I packed my suitcase and headed to Brazil for 10 days of intense research. I am a recent graduate of Marian University in Indianapolis, with a future as a high school psychology and government teacher, and as such I was interested in the question of gender equality within the classroom setting. I had originally set out to study the inclusion of women in the history curriculum and classroom specifically, but due to our schedule and the pull of the Brazilian citizens I met, my topic widened to include how gender stereotypes limit the quality of the education, the discontent in the current educational system in Brazil, and the changes that Brazilians wish to see in their schools and societies
Loss of the Nutrient Sensor TAS1R3 Leads to Reduced Bone Resorption
No full textThe taste receptor type 1 (TAS1R) family of heterotrimeric G protein-coupled receptors participates in monitoring energy and nutrient status. TAS1R member 3 (TAS1R3) is a bi-functional protein that recognizes amino acids such as L-glycine and L-glutamate or sweet molecules such as sucrose and fructose when dimerized with TAS1R member 1 (TAS1R1) or TAS1R member 2 (TAS1R2), respectively. It was recently reported that deletion of TAS1R3 expression in Tas1R3 mutant mice leads to increased cortical bone mass but the underlying cellular mechanism leading to this phenotype remains unclear. Here, we independently corroborate the increased thickness of cortical bone in femurs of 20-week-old male Tas1R3 mutant mice and confirm that Tas1R3 is expressed in the bone environment. Tas1R3 is expressed in undifferentiated bone marrow stromal cells (BMSCs) in vitro and its expression is maintained during BMP2-induced osteogenic differentiation. However, levels of the bone formation marker procollagen type I N-terminal propeptide (PINP) are unchanged in the serum of 20-week-old Tas1R3 mutant mice as compared to controls. In contrast, levels of the bone resorption marker collagen type I C-telopeptide are reduced greater than 60% in Tas1R3 mutant mice. Consistent with this, Tas1R3 and its putative signaling partner Tas1R2 are expressed in primary osteoclasts and their expression levels positively correlate with differentiation status. Collectively, these findings suggest that high bone mass in Tas1R3 mutant mice is due to uncoupled bone remodeling with reduced osteoclast function and provide rationale for future experiments examining the cell-type-dependent role for TAS1R family members in nutrient sensing in postnatal bone remodeling
The Media\u27s Impact on Beauty and The Sexualization of Women
Get PDFThis paper compares the sexualization of Brazilian women and women from the United States. By juxtaposing the standard of beauty in Brazil to the standard of beauty in the States, comparisons could be made between what men, women, and the media consider “beautiful”, and how the definition changes between these groups. In order to reach a conclusion, participant observation was done in various regions of Brazil, during which student interviews took place
Experience with and Perception of Research Among First Year Osteopathic Medical Students
Get PDFThere are limited data regarding the level of 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. In the present study, we extended that survey to Marian University in order to determine the level of research experience and interest among first-year osteopathic medical students. Based on a response rate of 41%, an overwhelming majority of respondents reported prior research experience (\u3e80%), with 13% of those students having garnered peer-reviewed publication(s). This is consistent with a strong perception of research being valuable, with 96.92% indicating some level of importance and 27.69% indicating very or extremely important. Interestingly, fewer respondents (53.34%) are either currently participating in research or affirmed interest in performing research during medical school, with the highest level of interest in clinical research (32.37%) followed by basic science (20.23%). Regarding incentives that might encourage participation in research, respondents prefer monetary compensation (40.19%) and/or extra credit in courses (39.25%). Reported barriers to performing research include possible negative impact on coursework (65.93%) and preference for other extracurricular activities (23.08%). Although a majority of the students (81.54%) reported awareness that research opportunities are available at MU-COM, fewer (50.79%) 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 of availability and enhancement of the research environment through incentivization and/or removal of perceived barriers
Utilizing MUShare: An Approach to Scholarly Communications
Get PDFIn this session you’ll learn about the concepts behind scholarly communication seen through instructional tools such as Institutional Repositories, Open Educational Resources, and Open Access initiatives. Put that knowledge into practice by shaping the development of our newly implemented IR, MUShare
6-MERCAPTOPURINE FOR SEVERE ATOPIC DERMATITIS INA LACTOSE-ALLERGIC CHILD
No full text6-MERCAPTOPURINE FOR SEVERE ATOPIC DERMATITIS IN A LACTOSE-ALLERGIC CHILD Pediatric atopic dermatitis (AD) is encountered routinely in the gen- eral dermatology clinic, and most children with AD have readily- manageable mild to moderate disease. For severe AD that is resis- tant to topical corticosteroids and calcineurin inhibitors, the use of several steroid-sparing agents has been described in the literature, including cyclosporine, mycophenolate mofetil, methotrexate, and azathioprine. Herein we report what is to our knowledge the first use of 6-mercaptopurine (6MP) for pediatric AD. The patient was a 13-year-old boy with a long-standing history of severe atopic dermatitis. Previous treatments with topical corticos- teroids and heavy emollients were unsuccessful. The patient’s med- ical history was complicated by persistent asthma, food allergies, massively elevated IgE, and adrenal insufficiency related to chronic use of inhaled corticosteroids. Azathioprine and omalizumab were the main considerations for long term steroid-sparing agents, how- ever it was ultimately decided that the IgE levels were too high to safely proceed with omalizumab. Given his numerous food aller- gies, the composition of commercially available azathioprine was carefully reviewed and all were found to contain lactose. However, 6MP was determined not to contain lactose and was initiated. 6MP is the active metabolite of azathioprine. While originally approved for the induction and maintenance of acute lymphoblastic leukemia, 6MP has also been used for Crohns disease and ulcera- tive colitis. We followed the previously published dosing protocols for pediatric Crohns disease after checking baseline labwork, including thiopurine methyltransferase enzyme activity. The patient has tolerated the 6MP well and has maintained a significant reduc- tion of AD severity after an initial course of cyclosporine. This is therefore the first documented case of using 6MP as a lac- tose-free steroid sparing agent for the treatment of severe pediatric AD
Summer 2017 Women’s Rights and Women’s Empowerment Study Abroad: Brazil
Get PDFApplication used for the Women’s Rights and Women’s Empowerment study abroad initiative in Brazil