64 research outputs found
Bioluminescent Imaging of Trypanosoma brucei Shows Preferential Testis Dissemination Which May Hamper Drug Efficacy in Sleeping Sickness
Monitoring Trypanosoma spread using real-time imaging in vivo provides a fast method to evaluate parasite distribution especially in immunoprivileged locations. Here, we generated monomorphic and pleomorphic recombinant Trypanosoma brucei expressing the Renilla luciferase. In vitro luciferase activity measurements confirmed the uptake of the coelenterazine substrate by live parasites and light emission. We further validated the use of Renilla luciferase-tagged trypanosomes for real-time bioluminescent in vivo analysis. Interestingly, a preferential testis tropism was observed with both the monomorphic and pleomorphic recombinants. This is of importance when considering trypanocidal drug development, since parasites might be protected from many drugs by the blood-testis barrier. This hypothesis was supported by our final study of the efficacy of treatment with trypanocidal drugs in T. brucei-infected mice. We showed that parasites located in the testis, as compared to those located in the abdominal cavity, were not readily cleared by the drugs
La Grange Comprehensive Plan 2018 - 2038
In the Fall of 2017, the City of La Grange and Texas Target Communities partnered to create
a task force to represent the community. The task force was integral to the planning process,
contributing the thoughts, desires, and opinions of community membersâas well as their
enthusiasm about La Grangeâs future. This fifteen-month planning process ended in August
2018. The result of this collaboration is the La Grange Comprehensive Plan, which is the
official policy guide for the communityâs growth over the next twenty years.La Grange Comprehensive Plan 2018 - 2038 provides a guide for the future growth of the City.
This document was developed by Texas Target Communities in partnership with the City of
La Grange.Texas Target Communitie
Meiofauna in the Gollum Channels and the Whittard Canyon, Celtic MarginâHow Local Environmental Conditions Shape Nematode Structure and Function
The Gollum Channels and Whittard Canyon (NE Atlantic) are two areas that receive high input of organic matter and phytodetritus from euphotic layers, but they are typified by different trophic and hydrodynamic conditions. Sediment biogeochemistry was analysed in conjunction with structure and diversity of the nematode community and differences were tested between study areas, water depths (700 m vs 1000 m), stations, and sediment layers. The Gollum Channels and Whittard Canyon harboured high meiofauna abundances (1054â1426 ind. 10 cmâ2) and high nematode diversity (total of 181 genera). Next to enhanced meiofauna abundance and nematode biomass, there were signs of high levels of organic matter deposition leading to reduced sedimentary conditions, which in turn structured the nematode community. Striking in this respect was the presence of large numbers of âchemosyntheticâ Astomonema nematodes (Astomonema southwardorum, Order Monhysterida, Family Siphonolaimidae). This genus lacks a mouth, buccal cavity and pharynx and possesses a rudimentary gut containing internal, symbiotic prokaryotes which have been recognised as sulphur-oxidising bacteria. Dominance of Astomonema may indicate the presence of reduced environments in the study areas, which is partially confirmed by the local biogeochemical environment. The nematode communities were mostly affected by sediment layer differences and concomitant trophic conditions rather than other spatial gradients related to study area, water depth or station differences, pointing to small-scale heterogeneity as the main source of variation in nematode structure and function. Furthermore, the positive relation between nematode standing stocks, and quantity and quality of the organic matter was stronger when hydrodynamic disturbance was greater. Analogically, this study also suggests that structural diversity can be positively correlated with trophic conditions and that this relation is tighter when hydrodynamic disturbance is greater
Regulation of MicroRNA Biogenesis: A miRiad of mechanisms
microRNAs are small, non-coding RNAs that influence diverse biological functions through the repression of target genes during normal development and pathological responses. Widespread use of microRNA arrays to profile microRNA expression has indicated that the levels of many microRNAs are altered during development and disease. These findings have prompted a great deal of investigation into the mechanism and function of microRNA-mediated repression. However, the mechanisms which govern the regulation of microRNA biogenesis and activity are just beginning to be uncovered. Following transcription, mature microRNA are generated through a series of coordinated processing events mediated by large protein complexes. It is increasingly clear that microRNA biogenesis does not proceed in a 'one-size-fits-all' manner. Rather, individual classes of microRNAs are differentially regulated through the association of regulatory factors with the core microRNA biogenesis machinery. Here, we review the regulation of microRNA biogenesis and activity, with particular focus on mechanisms of post-transcriptional control. Further understanding of the regulation of microRNA biogenesis and activity will undoubtedly provide important insights into normal development as well as pathological conditions such as cardiovascular disease and cancer
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
International Consensus Statement on Rhinology and Allergy: Rhinosinusitis
Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICARâRS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICARâRSâ2021 as well as updates to the original 140 topics. This executive summary consolidates the evidenceâbased findings of the document. Methods: ICARâRS presents over 180 topics in the forms of evidenceâbased reviews with recommendations (EBRRs), evidenceâbased reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICARâRSâ2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidenceâbased management algorithm is provided. Conclusion: This ICARâRSâ2021 executive summary provides a compilation of the evidenceâbased recommendations for medical and surgical treatment of the most common forms of RS
Reduction of Fan and Compressor Wake Defect Using Plasma Actuation for Tonal Noise Reduction
Quality assessment practice in systematic reviews of mediation studies : results from an overview of systematic reviews
Quality assessment practice in systematic reviews of mediation studies : results from an overview of systematic reviews
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