The chemistry and biology of mycolactones

Mycolactones are a group of macrolides excreted by the human pathogen Mycobacterium ulcerans, which exhibit cytotoxic, immunosuppressive and analgesic properties. As the virulence factor of M. ulcerans, mycolactones are central to the pathogenesis of the neglected disease Buruli ulcer, a chronic and debilitating medical condition characterized by necrotic skin ulcers. Due to their complex structure and fascinating biology, mycolactones have inspired various total synthesis endeavors and structure–activity relationship studies. Although this review intends to cover all synthesis efforts in the field, special emphasis is given to the comparison of conceptually different approaches and to the discussion of more recent contributions. Furthermore, a detailed discussion of molecular targets and structure–activity relationships is provided

Emergence of a unique group of necrotizing mycobacterial diseases.

Although most diseases due to pathogenic mycobacteria are caused by Mycobacterium tuberculosis, several other mycobacterial diseases-caused by M. ulcerans (Buruli ulcer), M. marinum, and M. haemophilum-have begun to emerge. We review the emergence of diseases caused by these three pathogens in the United States and around the world in the last decade. We examine the pathophysiologic similarities of the diseases (all three cause necrotizing skin lesions) and common reservoirs of infection (stagnant or slow-flowing water). Examination of the histologic and pathogenic characteristics of these mycobacteria suggests differences in the modes of transmission and pathogenesis, though no singular mechanism for either characteristic has been definitively described for any of these mycobacteria

Mosquito Infection Responses to Developing Filarial Worms

Human lymphatic filariasis is a mosquito-vectored disease caused by the nematode parasites Wuchereria bancrofti, Brugia malayi and Brugia timori. These are relatively large roundworms that can cause considerable damage in compatible mosquito vectors. In order to assess how mosquitoes respond to infection in compatible mosquito-filarial worm associations, microarray analysis was used to evaluate transcriptome changes in Aedes aegypti at various times during B. malayi development. Changes in transcript abundance in response to the different stages of B. malayi infection were diverse. At the early stages of midgut and thoracic muscle cell penetration, a greater number of genes were repressed compared to those that were induced (20 vs. 8). The non-feeding, intracellular first-stage larvae elicited few differences, with 4 transcripts showing an increased and 9 a decreased abundance relative to controls. Several cecropin transcripts increased in abundance after parasites molted to second-stage larvae. However, the greatest number of transcripts changed in abundance after larvae molted to third-stage larvae and migrated to the head and proboscis (120 induced, 38 repressed), including a large number of putative, immunity-related genes (∼13% of genes with predicted functions). To test whether the innate immune system of mosquitoes was capable of modulating permissiveness to the parasite, we activated the Toll and Imd pathway controlled rel family transcription factors Rel1 and Rel2 (by RNA interference knockdown of the pathway's negative regulators Cactus and Caspar) during the early stages of infection with B. malayi. The activation of either of these immune signaling pathways, or knockdown of the Toll pathway, did not affect B. malayi in Ae. aegypti. The possibility of LF parasites evading mosquito immune responses during successful development is discussed

The impact of participation in a leadership development program on transformational leadership behaviors

Organizational leaders use leadership development programs to develop leaders and remain competitive in a global economy. U.S. companies spend increasingly more on learning and development programs as organizational leaders realize the immediate need to develop and evaluate leaders internally (American Society of Training and Development, 2012). Effective leadership is important to Choctaw Nation because tribal leaders must satisfy traditional business objectives, manage tribal interests and policies, and increase economic growth in the community to promote sovereignty (Champagne, 2004; Cramblit, 2002; National Indian Gaming Commission, 2013). Choctaw Nation of Oklahoma developed Choctaw U to develop leaders within the employee population internally, but leaders at Choctaw Nation do not know if participation in the Choctaw U leadership development program impacts participants’ leadership behavior. The purpose of this quantitative quasi-experimental study was to examine the impact of participation in an eight-week leadership development program on participants’ transformational leadership behavior. The research was conducted using electronic assessments, and the participants were selected from the 2015 Choctaw U class using convenience sampling. The participants completed the electronic Multifactor Leadership Questionnaire, pretest and posttest, to provide quantitative data on transformational leadership behavior. A MANOVA design was used to analyze the data and determine if a statistically significant relationship exists between participation in an eight-week transformational leadership development program and participants’ transformational leadership behavior. The results of this study suggest that participation in an eight-week leadership development program does not significantly impact participants transformational leadership behavior. Further inquiry and research may validate these findings

Immunity in the bovine to T. congolense induced by self cure or chemotherapy

Meeting: Conference on Recent Advances in the Knowledge of Pathogenicity of Trypanosomes, 20-23 Nov. 1978, Nairobi, KEIn IDL-329