Absence of \u3ci\u3esodA\u3c/i\u3e Increases the Levels of Oxidation of Key Metabolic Determinants of \u3ci\u3eBorrelia burgdorferi\u3c/i\u3e

Borrelia burgdorferi, the causative agent of Lyme disease, alters its gene expression in response to environmental signals unique to its tick vector or vertebrate hosts. B. burgdorferi carries one superoxide dismutase gene (sodA) capable of controlling intracellular superoxide levels. Previously, sodA was shown to be essential for infection of B. burgdorferi in the C3H/HeN model of Lyme disease. We employed two-dimensional electrophoresis (2-DE) and immunoblot analysis with antibodies specific to carbonylated proteins to identify targets that were differentially oxidized in the soluble fractions of the sodA mutant compared to its isogenic parental control strain following treatment with an endogenous superoxide generator, methyl viologen (MV, paraquat). HPLC-ESI-MS/MS analysis of oxidized proteins revealed that several proteins of the glycolytic pathway (BB0057, BB0020, BB0348) exhibited increased carbonylation in the sodA mutant treated with MV. Levels of ATP and NAD/NADH were reduced in the sodA mutant compared with the parental strain following treatment with MV and could be attributed to increased levels of oxidation of proteins of the glycolytic pathway. In addition, a chaperone, HtpG (BB0560), and outer surface protein A (OspA, BBA15) were also observed to be oxidized in the sodA mutant. Immunoblot analysis revealed reduced levels of Outer surface protein C (OspC), Decorin binding protein A (DbpA), fibronectin binding protein (BBK32), RpoS and BosR in the sodA mutant compared to the control strains. Viable sodA mutant spirochetes could not be recovered from both gp91/phox−⁄− and iNOS deficient mice while borrelial DNA was detected in multiple tissues samples from infected mice at significantly lower levels compared to the parental strain. Taken together, these observations indicate that the increased oxidation of select borrelial determinants and reduced levels of critical pathogenesis-associated lipoproteins contribute to the in vivo deficit of the sodA mutant in the mouse model of Lyme disease. This study, utilizing the sodA mutant, has provided insights into adaptive capabilities critical for survival of B. burgdorferi in its hosts

Modulation of substrate adhesion dynamics via microtubule targeting requires kinesin-1

Recent studies have shown that the targeting of substrate adhesions by microtubules promotes adhesion site disassembly (Kaverina, I., O. Krylyshkina, and J.V. Small. 1999. J. Cell Biol. 146:1033–1043). It was accordingly suggested that microtubules serve to convey a signal to adhesion sites to modulate their turnover. Because microtubule motors would be the most likely candidates for effecting signal transmission, we have investigated the consequence of blocking microtubule motor activity on adhesion site dynamics. Using a function-blocking antibody as well as dynamitin overexpression, we found that a block in dynein–cargo interaction induced no change in adhesion site dynamics in Xenopus fibroblasts. In comparison, a block of kinesin-1 activity, either via microinjection of the SUK-4 antibody or of a kinesin-1 heavy chain construct mutated in the motor domain, induced a dramatic increase in the size and reduction in number of substrate adhesions, mimicking the effect observed after microtubule disruption by nocodazole. Blockage of kinesin activity had no influence on either the ability of microtubules to target substrate adhesions or on microtubule polymerisation dynamics. We conclude that conventional kinesin is not required for the guidance of microtubules into substrate adhesions, but is required for the focal delivery of a component(s) that retards their growth or promotes their disassembly

Threats to seabirds: A global assessment

We present the first objective quantitative assessment of the threats to all 359 species of seabirds, identify the main challenges facing them, and outline priority actions for their conservation. We applied the standardised Threats Classification Scheme developed for the IUCN Red List to objectively assess threats to each species and analysed the data according to global IUCN threat status, taxonomic group, and primary foraging habitat (coastal or pelagic). The top three threats to seabirds in terms of number of species affected and average impact are: invasive alien species, affecting 165 species across all the most threatened groups; bycatch in fisheries, affecting fewer species (100) but with the greatest average impact; and climate change/severe weather, affecting 96 species. Overfishing, hunting/trapping and disturbance were also identified as major threats to seabirds. Reversing the top three threats alone would benefit two-thirds of all species and c. 380 million individual seabirds (c. 45% of the total global seabird population). Most seabirds (c. 70%), especially globally threatened species, face multiple threats. For albatrosses, petrels and penguins in particular (the three most threatened groups of seabirds), it is essential to tackle both terrestrial and marine threats to reverse declines. As the negative effects of climate change are harder to mitigate, it is vital to compensate by addressing other major threats that often affect the same species, such as invasive alien species, bycatch and overfishing, for which proven solutions exist

Absence of sodA Increases the Levels of Oxidation of Key Metabolic Determinants of Borrelia burgdorferi

Borrelia burgdorferi, the causative agent of Lyme disease, alters its gene expression in response to environmental signals unique to its tick vector or vertebrate hosts. B. burgdorferi carries one superoxide dismutase gene (sodA) capable of controlling intracellular superoxide levels. Previously, sodA was shown to be essential for infection of B. burgdorferi in the C3H/HeN model of Lyme disease. We employed two-dimensional electrophoresis (2-DE) and immunoblot analysis with antibodies specific to carbonylated proteins to identify targets that were differentially oxidized in the soluble fractions of the sodA mutant compared to its isogenic parental control strain following treatment with an endogenous superoxide generator, methyl viologen (MV, paraquat). HPLC-ESI-MS/MS analysis of oxidized proteins revealed that several proteins of the glycolytic pathway (BB0057, BB0020, BB0348) exhibited increased carbonylation in the sodA mutant treated with MV. Levels of ATP and NAD/NADH were reduced in the sodA mutant compared with the parental strain following treatment with MV and could be attributed to increased levels of oxidation of proteins of the glycolytic pathway. In addition, a chaperone, HtpG (BB0560), and outer surface protein A (OspA, BBA15) were also observed to be oxidized in the sodA mutant. Immunoblot analysis revealed reduced levels of Outer surface protein C (OspC), Decorin binding protein A (DbpA), fibronectin binding protein (BBK32), RpoS and BosR in the sodA mutant compared to the control strains. Viable sodA mutant spirochetes could not be recovered from both gp91/phox-⁄- and iNOS deficient mice while borrelial DNA was detected in multiple tissues samples from infected mice at significantly lower levels compared to the parental strain. Taken together, these observations indicate that the increased oxidation of select borrelial determinants and reduced levels of critical pathogenesis-associated lipoproteins contribute to the in vivo deficit of the sodA mutant in the mouse model of Lyme disease. This study, utilizing the sodA mutant, has provided insights into adaptive capabilities critical for survival of B. burgdorferi in its hosts

Using globally threatened pelagic birds to identify priority sites for marine conservation in the South Atlantic Ocean

The Convention on Biological Diversity aspires to designate 10% of the global oceans as Marine Protected Areas (MPAs), but so far, few MPAs protect pelagic species in the high seas. Transparent scientific approaches are needed to ensure that these encompass areas with high biodiversity value. Here we used the distribution of all globally threatened seabirds breeding in a centrally located archipelago (Tristan da Cunha) to provide guidance on where MPAs could be established in the South Atlantic Ocean. We combined year-round tracking data from six species, and used the systematic conservation-planning tool, 'Zonation', to delineate areas that would protect the largest proportion of each population. The areas used most intensively varied among species and seasons. Combining the sites used by all six species suggested that the most important areas of the South Atlantic are located south of South Africa, around the central South Atlantic between 30 degrees S and 55 degrees S, and near South America. We estimated that the longline fishing effort in these intensively used areas is around 11 million hooks on average each year, highlighting the need for improved monitoring of seabird bycatch rates and the enforcement of compliance with bird bycatch mitigation requirements by fisheries. There was no overlap between the identified areas and any of the existing MPAs in the South Atlantic. The conservation of these highly mobile, pelagic species cannot be achieved by single countries, but requires a multi-national approach at an ocean-basin scale, such as an agreement for the conservation of biodiversity beyond national jurisdiction under the United Nation Convention on the Law of the Sea

High-Redshift QSOs in the SWIRE Survey and the z~3 QSO Luminosity Function

We use a simple optical/infrared (IR) photometric selection of high-redshift QSOs that identifies a Lyman Break in the optical photometry and requires a red IR color to distinguish QSOs from common interlopers. The search yields 100 z~3 (U-dropout) QSO candidates with 19<r'<22 over 11.7 deg^2 in the ELAIS-N1 (EN1) and ELAIS-N2 (EN2) fields of the Spitzer Wide-area Infrared Extragalactic (SWIRE) Legacy Survey. The z~3 selection is reliable, with spectroscopic follow-up of 10 candidates confirming they are all QSOs at 2.83<z<3.44. We find that our z~4$ (g'-dropout) sample suffers from both unreliability and incompleteness but present 7 previously unidentified QSOs at 3.50<z<3.89. Detailed simulations show our z~3 completeness to be ~80-90% from 3.0<z<3.5, significantly better than the ~30-80% completeness of the SDSS at these redshifts. The resulting luminosity function extends two magnitudes fainter than SDSS and has a faint end slope of beta=-1.42 +- 0.15, consistent with values measured at lower redshift. Therefore, we see no evidence for evolution of the faint end slope of the QSO luminosity function. Including the SDSS QSO sample, we have now directly measured the space density of QSOs responsible for ~70% of the QSO UV luminosity density at z~3. We derive a maximum rate of HI photoionization from QSOs at z~3.2, Gamma = 4.8x10^-13 s^-1, about half of the total rate inferred through studies of the Ly-alpha forest. Therefore, star-forming galaxies and QSOs must contribute comparably to the photoionization of HI in the intergalactic medium at z~3.Comment: Accepted for publication in ApJ. emulateapj format. 23 pages, 17 figure

Anesthesia of Epinephelus marginatus with essential oil of Aloysia polystachya: an approach on blood parameters

This study investigated the anesthetic potential of the essential oil (EO) of Aloysia polystachya in juveniles of dusky grouper (Epinephelus marginatus). Fish were exposed to different concentrations of EO of A. polystachya to evaluate time of induction and recovery from anesthesia. In the second experiment, fish were divided into four groups: control, ethanol and 50 or 300 mu L L-1 EO of A. polystachya, and each group was submitted to induction for 3.5 min and recovery for 5 or 10 min. The blood gases and glucose levels showed alterations as a function of the recovery times, but Na+ and K+ levels did not show any alteration. In conclusion, the EO from leaves of A. polystachya is an effective anesthetic for dusky grouper, because anesthesia was reached within the recommended time at EO concentrations of 300 and 400 mu L L-1. However, most evaluated blood parameters showed compensatory responses due to EO exposure.Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul/Programa de Apoio a Nucleos de Excelencia (FAPERGS/PRONEX) [10/0016-8]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [470964/2009-0]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (CAPES)info:eu-repo/semantics/publishedVersio

Association of angiotensin-converting enzyme inhibitor therapy and comorbidity in diabetes: results from the Vermont diabetes information system

<p>Abstract</p> <p>Background</p> <p>Angiotensin converting enzyme inhibitors (ACE inhibitors) reduce peripheral vascular resistance via blockage of angiotensin converting enzyme (ACE). ACE inhibitors are commonly used to treat congestive heart failure and high blood pressure, but other effects have been reported. In this study, we explored the association between ACE inhibitor therapy and the prevalence of comorbid conditions in adults with diabetes</p> <p>Methods</p> <p>We surveyed 1003 adults with diabetes randomly selected from community practices. Patients were interviewed at home and self-reported their personal and clinical characteristics including comorbidity. Current medications were obtained by direct observation of medication containers. We built logistic regression models with the history of comorbidities as the outcome variable and the current use of ACE inhibitors as the primary predictor variable. We adjusted for possible confounding by social (age, sex, alcohol drinking, cigarette smoking) and clinical factors (systolic blood pressure, body mass index (BMI), glycosolated hemoglobin (A1C), number of comorbid conditions, and number of prescription medications).</p> <p>Results</p> <p>ACE users reported a history of any cancer (except the non-life-threatening skin cancers) less frequently than non-users (10% <it>vs</it>. 15%; odd ratio = 0.59; 95% confidence interval [0.39, 0.89]; <it>P </it>= 0.01); and a history of stomach ulcers or peptic ulcer disease less frequently than non-users (12% <it>vs</it>. 16%, odd ratio = 0.70, [0.49, 1.01], <it>P </it>= 0.06). After correcting for potential confounders, ACE inhibitors remained significantly inversely associated with a personal history of cancer (odds ratio = 0.59, [0.39, 0.89]; <it>P </it>= 0.01) and peptic ulcer disease (odd ratio = 0.68, [0.46, 1.00], <it>P </it>= 0.05).</p> <p>Conclusion</p> <p>ACE inhibitor use is associated with a lower likelihood of a history of cancer and peptic ulcers in patients with diabetes. These findings are limited by the cross sectional study design, self-report of comorbid diagnoses, and lack of information on the timing and duration of ACE inhibitor use. Further research is needed to confirm these associations and understand their mechanisms.</p

Self-management support interventions to reduce health care utilisation without compromising outcomes: a systematic review and meta-analysis

Background: There is increasing interest in the role of �self-management� interventions to support the management of long-term conditions in health service settings. Self-management may include patient education, support for decision-making, self-monitoring and psychological and social support. Self-management support has potential to improve the efficiency of health services by reducing other forms of utilisation (such as primary care or hospital use), but a shift to self-management may lead to negative outcomes, such as patients who feel more anxious about their health, are less able to cope, or who receive worse quality of care, all of which may impact on their health and quality of life. We sought to determine which models of self-management support are associated with significant reductions in health services utilisation without compromising outcomes among patients with long-term conditions. Methods: We used systematic review with meta-analysis. We included randomised controlled trials in patients with long-term conditions which included self-management support interventions and reported measures of service utilisation or costs, as well as measures of health outcomes (standardized disease specific quality of life, generic quality of life, or depression/anxiety).We searched multiple databases (CENTRAL, CINAHL, Econlit, EMBASE, HEED, MEDLINE, NHS EED and PsycINFO) and the reference lists of published reviews. We calculated effects sizes for both outcomes and costs, and presented the results in permutation plots, as well as conventional meta-analyses. Results: We included 184 studies. Self-management support was associated with small but significant improvements in health outcomes, with the best evidence of effectiveness in patients with diabetic, respiratory, cardiovascular and mental health conditions. Only a minority of self-management support interventions reported reductions in health care utilisation in association with decrements in health. Evidence for reductions in utilisation associated with self-management support was strongest in respiratory and cardiovascular problems. Studies at higher risk of bias were more likely to report benefits. Conclusions: Self-management support interventions can reduce health service utilization without compromising patient health outcomes, although effects were generally small, and the evidence was strongest in respiratory and cardiovascular disorders. Further work is needed to determine which components of self-management support are most effective

Changing foreign policy: the Obama Administration’s decision to oust Mubarak

This paper analyses the decision of the Obama administration to redirect its foreign policy towards Egypt in the wake of the Arab Spring. It attempts to highlight the issue of how governments deal with decision-making at times of crisis, and under which circumstances they take critical decisions that lead to major shifts in their foreign policy track record. It focuses on the process that led to a reassessment of US (United States) foreign policy, shifting from decades of support to the autocratic regime of Hosni Mubarak, towards backing his ouster. Specifically, the paper attempts to assess to what extent the decision to withdraw US support from a longstanding state-leader and ally in the Middle East can be seen as a foreign policy change (FPC). A relevant research question this paper pursues is: how can the withdrawal of US support to a regime considered as an ally be considered, in itself, as a radical FPC