4,861 research outputs found

    Disruption of the developmental programme of Trypanosoma brucei by genetic ablation of TbZFP1, a differentiation-enriched CCCH protein

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    The regulation of differentiation is particularly important in microbial eukaryotes that inhabit multiple environments. The parasite Trypanosoma brucei is an extreme example of this, requiring exquisite gene regulation during transmission from mammals to the tsetse fly vector. Unusually, trypanosomes rely almost exclusively on post-transcriptional mechanisms for regulated gene expression. Hence, RNA binding proteins are potentially of great significance in controlling stage-regulated processes. We have previously identified TbZFP1 as a trypanosome molecule transiently enriched during differentiation to tsetse midgut procyclic forms. This small protein (101 amino acids) contains the unusual CCCH zinc finger, an RNA binding motif. Here, we show that genetic ablation of TbZFP1 compromises repositioning of the mitochondrial genome, a specific event in the strictly regulated differentiation programme. Despite this, other events that occur both before and after this remain intact. Significantly, this phenotype correlates with the TbZFP1 expression profile during differentiation. This is the first genetic disruption of a developmental regulator in T. brucei. It demonstrates that programmed events in parasite development can be uncoupled at the molecular level. It also further supports the importance of CCCH proteins in key aspects of trypanosome cell function

    A PC parallel port button box provides millisecond response time accuracy under Linux

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    For psychologists, it is sometimes necessary to measure people's reaction times to the nearest millisecond. This article describes how to use the PC parallel port to receive signals from a button box to achieve millisecond response time accuracy. The workings of the parallel port, the corresponding port addresses, and a simple Linux program for controlling the port are described. A test of the speed and reliability of button box signal detection is reported. If the reader is moderately familiar with Linux, this article should provide sufficient instruction for him or her to build and test his or her own parallel port button box. This article also describes how the parallel port could be used to control an external apparatus

    Cytochrome oxidase subunit VI of Trypanosoma brucei is imported without a cleaved presequence and is developmentally regulated at both RNA and protein levels

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    Mitochondrial respiration in the African trypanosome undergoes dramatic developmental stage regulation. This requires co-ordinated control of components encoded by both the nuclear genome and the kinetoplast, the unusual mitochondrial genome of these parasites. As a model for understanding the co-ordination of these genomes, we have examined the regulation and mitochondrial import of a nuclear-encoded component of the cytochrome oxidase complex, cytochrome oxidase subunit VI (COXVI). By generating transgenic trypanosomes expressing intact or mutant forms of this protein, we demonstrate that COXVI is not imported using a conventional cleaved presequence and show that sequences at the N-terminus of the protein are necessary for correct mitochondrial sorting. Analyses of endogenous and transgenic COXVI mRNA and protein expression in parasites undergoing developmental stage differentiation demonstrates a temporal order of control involving regulation in the abundance of, first, mRNA and then protein. This represents the first dissection of the regulation and import of a nuclear-encoded protein into the cytochrome oxidase complex in these organisms, which were among the earliest eukaryotes to possess a mitochondrion

    NGO Coalitions and the Global Access to Medicines Campaign: the Impact of Intellectual Property Rights on Developing Countries

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    Matthews, NGO Coalitions and the Global Access to Medicines Campaign: The Impact of Intellectual Property Rights on Developing Countries, 2012, Palgrave Macmillan reproduced with permission of Palgrave Macmillan. This extract is taken from the author's original manuscript and has not been edited. The definitive, published, version of record is available here: http://www.palgrave.com/products/title.aspx?pid=491656 and http://www.palgraveconnect.com/pc/doifinder/10.1057/9781137284730

    Millisecond accuracy video display using OpenGL under Linux

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    To measure people’s reaction times to the nearest millisecond, it is necessary to know exactly when a stimulus is displayed. This article describes how to display stimuli with millisecond accuracy on a normal CRT monitor, using a PC running Linux. A simple C program is presented to illustrate how this may be done within X Windows using the OpenGL rendering system. A test of this system is reported that demonstrates that stimuli may be consistently displayed with millisecond accuracy. An algorithm is presented that allows the exact time of stimulus presentation to be deduced, even if there are relatively large errors in measuring the display time

    Frontmatter (Titlepage, Table of Contents, Author List, PC List, Reviewer List)

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    Front matter including table of contents, author list, PC list, and reviewer list

    Data for: Distinguishing cyanobacteria from algae in optically complex inland waters using a radiative transfer inversion algorithm

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    Ecolight-input-combined.xls Input for ecolight-s runs - biogeophysical and atmospheric parameters used for inversion algorithm and forward modelling.Biogeophysical parameters: Chla=chlorophyll conc mg/m3, PC = phycocyanin (mg/m3), TSS=suspended solids (g/m3), ISS=inorganic solids (g/m3), ag440=absorption by gelbstoff at 440nm(1/m),ap440=absorption by particulate matter at 440 nm (1/m), adp440=absorption by depigmentede matter at 440 nm(1/m), S = slope coefficient, Zsd = sechi disk depth (m). Atmospheric parameters: J = julian day, Lat & Lon = Latitude &longitude, GMT=greenwhich meridian time, Theta=solar zenith in degrees, pres=atm. pressure in inches mercury, am=air mass type, rh=rel humidity, wv=precipitable water vapour in cm, wsm = 24 hour mean sind speed (m/s), ws = wind speed (m/s), vis=visibility in km, ro3=ozone in Dobson units, AOT550 is aerosol optical thickness at 550 nm, cloud=cloud from 0-1, Wind dir in degrees (0 = N).Rrs_combined.xlsxRemote sensing reflectance measured using ASD Fieldspec 3 and methods of Meuller 2003 (Ocean optics protocols). Column headers correspond to sample numbers. First column is wavelength 350 to 999 nm. Data corresponds to Ecolight_inputs_combined.xls. Further details contained in files

    Identification and stage-specific association with the translational apparatus of TbZFP3, a CCCH protein that promotes trypanosome life-cycle development

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    The post-transcriptional control of gene expression is becoming increasingly important in the understanding of regulated events in eukaryotic cells. The parasitic kinetoplastids have a unique reliance on such processes, because their genome is organized into polycistronic transcription units in which adjacent genes are not coordinately regulated. Indeed, the number of RNA-binding proteins predicted to be encoded in the genome of kinetoplastids is unusually large, invoking the presence of unique RNA regulators dedicated to gene expression in these evolutionarily ancient organisms. Here, we report that a small CCCH zinc finger protein, TbZFP3, enhances development between life-cycle stages in Trypanosoma brucei. Moreover, we demonstrate that this protein interacts both with the translational machinery and with other small CCCH proteins previously implicated in trypanosome developmental control. Antibodies to this protein also co-immunoprecipitate EP procyclin mRNA and encode the major surface antigen of insect forms of T. brucei. Strikingly, although TbZFP3 is constitutively expressed, it exhibits developmentally regulated association with polyribosomes, and mutational analysis demonstrates that this association is essential for the expression of phenotype. TbZFP3 is therefore a novel regulator of developmental events in kinetoplastids that acts at the level of the post-transcriptional control of gene expression
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