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Coxiella burnetii is an important zoonotic bacterial pathogen of global importance, causing the disease Q fever in a wide range of animal hosts. Ruminant livestock, in particular sheep and goats, are considered the main reservoir of human infection. Vaccination is a key control measure, and two commercial vaccines based on formalin-inactivated C. burnetii bacterins are currently available for use in livestock and humans. However, their deployment is limited due to significant reactogenicity in individuals previously sensitized to C. burnetii antigens. Furthermore, these vaccines interfere with available serodiagnostic tests which are also based on C. burnetii bacterin antigens. Defined subunit antigen vaccines offer significant advantages, as they can be engineered to reduce reactogenicity and co-designed with serodiagnostic tests to allow discrimination between vaccinated and infected individuals. This study aimed to investigate the diversity of antibody responses to C. burnetii vaccination and/or infection in cattle, goats, humans, and sheep through genome-wide linear epitope mapping to identify candidate vaccine and diagnostic antigens within the predicted bacterial proteome. Using high-density peptide microarrays, we analyzed the seroreactivity in 156 serum samples from vaccinated and infected individuals to peptides derived from 2,092 open-reading frames in the C. burnetii genome. We found significant diversity in the antibody responses within and between species and across different types of C. burnetii exposure. Through the implementation of three different vaccine candidate selection methods, we identified 493 candidate protein antigens for protein subunit vaccine design or serodiagnostic evaluation, of which 65 have been previously described. This is the first study to investigate multi-species seroreactivity against the entire C. burnetii proteome presented as overlapping linear peptides and provides the basis for the selection of antigen targets for next-generation Q fever vaccines and diagnostic tests.

The bacterium Coxiella burnetii can cause the disease Q-fever in a wide range of animal hosts. Ruminants, including sheep, are thought to play a pivotal role in the transmission of C. burnetii to humans; however, the only existing livestock vaccine, namely, Coxevac® (Ceva Animal Health Ltd., Libourne, France), a killed bacterin vaccine based on phase I C. burnetii strain Nine-Mile, is only approved for use in goats and cattle. In this study, a pregnant ewe challenge model was used to determine the protective effects of Coxevac® and an experimental bacterin vaccine based on phase II C. burnetii against C. burnetii challenge. Prior to mating, ewes (n = 20 per group) were vaccinated subcutaneously with either Coxevac®, the phase II vaccine, or were unvaccinated. A subset of pregnant ewes (n = 6) from each group was then challenged 151 days later (~100 days of gestation) with 106 infectious mouse doses of C. burnetii, Nine-Mile strain RSA493. Both vaccines provided protection against C. burnetii challenge as measured by reductions in bacterial shedding in faeces, milk and vaginal mucus, and reduced abnormal pregnancies, compared to unvaccinated controls. This work highlights that the phase I vaccine Coxevac® can protect ewes against C. burnetii infection. Furthermore, the phase II vaccine provided comparable levels of protection and may offer a safer and cost-effective alternative to the currently licensed vaccine.

Rodent models of arthritis have been extensively used in the elucidation of rheumatoid arthritis (RA) pathogenesis and are instrumental in the development of therapeutic strategies. Here we utilise delayed-type hypersensitivity arthritis (DTHA), a model in C57BL/6 mice affecting one paw with synchronised onset, 100% penetrance and low variation. We investigate the role of regulatory T cells (Tregs) in DTHA through selective depletion of Tregs and the role of IL-17 in connection with Treg depletion. Given the relevance of Tregs in RA, and the possibility of developing Treg-directed therapies, this approach could be relevant for advancing the understanding of Tregs in inflammatory arthritis. Selective depletion of Tregs was achieved using a Foxp3-DTR-eGFP mouse, which expresses the diphtheria toxin receptor (DTR) and enhanced green fluorescent protein (eGFP) under control of the Foxp3 gene. Anti-IL-17 monoclonal antibody (mAb) was used for IL-17 blockade. Numbers and activation of Tregs increased in the paw and its draining lymph node in DTHA, and depletion of Tregs resulted in exacerbation of disease as shown by increased paw swelling, increased infiltration of inflammatory cells, increased bone remodelling and increased production of inflammatory mediators, as well as increased production of anti-citrullinated protein antibodies. Anti-IL-17 mAb treatment demonstrated that IL-17 is important for disease severity in both the presence and absence of Tregs, and that IL-17 blockade is able to rescue mice from the exacerbated disease caused by Treg depletion and caused a reduction in RANKL, IL-6 and the number of neutrophils. We show that Tregs are important for the containment of inflammation and bone remodelling in DTHA. To our knowledge, this is the first study using the Foxp3-DTR-eGFP mouse on a C57BL/6 background for Treg depletion in an arthritis model, and we here demonstrate the usefulness of the approach to study the role of Tregs and IL-17 in arthritis.

Abstrak – Apakah Akuntansi dan Etika Membuat Tujuan Perusahaan Menjadi Lebih Mulia? Tujuan Utama - Penelitian ini bertujuan untuk merumuskan tujuan perusahaan yang lebih mulia atau Authentic Higher Purpose (AHP) dengan mengaplikasikan utilitarisme dari filsafat etika. Metode - Penelitian ini menggunakan metode studi kasus melalui focused group discussion. Beberapa manajemen puncak sebuah perusahaan yang terkait sektor tersebut menjadi informan dalam penelitian ini. Temuan Utama - Penelitian ini merumuskan sistem kepercayaan perusahaan yang mengandung AHP yaitu kesetaraan sosial dan kesejahteraan pedagang. Sistem tersebut melampaui tujuan bisnis biasa yang cenderung berkisar pada keuntungan perusahaan. Hasil temuan menunjukkan relevansi levers of control (LoC) yang digunakan akuntansi manajemen untuk membantu organisasi melakukan kontrol pada level strategis. Implikasi Teori dan Kebijakan – Tujuan perusahaan tidak lagi hanya berpusat pada kepentingan perusahaan semata, melainkan juga dampak sosial bagi pihak lain. AHP berkontribusi bagi pengembangan akuntansi manajemen. Kebaruan Penelitian - Penelitian ini memberikan kebaruan pada topik LoC dalam akuntansi manajemen melalui rumusan AHP yang didukung filsafat etika. Abstract – Do Accounting and Ethics Make Company Goals Greater? Main Purpose - This study aims to formulate Authentic Higher Purpose (AHP) company goals by applying utilitarianism from ethical philosophy. Method – This study uses the case study method through focused group discussion. Several top management of a company related to this sector became informants in this study. Main Findings - This study formulates a corporate belief system that contains AHP, namely social equality and merchant welfare. The system goes beyond the usual business objectives, which revolve around corporate profits. The findings show the relevance of the levers of control (LoC) used by management accounting to help organizations exercise control at a strategic level. Theory and Practical Implications – Company goals are no longer solely centred on corporate interests but also on social impacts for other parties. AHP contributed to the development of management accounting. Novelty - This research provides novelty on LoC in management accounting through the AHP formulation, which is supported by ethical philosophy.

Belief systems, which are one of the four levers of control, play a vital role in an organization. This study is primarily aimed at examining the effects of belief systems on managerial performance. Since the four levers of control jointly function in management control systems, we extend our study by investigating whether the contingent-fit between strategic risk, strategic uncertainty, and the other three levers of control (i.e., boundary systems, diagnostic control, and interactive control) strengthens the association between belief systems and managerial performance. A survey questionnaire was distributed to the upper-level management of various companies or strategic business units in Indonesia during the fourth quarter of 2017, resulting in 81 respondents. Hypotheses testing were conducted using the OLS regression model. This research found that belief systems are positively associated with managerial performance, indicating that the implementation of effective belief systems leads to higher managerial performance. This study also found that the contingent-fit between strategic risk, strategic uncertainty, and the other three levers of control does not have any effect on how belief systems are positively associated with managerial performance. This finding indicates that although management does not adopt a fit combination between its level of strategic risk and strategic uncertainty and the boundary systems, diagnostic control, and interactive control, it can still achieve good performance as long as strong belief systems are implemented. These findings confirm the critical role of belief systems in the levers of control. Thus, management needs to ensure the establishment of more effective belief systems if the company or business unit wants to produce optimal performance.

Asma merupakan penyakit inflamasi kronik saluran nafas yang ditandai dengan terjadinya hiperesponsif saluran nafas dan penyempitan saluran nafas secara reversibel. Asma hingga kini masih merupakan masalah kesehatan utama di dunia. Pemberian obat-obatan anti asma merupakan penatalaksanaan penyakit tersebut. Namun demikian terdapat masalah efek samping obat dan masalah biaya yang dikeluarkan untuk pembelian obat tersebut, apalagi asma merupakan penyakit kronis yang memerlukan pengobatan jangka panjang. Dengan demikian maka perlu pengembangan obat antiasma berbasis tumbuhan obat dengan biaya yang lebih terjangkau dan efek samping yang lebih sedikit. Penelitian ini dilakukan untuk menguji potensi ekstrak etanol Centella asiatica (L.) Urb. yang secara tradisional digunakan etnis Dayak sebagai obat batuk. Penelitian ini dilakukan untuk melihat aktivitas trakeospasmolitik ekstrak etanol C. asiatica pada organ terpisah trakea marmut untuk melihat efek antiasma. Hasil penelitian menunjukkan ekstrak C. asiatica memiliki aktivitas trakeospasmolitik yang signifikan jika dibandingkan dengan kontrol negatif. Meskipun nilai E maks C. asiatica lebih rendah daripada aminofilin, namun nilai EC50 tidak jauh berbeda dengan aminofilin sebagai kontrol positif. Kesimpulan penelitian ini adalah ekstrak etanol C. asiatica memiliki efek antiasma berdasarkan aktivitas trakeospasmolitiknya. Kata kunci: Centella asiatica, spasmolitik, organ terpisah trakea