Evolution and diversity of secretome genes in the apicomplexan parasite Theileria annulata

<b>BACKGROUND</b>: Little is known about how apicomplexan parasites have evolved to infect different host species and cell types. Theileria annulata and Theileria parva invade and transform bovine leukocytes but each species favours a different host cell lineage. Parasite-encoded proteins secreted from the intracellular macroschizont stage within the leukocyte represent a critical interface between host and pathogen systems. Genome sequencing has revealed that several Theileria-specific gene families encoding secreted proteins are positively selected at the inter-species level, indicating diversification between the species. We extend this analysis to the intra-species level, focusing on allelic diversity of two major secretome families. These families represent a well-characterised group of genes implicated in control of the host cell phenotype and a gene family of unknown function. To gain further insight into their evolution and function, this study investigates whether representative genes of these two families are diversifying or constrained within the T. annulata population. <b>RESULTS</b>: Strong evidence is provided that the sub-telomerically encoded SVSP family and the host-nucleus targeted TashAT family have evolved under contrasting pressures within natural T. annulata populations. SVSP genes were found to possess atypical codon usage and be evolving neutrally, with high levels of nucleotide substitutions and multiple indels. No evidence of geographical sub-structuring of allelic sequences was found. In contrast, TashAT family genes, implicated in control of host cell gene expression, are strongly conserved at the protein level and geographically sub-structured allelic sequences were identified among Tunisian and Turkish isolates. Although different copy numbers of DNA binding motifs were identified in alleles of TashAT proteins, motif periodicity was strongly maintained, implying conserved functional activity of these sites. <b>CONCLUSIONS</b>: This analysis provides evidence that two distinct secretome genes families have evolved under contrasting selective pressures. The data supports current hypotheses regarding the biological role of TashAT family proteins in the management of host cell phenotype that may have evolved to allow adaptation of T. annulata to a specific host cell lineage. We provide new evidence of extensive allelic diversity in representative members of the enigmatic SVSP gene family, which supports a putative role for the encoded products in subversion of the host immune response

Extremophiles and their application to veterinary medicine

<p/> <p>Extremophiles are organisms that can grow and thrive in harsh conditions, e.g., extremes of temperature, pH, salinity, radiation, pressure and oxygen tension. Thermophilic, halophilic and radiation-resistant organisms are all microbes, some of which are able to withstand multiple extremes. Psychrophiles, or cold-loving organisms, include not only microbes, but fish that live in polar waters and animals that can withstand freezing. Extremophiles are structurally adapted at a molecular level to withstand these conditions. Thermophiles have particularly stable proteins and cell membranes, psychrophiles have flexible cellular proteins and membranes and/or antifreeze proteins, salt-resistant halophiles contain compatible solutes or high concentrations of inorganic ions, and acidophiles and alkaliphiles are able to pump ions to keep their internal pH close to neutrality. Their interest to veterinary medicine resides in their capacity to be pathogenic, and as sources of enzymes and other molecules for diagnostic and pharmaceutical purposes. In particular, thermostable DNA polymerases are a mainstay of PCR-based diagnostics.</p

Development and Composition of the Warty Layer in Balsam Fir. I. Development

The deposition and ultrastructure of the warty layer in developing tracheids of balsam fir [Abies balsamea (L.) Mill.] were studied by means of transmission electron microscopy. The wart structure gradually was developed external to the plasma membrane after secondary wall deposition and the greater part of lignification were complete. Warts were synthesized first in the cell corners and pit cavities and then on the remainder of the cell walls. No cytoplasmic organelle was found to be associated specifically with wart formation. After the warty layer was elaborated, the cytoplasm disappeared from the cell, leaving no discernible trace of disorganized residue. The bulk of the wart structure exhibited staining properties similar to those of lignin. However, the basal portions of individual warts were sometimes less darkly stained than the outer portions, indicating possible heterogeneous composition

Development and Composition of the Warty Layer in Balsam Fir. II. Composition

From its response to various chemical, physical, fungal, and enzymatic treatments, it was concluded that the warty layer in balsam fir consisted largely of a ligninlike material that was visibly more resistant to extraction than a large fraction of other lignin in the fiber cell wall. Since the warts were the cell-wall component most accessible to the treatment solutions, it is probable that the material in the warty layer was more concentrated and condensed than lignin in other parts of the wall. Vacuum drying at 105 C appeared to condense the wart structure still further, making it even more resistant to most treatments. Gel filtration indicated that the warty layer was extracted as a high molecular weight material by certain treatments. The warty layer may act as a barrier that slows the penetration of liquids into the cell wall and thereby may cause different rates of delignification for different wood species. The basal component of individual warts and some of the accompanying encrustant on the inner surface of the cell wall were found to contain an amorphous carbohydrate, probably a pentosan or a pectic substance. Attempts at physical isolation of the warts were largely unsuccessful

Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands

Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-l, lymphoid-enhancer binding factor 1, and TATA-box binding protein. These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays. When used in combination, the polyamides inhibit virus replication by >99% in isolated human peripheral blood lymphocytes, with no detectable cell toxicity, The ability of small molecules to target predetermined DNA sequences located within RNA polymerase II promoters suggests a general approach for regulation of gene expression, as well as a mechanism for the inhibition of viral replication

Coupled Particle Transport and Pattern Formation in a Nonlinear Leaky-Box Model

Effects of particle-particle coupling on particle characteristics in nonlinear leaky-box type descriptions of the acceleration and transport of energetic particles in space plasmas are examined in the framework of a simple two-particle model based on the Fokker-Planck equation in momentum space. In this model, the two particles are assumed coupled via a common nonlinear source term. In analogy with a prototypical mathematical system of diffusion-driven instability, this work demonstrates that steady-state patterns with strong dependence on the magnetic turbulence but a rather weak one on the coupled particles attributes can emerge in solutions of a nonlinearly coupled leaky-box model. The insight gained from this simple model may be of wider use and significance to nonlinearly coupled leaky-box type descriptions in general

Effects of colour-coded compartmentalised syringe trays on anaesthetic drug error detection under cognitive load

oai:repository.derby.ac.uk:q4qv7Background Anaesthetic drug administration is complex, and typical clinical environments can entail significant cognitive load. Colour-coded anaesthetic drug trays have shown promising results for error identification and reducing cognitive load. Methods We used experimental psychology methods to test the potential benefits of colour-coded compartmentalised trays compared with conventional trays in a simulated visual search task. Effects of cognitive load were also explored through an accompanying working memory-based task. We hypothesised that colour-coded compartmentalised trays would improve drug-detection error, reduce search time, and reduce cognitive load. This comprised a cognitive load memory task presented alongside a visual search task to detect drug errors. Results All 53 participants completed 36 trials, which were counterbalanced across the two tray types and 18 different vignettes. There were 16 error-present and 20 error-absent trials, with 18 trials presented for each preloaded tray type. Syringe errors were detected more often in the colour-coded trays than in the conventional trays (91% vs 83%, respectively; P=0.006). In signal detection analysis, colour-coded trays resulted in more sensitivity to the error signal (2.28 vs 1.50, respectively; P<0.001). Confidence in response accuracy correlated more strongly with task performance for the colour-coded tray condition, indicating improved metacognitive sensitivity to task performance (r=0.696 vs r=0.447). Conclusions Colour coding and compartmentalisation enhanced visual search efficacy of drug trays. This is further evidence that introducing standardised colour-coded trays into operating theatres and procedural suites would add an additional layer of safety for anaesthetic procedures

Supporting public involvement in interview and other panels: a systematic review.

BACKGROUND: Members of the public are increasingly being invited to become members of a variety of different panels and boards. OBJECTIVE: This study aimed to systematically search the literature to identify studies relating to support or training provided to members of the public who are asked to be members of an interview panel. SEARCH STRATEGY: A systematic search for published and unpublished studies was carried out from June to September 2015. The search methods included electronic database searching, reference list screening, citation searching and scrutinizing online sources. INCLUSION CRITERIA: We included studies of any design including published and unpublished documents which outlined preparation or guidance relating to public participants who were members of interview panels or representatives on other types of panels or committees. DATA SYNTHESIS: Results were synthesised via narrative methods. MAIN RESULTS: Thirty-six documents were included in the review. Scrutiny of this literature highlighted ten areas which require consideration when including members of the public on interview panels: financial resources; clarity of role; role in the interview process; role in evaluation; training; orientation/induction; information needs; terminology; support; and other public representative needs such as timing, accessibility and support with information technology. DISCUSSION AND CONCLUSIONS: The results of the review emphasize a range of elements that need to be fully considered when planning the involvement of public participants on interview panels. It highlights potential issues relating to the degree of involvement of public representatives in evaluating/grading decisions and the need for preparation and on-going support