Estimation of the subunit stoichiometry of the membrane-associated daptomycin oligomer by FRET

The final publication is available at Elsevier via http://doi.org/10.1016/j.bbamem.2012.02.019 © 2012. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Daptomycin is a lipopeptide antibiotic that kills Gram-positive bacteria by depolarizing their cell membranes. This antibacterial action of daptomycin is correlated with the formation of membrane-associated oligomers. We here examine the number of subunits contained in one oligomer using fluorescence resonance energy transfer (FRET). The results suggest that the oligomer contains approximately 6 to 7 subunits, or possibly twice this number if it spans both membrane monolayers.This work was supported by an NSERC operating grant to M. Palmer. J. Muraih was supported by a scholarship from the government of Iraq

mol2chemfig, a tool for rendering chemical structures from molfile or SMILES format to LATE X code

© 2012 Brefo-Mensah and Palmer; licensee Chemistry Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Brefo-Mensah, E. K., & Palmer, M. (2012). mol2chemfig, a tool for rendering chemical structures from molfile or SMILES format to LATE X code. Journal of Cheminformatics, 4(1), 24. https://doi.org/10.1186/1758-2946-4-24Displaying chemical structures in LATE X documents currently requires either hand-coding of the structures using one of several LATE X packages, or the inclusion of finished graphics files produced with an external drawing program. There is currently no software tool available to render the large number of structures available in molfile or SMILES format to LATE X source code. We here present mol2chemfig, a Python program that provides this capability. Its output is written in the syntax defined by the chemfig TE X package, which allows for the flexible and concise description of chemical structures and reaction mechanisms. The program is freely available both through a web interface and for local installation on the user’s computer

Mapping and explaining the productivity of Pinus radiata in New Zealand

Mapping Pinus radiata productivity for New Zealand not only provides useful information for forest owners, industry stakeholders and policy managers, but also enables current and future plantations to be visualised, quantified, and planned. Using an extensive set of permanent sample plots, split into fitting (n = 1,146) and validation (n = 618) datasets, models of P. radiata 300 Index (an index of volume mean annual increment) and Site Index (an index of height growth) were developed using a regression kriging technique. Spatial predictions were accurate and accounted for 61% and 70% of the variance for 300 Index and Site Index, respectively. Productivity predicted from these surfaces for the entire plantation estate averaged 27.4 m³ ha⁻¹ yr⁻¹ for the 300 Index and 30.4 m for Site Index. Surfaces showed wide regional variation in this productivity, which was attributable mainly to variation in air temperature and root-zone water storage from site to site

Report to the California Public Utilities Commission Regarding Ex Parte Communications and Related Practices

Part I contains the analysis of existing law. We review the statutes and regulations governing ex parte communications before the CPUC, examine corresponding laws of other jurisdictions, and compare the CPUC statutes and regulations with those of the other jurisdictions. In Part II we examine actual ex parte practices before the CPUC. Based on data obtained from notices filed on the Commission’s website by parties to rate-setting cases, we provide a quantitative characterization of the extent and nature of noticed ex parte communications over the past roughly 22 years. We then place ex parte communications within the context of the CPUC’s proceedings. Part III provides the results of an interview process we undertook to hear the experiences and opinions of people with a stake or an interest in CPUC decision-making, including representatives of regulated utilities, intervenor groups who generally (but not always) appear in CPUC rate-setting cases in opposition to the positions of utilities, companies and industry groups who generally oppose specific utilities’ positions, legislators and legislative staff, public critics of CPUC ex parte practices, CPUC staff (administrative law judges (ALJs), attorneys, and technical staff), and the CPUC Commissioners and their staffs. Then, in Part IV, we present our analysis of this information and our recommendations for changes to statutes, CPUC rules, and Commission practices

Characterization of daptomycin oligomerization with perylene excimer fluorescence: Stoichiometric binding of phosphatidylglycerol triggers oligomer formation

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.bbamem.2011.10.027 © 2012. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Daptomycin is a lipopeptide antibiotic that binds to and depolarizes bacterial cell membranes. Its antibacterial activity requires calcium and correlates with the content of phosphatidylglycerol in the target membrane. Daptomycin has been shown to form oligomers on liposome membranes. We here use perylene excimer fluorescence to further characterize the membrane-associated oligomer. To this end, the N-terminal fatty acyl chain was replaced with perylene-butanoic acid. The perylene derivative retains one third of the antibacterial activity of native daptomycin. On liposomes containing phosphatidylcholine and phosphatidylglycerol, as well as on Bacillus subtilis cells, the perylene-labeled daptomycin forms excimers, which shows that the N-terminal acyl chains of neighboring oligomer subunits are in immediate contact with one another. In a lipid bicelle system, oligomer formation can be titrated with stoichiometric amounts of phosphatidylglycerol. Therefore, the interaction of daptomycin with a single molecule of phosphatidylglycerol is sufficient to trigger daptomycin oligomerization.NSERC operating grants to M. Palmer and S. D. Taylor. || J. Muraih was supported by a scholarship from the government of Ira

Stagnation Point Radiative Heating Relations for Venus Entry

Improved analytic expressions for calculating the stagnation point radiative heating during entry into the atmosphere of Venus have been developed. These analytic expressions can be incorporated into entry trajectory simulation codes. Together with analytical expressions for convective heating at the stagnation point, the time-integrated total heat load at the stagnation point is used in determining the thickness of protective material required, and hence the mass of the fore body heatshield of uniform thickness

Alignment of patient and primary care practice member perspectives of chronic illness care: a cross-sectional analysis

Polly H. Noel and Luci K. Leykum are with the South Texas Veterans Health Care System, 7400 Merton Minter Blvd, San Antonio, TX 78229, USA -- Polly H. Noel, Ray F. Palmer, Raquel L. Romero, Luci K. Leykum, Holly J. Lanham, and Krista W. Bowers are with the Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229, USA -- Michael L. Parchman is with the MacColl Center for Healthcare Innovation, Group Health Research Institute, Group Health Cooperative, 1730 Minor Ave 1600, Seattle, WA 98101, USA -- Holly J. Leykum is with the The McCombs School of Business, The University of Texas at Austin, 2110 Speedway, Stop B6000, Austin, TX 78712, USA -- John E. Zeber is with the Central Texas Veterans Health Care System, 1901 S. 1st St, Temple, TX 76504, USA and Scott and White Healthcare Center for Applied Health Research, 2401 S. 31st St, Temple, TX 76508, USABackground: Little is known as to whether primary care teams’ perceptions of how well they have implemented the Chronic Care Model (CCM) corresponds with their patients’ own experience of chronic illness care. We examined the extent to which practice members’ perceptions of how well they organized to deliver care consistent with the CCM were associated with their patients’ perceptions of the chronic illness care they have received. Methods: Analysis of baseline measures from a cluster randomized controlled trial testing a practice facilitation intervention to implement the CCM in small, community-based primary care practices. All practice “members” (i.e., physician providers, non-physician providers, and staff) completed the Assessment of Chronic Illness Care (ACIC) survey and adult patients with 1 or more chronic illnesses completed the Patient Assessment of Chronic Illness Care (PACIC) questionnaire. Results: Two sets of hierarchical linear regression models accounting for nesting of practice members (N = 283) and patients (N = 1,769) within 39 practices assessed the association between practice member perspectives of CCM implementation (ACIC scores) and patients’ perspectives of CCM (PACIC). ACIC summary score was not significantly associated with PACIC summary score or most of PACIC subscale scores, but four of the ACIC subscales were consistently associated with PACIC summary score and the majority of PACIC subscale scores after controlling for patient characteristics. The magnitude of the coefficients, however, indicates that the level of association is weak. Conclusions: The ACIC and PACIC scales appear to provide complementary and relatively unique assessments of how well clinical services are aligned with the CCM. Our findings underscore the importance of assessing both patient and practice member perspectives when evaluating quality of chronic illness care.Information, Risk, and Operations Management (IROM)[email protected]

Daptomycin forms cation- and size-selective pores in model membranes

The final publication is available at Elsevier via http://doi.org/10.1016/j.bbamem.2014.05.014 © 2014. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Daptomycin is a lipopeptide antibiotic that is used clinically to treat severe infections caused by Gram-positive bacteria. Its bactericidal action involves the calcium-dependent binding to membranes containing phosphatidylglycerol, followed by the formation of membrane-associated oligomers. Bacterial cells exposed to daptomycin undergo membrane depolarization, suggesting the formation of channels or pores in the target membranes. We here used a liposome model to detect and characterize the permeability properties of the daptomycin pores. The pores are selective for cations, with permeabilities being highest for Na+, K+, and other alkali metal ions. The permeability is approximately twice lower for Mg++, and lower again for the organic cations choline and hexamethonium. Anions are excluded, as is the zwitterion cysteine. These observations account for the observed depolarization of bacterial cells by daptomycin and suggest that under typical in vivo conditions depolarization is mainly due to sodium influx.CHRP grant to M. Palmer by NSERC and CIHR (CHRP398954-2011

The Number Systems Tower

For high school and college instructors and students, this paper connects number systems, field axioms, and polynomials. It also considers other properties such as cardinality, density, subset, and superset relationships. Additional aspects of this paper include gains and losses through sequences of number systems. The paper ends with a great number of activities for classroom use

Achievement of combined goals of low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol with three different statins: Results from VOYAGER

AbstractBackgroundGuidelines suggest that the combination of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) is the most clinically relevant goal for lipid-lowering treatments.MethodsData from VOYAGER, an individual patient data meta-analysis including 32,258 patients from 37 clinical trials, was used to determine the percentage of patients reaching combined goals of LDL-C and non-HDL-C following treatment with simvastatin, atorvastatin, or rosuvastatin. Paired comparisons were made between each dose of rosuvastatin and the same or higher doses of simvastatin and atorvastatin.ResultsEach dose of rosuvastatin brought significantly more patients to the combined goal of LDL-C < 100 mg/dL and non-HDL-C < 130 mg/dL than the same or double dose of atorvastatin; atorvastatin 80 mg was significantly superior to rosuvastatin 10 mg (all p < 0.001). Each dose of rosuvastatin helped significantly more patients reach the combined goal than any dose of simvastatin (all p < 0.001), except for rosuvastatin 10 mg versus simvastatin 80 mg (non-significant). Also, each dose of rosuvastatin helped significantly more patients to reach the combined goal of LDL-C < 70 mg/dL and non-HDL-C < 100 mg/dL than the same or double dose of atorvastatin (all p < 0.001). Every dose of rosuvastatin was significantly superior to all doses of simvastatin (all p ≤ 0.020), except for rosuvastatin 10 mg versus simvastatin 40 mg and 80 mg (non-significant).ConclusionsPhysicians' choice of statin and dose is important in helping patients achieve the combined LDL-C and non-HDL-C goals recommended in established guidelines