Bloodstream form trypanosoma brucei depend upon multiple metacaspases associated with RAB11-positive endosomes

Trypanosoma brucei possesses five metacaspase genes. Of these, MCA2 and MCA3 are expressed only in the mammalian bloodstream form of the parasite, whereas MCA5 is expressed also in the insect procyclic form. Triple RNAi analysis showed MCA2, MCA3 and MCA5 to be essential in the bloodstream form, with parasites accumulating pre-cytokinesis. Nevertheless, triple null mutants (Δmca2/3Δmca5) could be isolated after sequential gene deletion. Thereafter, Δmca2/3Δmca5 mutants were found to grow well both in vitro in culture and in vivo in mice. We hypothesise that metacaspases are essential for bloodstream form parasites, but they have overlapping functions and their progressive loss can be compensated for by activation of alternative biochemical pathways. Analysis of Δmca2/3Δmca5 revealed no greater or lesser susceptibility to stresses reported to initiate programmed cell death, such as treatment with prostaglandin D2. The metacaspases were found to colocalise with RAB11, a marker for recycling endosomes. However, variant surface glycoprotein (VSG) recycling processes and the degradation of internalised anti-VSG antibody were found to occur similarly in wild type, Δmca2/3Δmca5 and triple RNAi induced parasites. Thus, the data provide no support for the direct involvement of T. brucei metacaspases in programmed cell death and suggest that the proteins have a function associated with RAB11 vesicles that is independent of known recycling processes of RAB11-positive endosomes

CHAPTER 12. INFORMING INQUIRY INTO WRITING ACROSS THE LIFESPAN FROM PERSPECTIVES ON STUDENTS WITH LEARNING DISABILITIES OR AUTISM SPECTRUM DISORDER

The value of writing is not limited to single points of time in our lives but serves many different purposes across the lifespan (Bazerman et al., 2018). For instance, young children begin to experiment with writing as early as two years of age, using it as a vehicle for play, communication, and self-expression (Rowe, 2008). With the advent of school, the purposes for writing expand greatly to include writing to inform, persuade, describe, summarize, learn, and narrate to identify just some of the ways children, adolescents, and young adults learn to write and use writing as part of their education. During adulthood, writing is a staple of life at both work and home. White and blue collar workers commonly use writing to perform their jobs (Light, 2001), and adults frequently use writing throughout the day to initiate and maintain personal connections, as they tweet, text, email, and connect with each other using a variety of social networks and media (Freedman et al., 2016)

Enactments of a Minor Inquiry

In this article, we map conditions and enactments for a new plane of inquiry, what Mazzei named a minor inquiry. Informed by our collective thinking with Deleuze and Guattari’s discussion of a minor literature and its attendant characteristics, deterritorialization, political immediacy, and collective assemblage of enunciation, we present the conditions for inquiry on this new plane, provide enactments from our individual projects, and conclude with incitements for escaping the dogma of prescribed method

Robust incremental SLAM with consistency-checking

Incorrect landmark and loop closure measurements can cause standard SLAM algorithms to fail catastrophically. Recently, several SLAM algorithms have been proposed that are robust to loop closure errors, but it is shown in this paper that they cannot provide robust solutions when landmark measurement errors occur. The root cause of this problem is that the robust SLAM algorithms only focus on generating solutions that are locally consistent (i.e. each measurement agrees with its corresponding estimates) rather than globally consistent (i.e. all of the measurements in the solution agree with each other). Moreover, these algorithms do not attempt to maximize the number of correct measurements included in the solution, meaning that often correct measurements are ignored and the solution quality suffers as a result. This paper proposes a new formulation of the robust SLAM problem that seeks a globally consistent map that also maximizes the number of measurements included in the solution. In addition, a novel incremental SLAM algorithm, called incremental SLAM with consistency-checking, is developed to solve the new robust SLAM problem. Finally, simulated and experimental results show that the new algorithm significantly outperforms state-of-the-art robust SLAM methods for datasets with incorrect landmark measurements and can match their performance for datasets with incorrect loop closures.Charles Stark Draper Laboratory. Internal Research and Development Progra

Modulating the Expression of Disease Genes with RNA-Based Therapy

Conventional gene therapy has focused largely on gene replacement in target cells. However, progress from basic research to the clinic has been slow for reasons relating principally to the challenges of heterologous DNA delivery and regulation in vivo. Alternative approaches targeting RNA have the potential to circumvent some of these difficulties, particularly as the active therapeutic molecules are usually short oligonucleotides and the target gene transcript is under endogenous regulation. RNA-based strategies offer a series of novel therapeutic applications, including altered processing of the target pre-mRNA transcript, reprogramming of genetic defects through mRNA repair, and the targeted silencing of allele- or isoform-specific gene transcripts. This review examines the potential of RNA therapeutics, focusing on antisense oligonucleotide modification of pre-mRNA splicing, methods for pre-mRNA trans-splicing, and the isoform- and allele-specific applications of RNA interference

Connecting the time domain community with the Virtual Astronomical Observatory

The time domain has been identified as one of the most important areas of astronomical research for the next decade. The Virtual Observatory is in the vanguard with dedicated tools and services that enable and facilitate the discovery, dissemination and analysis of time domain data. These range in scope from rapid notifications of time-critical astronomical transients to annotating long-term variables with the latest modeling results. In this paper, we will review the prior art in these areas and focus on the capabilities that the VAO is bringing to bear in support of time domain science. In particular, we will focus on the issues involved with the heterogeneous collections of (ancillary) data associated with astronomical transients, and the time series characterization and classification tools required by the next generation of sky surveys, such as LSST and SKA.Comment: Submitted to Proceedings of SPIE Observatory Operations: Strategies, Processes and Systems IV, Amsterdam, 2012 July 2-

Whole body cryotherapy and recovery from exercise induced muscle damage: A systematic review

Introduction Cold therapies are used regularly in medicine for their analgesic and anti-inflammatory effects. Whole-body cryotherapy (WBC) involves exposure to air maintained between -110 and -160oC, and is hypothesised to reduce pain, local and systemic inflammation. WBC has recently become popular in an exercise and sporting context as a recovery method after skeletal muscle damage, however, research examining the efficacy of WBC in an athletic context is minimal. This review seeks to summarise the evidence for the effects of WBC on exercise recovery measures. Methods Electronic database searches were conducted from March to April 2013. Six large online databases were used; MEDLINE, SPORTDiscus, Scopus, Web of Science, PubMed and AMED. The search targeted human studies with an exercise task, and WBC intervention. Results included randomised controlled trials (RCT’s), uncontrolled trials and crossover designs. Results A total of 8 studies were included in the review. Two RCT’s, four crossover trials and two uncontrolled trials were identified. Five studies showed WBC had no effect on markers of muscle damage or inflammation post exercise, while 3 studies show a positive effect. Three out of the eight studies measured maximal muscle force production and subjective pain levels following exercise and WBC, with two showing WBC had a positive effect on muscle force recovery and pain. A meta-analysis was not conducted due to the heterogeneity of the studies. Conclusion The current evidence for the efficacy of WBC on exercise recovery is unclear. Published studies report mixed findings, and the study designs make these results difficult to interpret. As WBC is proposed as an aid to recovery in an athletic population, repeated measures of performance, muscle force production and pain are of importance to the athlete, however, are minimally reported in the literature. Cold water immersion (CWI) is widely used in an athletic setting for recovery, and has much literature supporting its use for the reduction of pain post-exercise. Well-designed RCT’s with controlled exercise interventions targeting performance measures are needed, in particular comparison of WBC with CWI data is needed for evaluation

Sensitive SERS nanotags for use with 1550 nm (retina-safe) laser excitation

Chalcogenopyrylium nanotags demonstrate an unprecedented SERS performance with a retina safe, 1550 nm laser excitation. These unique nanotags consisting of chalcogenopyrylium dyes and 100 nm gold nanoparticles produce exceptional SERS signals with picomolar detection limits obtained at this extremely red-shifted and eye-safe laser excitation

Grist: Grid-based Data Mining for Astronomy

The Grist project is developing a grid-technology based system as a research environment for astronomy with massive and complex datasets. This knowledge extraction system will consist of a library of distributed grid services controlled by a work ow system, compliant with standards emerging from the grid computing, web services, and virtual observatory communities. This new technology is being used to find high redshift quasars, study peculiar variable objects, search for transients in real time, and fit SDSS QSO spectra to measure black hole masses. Grist services are also a component of the "hyperatlas" project to serve high-resolution multi-wavelength imagery over the Internet. In support of these science and outreach objectives, the Grist framework will provide the enabling fabric to tie together distributed grid services in the areas of data access, federation, mining, subsetting, source extraction, image mosaicking, statistics, and visualization