Infinite stacking of alternating polyfluoroaryl rings and bromide anions

The crystal structure of 1-(4-bromo-2,3,5,6-tetrafluorophenyl)-3-benzylimidazolium bromide comprises columns of parallel bromotetrafluorophenyl rings with an interplanar distance of 6.936(6) Å separated by bromide anions

Isoprene oxidation by the gram-negative model bacterium variovorax sp. WS11

Plant-produced isoprene (2-methyl-1,3-butadiene) represents a significant portion of global volatile organic compound production, equaled only by methane. A metabolic pathway for the degradation of isoprene was first described for the Gram-positive bacterium Rhodococcus sp. AD45, and an alternative model organism has yet to be characterised. Here, we report the characterisation of a novel Gram-negative isoprene-degrading bacterium, Variovorax sp. WS11. Isoprene metabolism in this bacterium involves a plasmid-encoded iso metabolic gene cluster which differs from that found in Rhodococcus sp. AD45 in terms of organisation and regulation. Expression of iso metabolic genes is significantly upregulated by both isoprene and epoxyisoprene. The enzyme responsible for the initial oxidation of isoprene, isoprene monooxygenase, oxidises a wide range of alkene substrates in a manner which is strongly influenced by the presence of alkyl side-chains and differs from other well-characterised soluble diiron monooxygenases according to its response to alkyne inhibitors. This study presents Variovorax sp. WS11 as both a comparative and contrasting model organism for the study of isoprene metabolism in bacteria, aiding our understanding of the conservation of this biochemical pathway across diverse ecological niches

The Role of Harvey-ras in Mouse Skin Tumorigenesis

This thesis outlines two alternative approaches to investigating the role of H-ras in mouse skin tumour development. The first, the in vitro approach utilises a number of unique cell lines representative of a late stage of tumorigenesis, the conversion from a well differentiated squamous carcinoma to a undifferentiated spindle form. Through manipulation of the gene dosage ratio of mutant:normal H-ras in these cell lines, by plasmid transfection and virus infection, it was hoped to provide some clues as to the function of H-ras in this late stage transition event. The second approach involves the technique of gene targeting. The aim of this approach was to create a mouse hemizygous or completely deficient in H-ras and to examine the effects in the context of both chemical carcinogenesis studies and normal mouse development. Initial observations of the squamous/spindle transition event showed that the cell lines representative of both phenotypes were characteristically very different. The squamous cell line B9 produced a well differentiated tumour when injected into nude mice whereas the spindle cell lines A5 and D3 gave rise to aggressive, disorganised tumours with a much reduced latency. Genetic analysis of the cell lines showed that the most dramatic difference between the squamous and spindle derivatives was in the copy number and expression levels of H-ras. Both spindle cell lines A5 and D3 showed an approximate 5-10 fold increase in mutant H-ras, best explained by a genetic amplification mechanism. Experimentally overexpressing mutant H-ras in the squamous cells, and vice versa the levels of normal H-ras in the spindle variants, was unable to mimic the conversion event. However it was found that several A5 and D3 transfectant clones showed a dramatic reduction in tumorigenicity. This correlated not with the levels of the introduced normal H-ras but the absolute levels of endogenous mutant H-ras. Spontaneous loss of mutant copies of H-ras resulted in clones that morphologically resembled spindle cells yet produced tumours with a vastly increased latency period. It seems therefore that in this system mutant H-ras is the critical determinant of tumorigenicity, and relates perhaps to the growth of the tumour cell in vivo, possibly providing the driving force for the conversion. However, alteration of the H-ras gene dosage ratio was not in itself sufficient for the transition of a squamous to a spindle cell carcinoma, implying that another locus as yet unknown must play a role in controlling the epithelial phenotype. Finally, the gene targeting approach, provides a means to examining the earlier stages of mouse skin tumorigenesis, in particular the proposed role of normal H-ras in suppressing the development of papillomas from an initiated cell. For instance, if the consistent duplication of the chromosome carrying the mutant H-ras gene, seen in the development of papillomas, is related to overcoming a suppressive effect of normal H-ras, then carcinogen treatment of a mouse deficient in H-ras may result in a mouse more susceptible to tumorigenesis. Experiments with the gene targeting technique are on going and as yet no targeted ES cell clone has been isolated, but hope remains that this approach will provide new insights into the functions of H-ras both in early tumorigenesis and normal development

Rockets, Men and Medicine

Space Medicine has at last become an accepted entity in the vast field of medical research after many years of ridicule and scorn. The recent successes of the U .S.S.R. and U .S.A. in launching earth and sun satellites would seem adequate to justify the existence of space medicine. It seems Man's avowed intention to conquer the third dimension, the vertical, which leads to space and as such it is the duty of the medical scientist to make this journey as safe as possible for the would-be space traveller.Space is not a well defined region since it has no accurate topographical boundaries and in the context of this article the best way of defining space is to think in terms of levels of space equivalency, i.e. levels at which various protective functions of the Earth's atmosphere are lost so creating a space-like state for a certain phenomenon at a particular altitude. From the viewpoint of respiratory physiology space begins at a height of 52,500 feet since the effects of explosive decompression assume a constant value at and over this level. In similar terms the atmosphere acts as a filter against cosmic factors and this function of itself provides a variety of space equivalencies ranging from sea level in the case of infra-red rays, to 10-20 miles for cosmic primaries and as high as 75 miles for visible light. Space, therefore, is a concept which of necessity is a variable and its effects may be just as varied

Precipitation Hardenable High Temperature Shape Memory Alloy

A composition of the invention is a high temperature shape memory alloy having high work output, and is made from (Ni+Pt+Y),Ti(100-x) wherein x is present in a total amount of 49-55 atomic % Pt is present in a total amount of 10-30 atomic %, Y is one or more of Au, Pd. and Cu and is present in a total amount of 0 to 10 atomic %. The alloy has a matrix phase wherein the total concentration of Ni, Pt, and the one or more of Pd. Au, and Cu is greater than 50 atomic %

Precipitation-Strengthened, High-Temperature, High-Force Shape Memory Alloys

Shape memory alloys (SMAs) are an enabling component in the development of compact, lightweight, durable, high-force actuation systems particularly for use where hydraulics or electrical motors are not practical. However, commercial shape memory alloys based on NiTi are only suitable for applications near room temperature, due to their relatively low transformation temperatures, while many potential applications require higher temperature capability. Consequently, a family of (Ni,Pt)(sub 1-x)Ti(sub x) shape memory alloys with Ti concentrations ranging from about 15 to 25 at.% have been developed for applications in which there are requirements for SMA actuators to exert high forces at operating temperatures higher than those of conventional binary NiTi SMAs. These alloys can be heat treated in the range of 500 C to produce a series of fine precipitate phases that increase the strength of alloy while maintaining a high transformation temperature, even in Ti-lean compositions

Epstein Barr Virus Associated B-Cell Lymphomas and Iatrogenic Lymphoproliferative Disorders

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, affecting up to 90% of the population. EBV was first identified as an oncogenic virus in a Burkitt lymphoma cell line, though subsequently has been found to drive a variety of malignancies, including diffuse large B-cell lymphoma (DLBCL) and other lymphoma subtypes. EBV has a tropism for B-lymphocytes and has the unique ability to exist in a latent state, evading the host immune response. In cases of impaired cell mediated immunity, as in patients with advanced age or iatrogenic immune suppression, the virus is able to proliferate in an unregulated fashion, expressing viral antigens that predispose to transformation. EBV-positive DLBCL not otherwise specified, which has been included as a revised provisional entity in the 2016 WHO classification of lymphoid malignancies, is thought to commonly occur in older patients with immunosenescence. Similarly, it is well-established that iatrogenic immune suppression, occurring in both transplant and non-transplant settings, can predispose to EBV-driven lymphoproliferative disorders. EBV-positive lymphoproliferative disorders are heterogeneous, with variable clinical features and prognoses depending on the context in which they arise. While DLBCL is the most common subtype, other histologic variants, including Burkitt lymphoma, NK/T-cell lymphoma, and Hodgkin lymphoma can occur. Research aimed at understanding the underlying biology and disease prevention strategies in EBV-associated lymphoproliferative diseases are ongoing. Additionally, personalized treatment approaches, such as immunotherapy and adoptive T-cell therapies, have yielded encouraging results, though randomized trials are needed to further define optimal management

Sphingopyxis sp. Strain OPL5, an Isoprene-Degrading Bacterium from the Sphingomonadaceae Family Isolated from Oil Palm Leaves

The volatile secondary metabolite, isoprene, is released by trees to the atmosphere in enormous quantities, where it has important effects on air quality and climate. Oil palm trees, one of the highest isoprene emitters, are increasingly dominating agroforestry over large areas of Asia, with associated uncertainties over their effects on climate. Microbes capable of using isoprene as a source of carbon for growth have been identified in soils and in the tree phyllosphere, and most are members of the Actinobacteria. Here, we used DNA stable isotope probing to identify the isoprene-degrading bacteria associated with oil palm leaves and inhabiting the surrounding soil. Among the most abundant isoprene degraders of the leaf-associated community were members of the Sphingomonadales, although no representatives of this order were previously known to degrade isoprene. Informed by these data, we obtained representatives of the most abundant isoprene degraders in enrichments, including Sphingopyxis strain OPL5 (Sphingomonadales), able to grow on isoprene as the sole source of carbon and energy. Sequencing of the genome of strain OPL5, as well as a novel Gordonia strain, confirmed their pathways of isoprene degradation and broadened our knowledge of the genetic and taxonomic diversity of this important bacterial trait

Inhibition of ammonia monooxygenase from ammonia oxidising archaea by linear and aromatic alkynes

Ammonia monooxygenase (AMO) is a key nitrogen-transforming enzyme belonging to the same copper-dependent membrane monooxygenase family (CuMMO) as the particulate methane monooxygenase (pMMO). The AMO from ammonia-oxidizing archaea (AOA) is very divergent from both the AMO of ammonia-oxidizing bacteria (AOB) and the pMMO from methanotrophs, and little is known about the structure or substrate range of the archaeal AMO. This study compares inhibition by C 2 to C 8 linear 1-alkynes of AMO from two phylogenetically distinct strains of AOA, " Candidatus Nitrosocosmicus franklandus" C13 and " Candidatus Nitrosotalea sinensis" Nd2, with AMO from Nitrosomonas europaea and pMMO from Methylococcus capsulatus (Bath). An increased sensitivity of the archaeal AMO to short-chain-length alkynes (≤C 5) appeared to be conserved across AOA lineages. Similarities in C 2 to C 8 alkyne inhibition profiles between AMO from AOA and pMMO from M. capsulatus suggested that the archaeal AMO has a narrower substrate range than N. europaea AMO. Inhibition of AMO from " Ca Nitrosocosmicus franklandus" and N. europaea by the aromatic alkyne phenylacetylene was also investigated. Kinetic data revealed that the mechanisms by which phenylacetylene inhibits " Ca Nitrosocosmicus franklandus" and N. europaea are different, indicating differences in the AMO active site between AOA and AOB. Phenylacetylene was found to be a specific and irreversible inhibitor of AMO from " Ca Nitrosocosmicus franklandus," and it does not compete with NH 3 for binding at the active site. IMPORTANCE Archaeal and bacterial ammonia oxidizers (AOA and AOB, respectively) initiate nitrification by oxidizing ammonia to hydroxylamine, a reaction catalyzed by ammonia monooxygenase (AMO). AMO enzyme is difficult to purify in its active form, and its structure and biochemistry remain largely unexplored. The bacterial AMO and the closely related particulate methane monooxygenase (pMMO) have a broad range of hydrocarbon cooxidation substrates. This study provides insights into the AMO of previously unstudied archaeal genera, by comparing the response of the archaeal AMO, a bacterial AMO, and pMMO to inhibition by linear 1-alkynes and the aromatic alkyne, phenylacetylene. Reduced sensitivity to inhibition by larger alkynes suggests that the archaeal AMO has a narrower hydrocarbon substrate range than the bacterial AMO, as previously reported for other genera of AOA. Phenylacetylene inhibited the archaeal and bacterial AMOs at different thresholds and by different mechanisms of inhibition, highlighting structural differences between the two forms of monooxygenase

Water consumption, not expectancies about water consumption, affects cognitive performance in adults

Research has shown that water supplementation positively affects cognitive performance in children and adults. The present study considered whether this could be a result of expectancies that individuals have about the effects of water on cognition. Forty seven participants were recruited and told the study was examining the effects of repeated testing on cognitive performance. They were assigned either to a condition in which positive expectancies about the effects of drinking water were induced, or a control condition in which no expectancies were induced. Within these groups, approximately half were given a drink of water, while the remainder were not. Performance on a thirst scale, letter cancellation, digit span forwards and backwards and a simple reaction time task was assessed at baseline (before the drink) and 20 minutes and 40 minutes after water consumption. Effects of water, but not expectancy, were found on subjective thirst ratings and letter cancellation task performance, but not on digit span or reaction time. This suggests that water consumption effects on letter cancellation are due to the physiological effects of water, rather than expectancies about the effects of drinking water