Ureteropelvic junction obstruction caused by metastatic cholangiocarcinoma

We describe the rare case of a 61-year-old female with right ureteropelvic junction (UPJ) obstruction caused by metastatic cholangiocarcinoma. Her past medical history was notable for cholangiocarcinoma treated with neoadjuvant chemoradiation and two orthotopic liver transplants six years earlier. Urology was consulted when she presented with flank pain and urinary tract infection. Diagnostic workup demonstrated right UPJ obstruction. She was managed acutely with percutaneous nephrostomy. She subsequently underwent robotic pyeloplasty and intrinsic obstruction of the UPJ was discovered. Histological examination revealed adenocarcinoma, consistent with systemic recurrence of the patient\u27s known cholangiocarcinoma

The Stac Fada “impact ejecta” layer: not what it seems

The Stac Fada Member (SFM) forms part of the Stoer Group of the Torridonian of NW Scotland. The SFM is unique in the Torridonian, being characterized by the presence of greenish altered glass clasts. Its origin has been debated for decades with several hypotheses being proposed but all invoking some connection with volcanic activity in the region. More recently, Amor et al. suggested that the SFM represents “a chord section through the continuous ejecta blanket surrounding an impact crater”. Here, we confirm the presence of shocked material within the SFM and then discuss its origin

Advanced Methods for Spatial Analysis of Bioaerosol Long-Range Transport Processes

Research on bioaerosol is still in its infancy. The dynamics and, therefore, the effects on atmospheric processes and the biosphere are often underestimated, or have not yet been sufficiently investigated. Atmospheric models such as FLEXPART and HYSPLIT enable researchers to simulate the transport of particles in the atmosphere and provide information on where air-parcels originate from. In the following, we present two methods for combining results of these models with spatial information, e.g., about vegetation. The first method shows how spatial CORINE land cover distribution can be analyzed within the boundaries of HYSPLIT trajectories. In a second method, FLEXPART simulations are used in combination with COSMO rain data and tree maps to generate maps that indicate the potential origin of bioaerosol for selected periods of time

The mesoproterozoic Stac Fada Member, NW Scotland : an impact origin confirmed but refined

Funding to GRO from the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant program and the Canadian Space Agency (CSA) Canadian Analogue Research Network and Field Investigation programs is gratefully acknowledged. Part of LF’s work was supported by the Department of Foreign Affairs and International Trade (DFAIT), Government of Canada.The origin of the Stac Fada Member has been debated for decades with several early hypotheses being proposed, but all invoking some connection to volcanic activity. In 2008, the discovery of shocked quartz led to the hypothesis that the Stac Fada Member represents part the continuous ejecta blanket of a meteorite impact crater, the location of which was, and remains, unknown. In this paper, we confirm the presence of shock-metamorphosed and -melted material in the Stac Fada Member; however, we also show that its properties are unlike any other confirmed and well documented proximal impact ejecta deposits on Earth. Instead, the properties of the Stac Fada Member are most similar to the Onaping Formation of the Sudbury impact structure (Canada) and impact melt-bearing breccias from the Chicxulub impact structure (Mexico). We thus propose that, like the Sudbury and Chicxulub deposits, Melt Fuel Coolant Interactions – akin to what occur during phreatomagmatic volcanic eruptions – played a fundamental role in the origin of the Stac Fada Member. We conclude that these rocks are not primary impact ejecta but instead were deposited beyond the extent of the continuous ejecta blanket as high-energy ground-hugging sediment gravity flows.PostprintPeer reviewe

The prosequence of procaricain forms an α-helical domain that prevents access to the substrate-binding cleft

AbstractBackground Cysteine proteases are involved in a variety of cellular processes including cartilage degradation in arthritis, the progression of Alzheimer's disease and cancer invasion: these enzymes are therefore of immense biological importance. Caricain is the most basic of the cysteine proteases found in the latex of Carica papaya. It is a member of the papain superfamily and is homologous to other plant and animal cysteine proteases. Caricain is naturally expressed as an inactive zymogen called procaricain. The inactive form of the protease contains an inhibitory proregion which consists of an additional 106 N-terminal amino acids; the proregion is removed upon activation.Results The crystal structure of procaricain has been refined to 3.2 å resolution; the final model consists of three non-crystallographically related molecules. The proregion of caricain forms a separate globular domain which binds to the C-terminal domain of mature caricain. The proregion also contains an extended polypeptide chain which runs through the substrate-binding cleft, in the opposite direction to that of the substrate, and connects to the N terminus of the mature region. The mature region does not undergo any conformational change on activation.Conclusions We conclude that the rate-limiting step in the in vitro activation of procaricain is the dissociation of the prodomain, which is then followed by proteolytic cleavage of the extended polypeptide chain of the proregion. The prodomain provides a stable scaffold which may facilitate the folding of the C-terminal lobe of procaricain

An interpretation of fluctuations in enzyme catalysis rate, spectral diffusion, and radiative component of lifetimes in terms of electric field fluctuations

Time-dependent fluctuations in the catalysis rate ({delta}k(t)) observed in single-enzyme experiments were found in a particular study to have an autocorrelation function decaying on the same time scale as that of spectral diffusion {delta}{omega}0(t). To interpret this similarity, the present analysis focuses on a factor in enzyme catalysis, the local electrostatic interaction energy (E) at the active site and its effect on the activation free energy barrier. We consider the slow fluctuations of the electrostatic interaction energy ({delta}E(t)) as a contributor to {delta}k(t) and relate the latter to {delta}{omega}0(t). The resulting relation between {delta}k(t) and {delta}{omega}0(t) is a dynamic analog of the solvatochromism used in interpreting solvent effects on organic reaction rates. The effect of the postulated {delta}E(t) on fluctuations in the radiative component ({delta}{gamma}Formula(t)) of the fluorescence decay of chromophores in proteins also is examined, and a relation between {delta}{gamma}Formula(t) and {delta}{omega}0(t) is obtained. Experimental tests will determine whether the correlation functions for {delta}k(t), {delta}{omega}0(t), and {delta}{gamma}Formula are indeed similar for any enzyme. Measurements of dielectric dispersion, {varepsilon}({omega}), for the enzyme discussed elsewhere will provide further insight into the correlation function for {delta}E(t). They also will determine whether fluctuations in the nonradiative component {gamma}Formula of the lifetime decay has a different origin, fluctuations in distance for example

Discrimination, labour markets and the Labour Market Prospects of Older Workers: What Can a Legal Case Teach us?

As governments become increasingly concerned about the fiscal implications of the ageing population, labour market policies have sought to encourage mature workers to remain in the labour force. The ‘human capital’ discourses motivating these policies rest on the assumption that older workers armed with motivation and vocational skills will be able to return to fulfilling work. This paper uses the post-redundancy recruitment experiences of former Ansett Airlines flight attendants to develop a critique of these expectations. It suggests that policies to increase older workers’ labour market participation will not succeed while persistent socially constructed age- and gender- typing shape labour demand. The conclusion argues for policies sensitive to the institutional structures that shape employer preferences, the competitive rationality of discriminatory practices, and the irresolvable tension between workers’ human rights and employers’ property rights

The enhancing of a cysteine proteinase activity at acidic pH by protein engineering, the role of glutamic 50 in the enzyme mechanism of caricain

AbstractCarica papaya produces four cysteine proteinases. Calculations show that the Cys25, His159 essential ion pair is fully ionised at pH 2.99, where activity cannot be detected, but apparently an additional ionisation with a pKa of 4 is essential for activity (an electrostatic switch). Caricain (EC 3.4.22.30) wt and D158E genetic backgrounds were used to study the contribution of E50A to activity. E50 or E135 are candidates for the switch, E50A would be expected to reduce activity. However, activity increased at pH 5.0 in both backgrounds and at the pH optimum in D158E E50A but decreased slightly in the wt background. This challenges the hypothesis of an electrostatic switch

Species Richness, rRNA Gene Abundance, and Seasonal Dynamics of Airborne Plant-Pathogenic Oomycetes

Oomycetes, also named Peronosporomycetes, are one of the most important and widespread groups of plant pathogens, leading to significant losses in the global agricultural productivity. They have been studied extensively in ground water, soil, and host plants, but their atmospheric transport vector is not well characterized. In this study, the occurrence of airborne Oomycetes was investigated by Sanger sequencing and quantitative PCR of coarse and fine aerosol particle samples (57 filter pairs) collected over a 1-year period (2006–2007) and full seasonal cycle in Mainz, Germany. In coarse particulate matter, we found 55 different hypothetical species (OTUs), of which 54 were plant pathogens and 29 belonged to the genus Peronospora (downy mildews). In fine particulate matter (<3 μm), only one species of Hyaloperonospora was found in one sample. Principal coordinate analysis of the species composition revealed three community clusters with a dependence on ambient temperature. The abundance of Oomycetes rRNA genes was low in winter and enhanced during spring, summer, and fall, with a dominance of Phytophthora, reaching a maximum concentration of ∼1.6 × 106 rRNA genes per cubic meter of sampled air in summer. The presence and high concentration of rRNA genes in air suggests that atmospheric transport, which can lead to secondary infection, may be more important than currently estimated. This illustrates the need for more current and detailed datasets, as potential seasonal shifts due to changing meteorological conditions may influence the composition of airborne Oomycetes. An insight into the dynamics of airborne plant pathogens and their major drivers should be useful for improved forecasting and management of related plant diseases

FAD binding, cobinamide binding and active site communication in the corrin reductase (CobR)

Adenosylcobalamin, the coenzyme form of vitamin B12, is one Nature's most complex coenzyme whose de novo biogenesis proceeds along either an anaerobic or aerobic metabolic pathway. The aerobic synthesis involves reduction of the centrally chelated cobalt metal ion of the corrin ring from Co(II) to Co(I) before adenosylation can take place. A corrin reductase (CobR) enzyme has been identified as the likely agent to catalyse this reduction of the metal ion. Herein, we reveal how Brucella melitensis CobR binds its coenzyme FAD (flavin dinucleotide) and we also show that the enzyme can bind a corrin substrate consistent with its role in reduction of the cobalt of the corrin ring. Stopped-flow kinetics and EPR reveal a mechanistic asymmetry in CobR dimer that provides a potential link between the two electron reduction by NADH to the single electron reduction of Co(II) to Co(I)