Partial (13)C isotopic enrichment of nucleoside monophosphates: useful reporters for NMR structural studies

Analysis of the (13)C isotopic labeling patterns of nucleoside monophosphates (NMPs) extracted from Escherichia coli grown in a mixture of C-1 and C-2 glucose is presented. By comparing our results to previous observations on amino acids grown in similar media, we have been able to rationalize the labeling pattern based on the well-known biochemistry of nucleotide biosynthesis. Except for a few notable absences of label (C4 in purines and C3′ in ribose) and one highly enriched site (C1′ in ribose), most carbons are randomly enriched at a low level (an average of 13%). These sparsely labeled NMPs give less complex NMR spectra than their fully isotopically labeled analogs due to the elimination of most (13)C–(13)C scalar couplings. The spectral simplicity is particularly advantageous when working in ordered systems, as illustrated with guanosine diphosphate (GDP) bound to ADP ribosylation factor 1 (ARF1) aligned in a liquid crystalline medium. In this system, the absence of scalar couplings and additional long-range dipolar couplings significantly enhances signal to noise and resolution

Combination Therapy with Ciprofloxacin plus Azlocillin against Pseudomonas aeruginosa: Effect of Simultaneous versus Staggered Administration in an In Vitro Model of Infection

The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv] every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two-compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin. These enhanced effects of the combination were corroborated by an increase in the peak and duration of bactericidal activity in the analogous "serum” compartment of the model. These data show the potential usefulness of simultaneous dosing of an antipseudomonal µ-lactam with ciprofloxacin against P. aeruginos

Urban Evolution: The Role of Water

The structure, function, and services of urban ecosystems evolve over time scales from seconds to centuries as Earth’s population grows, infrastructure ages, and sociopolitical values alter them. In order to systematically study changes over time, the concept of “urban evolution” was proposed. It allows urban planning, management, and restoration to move beyond reactive management to predictive management based on past observations of consistent patterns. Here, we define and review a glossary of core concepts for studying urban evolution, which includes the mechanisms of urban selective pressure and urban adaptation. Urban selective pressure is an environmental or societal driver contributing to urban adaptation. Urban adaptation is thesequential process by which an urban structure, function, or services becomes more fitted to its changing environment or human choices. The role of water is vital to driving urban evolution as demonstrated by historical changes in drainage, sewage flows, hydrologic pulses, and long-term chemistry. In the current paper, we show how hydrologic traits evolve across successive generations of urban ecosystems via shifts in selective pressures and adaptations over time. We explore multiple empirical examples including evolving: (1) urban drainage from stream burial to stormwater management; (2) sewage flows and water quality in response to wastewater treatment; (3) amplification of hydrologic pulses due to the interaction between urbanization and climate variability; and (4) salinization and alkalinization of fresh water due to human inputs and accelerated weathering. Finally, we propose a new conceptual model for the evolution of urban waters from the Industrial Revolution to the present day based on empirical trends and historical information. Ultimately, we propose that water itself is a critical driver of urban evolution that forces urban adaptation, which transforms the structure, function, and services of urban landscapes, waterways, and civilizations over time

Pharmacy Adherence Measures to Assess Adherence to Antiretroviral Therapy: Review of the Literature and Implications for Treatment Monitoring

Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medication possession ratio (MPR), pill count (PC), and pill pick-up (PPU). Data exist to recommend PAMs over self-reported adherence. PAMs consistently predicted patient outcomes, but additional studies are needed to determine the most predictive PAM parameters. Current evidence suggests that shorter duration of adherence assessment (≤6 months) and use of PAMs to predict future outcomes may be less accurate. PAMs which incorporate the number of days for which ART was prescribed without the counting of remnant pills, are reasonable minimum-resource methods to assess adherence to AR