bluuebunny/crossref_metadata_2025 huggingface dataset:
Landau damping of a driven plasma wave from laser pulses
Authors: Bu Zhigang , Ji Peiyong
Published: January 2012

The interaction between a laser pulse and a driven plasma wave with a phase velocity approaching the speed of light is studied, and our investigation is focused on the Gaussian laser pulse. It is demonstrated that when the resonance condition between the plasma wave and the laser pulse is satisfied, the Landau damping phenomenon of the plasma wave originated from the laser pulse will emerge. The dispersion relations for the plasma waves in resonance and non-resonance regions are obtained. It is proved that the Landau damping rate for a driven plasma wave is γ>0 in the resonance region, so the laser pulse can produce an inverse damping effect, namely Landau growth effect, which leads an instability for the plasma wave. The Landau growth means that the energy is transmitted from the laser pulse to the plasma wave, which could be an effective process for enhancing the plasma wave.
Effective interactions in lysozyme aqueous solutions: A small-angle neutron scattering and computer simulation study
Authors: Abramo M. C. , Caccamo C. , Costa D. , Pellicane G. , Ruberto R. , Wanderlingh U.
Published: January 2012

We report protein-protein structure factors of aqueous lysozyme solutions at different pH and ionic strengths, as determined by small-angle neutron scattering experiments. The observed upturn of the structure factor at small wavevectors, as the pH increases, marks a crossover between two different regimes, one dominated by repulsive forces, and another one where attractive interactions become prominent, with the ensuing development of enhanced density fluctuations. In order to rationalize such experimental outcome from a microscopic viewpoint, we have carried out extensive simulations of different coarse-grained models. We have first studied a model in which macromolecules are described as soft spheres interacting through an attractive r−6 potential, plus embedded pH-dependent discrete charges; we show that the uprise undergone by the structure factor is qualitatively predicted. We have then studied a Derjaguin-Landau-Verwey-Overbeek (DLVO) model, in which only central interactions are advocated; we demonstrate that this model leads to a protein-rich/protein-poor coexistence curve that agrees quite well with the experimental counterpart; experimental correlations are instead reproduced only at low pH and ionic strengths. We have finally investigated a third, “mixed” model in which the central attractive term of the DLVO potential is imported within the distributed-charge approach; it turns out that the different balance of interactions, with a much shorter-range attractive contribution, leads in this latter case to an improved agreement with the experimental crossover. We discuss the relationship between experimental correlations, phase coexistence, and features of effective interactions, as well as possible paths toward a quantitative prediction of structural properties of real lysozyme solutions.
Mechanisms for thermal conduction in hydrogen hydrate
Authors: English Niall J. , Gorman Paul D. , MacElroy J. M. D.
Published: January 2012

Extensive equilibrium molecular dynamics simulations have been performed to investigate thermal conduction mechanisms via the Green-Kubo approach for (type II) hydrogen hydrate, at 0.05 kbar and between 30 and 250 K, for both lightly filled H2 hydrates (1s4l) and for more densely filled H2 systems (2s4l), in which four H2 molecules are present in the large cavities, with respective single- and double-occupation of the small cages. The TIP4P water model was used in conjunction with a fully atomistic hydrogen potential along with long-range Ewald electrostatics. It was found that substantially less damping in guest-host energy transfer is present in hydrogen hydrate as is observed in common type I clathrates (e.g., methane hydrate), but more akin in to previous results for type II and H methane hydrate polymorphs. This gives rise to larger thermal conductivities relative to common type I hydrates, and also larger than type II and H methane hydrate polymorphs, and a more crystal-like temperature dependence of the thermal conductivity.
Magnetic study of Cu1−xMnxO (0 ≤ x ≤ 0.08) nanoparticles
Authors: Hussain Shahzad , Mumtaz A. , Hasanain S. K. , Usman M.
Published: January 2012

Cu1−xMnxO (0 ≤ x ≤ 0.08) nanoparticles were synthesized by a coprecipitation method. Powder x ray analysis reveals that samples show a pure CuO phase for x ≤ 0.06 and the appearance of a secondary phase CuMn2O4 for x > 0.06. The unit cell volume expands with increasing Mn concentration up to x = 0.06 and remains constant on further increase in Mn concentration. The undoped sample shows the behavior of pure CuO with antiferromagnetic transitions at TN1 = 228 K and TN2 = 214 K. Inclusion of Mn into the Cu sublattice turned antiferromagnetic CuO into a ferromagnet. The origin of ferromagnetism is analyzed on the basis of different possible interactions. It is believed that the indirect coupling between Mn ions mediated by O and Cu ions helps to stabilize the ferromagnetism.
Mode tuning of photonic crystal nanocavities by photoinduced non-thermal oxidation
Authors: Intonti Francesca , Caselli Niccolò , Vignolini Silvia , Riboli Francesco , Kumar Santosh , Rastelli Armando , Schmidt Oliver G. , Francardi Marco , Gerardino Annamaria , Balet Laurent , Li Lianhe H. , Fiore Andrea , Gurioli Massimo
Published: January 2012

A method to achieve photoinduced tuning of PhC nanocavity modes is discussed and implemented. It is based on light induced oxidation in air atmosphere with very low thermal budget which produces a local reduction of the GaAs membrane effective thickness and a large blueshift of the nanocavity modes. It is also shown that green light is much more efficient in inducing the micro-oxidation with respect to near infrared light. The observed behaviour is attributed to oxide growth promoted by photoenhanced reactivity.
Fragility of supercooled liquids from differential scanning calorimetry traces: Theory and experiment
Authors: Fivez J. , Longuemart S. , Glorieux C.
Published: January 2012

Starting from the Debye model for frequency-dependent specific heat and the Vogel-Fulcher-Tammann (VFT) model for its relaxation time, an analytic expression is presented for the heat capacity versus temperature trace for differential scanning calorimetry (DSC) of glass transitions, suggesting a novel definition of the glass transition temperature based on a dimensionless criterion. An explicit expression is presented for the transition temperature as a function of the VFT parameters and the cooling rate, and for the slope as a function of fragility. Also a generalization of the results to non-VFT and non-Debye relaxation is given. Two unique ways are proposed to tackle the inverse problem, i.e., to extract the fragility from an experimental DSC trace. Good agreement is found between theoretically predicted DSC traces and experimental DSC traces for glycerol for different cooling rates.
Note: Bending compliances of generalized symmetric notch flexure hinges
Authors: Lobontiu Nicolae
Published: January 2012

The bending compliances of generalized notch flexure hinges with transverse or transverse-and-axial symmetry are studied in two particular reference frames. For an end-point reference frame, the cross compliance and the rotary compliance are proportional. When the reference frame is placed at the flexure's midpoint, the cross compliance is zero. The translatory and rotary compliances of only half the flexure hinge are sufficient to calculate the overall compliances of a transverse-symmetry flexure configuration. Similarly, the overall bending compliances of a flexure hinge with transverse-and-axial symmetry require prior calculation of the translatory and rotary compliances of a quarter flexure solely.
Growth orientation dependent photoluminescence of GaAsN alloys
Authors: Han Xiuxun , Tanaka Tomohiro , Kojima Nobuaki , Ohshita Yoshio , Yamaguchi Masafumi , Sato Shinichiro
Published: January 2012

We report photoluminescence (PL) studies of both as-grown and electron-irradiated GaAsN epilayers on (311)A/B and (100) GaAs substrates. A long room-temperature (RT) PL lifetime, as well as an enhanced N incorporation, is observed in (311)B GaAsN epilayers as compared with (311)A and (100) samples. There is no direct correlation between the RT PL lifetime and the emission intensity from Ga vacancy complex detected at low temperature. The lifetime damage coefficient is relatively low for (311)B GaAsN. The irradiation-induced nonradiative recombination defects are suggested to be N- and/or As-related according to a geometrical analysis based on the tetrahedral coordination of GaAsN crystal.
First Synthesis of Diindeno[1,2-g:1',2'-s]rubicene Derivatives and their Evaluation as Semiconductors
Authors: Bown Mark , Dunn Christopher J. , Forsyth Craig M. , Kemppinen Peter , Singh Th. Birendra , Skidmore Melissa A. , Winzenberg Kevin N.
Published: January 2012

Solution-processable derivatives 4a–d of the novel diindeno[1,2-g:1′,2′-s]rubicene ring system have been prepared in three steps from 1,5-dichloroanthraquinone. Charge extraction by linearly increasing voltage measurements indicates that 4a–d have bulk mobilities <10–7 cm2 V–1 s–1. Consistent with these low mobility values, field-effect transistors fabricated from 4a–d show poor performance. X-ray crystallographic analyses indicate that in the crystalline state, molecules of compounds 4b–d pack in a manner that hinders π–π stacking, thus preventing strong electronic coupling between molecules that is essential for high charge mobility semiconductor performance.
Response of diffusive equilibrium in thin films (DET) and diffusive gradients in thin films (DGT) trace metal profiles in sediments to phytodetritus mineralisation
Authors: Gao Yue , Leermakers Martine , Pede Annelies , Magnier Aurelie , Sabbe Koen , Lourino Cabana Beatriz , Billon Gabriel , Baeyens Willy , Gillan David C.
Published: January 2012

Environmental contextContaminated sediments can have a large and lasting effect on marine ecosystems. It was discovered that significant amounts of pollutants, especially arsenic, were released from contaminated sediments during a phytoplankton bloom in the Belgian Continental Zone. Once released to the water column, these pollutants can accumulate up marine food chains and be a source of contaminants to humans.
AbstractField data from the Belgian Continental Zone showed elevated trace metal concentrations at the sediment–water interface after the occurrence of a phytoplankton bloom. In the present study, laboratory incubation experiments were used to investigate the effect of the phytodetritus remineralisation process on the release of trace metals from contaminated muddy sediments. This remineralisation process was followed by the measurement of chlorophyll-a and dissolved organic carbon levels in the top sediment layers. Two gel techniques, diffusive equilibrium in thin films (DET) and diffusive gradients in thin films (DGT), were used to assess vertical metal profiles in the sediment pore waters and to calculate the metal effluxes. These metal effluxes compared very well with the trace metal concentration variations in the overlying water of the sediment. Much higher effluxes of Mn, Co and As were observed after 2 days of incubation in the microcosms which received additions of phytodetritus. This trend gradually decreased after 7 days of incubation, suggesting that the elevated efflux of trace metals was proportional to the quantity of phytodetritus mineralised at the sediment–water interface. The release of large amounts of toxic elements from the sediments after phytoplankton blooms can therefore potentially affect the marine ecosystem in the Belgian Continental Zone.
A conceptual framework identifying sources of risk to patient safety in primary care
Authors: McLeod Logan , Kingston-Riechers JoAnn , Jonsson Egon
Published: January 2012

The potential risks to patient safety in a primary care setting are different than the risks to patient safety in an acute care setting. The main differences arise from the organisational structures of primary care delivery and the greater involvement of patients in their care. To account for these differences, we present the Patient Safety in Primary Care Framework to conceptualise the sources of risk to patient safety.
The contraceptive Implant
Authors: Gajria Camille , Wilkinson Dawn
Published: January 2012

The UK has one of the widest ranges of contraception available; yet, one-third of pregnancies remain unplanned. In response to the Department of Health's National Strategy for Sexual Health and HIV, the National Institute for Health and Clinical Excellence (NICE) produced guidelines on long-acting reversible contraception (LARC). LARC is promoted as an effective way to reduce unintended pregnancies. The National Strategy specifically emphasized the need for primary care teams to support women in making informed choices about their contraceptive options. This article discusses one form, the contraceptive implant.
Establishing MIC breakpoints and the interpretation of in vitro susceptibility tests
Authors: MacGowan Alasdair P. , Wise Richard
Published: January 2012

The purpose of undertaking susceptibility testing, by whatever method, is to attempt to integrate the susceptibility of a population of potential pathogens with the pharmacokinetics of the antimicrobial and, whenever possible, to review this relationship in the light of clinical experience following therapy in clinical trials. Breakpoints are discriminatory antimicrobial concentrations used in the interpretation of results of susceptibility testing to define isolates as susceptible, intermediate or resistant. Clinical, pharmacological and microbiological considerations are important in setting breakpoints, and the ideal mix of these factors is unknown. Different countries have different approaches to this problem but, by and large, these approaches have much in common. This paper attempts to summarize the philosophy of the British Society for Antimicrobial Chemotherapy (BSAC) Working Party in its approach to setting breakpoints and to update the activities of the Working Party since it initially published breakpoints, approximately 10 years ago. The formula outlined by the BSAC Working Party in 1991 has been used to set the breakpoints presented here. The Working Party accepts that in the light of new knowledge, there is a need to reassess how breakpoints are defined, and this paper also summarizes the future activities of the Working Party.
Detection of methicillin/oxacillin resistance in staphylococci
Authors: Brown Derek F. J.
Published: January 2012

Methicillin/oxacillin-resistant staphylococci are heterogeneous in their expression of resistance to β-lactam agents and the test conditions have a major effect on the expression and therefore the detection of resistance. Conflicting recommendations regarding the most reliable method for routine use are partly related to differences between strains and there may be a variable interaction between the factors affecting the expression of resistance, including the agent tested, the medium, the NaCl concentration, the inoculum, temperature and period of incubation and the reading of endpoints. ‘Borderline’ resistant strains may have altered PBPs or be penicillinase hyperproducers, and these can be difficult to distinguish from resistant strains that carry the mecA gene. Recommended methods for MIC and disc diffusion testing are described, although it is unlikely that any single method will detect all resistant strains. Some rapid and/or automated methods are also available, including latex agglutination techniques for the detection of PBP2a. The gold standard method for the detection of resistance mediated by mecA is PCR, which is most commonly used as a reference method at present.
Structures of ketolides and macrolides determine their mode of interaction with the ribosomal target site
Authors: Douthwaite Stephen , Champney W. Scott
Published: January 2012

Ketolides are the most recent generation of antimicrobials derived from the 14-membered ring macrolide, erythromycin A. The main structural feature that differentiates ketolides from erythromycin is the keto group, which replaces the l-cladinose moiety at position 3 of the macrolactone ring. The keto group bestows greater acid stability on the drugs, and enables them to bind to their ribosomal target without causing expression of MLSB resistance in inducible strains. Several ketolides are described here, including ABT 773 and telithromycin (HMR 3647), both of which possess a carbamate at C11/C12 of the macrolactone ring. In telithromycin, which is the first ketolide to be approved for clinical use, the carbamate is linked to an alkyl-aryl extension, which is responsible for the increased potency of this compound relative to macrolides. This review examines how the structural differences between macrolides and the new ketolides are related to their antimicrobial activities in inhibiting protein synthesis and blocking the assembly of new ribosomal subunits.
Neonatal candidosis: clinical picture, management controversies and consensus, and new therapeutic options
Authors: Leibovitz Eugene
Published: January 2012

Candida infections are increasingly being recognized as a major cause of septicaemia in neonatal intensive care units, and are associated with high morbidity (25%) and mortality (25–54%). Low birth weight pre-term infants are especially vulnerable to this devastating disease. The most frequently encountered fungal infections are caused by Candida albicans, Candida parapsilosis and, rarely, by Candida tropicalis. Amphotericin B (with or without flucytosine) is the treatment of choice for Candida infections in neonates. Conventional amphotericin B use is often limited by its severe side effects, although these tend to be fewer in neonates than in adults. Possible alternatives to amphotericin B include triazoles (such as fluconazole) and lipid preparations of amphotericin B. Liposomal encapsulation of amphotericin B has been shown to decrease the toxicity of the drug while maintaining its antifungal activity. The liposomal formulation AmBisome has proved to be effective in the treatment of severe fungal infections in adult and paediatric immunocompromised patients who fail to respond to conventional amphotericin B. The experience with AmBisome in the treatment of fungal infections in neonates is limited, and the drug has been used mainly in infants either failing conventional amphotericin B or having intolerable toxicity. Pharmacokinetic studies have not yet been performed in neonates. Three uncontrolled studies published between 1997 and 1998 on AmBisome (dose range 1–7 mg/kg/day) in the treatment of neonatal candidosis revealed that the drug was effective and safe. New information is accumulating on the safe use of high-dose AmBisome (5–7 mg/kg/day) in very low birth weight infants, and successful use of the drug as first-line therapy of neonatal candidosis. These promising results suggest a potential role for AmBisome as an additional first-line treatment of systemic candidosis in neonates.
Amphotericin B: spectrum and resistance
Authors: Ellis David
Published: January 2012

Amphotericin B is a polyene macrolide antibiotic derived from the actinomycete Streptomyces nodosus. Of the 200 known polyene agents, amphotericin B is the only one with toxicities that are sufficiently limited to permit intravenous administration. All polyenes have a common mechanism of action in that they preferentially bind to ergosterol, the primary sterol in the fungal cell membrane. The consequence of this binding includes disruption of the osmotic integrity of the membrane, with leakage of intracellular potassium and magnesium, and also the disruption of oxidative enzymes in target cells. Amphotericin B has a relatively broad spectrum of action and is useful in treating cases of candidosis, cryptococcosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, coccidioidomycosis, aspergillosis, extracutaneous sporotrichosis and mucormycosis, and some cases of hyalohyphomycosis and phaeohyphomycosis. Resistance (MIC > 2 mg/L) tends to be species-dependent and emerges uncommonly and slowly in isolates from patients treated with amphotericin B. These include some individual strains of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae, which may acquire resistance during treatment. Some isolates of Scedosporium apiospermum, Fusarium spp. and Sporothrix schenckii also show primary resistance, whereas all strains of Scedosporium prolificans demonstrate resistance. The main problems associated with the use of conventional amphotericin B have always been due to its poor aqueous solubility and toxicity rather than antifungal resistance.
Prophylaxis and treatment of patients with aspergillosis: an overview, including the Royal Melbourne Hospital experience
Authors: Grigg Andrew
Published: January 2012

Patients receiving allogeneic bone marrow transplants are at risk of developing Aspergillus infections. The pre-transplant risk factors for the development of invasive disease include prolonged neutropenia, colonization with Aspergillus sp. or a prior history of fungal infection. Post-transplant risk factors include severe graft-versus-host disease with concomitant high-dose corticosteroid therapy, and colonization with Aspergillus sp. The antifungal prophylaxis of selected high-risk pre-transplant patients at the Royal Melbourne Hospital includes granulocyte transfusions and AmBisome. In high-risk patients post-engraftment, prophylaxis consists of oral itraconazole, or if it cannot be tolerated, AmBisome. Antifungal prophylaxis is discontinued upon resolution of neutropenia, when prednisolone dose falls below 10 mg/day or when Aspergillus colonization disappears. Following this regimen, there has been only one death due to fungal infection in over 80 consecutive allograft patients. This patient was infected with an amphotericin B-resistant organism.
Liposomal amphotericin B versus conventional amphotericin B in the empirical treatment of persistently febrile neutropenic patients
Authors: Cagnoni Pablo J.
Published: January 2012

Liposomal amphotercin B was compared with conventional amphotericin B for empirical antifungal therapy in febrile neutropenic patients in a randomized, double-blind, multicentre trial. Using a composite end-point, the two drugs were equivalent in overall efficacy. However, the liposomal amphotericin B treatment group had fewer proven fungal infections, fewer infusion-related side effects and less nephrotoxicity. Patient data from that study were analysed to compare the pharmacoeconomics of liposomal versus conventional amphotericin B therapy. Itemized billing data from 414 patients were collected and analysed. Hospital costs from first dose were significantly higher for all patients who received liposomal amphotericin B ($48 962 versus $43 183, P = 0.02). However, hospital costs were very sensitive to the cost of the study medication ($39 648 versus $43 048, when acquisition costs are not included, P = 0.4). Using decision analysis models and sensitivity analyses to vary the cost of study medications and risk of nephrotoxicity, the break-even points for the cost of liposomal therapy were calculated to range from $72 to $87 per 50 mg for all patients, and $83 to $112 per 50 mg in allogeneic bone marrow transplant patients. Therefore, the drug acquisition costs and the risk of nephrotoxicity are important factors in determining the cost-effectiveness of liposomal amphotericin B as empirical therapy in persistently febrile neutropenic patients. In a recent randomized double-blind study comparing liposomal amphotericin B at 3 or 5 mg/kg/day with amphotericin B lipid complex (ABLC) 5 mg/kg/day as empirical antifungal treatment in patients with febrile neutropenia, liposomal amphotericin B was associated with less toxicity than ABLC, both in terms of infusion-related reactions and nephrotoxicity. The incidence of study drug discontinuation due to toxicity was: liposomal amphotericin B 3 mg/kg/day, 14%; liposomal amphotericin B 5 mg/kg/day, 15%; and ABLC, 42% (P < 0.001).
Global antibiotic resistance in Streptococcus pneumoniae
Authors: Adam Dieter
Published: January 2012

The last two decades of the 20th century were marked by an increasing resistance rate among several bacteria. Threat of resistance is present in Staphylococcus spp., Enterococcus spp., Pseudomonas spp. and Enterobacteriaceae, which are the major pathogens in nosocomial infections. In the community, too, increasing resistance can be observed and is attributed mainly (but not exclusively) to Streptococcus pneumoniae and Haemophilus influenzae . To scrutinize this trend, resistance surveillance in the community was established about 10 years ago. One of the multinational, longitudinal surveillance programmes in place is the Alexander Project, which was established in 1992 to monitor the susceptibility of the major community-acquired lower respiratory tract pathogens to a range of antibacterial drugs. The Alexander Project has revealed a tendency towards increasing resistance of S. pneumoniae to penicillin and macrolide therapy. Within Europe, the prevalence of penicillin resistance among S. pneumoniae isolates is particularly high in France and Spain. Macrolide resistance in S. pneumoniae is also a growing problem in European countries such as France, Spain, Belgium and Italy, where the extent of macrolide resistance in S. pneumoniae now exceeds that of penicillin resistance.
Antibacterial activity of oral antibiotics against community–acquired respiratory pathogens from three European countries
Authors: Schito Gian Carlo , Georgopoulos Apostolos , Prieto José
Published: January 2012

Antimicrobial resistance is universally recognized as a major problem. A European resistance survey was established to monitor the activity of widely used oral antibiotics against common respiratory tract pathogens. Studies were conducted in Italy, Spain and Austria to monitor resistance patterns among respiratory Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus aureus and Klebsiella pneumoniae to amoxicillin, co-amoxiclav, penicillin, cefaclor, cefadroxil, cefalexin, cefprozil, cefuroxime, cefixime, ceftibuten, cefpodoxime, clarithromycin and azithromycin (the antibiotics tested varying slightly from country to country). Minimum inhibitory concentrations were determined using the NCCLS-recommended broth microdilution method. Among the antibiotics tested, cefpodoxime, an oral cephalosporin, was remarkably active against the major respiratory pathogens in all three countries. Cefpodoxime was more potent than cefaclor, cefixime and ceftibuten against pneumococci, especially against strains with decreased sensitivity to penicillin, and more active than cefaclor and cefuroxime against Gram-negative respiratory pathogens. Pneumococci and staphylococci displayed a very high level of in vitro macrolide resistance. These data indicate that cefpodoxime represents an appropriate choice in the treatment of community-acquired respiratory tract infection in the three countries surveyed.
Interstitial tissue concentrations of cefpodoxime
Authors: Liu Ping , Müller Markus , Grant Maria , Webb Alistair I. , Obermann Bernd , Derendorf Hartmut
Published: January 2012

Microdialysis is a technique that allows the measurement of concentrations of free antibiotic in tissue. The free antibiotic concentration is responsible for the antibacterial effect at the target site. We used microdialysis in animal and human studies to investigate the tissue penetration of cefpodoxime. In the animal study, total plasma and free muscle and lung concentrations of cefpodoxime were measured after male Wistar rats had received either 10 mg/kg or 20 mg/kg iv cefpodoxime over 5 h or a continuous iv infusion of 260 µg/h cefpodoxime after a loading dose of 6 mg/kg. Free muscle concentrations of cefpodoxime were similar to free lung concentrations and therefore provided a surrogate measure of cefpodoxime concentrations at the pulmonary target site. In an open, randomized, two-way crossover, single-dose study in six healthy male volunteers, total plasma and free muscle concentrations were measured after a single oral dose of cefpodoxime 400 mg or cefixime 400 mg. The total plasma concentrations of each antibiotic were similar and higher than free muscle concentrations. The tissue penetration of cefpodoxime was, however, greater than that of cefixime, as shown by two-fold higher peak free muscle concentrations after dosing with cefpodoxime than with cefixime (2.1 mg/L versus 0.9 mg/L). In addition, the area under the curve for tissue (AUC t ) of cefpodoxime (400 mg) was more than double that of cefixime (400 mg), based on free antibiotic concentrations (15.4 mg·h/L versus 7.3 mg·h/L). These findings indicate that, taking into account pharmacokinetic/pharmacodynamic considerations, cefpodoxime is likely to be more efficacious than cefixime, due to its greater tissue penetration.
Rates and Patterns of Molecular Evolution in Inbred and Outbred Arabidopsis
Authors: Wright Stephen I. , Lauga Beatrice , Charlesworth Deborah
Published: January 2012

The evolution of self-fertilization is associated with a large reduction in the effective rate of recombination and a corresponding decline in effective population size. If many spontaneous mutations are slightly deleterious, this shift in the breeding system is expected to lead to a reduced efficacy of natural selection and genome-wide changes in the rates of molecular evolution. Here, we investigate the effects of the breeding system on molecular evolution in the highly self-fertilizing plant Arabidopsis thaliana by comparing its coding and noncoding genomic regions with those of its close outcrossing relative, the self-incompatible A. lyrata. More distantly related species in the Brassicaceae are used as outgroups to polarize the substitutions along each lineage. In contrast to expectations, no significant difference in the rates of protein evolution is observed between selfing and outcrossing Arabidopsis species. Similarly, no consistent overall difference in codon bias is observed between the species, although for low-biased genes A. lyrata shows significantly higher major codon usage. There is also evidence of intron size evolution in A. thaliana, which has consistently smaller introns than its outcrossing congener, potentially reflecting directional selection on intron size. The results are discussed in the context of heterogeneity in selection coefficients across loci and the effects of life history and population structure on rates of molecular evolution. Using estimates of substitution rates in coding regions and approximate estimates of divergence and generation times, the genomic deleterious mutation rate (U) for amino acid substitutions in Arabidopsis is estimated to be approximately 0.2–0.6 per generation.
Evolution of the Sulfide-Binding Function Within the Globin Multigenic Family of the Deep-Sea Hydrothermal Vent Tubeworm Riftia pachyptila
Authors: Bailly Xavier , Jollivet Didier , Vanin Stephano , Deutsch Jean , Zal Franck , Lallier François , Toulmond André
Published: January 2012

The giant extracellular hexagonal bilayer hemoglobin (HBL-Hb) of the deep-sea hydrothermal vent tube worm Riftia pachyptila is able to transport simultaneously O2 and H2S in the blood from the gills to a specific organ: the trophosome that harbors sulfide-oxidizing endosymbionts. This vascular HBL-Hb is made of 144 globins from which four globin types (A1, A2, B1, and B2) coevolve. The H2S is bound at a specific location (not on the heme site) onto two of these globin types. In order to understand how such a function emerged and evolved in vestimentiferans and other related annelids, six partial cDNAs corresponding to the six globins known to compose the multigenic family of R. pachyptila have been identified and sequenced. These partial sequences (ca. 120 amino acids, i.e., 80% of the entire protein) were used to reconstruct molecular phylogenies in order to trace duplication events that have led to the family organization of these globins and to locate the position of the free cysteine residues known to bind H2S. From these sequences, only two free cysteine residues have been found to occur, at positions Cys + 1 (i.e., 1 a.a. from the well-conserved distal histidine) and Cys + 11 (i.e., 11 a.a. from the same histidine) in globins B2 and A2, respectively. These two positions are well conserved in annelids, vestimentiferans, and pogonophorans, which live in sulfidic environments. The structural comparison of the hydrophobic environment that surrounds these cysteine residues (the sulfide-binding domain) using hydrophobic cluster analysis plots, together with the cysteine positions in paralogous strains, suggests that the sulfide-binding function might have emerged before the annelid radiation in order to detoxify this toxic compound. Moreover, globin evolutionary rates are highly different between paralogous strains. This suggests that either the two globin subfamilies involved in the sulfide-binding function (A2 and B2) have evolved under strong directional selective constraints (negative selection) and that the two other globins (A1 and B1) have accumulated more substitutions through positive selection or have evolved neutrally after a relaxation of selection pressures. A likely scenario on the evolution of this multigenic family is proposed and discussed from this data set.
Mitochondrial DNA Sequence Evolution and Phylogeny of the Atlantic Alcidae, Including the Extinct Great Auk (Pinguinus impennis)
Authors: Moum Truls , Arnason Ulfur , Árnason Einar
Published: January 2012

The Atlantic auk assemblage includes four extant species, razorbill (Alca torda), dovekie (Alle alle), common murre (Uria aalge), and thick-billed murre (U. lomvia), and one recently extinct species, the flightless great auk (Pinguinus impennis). To determine the phylogenetic relationships among the species, a contiguous 4.2-kb region of the mitochondrial genome from the extant species was amplified using PCR. This region included one ribosomal RNA gene, four transfer RNA genes, two protein-coding genes, the control region, and intergenic spacers. Sets of PCR primers for amplifying the same region from great auk were designed from sequences of the extant species. The authenticity of the great auk sequence was ascertained by alternative amplifications, cloning, and separate analyses in an independent laboratory. Phylogenetic analyses of the entire assemblage, made possible by the great auk sequence, fully resolved the phylogenetic relationships and split it into two primary lineages, Uria versus Alle, Alca, and Pinguinus. A sister group relationship was identified between Alca and Pinguinus to the exclusion of Alle. Phylogenetically, the flightless great auk originated late relative to other divergences within the assemblage. This suggests that three highly divergent species in terms of adaptive specializations, Alca, Alle, and Pinguinus, evolved from a single lineage in the Atlantic Ocean, in a process similar to the initial adaptive radiation of alcids in the Pacific Ocean.
Analysis of Lamprey and Hagfish Genes Reveals a Complex History of Gene Duplications During Early Vertebrate Evolution
Authors: Escriva Hector , Manzon Lori , Youson John , Laudet Vincent
Published: January 2012

It has been proposed that two events of duplication of the entire genome occurred early in vertebrate history (2R hypothesis). Several phylogenetic studies with a few gene families (mostly Hox genes and proteins from the MHC) have tried to confirm these polyploidization events. However, data from a single locus cannot explain the evolutionary history of a complete genome. To study this 2R hypothesis, we have taken advantage of the phylogenetic position of the lamprey to study the history of gene duplications in vertebrates. We selected most gene families that contain several paralogous genes in vertebrates and for which lamprey genes and an out-group are known in databases. In addition, we isolated members of the nuclear receptor superfamily in lamprey. Hagfish genes were also analyzed and found to confirm the lamprey gene analysis. Consistent with the 2R hypothesis, the phylogenetic analysis of 33 selected gene families, dispersed through the whole genome, revealed that one period of gene duplication arose before the lamprey-gnathostome split and this was followed by a second period of gene duplication after the lamprey-gnathostome split. Nevertheless, our analysis suggests that numerous gene losses and other gene-genome duplications occurred during the evolution of the vertebrate genomes. Thus, the complexity of all the paralogy groups present in vertebrates should be explained by the contribution of genome duplications (2R hypothesis), extra gene duplications, and gene losses.
Patterns of Nucleotide Substitution Among Simultaneously Duplicated Gene Pairs in Arabidopsis thaliana
Authors: Zhang Liqing , Vision Todd J. , Gaut Brandon S.
Published: January 2012

We characterized rates and patterns of synonymous and nonsynonymous substitution in 242 duplicated gene pairs on chromosomes 2 and 4 of Arabidopsis thaliana. Based on their collinear order along the two chromosomes, the gene pairs were likely duplicated contemporaneously, and therefore comparison of genetic distances among gene pairs provides insights into the distribution of nucleotide substitution rates among plant nuclear genes. Rates of synonymous substitution varied 13.8-fold among the duplicated gene pairs, but 90% of gene pairs differed by less than 2.6-fold. Average nonsynonymous rates were ≈fivefold lower than average synonymous rates; this rate difference is lower than that of previously studied nonplant lineages. The coefficient of variation of rates among genes was 0.65 for nonsynonymous rates and 0.44 for synonymous rates, indicating that synonymous and nonsynonymous rates vary among genes to roughly the same extent. The causes underlying rate variation were explored. Our analyses tentatively suggest an effect of physical location on synonymous substitution rates but no similar effect on nonsynonymous rates. Nonsynonymous substitution rates were negatively correlated with GC content at synonymous third codon positions, and synonymous substitution rates were negatively correlated with codon bias, as observed in other systems. Finally, the 242 gene pairs permitted investigation of the processes underlying divergence between paralogs. We found no evidence of positive selection, little evidence that paralogs evolve at different rates, and no evidence of differential codon usage or third position GC content.
Recreating a Functional Ancestral Archosaur Visual Pigment
Authors: Chang Belinda S. W. , Jönsson Karolina , Kazmi Manija A. , Donoghue Michael J. , Sakmar Thomas P.
Published: January 2012

The ancestors of the archosaurs, a major branch of the diapsid reptiles, originated more than 240 MYA near the dawn of the Triassic Period. We used maximum likelihood phylogenetic ancestral reconstruction methods and explored different models of evolution for inferring the amino acid sequence of a putative ancestral archosaur visual pigment. Three different types of maximum likelihood models were used: nucleotide-based, amino acid–based, and codon-based models. Where possible, within each type of model, likelihood ratio tests were used to determine which model best fit the data. Ancestral reconstructions of the ancestral archosaur node using the best-fitting models of each type were found to be in agreement, except for three amino acid residues at which one reconstruction differed from the other two. To determine if these ancestral pigments would be functionally active, the corresponding genes were chemically synthesized and then expressed in a mammalian cell line in tissue culture. The expressed artificial genes were all found to bind to 11-cis-retinal to yield stable photoactive pigments with λmax values of about 508 nm, which is slightly redshifted relative to that of extant vertebrate pigments. The ancestral archosaur pigments also activated the retinal G protein transducin, as measured in a fluorescence assay. Our results show that ancestral genes from ancient organisms can be reconstructed de novo and tested for function using a combination of phylogenetic and biochemical methods.
Identification of Essential Amino Acid Changes in Paired Domain Evolution Using a Novel Combination of Evolutionary Analysis and In Vitro and In Vivo Studies
Authors: Sun Hongmin , Merugu Srinivas , Gu Xun , Kang Yuan Yuan , Dickinson Douglas P. , Callaerts Patrick , Li Wen-Hsiung
Published: January 2012

Pax genes are defined by the presence of a paired box that encodes a DNA-binding domain of 128 amino acids. They are involved in the development of the central nervous system, organogenesis, and oncogenesis. The known Pax genes are divided into five groups within two supergroups. By means of a novel combination of evolutionary analysis, in vitro binding assays and in vivo functional analyses, we have identified the key residues that determine the differing DNA-binding properties of the two supergroups and of the Pax-2, 5, 8 and Pax-6 subgroups within supergroup I. The differences in binding properties between the two supergroups are largely caused by amino acid changes at residues 20 and 121 of the paired domain. Although the paired domains of the Pax-2, 5, 8 and the Pax-6 group differ by >19 amino acids, their distinct DNA-binding properties are determined almost completely by a single amino acid change. Thus, a small number of amino acid changes can account in large part for the divergence in binding properties among the known paired domains. Our approach for selecting candidate sites responsible for the functional divergence between genes should also be useful for studying other gene families.
Contribution of Homoplasy and of Ancestral Polymorphism to the Evolution of Genes in Anthropoid Primates
Authors: O'hUigin Colm , Satta Yoko , Takahata Naoyuki , Klein Jan
Published: January 2012

Molecular phylogenies of lineages that split from one another in short succession are often difficult to resolve because different loci and different sites within the same locus yield incongruent relationships. The incongruity is commonly attributed to two causes: differential assortment of ancestral polymorphisms and homoplasy. To assess the relative contribution of these two causes, sequences of 57 segments from 51 loci in six primate lineages (human, chimpanzee, gorilla, orangutan, macaque, and tamarin, abbreviated as H, C, G, O, M, and T, respectively) were subjected to “partitioning” analysis, in which phylogenetically informative sites were identified in all 15 pairwise comparisons of each of the 57 segments and tallied for their support or lack thereof for each of the theoretically possible phylogenies. The six lineages include one of the best known cases of a difficult-to-resolve phylogeny: the trichotomy (H, C, G), in which the three lineages may have diverged from each other within a short period of time. In this period many of the ancestral polymorphisms apparently persisted and yielded phylogenetically incongruent signals. By contrast, no ancestral polymorphism is expected to have survived during the interval separating the divergences of the O, M, and T lineages from the ancestor of the (H, C, G) group. Any phylogenetic incompatibilities at sites in the O, M, and T lineages relative to the (H, C, G) group are therefore presumably the result of homoplasy. The frequency of homoplasy estimated in this manner is unexpectedly high: 12% for the (H, C, G) clade and 19% for the (H, C, G, O) clade. At least three-quarters of the 48% incompatibility observed in the (H, C) clade is attributable to the sorting out of ancestral polymorphisms coupled with intragenic recombination. Possible reasons for this high level of homoplasy in the O, M, and T lineages are discussed, and a computer simulation has been carried out to produce a model explaining the observed data.
Kinesin-Related Genes from Diplomonad, Sponge, Amphioxus, and Cyclostomes: Divergence Pattern of Kinesin Family and Evolution of Giardial Membrane–Bounded Organella
Authors: Iwabe Naoyuki , Miyata Takashi
Published: January 2012

To understand the question of whether divergence of eukaryotic genes by gene duplications and domain shufflings proceeded gradually or intermittently during evolution, we have cloned and sequenced Giardia lamblia cDNAs encoding kinesins and kinesin-related proteins and have obtained 13 kinesin-related cDNAs, some of which are likely homologs of vertebrate kinesins involved in vesicle transfer to ER, Golgi, and plasma membrane. A phylogenetic tree of the kinesin family revealed that most gene duplications that gave rise to different kinesin subfamilies with distinct functions have been completed before the earliest divergence of extant eukaryotes. This suggests that the complex endomembrane system has arisen very early in eukaryotic evolution, and the diminutive ER and Golgi apparatus recognized in the giardial cells, together with the absence of mitochondria, might be characters acquired secondarily during the evolution of parasitism. To understand the divergence pattern of the kinesin family in the lineage leading to vertebrates, seven more Unc104-related cDNAs have been cloned from sponge, amphioxus, hagfish, and lamprey. The divergence pattern of the animal Unc104/KIF1 subfamily is characterized by two active periods in gene duplication interrupted by a considerably long period of silence, instead of proceeding gradually: animals underwent extensive gene duplications before the parazoan-eumetazoan split. In the early evolution of vertebrates around the cyclostome-gnathostome split, further gene duplications occurred, by which a variety of genes with similar structures over the entire regions were generated. This pattern of divergence is similar to those of animal genes involved in cell-cell communication and developmental control.
Codon and Rate Variation Models in Molecular Phylogeny
Authors: Schadt Eric , Lange Kenneth
Published: January 2012

This article generalizes previous models for codon substitution and rate variation in molecular phylogeny. Particular attention is paid to (1) reversibility, (2) acceptance and rejection of proposed codon changes, (3) varying rates of evolution among codon sites, and (4) the interaction of these sites in determining evolutionary rates. To accommodate spatial variation in rates, Markov random fields rather than Markov chains are introduced. Because these innovations complicate maximum likelihood estimation in phylogeny reconstruction, it is necessary to formulate new algorithms for the evaluation of the likelihood and its derivatives with respect to the underlying kinetic, acceptance, and spatial parameters. To derive the most from maximum likelihood analysis of sequence data, it is useful to compute posterior probabilities assigning residues to internal nodes and evolutionary rate classes to codon sites. It is also helpful to search through tree space in a way that respects accepted phylogenetic relationships. Our phylogeny program LINNAEUS implements algorithms realizing these goals. Readers may consult our companion article in this issue for several examples.