Is NO the Answer? The Nitric Oxide Pathway Can Support Bone Morphogenetic Protein 2 Mediated Signaling

The growth factor bone morphogenetic protein 2 (BMP2) plays an important role in bone development and repair. Despite the positive effects of BMP2 in fracture healing, its use is associated with negative side effects and poor cost effectiveness, partly due to the large amounts of BMP2 applied. Therefore, reduction of BMP2 amounts while maintaining efficacy is of clinical importance. As nitric oxide (NO) signaling plays a role in bone fracture healing and an association with the BMP2 pathway has been indicated, this study aimed to investigate the relationship of BMP2 and NO pathways and whether NO can enhance BMP2-induced signaling and osteogenic abilities in vitro. To achieve this, the stable BMP reporter cell line C2C12BRELuc was used to quantify BMP signaling, and alkaline phosphatase (ALP) activity and gene expression were used to quantify osteogenic potency. C2C12BRELuc cells were treated with recombinant BMP2 in combination with NO donors and substrate (Deta NONOate, SNAP & L-Arginine), NOS inhibitor (LNAME), soluble guanylyl cyclase (sGC) inhibitor (LY83583) and activator (YC-1), BMP type-I receptor inhibitor (LDN-193189), or protein kinase A (PKA) inhibitor (H89). It was found that the NOS enzyme, direct NO application, and sGC enhanced BMP2 signaling and improved BMP2 induced osteogenic activity. The application of a PKA inhibitor demonstrated that BMP2 signaling is enhanced by the NO pathway via PKA, underlining the capability of BMP2 in activating the NO pathway. Collectively, this study proves the ability of the NO pathway to enhance BMP2 signaling

Assessment of Bones Deficient in Fibrillin-1 Microfibrils Reveals Pronounced Sex Differences.

Defects in the extracellular matrix protein fibrillin-1 that perturb transforming growth factor beta (TGFβ) bioavailability lead to Marfan syndrome (MFS). MFS is an autosomal-dominant disorder, which is associated with connective tissue and skeletal defects, among others. To date, it is unclear how biological sex impacts the structural and functional properties of bone in MFS. The aim of this study was to investigate the effects of sex on bone microarchitecture and mechanical properties in mice with deficient fibrillin-1, a model of human MFS. Bones of 11-week-old male and female Fbn1mgR/mgR mice were investigated. Three-dimensional micro-computed tomography of femora and vertebrae revealed a lower ratio of trabecular bone volume to tissue volume, reduced trabecular number and thickness, and greater trabecular separation in females vs. males. Three-point bending of femora revealed significantly lower post-yield displacement and work-to-fracture in females vs. males. Mechanistically, we found higher Smad2 and ERK1/2 phosphorylation in females vs. males, demonstrating a greater activation of TGFβ signaling in females. In summary, the present findings show pronounced sex differences in the matrix and function of bones deficient in fibrillin-1 microfibrils. Consequently, sex-specific analysis of bone characteristics in patients with MFS may prove useful in improving the clinical management and life quality of these patients, through the development of sex-specific therapeutic approaches

Bursa-Derived cells show a distinct mechano-response to physiological and pathological loading in vitro

The mechano-response of highly loaded tissues such as bones or tendons is well investigated, but knowledge regarding the mechano-responsiveness of adjacent tissues such as the subacromial bursa is missing. For a better understanding of the physiological role of the bursa as a friction-reducing structure in the joint, the study aimed to analyze whether and how bursa-derived cells respond to physiological and pathological mechanical loading. This might help to overcome some of the controversies in the field regarding the role of the bursa in the development and healing of shoulder pathologies. Cells of six donors seeded on collagen-coated silicon dishes were stimulated over 3 days for 1 or 4 h with 1, 5, or 10% strain. Orientation of the actin cytoskeleton, YAP nuclear translocation, and activation of non-muscle myosin II (NMM-II) were evaluated for 4 h stimulations to get a deeper insight into mechano-transduction processes. To investigate the potential of bursa-derived cells to adapt their matrix formation and remodeling according to mechanical loading, outcome measures included cell viability, gene expression of extracellular matrix and remodeling markers, and protein secretions. The orientation angle of the actin cytoskeleton increased toward a more perpendicular direction with increased loading and lowest variations for the 5% loading group. With 10% tension load, cells were visibly stressed, indicated by loss in actin density and slightly reduced cell viability. A significantly increased YAP nuclear translocation occurred for the 1% loading group with a similar trend for the 5% group. NMM-II activation was weak for all stimulation conditions. On the gene expression level, only the expression of TIMP2 was down-regulated in the 1 h group compared to control. On the protein level, collagen type I and MMP2 increased with higher/longer straining, respectively, whereas TIMP1 secretion was reduced, resulting in an MMP/TIMP imbalance. In conclusion, this study documents for the first time a clear mechano-responsiveness in bursa-derived cells with activation of mechano-transduction pathways and thus hint to a physiological function of mechanical loading in bursa-derived cells. This study represents the basis for further investigations, which might lead to improved treatment options of subacromial bursa-related pathologies in the future

A influência de instrumentos de políticas públicas para a conservação – uma ótica sobre o pagamento dos serviços ambientais

Os serviços ecossistêmicos são essenciais para a sobrevivência do ser humano. No entanto, devido ao processo de urbanização, a população perde a sensibilidade para com os recursos ambientais, trazendo como consequências impactos que podem se tornar irreversíveis. Ao tomar consciência da magnitude que esses impactos podem alcançar, o ser humano se vê na necessidade de alterar o entendimento acerca das cidades, desenvolvendo meios para o desenvolvimento sustentável. Atualmente, diversos instrumentos de gestão são utilizados para a conservação dos recursos ambientais, sendo um deles o pagamento por serviço ambiental (PSA). Assim, o objetivo deste trabalho foi levantar e compreender as contribuições do PSA para a configuração do território. A metodologia apresentou natureza exploratória, dividida nas etapas de busca bibliométrica e a análise dos artigos selecionados. Percebendo que se trata de um instrumento estratégico por envolver os três atores principais dentro da governança urbana (gestor público, população e o recurso natural),          notou-se que existe uma hibridização na tipologia de instrumento de política ambiental, além de romper as barreiras entre o rural e urbano. Assim, o PSA passa a fortalecer as relações entre cidadãos e os serviços ecossistêmicos, sendo uma excelente resposta para as demandas das agendas globais atuais

The Lantern, 2016-2017

• Our Lady of Perpetual Virginity • Essential Terms for the Audience • Stories Untold • Jesus Camp • The Second Avenue Schmear • Driving to the Beach • Thanks, Alice • Decay • Peanut Butter Rhapsody • Transactions • Traffic • Sissy • Melting Wings • Ocean • Small Town Summer • Third Story • Family Trees • Mixed, Just Like Me • Sour Graves • How Sweet the Sound • Goodnight, Halfmoon • I\u27m Going to Ask Him How • Music • Pizza • Manhoodlike • Meditations From a Bunk Bed in a Home on Mount Pocono • Soft • Twilight\u27s Palette • The Oracle • Cynicism • River Ganges • Pinata Body and Hearing the Gun Shot • Song With No Music • Of Mornings Considering Womanhood • 10 Hours in Philadelphia • To Cut • Sachrang • Bavarian Wave Swinger • Irish Rain • Remembrances, Well • The Roses • Buttermilk • The Universe Will Always Listen if You Ask Her, Which is Why I Like Her More Than God • A Lukewarm Light • A Thought of Death • Hobson • Decaying Light • Window Women • Dead Bee • The Imagery • For Rent • Mona Lisa MMXVIhttps://digitalcommons.ursinus.edu/lantern/1185/thumbnail.jp

Judicial decision-making within political parties: A political approach

How do German intra-party tribunals manage internal conflicts? More specifically, why do they accept some cases for trial but reject others? Required by law to strictly adhere to implement rule of law standards, German intra-party tribunals are designed to insulate conflict regulation from politics. Meanwhile, research on judicial politics highlights the role of political and strategic considerations in accepting cases for trial. Building on the latter, we develop a theory that emphasizes tribunals’ political concerns such as winning elections. We test our hypotheses with a mixed-effects logit model on a novel data set covering 1088 tribunal decisions in six German parties from 1967 until 2015. Our findings indicate that political factors exert a strong effect on tribunal case acceptance. Tribunals are more likely to accept cases when suffering electoral loss and after losing government office. Moreover, tribunals dismiss cases more easily when their parties display relatively high levels of policy agreement

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e. a controlling message) compared to no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly-internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared to the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly-internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing: Controlled motivation was associated with more defiance and less long-term behavioral intentions to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

An Integrated Marketing Communications Campaign for the Lincoln Saltdogs

Campaign Challenge To develop a campaign focused on increasing attendance at Saltdogs games while promoting an affordable and engaging form of entertainment for the Lincoln community. Target Audiences The campaign\u27s primary target markets are adults living in Lincoln with at least one child, possibly more, living at home. Budget The campaign\u27s budget is $50,000. Objectives The objectives of the campaign are to increase attendance at home Saltdogs games and to promote the Saltdogs in the Lincoln community. Creative Strategy The creative strategy for the campaign revolves around the theme, Join the pack. Pack the park. Creative elements include print, outdoor, radio and a social media video. Public Relations Public relations tactics for the campaign include social media, promotional events, and media kits meant to encourage fans to pack the park. Media The campaign weighs heavily on print, radio and outdoor media along with a social media video that is anticipated to go viral

Impact of Gentamicin-Loaded Bone Graft on Defect Healing in a Sheep Model

Infections of bone are severe complications, and an optimization of grafting material with antimicrobial drugs might be useful for prevention and treatment. This study aimed to investigate the influence of gentamicin-loaded bone graft on the healing of bone defects in a sheep model. Metaphyseal and diaphyseal drill hole defects (diameter: 6 mm, depth: 15 mm) were filled with graft or gentamicin-loaded graft (50 mg/g graft) or were left untreated. Analysis of regeneration after three and nine weeks, micro-computed tomography (μCT), and histology revealed a significant increase in bone formation in the drill hole defects, which began at the edges of the holes and grew over time into the defect center. The amount of graft decreased over time due to active resorption by osteoclasts, while osteoblasts formed new bone. No difference between the groups was seen after three weeks. After nine weeks, significantly less mineralized tissue was formed in the gentamicin-loaded graft group. Signs of inflammatory reactions were seen in all three groups. Even though the applied gentamicin concentration was based on the concentration of gentamicin mixed with cement, the healing process was impaired. When using local gentamicin, a dose-dependent, compromising effect on bone healing should be considered