Uracil DNA glycosylase (UDG) activities in Bradyrhizobium diazoefficiens: characterization of a new class of UDG with broad substrate specificity

Repair of uracils in DNA is initiated by uracil DNA glycosylases (UDGs). Family 1 UDGs (Ung) are the most efficient and ubiquitous proteins having an exquisite specificity for uracils in DNA. Ung are characterized by motifs A (GQDPY) and B (HPSPLS) sequences. We report a novel dimeric UDG, Blr0248 (BdiUng) from Bradyrhizobium diazoefficiens. Although BdiUng contains the motif A (GQDPA), it has low sequence identity to known UDGs. BdiUng prefers single stranded DNA and excises uracil, 5-hydroxymethyl-uracil or xanthine from it. BdiUng is impervious to inhibition by AP DNA, and Ugi protein that specifically inhibits family 1 UDGs. Crystal structure of BdiUng shows similarity with the family 4 UDGs in its overall fold but with family 1 UDGs in key active site residues. However, instead of a classical motif B, BdiUng has a uniquely extended protrusion explaining the lack of Ugi inhibition. Structural and mutational analyses of BdiUng have revealed the basis for the accommodation of diverse substrates into its substrate binding pocket. Phylogenetically, BdiUng belongs to a new UDG family. Bradyrhizobium diazoefficiens presents a unique scenario where the presence of at least four families of UDGs may compensate for the absence of an efficient family 1 homologue

Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition

Cyclooxygenase-2 (COX-2), the prostaglandin (PG)-synthesizing enzyme overexpressed in colorectal cancer (CRC), has pleiotropic, cancer-promoting effects. COX-2 inhibitors (CIBs) interfere with many cancer-associated processes and show promising antineoplastic activity, however, a common mechanism of CIB action has not yet been established. We therefore investigated by microarray the global response towards the CIB APHS at a dose significantly inhibiting the growth of three COX-2-positive CRC but not of two COX-2-negative cell lines. None of the genes significantly (p = 0.005) affected by APHS were common to all three cell lines and 83% of the altered pathways were cell line-specific. Quantitative polymerase chain reaction (QPCR) on selected pathways confirmed cell line-specific expression alterations induced by APHS. A low stringency data analysis approach using BRB array tools coupled with QPCR, however, identified small expression changes shared by all COX-2-positive cell lines in genes related to the WNT pathway, the key driver of colonic carcinogenesis. Our data indicates a substantial cell line-specificity of APHS-induced expression alterations in CRC cells and helps to explain the divergent effects reported for CIBs. Further, the shared inhibition of the WNT pathway by APHS suggests one potential common mechanism behind the antineoplastic effects of COX-2 inhibition

Racial differences in user experiences and perceived value of electronic symptom monitoring in a cohort of black and white bladder and prostate cancer patients

Purpose: Electronic patient-reported outcomes (ePROs) are increasingly being used for symptom monitoring during routine cancer care, but have rarely been evaluated in diverse patient populations. We assessed ePRO user experiences and perceived value among Black and White cancer patients. Methods: We recruited 30 Black and 49 White bladder and prostate cancer patients from a single institution. Participants reported symptoms using either a web-based or automated telephone interface over 3 months and completed satisfaction surveys and qualitative interviews focused on user experiences and value. Using a narrative mixed methods approach, we evaluated overall and race-specific differences in ePRO user experiences and perceived value. Results: Most participants selected the web-based system, but Blacks were more likely to use the automated telephone-based system than Whites. In satisfaction surveys, Whites more commonly reported ease in understanding and reporting symptoms compared with Blacks. Blacks more often reported that the ePRO system was helpful in facilitating symptom-related discussions with clinicians. During interviews, Blacks described how the ePRO helped them recognize symptoms, while Whites found value in better understanding and tracking symptoms longitudinally. Blacks also expressed preferences for paper-based ePRO options due to perceived ease in better understanding of symptom items. Conclusion: Electronic patient-reported outcomes are perceived as valuable for variable reasons by Black and White cancer populations, with greater perceived value for communicating with clinicians reported among Blacks. To optimize equitable uptake of ePROs, oncology practices should offer several ePRO options (e.g., web-based, phone-based), as well as paper-based options, and consider the e-health literacy needs of patients during implementation

Surface critical behavior of random systems at the ordinary transition

We calculate the surface critical exponents of the ordinary transition occuring in semi-infinite, quenched dilute Ising-like systems. This is done by applying the field theoretic approach directly in d=3 dimensions up to the two-loop approximation, as well as in $d=4-\epsilon$ dimensions. At $d=4-\epsilon$ we extend, up to the next-to-leading order, the previous first-order results of the $\sqrt{\epsilon}$ expansion by Ohno and Okabe [Phys.Rev.B 46, 5917 (1992)]. In both cases the numerical estimates for surface exponents are computed using Pade approximants extrapolating the perturbation theory expansions. The obtained results indicate that the critical behavior of semi-infinite systems with quenched bulk disorder is characterized by the new set of surface critical exponents.Comment: 11 pages, 11 figure

Predicting the public health benefit of vaccinating cattle against Escherichia coli O157

Identifying the major sources of risk in disease transmission is key to designing effective controls. However, understanding of transmission dynamics across species boundaries is typically poor, making the design and evaluation of controls particularly challenging for zoonotic pathogens. One such global pathogen is Escherichia coli O157, which causes a serious and sometimes fatal gastrointestinal illness. Cattle are the main reservoir for E. coli O157, and vaccines for cattle now exist. However, adoption of vaccines is being delayed by conflicting responsibilities of veterinary and public health agencies, economic drivers, and because clinical trials cannot easily test interventions across species boundaries, lack of information on the public health benefits. Here, we examine transmission risk across the cattle–human species boundary and show three key results. First, supershedding of the pathogen by cattle is associated with the genetic marker stx2. Second, by quantifying the link between shedding density in cattle and human risk, we show that only the relatively rare supershedding events contribute significantly to human risk. Third, we show that this finding has profound consequences for the public health benefits of the cattle vaccine. A naïve evaluation based on efficacy in cattle would suggest a 50% reduction in risk; however, because the vaccine targets the major source of human risk, we predict a reduction in human cases of nearly 85%. By accounting for nonlinearities in transmission across the human–animal interface, we show that adoption of these vaccines by the livestock industry could prevent substantial numbers of human E. coli O157 cases

Few smooth d-polytopes with n lattice points

We prove that, for fixed n there exist only finitely many embeddings of Q-factorial toric varieties X into P^n that are induced by a complete linear system. The proof is based on a combinatorial result that for fixed nonnegative integers d and n, there are only finitely many smooth d-polytopes with n lattice points. We also enumerate all smooth 3-polytopes with at most 12 lattice points. In fact, it is sufficient to bound the singularities and the number of lattice points on edges to prove finiteness.Comment: 20+2 pages; major revision: new author, new structure, new result

Boundary critical behavior at m-axial Lifshitz points for a boundary plane parallel to the modulation axes

The critical behavior of semi-infinite $d$-dimensional systems with $n$-component order parameter $\bm{\phi}$ and short-range interactions is investigated at an $m$-axial bulk Lifshitz point whose wave-vector instability is isotropic in an $m$-dimensional subspace of $\mathbb{R}^d$. The associated $m$ modulation axes are presumed to be parallel to the surface, where $0\le m\le d-1$. An appropriate semi-infinite $|\bm{\phi}|^4$ model representing the corresponding universality classes of surface critical behavior is introduced. It is shown that the usual O(n) symmetric boundary term $\propto \bm{\phi}^2$ of the Hamiltonian must be supplemented by one of the form $\mathring{\lambda} \sum_{\alpha=1}^m(\partial\bm{\phi}/\partial x_\alpha)^2$ involving a dimensionless (renormalized) coupling constant $\lambda$. The implied boundary conditions are given, and the general form of the field-theoretic renormalization of the model below the upper critical dimension $d^*(m)=4+{m}/{2}$ is clarified. Fixed points describing the ordinary, special, and extraordinary transitions are identified and shown to be located at a nontrivial value $\lambda^*$ if $\epsilon\equiv d^*(m)-d>0$. The surface critical exponents of the ordinary transition are determined to second order in $\epsilon$. Extrapolations of these $\epsilon$ expansions yield values of these exponents for $d=3$ in good agreement with recent Monte Carlo results for the case of a uniaxial ($m=1$) Lifshitz point. The scaling dimension of the surface energy density is shown to be given exactly by $d+m (\theta-1)$, where $\theta=\nu_{l4}/\nu_{l2}$ is the anisotropy exponent.Comment: revtex4, 31 pages with eps-files for figures, uses texdraw to generate some graphs; to appear in PRB; v2: some references and additional remarks added, labeling in figure 1 and some typos correcte

An argument for the use of Aristotelian method in bioethics

The main claim of this paper is that the method outlined and used in Aristotle's Ethics is an appropriate and credible one to use in bioethics. Here “appropriate” means that the method is capable of establishing claims and developing concepts in bioethics and “credible” that the method has some plausibility, it is not open to obvious and immediate objection. It begins by suggesting why this claim matters and then gives a brief outline of Aristotle's method. The main argument is made in three stages. First, it is argued that Aristotelian method is credible because it compares favourably with alternatives. In this section it is shown that Aristotelian method is not vulnerable to criticisms that are made both of methods that give a primary place to moral theory (such as utilitarianism) and those that eschew moral theory (such as casuistry and social science approaches). As such, it compares favourably with these other approaches that are vulnerable to at least some of these criticisms. Second, the appropriateness of Aristotelian method is indicated through outlining how it would deal with a particular case. Finally, it is argued that the success of Aristotle's philosophy is suggestive of both the credibility and appropriateness of his method.</p

High-quality permanent draft genome sequence of the Parapiptadenia rigida-nodulating Burkholderia sp. strain UYPR1.413

Burkholderia sp. strain UYPR1.413 is an aerobic, motile, Gram-negative, non-spore-forming rod that was isolated from a root nodule of Parapiptadenia rigida collected at the Angico plantation, Mandiyu, Uruguay, in December 2006. A survey of symbionts of P. rigida in Uruguay demonstrated that this species is nodulated predominantly by Burkholderia microsymbionts. Moreover, Burkholderia sp. strain UYPR1.413 is a highly efficient nitrogen fixing symbiont with this host. Currently, the only other sequenced isolate to fix with this host is Cupriavidus sp. UYPR2.512. Therefore, Burkholderia sp. strain UYPR1.413 was selected for sequencing on the basis of its environmental and agricultural relevance to issues in global carbon cycling, alternative energy production, and biogeochemical importance, and is part of the GEBA-RNB project. Here we describe the features of Burkholderia sp. strain UYPR1.413, together with sequence and annotation. The 10,373,764 bp high-quality permanent draft genome is arranged in 336 scaffolds of 342 contigs, contains 9759 protein-coding genes and 77 RNA-only encoding genes