A General Synthesis of Tris-Indole Derivatives as Potential Iron Chelators

The development of a novel route for the synthesis of a new class of compounds is described. The first tripodal, tris-indole amines are prepared by straightforward routes

Incorporating Virtually Immersive Environments as a Collaborative Medium for Virtual Teaming

Virtually immersive environments incorporate the use of various computer modelling and simulation techniques enabling geographically dispersed virtual project teams to interact within an artificially projected three-dimensional space online. This study focused on adoption of virtually immersive technologies as a collaborative media to support virtual teaming of both graduate and undergraduate-level project management students. The data and information from this study has implications for educators using virtually immersive environments in the classroom. In this study, we specifically evaluated two key components in this paper: 1) students' level of trust and; 2) students' willingness to use the technology, along with their belief about the virtual environment's ability to extend and improve knowledge sharing in their team work environment. We learned that while students did find the environment a positive add on for working collaboratively, there were students who were neither more nor less likely to use the technology for future collaborative ventures. Most of the students who were not very positive about the environment were “fence sitters” likely indicating needs related to additional training to improve communication skills. Finally, based on the full study results we have provided basic recommendations designed to support team trust building in the system along with interpersonal trust building to facilitate knowledge transfer and better strategic us of the technology

An evaluation of genotyping by sequencing (GBS) to map the <em>Breviaristatum-e (ari-e)</em> locus in cultivated barley

ABSTRACT: We explored the use of genotyping by sequencing (GBS) on a recombinant inbred line population (GPMx) derived from a cross between the two-rowed barley cultivar ‘Golden Promise’ (ari-e.GP/Vrs1) and the six-rowed cultivar ‘Morex’ (Ari-e/vrs1) to map plant height. We identified three Quantitative Trait Loci (QTL), the first in a region encompassing the spike architecture gene Vrs1 on chromosome 2H, the second in an uncharacterised centromeric region on chromosome 3H, and the third in a region of chromosome 5H coinciding with the previously described dwarfing gene Breviaristatum-e (Ari-e). BACKGROUND: Barley cultivars in North-western Europe largely contain either of two dwarfing genes; Denso on chromosome 3H, a presumed ortholog of the rice green revolution gene OsSd1, or Breviaristatum-e (ari-e) on chromosome 5H. A recessive mutant allele of the latter gene, ari-e.GP, was introduced into cultivation via the cv. ‘Golden Promise’ that was a favourite of the Scottish malt whisky industry for many years and is still used in agriculture today. RESULTS: Using GBS mapping data and phenotypic measurements we show that ari-e.GP maps to a small genetic interval on chromosome 5H and that alternative alleles at a region encompassing Vrs1 on 2H along with a region on chromosome 3H also influence plant height. The location of Ari-e is supported by analysis of near-isogenic lines containing different ari-e alleles. We explored use of the GBS to populate the region with sequence contigs from the recently released physically and genetically integrated barley genome sequence assembly as a step towards Ari-e gene identification. CONCLUSIONS: GBS was an effective and relatively low-cost approach to rapidly construct a genetic map of the GPMx population that was suitable for genetic analysis of row type and height traits, allowing us to precisely position ari-e.GP on chromosome 5H. Mapping resolution was lower than we anticipated. We found the GBS data more complex to analyse than other data types but it did directly provide linked SNP markers for subsequent higher resolution genetic analysis

The distinct features of microbial 'dysbiosis' of Crohn's disease do not occur to the same extent in their unaffected, genetically linked kindred

Background/Aims: Studying the gut microbiota in unaffected relatives of people with Crohn’s disease (CD) may advance our understanding of the role of bacteria in disease aetiology. Methods: Faecal microbiota composition (16S rRNA gene sequencing), genetic functional capacity (shotgun metagenomics) and faecal short chain fatty acids (SCFA) were compared in unaffected adult relatives of CD children (CDR, n = 17) and adult healthy controls, unrelated to CD patients (HUC, n = 14). The microbiota characteristics of 19 CD children were used as a benchmark of CD ‘dysbiosis’. Results: The CDR microbiota was less diverse (p = 0.044) than that of the HUC group. Local contribution of β-diversity analysis showed no difference in community structure between the CDR and HUC groups. Twenty one of 1,243 (1.8%) operational taxonomic units discriminated CDR from HUC. The metagenomic functional capacity (p = 0.207) and SCFA concentration or pattern were similar between CDR and HUC (p&#62;0.05 for all SCFA). None of the KEGG metabolic pathways were different between these two groups. Both of these groups (HUC and CDR) had a higher microbiota α-diversity (CDR, p = 0.026 and HUC, p&#60;0.001) with a community structure (β-diversity) distinct from that of children with CD. Conclusions: While some alterations were observed, a distinct microbial ‘dysbiosis’, characteristic of CD patients, was not observed in their unaffected, genetically linked kindred

A Natural Plasmid Uniquely Encodes Two Biosynthetic Pathways Creating a Potent Anti-MRSA Antibiotic

Background Understanding how complex antibiotics are synthesised by their producer bacteria is essential for creation of new families of bioactive compounds. Thiomarinols, produced by marine bacteria belonging to the genus Pseudoalteromonas, are hybrids of two independently active species: the pseudomonic acid mixture, mupirocin, which is used clinically against MRSA, and the pyrrothine core of holomycin. Methodology/Principal Findings High throughput DNA sequencing of the complete genome of the producer bacterium revealed a novel 97 kb plasmid, pTML1, consisting almost entirely of two distinct gene clusters. Targeted gene knockouts confirmed the role of these clusters in biosynthesis of the two separate components, pseudomonic acid and the pyrrothine, and identified a putative amide synthetase that joins them together. Feeding mupirocin to a mutant unable to make the endogenous pseudomonic acid created a novel hybrid with the pyrrothine via “mutasynthesis” that allows inhibition of mupirocin-resistant isoleucyl-tRNA synthetase, the mupirocin target. A mutant defective in pyrrothine biosynthesis was also able to incorporate alternative amine substrates. Conclusions/Significance Plasmid pTML1 provides a paradigm for combining independent antibiotic biosynthetic pathways or using mutasynthesis to develop a new family of hybrid derivatives that may extend the effective use of mupirocin against MRSA

The Actinomyosin Motor Drives Malaria Parasite Red Blood Cell Invasion but Not Egress.

Apicomplexa are obligate intracellular parasites that actively invade, replicate within, and egress from host cells. The parasite actinomyosin-based molecular motor complex (often referred to as the glideosome) is considered an important mediator of parasite motility and virulence. Mature intracellular parasites often become motile just prior to egress from their host cells, and in some genera, this motility is important for successful egress as well as for subsequent invasion of new host cells. To determine whether actinomyosin-based motility is important in the red blood cell egress and invasion activities of the malaria parasite, we have used a conditional genetic approach to delete GAP45, a primary component of the glideosome, in asexual blood stages of Plasmodium falciparum Our results confirm the essential nature of GAP45 for invasion but show that P. falciparum does not require a functional motor complex to undergo egress from the red blood cell. Malarial egress therefore differs fundamentally from induced egress in the related apicomplexan Toxoplasma gondiiIMPORTANCE Clinical malaria results from cycles of replication of single-celled parasites of the genus Plasmodium in red blood cells. Intracellular parasite replication is followed by a highly regulated, protease-dependent process called egress, in which rupture of the bounding membranes allows explosive release of daughter merozoites which rapidly invade fresh red cells. A parasite actinomyosin-based molecular motor (the glideosome) has been proposed to provide the mechanical force to drive invasion. Studies of the related parasite Toxoplasma gondii have shown that induced egress requires parasite motility, mediated by a functional glideosome. However, whether the glideosome has a similar essential role in egress of malaria merozoites from red blood cells is unknown. Here, we show that although a functional glideosome is required for red blood cell invasion by Plasmodium falciparum merozoites, it is not required for egress. These findings place further emphasis on the key role of the protease cascade in malarial egress

Determining how polymer-bubble interactions impact algal separation using the novel "Posi"-dissolved air flotation process

The novel dissolved air flotation (DAF) process that uses hydrophobically-modified polymers (HMPs) to generate positively charged bubbles (PosiDAF) has been shown to separate negatively charged algal cells without the need for coagulation-flocculation. Previous research has been limited to HMPs of poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) and, while they were effective at bench-scale, performance at pilot-scale was better using commercial poly(N,N-diallyl-N,N-dimethylammonium chloride) (PDADMAC). Hence, the aim of this research was to compare the effectiveness of PDADMAC modified with aliphatic and aromatic moieties in comparison to previously tested PDMAEMA HMPs in respect to algal cell separation and minimisation of effluent polymer concentration, as well as defining the underlying polymer-bubble interaction mechanisms. Polymer-bubble adhesion properties were measured using atomic force microscopy (AFM) while polymer concentration was monitored via zeta potential and, where possible, assays using fluorescence spectroscopy. Both PDADMAC functionalised with a fluorinated aromatic group (PDADMAC-BCF) and PDMAEMA modified with 1-bromodecane respectively, gave effective cell separation, while the treated effluent zeta potential values at maximum cell removal were lower than the other polymers trialled. The effluent polymer concentration when using PDADMAC-BCF was four times lower in comparison to another aromatically modified PDADMAC polymer. AFM studies indicated that, in contrast to the PDMAEMA-based polymers, the PDADMAC-based polymers did not adsorb closely to the bubble surface. The different polymer-bubble interactions indicate that separation mechanisms will also vary, potentially leading to differences in process effectiveness when explored at pilot scale

A Methodology for Risk Assessment to Improve the Resilience and Sustainability of Critical Infrastructure with Case Studies from the United States Army

Reliable performance of energy and water infrastructure is central to the mission readiness of the United States Army. These systems are vulnerable to coordinated attacks from an adversary as well as disruption from natural events. The objectives of this work were to investigate Army installations in North America, identify best practices for improving the resilience and sustainability of critical energy and water infrastructure, and develop a framework and methodology for analyzing the resilience of an installation under varying outage scenarios. This work was accomplished using a multi-layered decision process to identify unique case studies from the 117 active-duty domestic Army installations. A framework for analyzing and assessing the resilience of an installation was then developed to help inform stakeholders. Metered energy and water data from buildings across Fort Benning, GA were curated to inform the modeling framework, including a discrete-event simulation of the supply and demand for energy and water on the installation using ProModel. This simulation was used to study the scale of solutions required to address outage events of varying frequency, duration, and magnitude, the combination of which is described as the severity of outages at a given site. This project helps develop a framework to inform how installations might meet Army Directive 2020-03, which states that installations must be able to sustain mission requirements for a minimum of 14 days after a disruption has occurred