Search

Structural and functional diversity among the aminoacyl-tRNA synthetases prevent infiltration of the genetic code by noncognate amino acids. To explore whether these same features distinguish the synthetases as potential sources of resistance against antibiotic amino acid analogues, we investigated bacterial growth inhibition by S-(2-aminoethyl)- l-cysteine (AEC). Wild-type lysyl-tRNA synthetase (LysRS) and a series of active site variants were screened for their ability to restore growth of an Escherichia coliLysRS null strain at increasing concentrations of AEC. While wild-type E. coligrowth is completely inhibited at 5 µM AEC, two LysRS variants, Y280F and F426W, provided substantial resistance and allowed E. colito grow in the presence of up to 1 mM AEC. Elevated resistance did not reflect changes in the kinetics of amino acid activation or tRNA Lysaminoacylation, which showed at best 4−6-fold improvements, but instead correlated with the binding affinity for AEC, which was decreased ∼50-fold in the LysRS variants. In addition to changes in LysRS, AEC resistance has also been attributed to mutations in the L box riboswitch, which regulates expression of the lysCgene, encoding aspartokinase. The Y280F and F426W LysRS mutants contained wild-type L box riboswitches that responded normally to AEC in vitro, indicating that LysRS is the primary cellular target of this antibiotic. These findings suggest that the AEC resistance conferred by L box mutations is an indirect effect resulting from derepression of lysCexpression and increased cellular pools of lysine, which results in more effective competition with AEC for binding to LysRS.

Sterically hindered fullerenyl chromophore dyad and triads, C60(>DPAF-C9)x(x 1 and 2, respectively), in an acceptor−donor (A−D) molecular linkage of C60-(keto-fluorene)xwere synthesized and fully characterized. Attachment of two 3,5,5-trimethylhexyl groups on C9of the fluorene ring moiety greatly improves their solubility and makes direct intermolecular aromatic stacking contacts more difficult. They are the firstseries of fullerene derivatives showing high three-photon absorptivity (3PA). Accordingly, C60(>DPAF-C9)2exhibits 2PA and 3PA cross sections in the values of 0.824 × 10-48cm4s (or 82.4 GM) and 6.30 × 10-25cm6/GW2, respectively, in femtosecond region among the highest ones reported for many diphenylaminofluorene-derived AFX chromophores. Utilization of a keto linker located immediately between C60cage and fluorene chromophore moieties facilitates molecular polarization of the DPAF ring toward the C60cage. That may serve as the fundamental cause for correlation of enhanced A−D electron interactions to, ultimately, observed multiphoton absorption cross sections. By using nanosecond laser flash photolysis results taken at 355 nm as the reference, transient absorption data obtained from femtosecond pump−probe experiments at 800 nm unambiguously verified the occurrence of two-photon excitation processes of C60(>DPAF-C9) in air-saturated benzene and subsequent efficient energy transfer from the two-photon pumped DPAF-C9moiety to the C60cage moiety.

Utilization of two-photon (TP) excited fluorescence resonance energy transfer (FRET) within a light-harvesting dendrimer has proven to be a reliable method for the enhancement of the effective TP absorption efficiency of many FRET acceptor molecules. This light-harvesting approach has enabled TP photosensitization of singlet oxygen from a porphyrin in both aqueous and organic media using wavelengths more transmissive to human body tissue (750−1000 nm). This ability to utilize near-infrared irradiation to induce photochemical reactions is especially attractive for applications including in vivo photochemistry, oxygen sensing, and photodynamic cancer therapy. In efforts to further the applicability of this concept, we synthesized an array of novel photosensitizers by metalation of the porphyrin core with aluminum, silver, and zinc. Time-resolved fluorescence, transient absorption measurements, and TP excitation experiments demonstrated efficient TP excited FRET to produce the porphyrin excited state triplet which subsequently generates singlet oxygen by the aluminum and zinc metalated species. Singlet oxygen photosensitization efficiency was found to be most efficient using aluminum followed by zinc and least efficient using silver. In fact, silver metalated photosensitizers were found to be nonfluorescent and incapable of generating a measurable amount of singlet oxygen. With the proper choice of inserted metals, it was possible to tune the efficiency of TP induced singlet oxygen production.

Fluorosurfactants with several structural modifications have been synthesized, and the air/water interface and bulk aggregation properties investigated. The compounds were fluorinated ethylene oxide (EO) nonionics where the number and position of the hydrophilic group(s) has been radically altered to generate linear, bolaform, and Y-shaped analogues. A noticeable structure−interfacial packing relationship was observed via both tensiometric measurements and neutron reflection studies:  the limiting molecular areas, acmc, and surface excesses, Γcmc, are strongly dependent on the number and position of the EO headgroups. Differing bulk aqueous properties were also observed. Small-angle neutron scattering shows an evolution of micelle structure from cylindrical to disklike aggregates on changing from Y-shaped to bolaform molecular structure.

Two dithiadiazolyl radicals of formula [F2C6H3&z.ub1s;CNSSN&z.ub1e;] &z.rad; were prepared and characterised by X-ray crystallography; in the solid state the 2′,3′-difluoro isomer forms discrete twisted dimers through a spin-paired singly occupied–singly occupied molecular orbital interaction with an intra-dimer S · · ·   S distance of 3.020(4) Å, whereas the 2′,5′-isomer is composed of uniform stacks with unexpectedly long intra-stack S · · ·   S contacts [3.544(3) Å].

OBJECTIVES: To explore patients' understanding of chronic heart failure; to investigate their need for information and issues concerning communication. DESIGN: Qualitative analysis of in-depth interviews by a constant comparative approach. PARTICIPANTS: 27 patients identified by cardiology and care of the elderly physicians as having symptomatic heart failure (New York Heart Association functional class of II, III, or IV) and who had been admitted to hospital with heart failure in the past 20 months. RESULTS: Participants were aged 38-94 (mean 69 years); 20 had a New York Heart Association classification of III or IV. All had at least one concurrent illness. Participants sought information from the research interviewer about their heart failure, their prognosis, and likely manner of death. They also described several factors that could inhibit successful communication with their doctors. These included difficulties in getting to hospital appointments, confusion, short term memory loss, and the belief that doctors did not want to provide patients with too much knowledge. CONCLUSIONS: Good communication requires the ability both to listen and to impart relevant information. Effective and better ways of communicating with patients with chronic heart failure need to be tested. Disease specific barriers to effective communication, such as short term memory loss, confusion, and fatigue should be addressed. Strategies to help patients ask questions, including those related to prognosis, should be developed.

Obstructive sleep apnea (OSA) is a common disorder in children but can occasionally present with life-threatening hypoxemia. Obesity is a significant risk factor for poor outcomes of OSA treatment. Continuous positive airway pressure (CPAP) is indicated in children who are not candidates for or have an unsatisfactory response to adenotonsillectomy. Children acutely at risk for significant morbidity with other therapies are candidates for a tracheostomy. An eight-year-old patient with morbid obesity and severe OSA refractory to CPAP therapy was treated successfully with a novel noninvasive ventilation (NIV) mode with volume-assured pressure support (VAPS) and avoided tracheostomy.