Exploitation of the menshutkin reaction for the controlled assembly of halogen bonded architectures incorporating 1,2-diiodotetrafluorobenzene and 1,3,5-Triiodotrifluorobenzene

1,4-Diazabicyclo[2.2.2]octane (DABCO) forms well-defined co-crystals with 1,2-diiodotetrafluorobenzene (1,2-DITFB), [(1,2-DITFB)2DABCO], and 1,3,5-triiodotrifluorobenzene, [(1,3,5-TITFB)2DABCO]. Both systems exhibited lower-than-expected supramolecular connectivity, which inspired a search for polymorphs in alternative crystallization solvents. In dichloromethane solution, the Menshutkin reaction was found to occur, generating chloride anions and quaternary ammonium cations through the reaction between the solvent and DABCO. The controlled in situ production of chloride ions facilitated the crystallization of new halogen bonded networks, DABCO–CH2Cl[(1,2-DITFB)Cl] (zigzag X-bonded chains) and (DABCO–CH2Cl)3[(1,3,5-TITFB)2Cl3]·CHCl3 (2D pseudo-trigonal X-bonded nets displaying Borremean entanglement), propagating with charge-assisted C–I···Cl– halogen bonds. The method was found to be versatile, and substitution of DABCO with triethylamine (TEA) gave (TEA-CH2Cl)3[(1,2-DITFB)Cl3]·4(H2O) (mixed halogen bond hydrogen bond network with 2D supramolecular connectivity) and TEA-CH2Cl[(1,3,5-TITFB)Cl] (tightly packed planar trigonal nets). The co-crystals were typically produced in high yield and purity with relatively predictable supramolecular topology, particularly with respect to the connectivity of the iodobenzene molecules. The potential to use this synthetic methodology for crystal engineering of halogen bonded architectures is demonstrated and discussed.

Host-pathogen checkpoints and population bottlenecks in persistent and intracellular uropathogenic Escherichia coli bladder infection

Bladder infections affect millions of people yearly, and recurrent symptomatic infections (cystitis) are very common. The rapid increase in infections caused by multidrug-resistant uropathogens threatens to make recurrent cystitis an increasingly troubling public health concern. Uropathogenic Escherichia coli (UPEC) cause the vast majority of bladder infections. Upon entry into the lower urinary tract, UPEC face obstacles to colonization that constitute population bottlenecks, reducing diversity, and selecting for fit clones. A critical mucosal barrier to bladder infection is the epithelium (urothelium). UPEC bypass this barrier when they invade urothelial cells and form intracellular bacterial communities (IBCs), a process which requires type 1 pili. IBCs are transient in nature, occurring primarily during acute infection. Chronic bladder infection is common and can be either latent, in the form of the quiescent intracellular reservoir (QIR), or active, in the form of asymptomatic bacteriuria (ASB/ABU) or chronic cystitis. In mice, the fate of bladder infection, QIR, ASB, or chronic cystitis, is determined within the first 24 h of infection and constitutes a putative host–pathogen mucosal checkpoint that contributes to susceptibility to recurrent cystitis. Knowledge of these checkpoints and bottlenecks is critical for our understanding of bladder infection and efforts to devise novel therapeutic strategies.

Predicting structural disruption of proteins caused by crossover

We present a machine learning model that predicts a structural disruption score from a protein s primary structure. SCHEMA was introduced by Frances Arnold and colleagues as a method for determining putative recombination sites of a protein on the basis of the full (PDB) description of its structure. The present method provides an alternative to SCHEMA that is able to determine the same score from sequence data only. Circumventing the need for resolving the full structure enables the exploration of yet unresolved and even hypothetical sequences for protein design efforts. Deriving the SCHEMA score from a primary structure is achieved using a two step approach: first predicting a secondary structure from the sequence and then predicting the SCHEMA score from the predicted secondary structure. The correlation coefficient for the prediction is 0.88 and indicates the feasibility of replacing SCHEMA with little loss of precision.

Running shoes increase Achilles tendon load in walking : an acoustic propagation study

Background: Footwear remains a prime candidate for the prevention and rehabilitation of Achilles tendinopathy as it is thought to decrease tension in the tendon through elevation of the heel. However, evidence for this effect is equivocal. Purpose: This study used an acoustic transmission technique to investigate the effect of running shoes on Achilles tendon loading during barefoot and shod walking. Methods: Acoustic velocity was measured in the Achilles tendon of twelve recreationally–active males (age, 31±9 years; height, 1.78±0.06 m; weight, 81.0±16.9 kg) during barefoot and shod walking at matched self–selected speed (3.4±0.7 km/h). Standard running shoes incorporating a 10– mm heel offset were used. Vertical ground reaction force and spatiotemporal parameters were determined with an instrumented treadmill. Axial acoustic velocity in the Achilles tendon was measured using a custom built ultrasonic device. All data were acquired at a rate of 100 Hz during 10s of steady–state walking. Statistical comparisons between barefoot and shod conditions were made using paired t–tests and repeated measure ANOVAs. Results: Acoustic velocity in the Achilles tendon was highly reproducible and was typified by two maxima (P1, P2) and minima (M1, M2) during walking. Footwear resulted in a significant increase in step length, stance duration and peak vertical ground reaction force compared to barefoot walking. Peak acoustic velocity in the Achilles tendon (P1, P2) was significantly higher with running shoes. Conclusions: Peak acoustic velocity in the Achilles tendon was higher with footwear, suggesting that standard running shoes with a 10–mm heel offset increase tensile load in the Achilles tendon. Although further research is required, these findings question the therapeutic role of standard running shoes in Achilles tendinopathy.

Facile dearomatisation of porphyrins using palladium-catalysed hydrazination: the 5,15-diiminoporphodimethenes and their redox products

The synthesis, electronic absorption and 1H NMR spectra of a suite of novel porphyrinoids derived from meso-bromoporphyrins by palladium-catalysed aminations using ethyl and tert-butylcarbazates are reported. Instead of the expected carbazate-substituted porphyrins, a facile oxidative dearomatisation of the porphyrin ring occurs in high yield, especially for the nickel(II) complexes, resulting in high yields of 5,15-diiminoporphodimethenes (DIPDs). The analogous zinc(II) and free base DIPDs were also characterised, the former by X-ray crystallography. The oxidation and reduction reactions of DIPDs and their precursor carbazate porphyrins were studied. Density Functional Theory (DFT) was used to calculate the optimised geometries and frontier molecular orbitals of DIPD Ni8c and bis(azocarboxylate) 19c, and Time Dependent DFT calculations allowed the prediction of electronic absorption spectra, whose characteristics corresponded well with those of the observed solution spectra. In the latter case, the calculated low-energy absorptions were unlike those of a typical porphyrin, due to the near-degeneracy of the highest filled frontier orbitals, and the wide energy separation between the unfilled orbitals. This feature was present in the observed spectrum.

Ecosystem management along ephemeral rivers: Trading off socio-economic water supply and vegetation conservation under flood regime uncertainty

In ecosystems driven by water availability, plant community dynamics depend on complex interactions between vegetation, hydrology, and human water resources use. Along ephemeral rivers—where water availability is erratic—vegetation and people are particularly vulnerable to changes in each other's water use. Sensible management requires that water supply be maintained for people, while preserving ecosystem health. Meeting such requirements is challenging because of the unpredictable water availability. We applied information gap decision theory to an ecohydrological system model of the Kuiseb River environment in Namibia. Our aim was to identify the robustness of ecosystem and water management strategies to uncertainties in future flood regimes along ephemeral rivers. We evaluated the trade-offs between alternative performance criteria and their robustness to uncertainty to account for both (i) human demands for water supply and (ii) reducing the risk of species extinction caused by water mining. Increasing uncertainty of flood regime parameters reduced the performance under both objectives. Remarkably, the ecological objective (species coexistence) was more sensitive to uncertainty than the water supply objective. However, within each objective, the relative performance of different management strategies was insensitive to uncertainty. The ‘best’ management strategy was one that is tuned to the competitive species interactions in the Kuiseb environment. It regulates the biomass of the strongest competitor and, thus, at the same time decreases transpiration, thereby increasing groundwater storage and reducing pressure on less dominant species. This robust mutually acceptable strategy enables species persistence without markedly reducing the water supply for humans. This study emphasises the utility of ecohydrological models for resource management of water-controlled ecosystems. Although trade-offs were identified between alternative performance criteria and their robustness to uncertain future flood regimes, management strategies were identified that help to secure an ecologically sustainable water supply.

The Wzy O-antigen polymerase of Yersinia pseudotuberculosis O:2a has a dependence on the Wzz chain-length determinant for efficient polymerization

Lipopolysaccharide is a major immunogenic structure for the pathogen Yersinia pseudotuberculosis, which contains the O-specific polysaccharide (OPS) that is presented on the cell surface. The OPS contains many repeats of the oligosaccharide O-unit and exhibits a preferred modal chain length that has been shown to be crucial for cell protection in Yersinia. It is well established that the Wzz protein determines the preferred chain length of the OPS, and in its absence, the polymerization of O units by the Wzy polymerase is uncontrolled. However, for Y. pseudotuberculosis, a wzz mutation has never been described. In this study, we examine the effect of Wzz loss in Y. pseudotuberculosis serotype O:2a and compare the lipopolysaccharide chain-length profile to that of Escherichia coli serotype O111. In the absence of Wzz, the lipopolysaccharides of the two species showed significant differences in Wzy polymerization. Yersinia pseudotuberculosis O:2a exhibited only OPS with very short chain lengths, which is atypical of wzz-mutant phenotypes that have been observed for other species. We hypothesise that the Wzy polymerase of Y. pseudotuberculosis O:2a has a unique default activity in the absence of the Wzz, revealing the requirement of Wzz to drive O-unit polymerization to greater lengths.

Robots, the internet and teaching history in the age of the NBN and the Australian curriculum

Have you ever wished you were Doctor Who and could pop yourself and your students into a Tardis and teleport them to an historical event or to meet a historical figure? We all know that unfortunately time travel is not (yet) possible, but maybe student and teacher teleportation just might be – sort of. Over the past few centuries and in lieu of time travel our communities have developed museums as a means of experiencing some of our history...

Discovering future disaster management capability needs using scenario planning

In recent years disaster risk reduction efforts have focused on disturbances ranging from climate variability, seismic hazards, geo-political instability and public and animal health crises. These factors combined with uncertainty derived from inter-dependencies within and across systems of critical infrastructure create significant problems of governance for the private and public sector alike. The potential for rapid spread of impacts, geographically and virtually, can render a comprehensive understanding of disaster response and recovery needs and risk mitigation issues beyond the grasp of competent authority. Because of such cascading effects communities and governments at local and state-levels are unlikely to face single incidents but rather series of systemic impacts: often appearing concurrently. A further point to note is that both natural and technological hazards can act directly on socio-technical systems as well as being propagated by them: as network events. Such events have been categorised as ‘outside of the box,’ ‘too fast,’ and ‘too strange’ (Lagadec, 2004). Emergent complexities in linked systems can make disaster effects difficult to anticipate and recovery efforts difficult to plan for. Beyond the uncertainties of real world disasters, that might be called familiar or even regular, can we safely assume that the generic capability we use now will suit future disaster contexts? This paper presents initial scoping of research funded by the Bushfire and Natural Hazards Cooperative Research Centre seeking to define future capability needs of disaster management organisations. It explores challenges to anticipating the needs of representative agencies and groups active in before, during and after phases of emergency and disaster situations using capability deficit assessments and scenario assessment.

Medically-attended respiratory illnesses amongst pregnant women in Brisbane, Australia

There are limited community-based data on the burden of influenza and influenza-like illnesses during pregnancy to inform disease surveillance and control. We aimed to determine the incidence of medically-attended respiratory illnesses (MARI) in pregnant women and the proportion of women who are tested for respiratory pathogens at these visits. We conducted a nested retrospective cohort study of a non-random sample of women aged ≥18 years who had a live birth in maternity units in Brisbane, Queensland, from March 2012 to October 2014. The primary outcomes were self-reported doctor visits for MARI and laboratory investigations for respiratory pathogens. Descriptive analyses were performed. Among 1202 participants, 222 (18.5%, 95%CI 16.3%-20.7%) self-reported MARI during their pregnancy. Of those with an MARI, 20.3% (45/222) self-reported a laboratory test was performed. We were able to confirm with health service providers that 46.7% (21/45) of tests were undertaken, responses from providers were not received for the remainder. Whilst one in five women in this population reported a MARI in pregnancy, only 3.7% (45/1202) reported a clinical specimen had been arranged at the consultation and the ability to validate that self-report was problematic. As the focus on maternal immunisation increases, ascertainment of the aetiological agent causing MARI in this population will be required and efficient and reliable methods for obtaining those data at the community level need to be established.

The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD)

Objective: To replicate and refine the reported association of ankylosing spondylitis (AS) with two nonsynonymous single nucleotide polymorphisms (nsSNPs) on chromosome 16q22.1. Methods: Firstly, 730 independent UK patients with AS were genotyped for rs9939768 and rs6979 and allele frequencies were compared with 2879 previously typed historic disease controls. Secondly, the two data sets were combined in meta-analyses. Finally, 5 tagging SNPs, located between rs9939768 and rs6979, were analysed in 1604 cases and 1020 controls. Results: The association of rs6979 with AS was replicated, p=0.03, OR=1.14 (95% CI 1.01 to 1.28), and a trend for association with rs9939768 detected, p=0.06, OR=1.25 (95% CI 0.99 to 1.57). Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31 (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768 and rs6979, respectively. New associations with rs9033 and rs868213 (p=0.00002, OR=1.23 (95% CI 1.12 to 1.36) and p=0.00002 OR=1.45 (95% CI 1.22 to 1.72), respectively, were identified. Conclusions: The region on chromosome 16 that has been replicated in the present work is interesting as the highly plausible candidate gene, tumour necrosis factor receptor type 1 (TNFR1)-associated death domain (TRADD), is located between rs9033 and rs868213. It will require additional work to identify the primary genetic association(s) with AS.