bluuebunny/crossref_metadata_2025 huggingface dataset:
Relevance of hepatitis B surface antigen levels in patients with chronic hepatitis B during 5 year of tenofovir treatment
Authors: Singh A. K. , Sharma M. K. , Hissar S. S. , Gupta E. , Sarin S. K.
Published: August 2013

The role of quantitative hepatitis B surface antigen (HBsAg) levels in patients receiving highly potent oral antiviral therapy is controversial, and here, we determined the HBsAg response in 121 chronic hepatitis B patients treated with tenofovir 300 mg daily. During tenofovir treatment, HBsAg decline of ≥1.0 log from baseline was seen in 16.1%, 16.3%, 18.4%, 34.6%, 36.4% and 11.8%, 15.2%, 14.8%, 28.6%, 20% at years 1, 2, 3, 4, 5 for HBeAg‐positive and HBeAg‐negative patients, respectively. Early decline in HBsAg levels at week 4 was predictive of subsequent significant HBsAg level decline. HBeAg seroconversion occurred in 29.9% of HBeAg‐positive patients. On multinomial logistic regression, HBsAg level decline from baseline at week 4 and week 12 or any time subsequently did not correlate with HBeAg seroconversion and HBV DNA level decline from baseline at week 4 and week 12 (OR = 3.704; 95% CI = 1.511–9.076; P = 0.006 and OR = 1.732; 95% CI = 1.032–2.867; P = 0.037, respectively) was significantly predictive of seroconversion. A small proportion of chronic HBV‐infected patients treated with tenofovir exhibit a significant (≥1.0 log) decline in HBsAg levels. Early decline in HBsAg levels at week 4 was predictive of subsequent and significant HBsAg level decline. The HBsAg decline did not correlate with HBeAg seroconversion in HBeAg‐positive patients. Reduction in HBV DNA levels at week 4 and 12 correlated with seroconversion.
Testing for vocal individual discrimination in adult banded mongooses
Authors: Jansen D. A. W. A. M. , Cant M. A. , Manser M. B.
Published: August 2013

The ability to individually recognize conspecifics is acknowledged as one of the prerequisites for the development of sophisticated social relationships in group‐living species. It has been hypothesized that the discrimination of individual identities is crucial for the maintenance of social relationships and cooperation based on repeated interactions, and for the evolution of many social behaviours. Previous studies have shown that the close calls of the cooperatively breeding banded mongoose Mungos mungo are individually distinct. For instance, banded mongoose pups are able to distinguish between close calls of their escort and of a non‐escort. In this study, we used playbacks based on the recently proposed violation‐of‐expectation paradigm and a dominance/age class recognition setup to investigate whether adult banded mongooses use the individual signature of close calls to distinguish among adult group members. We found no evidence that the individual signature in close calls is used to discriminate identity in banded mongooses. Based on the previous work, we suggest that this is not because banded mongooses are incapable of using signatures as a means of individual discrimination, but because the benefits of such discrimination are low. The study highlights the importance of understanding the function of a signal (e.g. the expected response), timing and the biology of the species when designing and performing playback experiments.
Habitat type and distance to edge affect movement behavior of juvenile pond‐breeding salamanders
Authors: Pittman S. E. , Semlitsch R. D.
Published: August 2013

Behavioral strategies of natal dispersers in response to human‐altered habitat have far‐reaching implications for functional connectivity and local population dynamics. Spotted salamanders Ambystoma maculatum are forest‐dependent, pond‐breeding amphibians which metamorphose and disperse out of aquatic habitat with limited knowledge of the terrestrial habitat. We quantified the fine‐scale movement behavior and search strategies of recently metamorphosed spotted salamanders in three different habitat types (field, early successional forest and forest) and at varying distances from both hard (field and forest) and soft (early successional forest and forest) edges using fluorescent powder tracking. We found that salamanders moved straighter and with fewer turns through field habitat compared with both forest and early successional habitat. Salamanders significantly oriented movement toward forest when released in the field and when released on the edge between the forest and field. We found that salamander movement in the forest and early successional forest was approximated by a correlated random walk. Based on these results, dispersing spotted salamanders exhibit strong edge‐mediated behavior when differences between habitats are stark (forest and field) and can perceive forest habitat from distances of at least 10 m. These results indicate that dispersing juvenile salamanders exhibit reasonable behavioral rules when moving through habitat types of differing quality. Knowledge of these behavioral rules will improve predictions of the effects of habitat type and configuration on amphibian survival and dispersion in altered landscapes.
Evolution on a desert island: body size divergence between the reptiles ofNevada'sAnahoIsland and the mainland aroundPyramidLake
Authors: Keehn J. E. , Nieto N. C. , Tracy C. R. , Gienger C. M. , Feldman C. R.
Published: August 2013

Patterns of body size evolution on islands provide compelling cases of rapid and dramatic phenotypic evolution in terrestrial vertebrates, yet debate remains over the relative roles of predation and resource availability in driving such evolution. We compared the morphology of five reptile species (four lizards, one snake) fromAnahoIsland, a desert island inPyramidLake, Nevada, and the nearby mainland, using museum and live‐caught animals. We also examined head‐shape allometries to make inferences about dietary shifts and recorded tail‐regeneration frequencies (in lizards) to examine predation intensity. Compared with mainland samples, two phyrnosomatid lizard species are larger onAnaho (Callisaurus draconoidesandSceloporus occidentalis), whereas the largest (S. uniformis) is not different on the island. Conversely, the teiid lizardAspidoscelis tigrisis smaller in body and head size on the island, and the pitviperCrotalus oreganusis especially diminutive on the island, with males and females 25 and 15% smaller, respectively. Our results appear consistent with the hypothesis that body size is related to resource availability. The change in body size of the two smaller phrynosomatids may be due to interference competition. The reduction in body and head size inA. tigrissuggests a dietary shift, and the dramatic difference inC. oreganusis likely due to a switch in diet from mammals to lizards. Future work is needed to determine whether body size differences reflect genetic evolution or environmental differences in growth rates or resource use. Regardless,AnahoIsland, although remarkably young (earlyHolocene), appears to harbour a unique community of reptiles with distinct morphologies and possibly divergent life histories.
Increasing Returns to Schooling by Ability? A Comparison between the USA and Sweden
Authors: Nordin Martin , Rooth Dan‐Olof
Published: August 2013

This study uses US survey data and Swedish register data to estimate and compare the relationship between returns to schooling and ability. A significant and positive relationship is found for Sweden, but not for the USA. Based on the predictions of the optimal schooling model it is argues that measured differences in the relationship between returns to schooling and ability could depend upon on differences in the schooling systems between the countries. The findings suggest that a low price of higher education in Sweden makes a relationship between returns to schooling and ability observable in Sweden but not in the USA.
Inflation Targeting and the Consistency of Monetary Policy Decisions in Mexico: an Empirical Analysis with Discrete Choice Models
Authors: Muñoz Torres Rebeca I. , Shepherd David
Published: August 2013

This paper examines the nature of monetary policy decisions in Mexico using discrete choice models applied to the Central Bank's explicit monetary policy instrument. We find that monetary policy adjustments in Mexico have been strongly consistent with the CB's inflation targeting strategy. We also find evidence that monetary policy responds in a forward‐looking manner to deviations of inflation from the target and that observed policy adjustments exhibit asymmetric features, with stronger responses to positive than to negative deviations of inflation from the target and a greater likelihood of policy persistence during periods when monetary policy is tightened, compared with periods when policy is loosened.
Fine‐scale temporal adaptation within a salmonid population: mechanism and consequences
Authors: Gharrett Anthony J. , Joyce John , Smoker William W.
Published: August 2013

We demonstrate a clear example of local adaptation of seasonal timing of spawning and embryo development. The consequence is a population of pink salmon that is segmented into spawning groups that use the same limited habitat. We synthesize published observations with results of new analyses to demonstrate that genetic variation of these traits results in survival differentials related to that variation, and that density‐dependent embryo mortality and seasonally variable juvenile mortality are a mechanism of selection. Most examples of local adaptation in natural systems depend on observed correlations between environments and fitness traits, but do not fully demonstrate local adaptation: that the trait is genetically determined, exhibits different fitness in common environments or across different environments, and its variation is mechanistically connected to fitness differences. The geographic or temporal scales of local adaptation often remain obscure. Here, we show that heritable, fine‐scale differences of timing of reproductive migration in a pink salmon (Oncorhynchus gorbuscha) resulted in temporal structure that persisted several generations; the differences enable a density‐dependent population to pack more spawners into limited spawning habitat, that is, enhance its fitness. A balanced trade‐off of survivals results because embryos from early‐migrating fish have a lower freshwater survival (harsh early physical conditions and disturbance by late spawners), but emigrant fry from late‐migrating fish have lower marine survivals (timing of their vernal emergence into the estuarine environment). Such fine‐scale local adaptations increase the genetic portfolio of the populations and may provide a buffer against the impacts of climate change.
Stronger spatial genetic structure in recolonized areas than in refugia in the European beech
Authors: de Lafontaine Guillaume , Ducousso Alexis , Lefèvre Sophie , Magnanou Elodie , Petit Rémy J.
Published: August 2013

Extant rear‐edge populations located in former glacial refugia remain understudied despite their high conservation value. These populations should have experienced strong genetic drift due to their small size and long isolation. Moreover, the prolonged action of isolation by distance in refugial areas should result in stronger regional spatial genetic structure (SGS) than in recolonized areas, but empirical tests of this prediction are scarce. To fill this gap, we first used a set of 16 microsatellite markers to investigate the genetic structure of European beech in France in 65 populations from three refugial areas and one control recolonized (nonrefugial) area. Then, using the same approach, we reanalysed published isozyme data from 375 populations distributed across the entire species range. We found stronger genetic differentiation among populations in refugia than in recolonized areas. However, contrary to expectations, regional SGS was lower within refugia than within recolonized areas. Published studies presenting similar analyses suggest that our results could have generality across different biogeographical settings and types of organisms. Strong and prolonged genetic drift in refugial areas could have erased the signature of range expansions that is still visible in recolonized areas. Our results therefore suggest that Pleistocene population isolation has played a key role in increasing the genetic complexity of extant rear‐edge populations.
Malaria infections reinforce competitive asymmetry between two Ficedula flycatchers in a recent contact zone
Authors: Kulma Katarzyna , Low Matthew , Bensch Staffan , Qvarnström Anna
Published: August 2013

Parasites may influence the outcome of interspecific competition between closely related host species through lower parasite virulence in the host with which they share the longer evolutionary history. We tested this idea by comparing the prevalence of avian malaria (Haemosporidia) lineages and their association with survival in pied and collared flycatchers (Ficedula hypoleuca and F. albicollis) breeding in a recent contact zone on the Swedish island of Öland. A nested PCR protocol amplifying haemosporidian fragments of mtDNA was used to screen the presence of malaria lineages in 1048 blood samples collected during 6 years. Competitively inferior pied flycatchers had a higher prevalence of blood parasites, including the lineages that were shared between the two flycatcher species. Multistate mark–recapture models revealed a lower survival of infected versus uninfected female pied flycatchers, while no such effects were detected in male pied flycatchers or in collared flycatchers of either sex. Our results show that a comparatively new host, the collared flycatcher, appears to be less susceptible to a local northern European malarial lineage where the collared flycatchers have recently expanded their distribution. Pied flycatchers experience strong reproductive interference from collared flycatchers, and the additional impact of species‐specific blood parasite effects adds to this competitive exclusion. These results support the idea that parasites can strongly influence the outcome of interspecific competition between closely related host species, but that the invading species need not necessarily be more susceptible to local parasites.
Population genetic data of a model symbiotic cnidarian system reveal remarkable symbiotic specificity and vectored introductions across ocean basins
Authors: Thornhill Daniel J. , Xiang Yu , Pettay D. Tye , Zhong Min , Santos Scott R.
Published: August 2013

The Aiptasia–Symbiodinium symbiosis is a promising model for experimental studies of cnidarian–dinoflagellate associations, yet relatively little is known regarding the genetic diversity of either symbiotic partner. To address this, we collected Aiptasia from 16 localities throughout the world and examined the genetic diversity of both anemones and their endosymbionts. Based on newly developed SCAR markers, Aiptasia consisted of two genetically distinct populations: one Aiptasia lineage from Florida and a second network of Aiptasia genotypes found at other localities. These populations did not conform to the distributions of described Aiptasia species, suggesting that taxonomic re‐evaluation is needed in the light of molecular genetics. Associations with Symbiodinium further demonstrated the distinctions among Aiptasia populations. According to 18S RFLP, ITS2‐DGGE and microsatellite flanker region sequencing, Florida anemones engaged in diverse symbioses predominantly with members of Symbiodinium Clades A and B, but also C, whereas anemones from elsewhere harboured only S. minutum within Clade B. Symbiodinium minutum apparently does not form a stable symbiosis with other hosts, which implies a highly specific symbiosis. Fine‐scale differences among S. minutum populations were quantified using six microsatellite loci. Populations of S. minutum had low genotypic diversity and high clonality (R = 0.14). Furthermore, minimal population structure was observed among regions and ocean basins, due to allele and genotype sharing. The lack of genetic structure and low genotypic diversity suggest recent vectoring of Aiptasia and S. minutum across localities. This first ever molecular‐genetic study of a globally distributed cnidarian and its Symbiodinium assemblages reveals host–symbiont specificity and widely distributed populations in an important model system.
Production of indole alkaloids by metabolic engineering of the tryptophan pathway in rice
Authors: Dubouzet Joseph G. , Matsuda Fumio , Ishihara Atsushi , Miyagawa Hisashi , Wakasa Kyo
Published: August 2013

Tryptophan decarboxylase (TDC) converts tryptophan (Trp) into tryptamine, consequently increasing the metabolic flow of tryptophan derivatives into the production of secondary metabolites such as indole alkaloids. We inserted an expression cassette containing OsTDC, a putative tryptophan decarboxylase gene from rice, into an expression plasmid vector containing OASA1D, the feedback‐resistant anthranilate synthase alpha‐subunit mutant (OASA1D). Overexpression of OASA1D has been reported to significantly increase Trp levels in rice. The co‐expression of OsTDC and OASA1D in rice calli led to almost complete depletion of the Trp pool and a consequent increase in the tryptamine pool. This indicates that TDC inactivity is a contributory factor for the accumulation of Trp in rice transgenics overexpressing OASA1D. Metabolic profiling of the calli expressing OsTDC and OASA1D revealed the accumulation of serotonin and serotonin‐derived indole compounds (potentially pharmacoactive β‐carbolines) that have not been reported from rice. Rice calli overexpressing OASA1D:OASA1D is a novel system for the production of significant amounts of pharmacologically useful indole alkaloids in rice.
Regulation of MSK1‐Mediated NF‐κB Activation Upon UVB Irradiation
Authors: Carpenter Oliver L. , Wu Shiyong
Published: August 2013

Nuclear Factor Kappa‐B (NF‐κB) is a transcription factor that controls expression of genes involved in the immune and inflammatory responses as well as being a key component in the onset of cancers. In this study, we provided evidence that mitogen‐ and stress‐activated protein kinase (MSK1) is responsible for a noncanonical late‐phase activation of NF‐κB upon UVB irradiation. Our data demonstrated that following UVB irradiation, MSK1 is activated via phosphorylation at the 24 h time point coinciding with translocation of NF‐κB into the nucleus. Investigations into the signaling pathways upstream of MSK1 through the use of specific inhibitors for mitogen‐activated protein kinase and p38 revealed that both kinases are required for full phosphorylation during the late phase (24 h), while p38 is paramount for phosphorylation during the early phase (6 h). Electromobility shift assays (EMSA) showed that inhibition of MSK1 resulted in a marked reduction in NF‐κB binding affinity without altering the nuclear translocation of NF‐κB. Supershift EMSA implicate that the p65, but not p50, isoform of NF‐κB is involved in late‐phase activation in response to UVB irradiation. Together, the results of these studies shed light onto a novel pathway of MSK1‐mediated late‐phase activation of NF‐κB in response to UVB irradiation.
Altered Invariant Natural Killer T cell Subsets and its Functions in Patients with Oral Squamous Cell Carcinoma
Authors: Singh A. K. , Shukla N. K. , Das S. N.
Published: August 2013

Invariant natural killer T (iNKT) cells are glycolipid‐reactive T lymphocytes that share receptors and function with natural killer (NK) cells and reportedly play a pivotal role in various immune responses. However, iNKT cells are not well characterized in patients with oral squamous cell carcinoma (OSCC). We investigated the populations and functions of circulating iNKT (CD3+6B11+) cells from thirty‐eight patients with OSCC and twenty‐eight healthy donors by flow cytometry. Circulating iNKT cells were significantly lower (P < 0.01) in patients as compared to those in healthy controls. Further, iNKT subsets revealed a marked decrease in CD4−CD8− (double negative, DN) subset with concomitant increase in CD8+ subset in patients as compared to healthy controls (P = 0.03 and P < 0.01, respectively), whereas CD4+ subset was similarly distributed in both groups. The functional analysis demonstrated that residual iNKT cells from patients had impaired proliferative response to α‐galactosylceramide (α‐GalCer)‐pulsed dendritic cells (DCs) and Th2‐like cytokine profile. However, in vitro activation with α‐GalCer‐pulsed DCs restores IFN‐γ expression and enhances antitumour activity to human cancer cells lines (SCC‐4, KB and MCF7). It appears that the selectively enriched iNKT subsets and modulation of their function by specific ligand/agonist may be useful for cellular therapy in patients with OSCC. Further, reduced levels of iNKT cells and its DN subset may be used as potential prognostic factors for patients with OSCC.
Lack of Functional TSLP Receptors Mitigates Th2 Polarization and the Establishment and Growth of 4T1 Primary Breast Tumours but has Different Effects on Tumour Quantities in the Lung and Brain
Authors: Erdmann R. B. , Gartner J. G. , Leonard W. J. , Ellison C. A.
Published: August 2013

The 4T1 mammary carcinoma cell line produces TSLP. We had hypothesized that TSLP promotes the development of a permissive environment for the growth and metastasis of primary tumour and that this is associated with a Th2‐polarized antitumour immune response. We found that, in Tslpr−/− mice, the mean tumour diameters were smaller from days 27 to 40, and relatively fewer tumour cells were present in the lung, compared with wild‐type mice. Polarization of the Th2 cytokine profile was also diminished in Tslpr−/− mice. These findings confirmed those reported previously by others. Here, we further show that primary tumours are established less often in Tslpr−/− mice and that, unexpectedly, the relative number of tumour cells in the brain is greater in Tslpr−/− mice compared with wild‐type mice. Findings from our cytotoxicity assays show that 4T1‐directed lysis is undetectable in both WT and Tslpr−/− mice, ruling out the possibility that altered cytotoxic responses in Tslpr−/− mice are responsible for the differences we observed. In a human tissue microarray, positive staining for TSLP was seen in tumour cells from breast cancer tissue, but it was also seen in normal glandular epithelial cells from normal breast tissue, which has not been shown before. Thus, our findings provide new insight into the effects of TSLP in metastatic breast cancer.
Effects of stair‐climbing on balance, gait, strength, resting heart rate, and submaximal endurance in healthy seniors
Authors: Donath L. , Faude O. , Roth R. , Zahner L.
Published: August 2013

Stair‐climbing serves as a feasible opportunity to remain physically active within everyday‐life. Data on neuromuscular and cardiorespiratory performance after regular stair‐climbing in seniors are scarce. Forty‐eight seniors were stratified to a one‐ (taking every step, INT1) or two‐step strategy (every second step, INT2) or a control group (CON). Thirty‐nine seniors [females: n = 22, males: n = 17; age: 70.5 (SD 5.1) years; BMI: 25.8 (3.1) kg/m2] completed the 8‐week intervention (three weekly sessions). Before and after the intervention, balance, gait, strength, and submaximal endurance (at different intensities) were assessed. Maximal strength and explosive power did not improve significantly (0.10 < P < 0.78). Resting heart rate was significantly reduced in INT2 (−8/min) compared with INT1 (0/min, P = 0.02) and CON (0/min, P = 0.03). Compared with CON, perceived exertion for all intensities (0.007 < P < 0.03) and submaximal exercise heart rate during moderate uphill walking significantly decreased (−11/min; P < 0.05) in INT2. Step counts for forward beam balancing (4.5 cm width) increased in INT2 (P = 0.007) compared with CON. With more pronounced effects in INT2, stair‐climbing significantly improved resting and exercise heart rates, perceived exertion, and dynamic balance performance in healthy seniors and may contribute to better overall fitness, reduced fall risk, and less perceived strain during daily life activities.
Nonelite exercise‐related injuries: Participant reported frequency, management and perceptions of their consequences
Authors: Grice A. , Kingsbury S. R. , Conaghan P. G.
Published: August 2013

This mixed methods study explored the frequency of sport/exercise‐related injuries in nonelite sport, participant‐reported management and perceptions of potential injury consequences. Focus group participants, who trained two to four times a week and had previously sustained musculoskeletal sports‐related injuries, reported seeking medical advice secondary to advice from teammates or online research. General practitioners were viewed as gatekeepers to specialist secondary care and less able to effectively treat sport‐related injuries. Participants displayed limited awareness of potential future implications of injury, and considered physical and psychological benefits of exercise more valuable than potential injury‐associated risks. In the survey of physically active people, over half reported sustaining an exercise‐related injury (562/1002, 56%). Previously injured respondents were less likely to consider consulting a health professional for injury‐related advice than those with no injury history (45% vs 64%; P < 0.001) and more likely to continue exercising despite injury (51% vs 37%; P < 0.001). Concerns about injuries largely related to short‐term issues; only 32% were concerned about possible long‐term joint problems including osteoarthritis. Exercise‐related injury was common in nonelite exercise participants. There was some dissatisfaction with care pathways for sports‐related injuries and a lack of awareness about appropriate injury management and potential consequences of injury, particularly in the long‐term.
Primary hepatic aspergillosis following induction chemotherapy for acute leukemia
Authors: Chasan R. , Patel G. , Malone A. , Finn M. , Huprikar S.
Published: August 2013

Invasive aspergillosis (IA) contributes significantly to the burden of infectious complications in heavily immunosuppressed patients with acute leukemia. The infection is typically acquired via inhalation into the respiratory tract, and the lungs are most commonly involved. However, disseminated disease may occur and reports of isolated extrapulmonary infection suggest the gastrointestinal tract is likely an additional portal of entry for this organism. We describe a case of primary hepatic aspergillosis in a patient with acute myelogenous leukemia. The patient did not respond to medical therapy with antifungals and ultimately required surgical exploration and drainage. IA should be considered in an immunosuppressed patient with hepatic abscesses and may require a combined surgical and medical approach to therapy.
Generation of a phage‐display library of single‐domain camelid VHH antibodies directed against Chlamydomonas reinhardtii antigens, and characterization of VHHs binding cell‐surface antigens
Authors: Jiang Wenzhi , Rosenberg Julian N. , Wauchope Akelia D. , Tremblay Jacqueline M. , Shoemaker Charles B. , Weeks Donald P. , Oyler George A.
Published: August 2013

Single‐domain antibodies (sdAbs) are powerful tools for the detection, quantification, purification and subcellular localization of proteins of interest in biological research. We have generated camelid (Lama pacos) heavy chain‐only variable VH domain (VHH) libraries against antigens in total cell lysates from Chlamydomonas reinhardtii. The sdAbs in the sera from immunized animals and VHH antibody domains isolated from the library show specificity to C. reinhardtii and lack of reactivity to antigens from four other algae: Chlorella variabilis, Coccomyxa subellipsoidea, Nannochloropsis oceanica and Thalassiosira pseudonana. Antibodies were produced against a diverse representation of antigens as evidenced by sera ELISA and protein‐blot analyses. A phage‐display library consisting of the VHH region contained at least 106 individual transformants, and thus should represent a wide range of C. reinhardtii antigens. The utility of the phage library was demonstrated by using live C. reinhardtii cells to pan for VHH clones with specific recognition of cell‐surface epitopes. The lead candidate VHH clones (designated B11 and H10) bound to C. reinhardtii with EC50 values ≤0.5 nm. Treatment of cells with VHH B11 fused to the mCherry or green fluorescent proteins allowed brilliant and specific staining of the C. reinhardtii cell wall and analysis of cell‐wall genesis during cell division. Such high‐complexity VHH antibody libraries for algae will be valuable tools for algal researchers and biotechnologists.
A BAC physical map of aus rice cultivar ‘Kasalath’, and the map‐based genomic sequence of ‘Kasalath’ chromosome 1
Authors: Kanamori Hiroyuki , Fujisawa Masaki , Katagiri Satoshi , Oono Youko , Fujisawa Hiroko , Karasawa Wataru , Kurita Kanako , Sasaki Harumi , Mori Satomi , Hamada Masao , Mukai Yoshiyuki , Yazawa Takayuki , Mizuno Hiroshi , Namiki Nobukazu , Sasaki Takuji , Katayose Yuichi , Matsumoto Takashi , Wu Jianzhong
Published: August 2013

Comparative analysis using available genomic resources within closely related species is an effective way to investigate genomic sequence and structural diversity. Rice (Oryza sativa L.) has undergone significant physiological and morphological changes during its domestication and local adaptation. We present a complete bacterial artificial chromosome (BAC) physical map for the aus rice cultivar ‘Kasalath’, which covers 90% of the sequence of temperate japonica rice cultivar ‘Nipponbare’. Examination of physical distances between computational and experimental measurements of ‘Kasalath’ BAC insert size revealed the presence of more than 500 genomic regions that appear to have significant chromosome structural changes between the two cultivars. In particular, a genomic region on the long arm of ‘Kasalath’ chromosome 11 carrying a disease‐resistance gene cluster was greatly expanded relative to the ‘Nipponbare’ genome. We also decoded 41.37 Mb of high‐quality genomic sequence from ‘Kasalath’ chromosome 1. Extensive comparisons of chromosome 1 between ‘Kasalath’ and ‘Nipponbare’ led to the discovery of 317 843 single‐nucleotide polymorphisms (SNPs) and 66 331 insertion/deletion (indel) sites. Nearly two‐thirds of the expressed genes on rice chromosome 1 carried natural variations involving SNPs and/or indels that resulted in substitutions, insertions or deletions of amino acids in one cultivar relative to the other. We also observed gain and loss of genes caused by large indels. This study provides an important framework and an invaluable dataset for further understanding of the molecular mechanisms underlying the evolution and functions of the rice genome.
Soil Models and Vehicle System Dynamics
Authors: Contreras Ulysses , Li Guangbu , Foster Craig D. , Shabana Ahmed A. , Jayakumar Paramsothy , Letherwood Michael D.
Published: August 2013

The mechanical behavior of soils may be approximated using different models that depend on particular soil characteristics and simplifying assumptions. For this reason, researchers have proposed and expounded upon a large number of constitutive models and approaches that describe various aspects of soil behavior. However, there are few material models capable of predicting the behavior of soils for engineering applications and are at the same time appropriate for implementation into finite element (FE) and multibody system (MBS) algorithms. This paper presents a survey of some of the commonly used continuum-based soil models. The aim is to provide a summary of continuum-based soil models and examine their suitability for integration with the large-displacement FE absolute nodal coordinate formulation (ANCF) and MBS algorithms. Special emphasis is placed on the formulation of soils used in conjunction with vehicle dynamics models. The implementation of these soil models in MBS algorithms used in the analysis of complex vehicle systems is also discussed. Because semiempirical terramechanics soil models are currently the most widely used to study vehicle/soil interaction, a review of classical terramechanics models is presented in order to be able to explain the modes of displacements that are not captured by these simpler models. Other methods such as the particle-based and mesh-free models are also briefly reviewed. A Cam–Clay soil model is used in this paper to explain how such continuum-mechanics based soil models can be implemented in FE/MBS algorithms.
Microstructural Evolution of GdZ and DySZ Based EB-PVD TBC Systems After Thermal Cycling at High Temperature
Authors: Umar Munawar Ahmed , Schulz Uwe , Cerri Giovanni
Published: August 2013

Lower thermal conductivity and high temperature stability are the two properties which are highly desired from ceramic top coat materials in thermal barrier coating (TBC) systems. Gadolinium zirconate, Gd2Zr2O7 (GdZ) and dyprosia stabilized zirconia (DySZ) are two of the candidate materials with such properties and consequently the TBC system would be able to work at higher turbine inlet temperature (TIT) or the lifetime can be increased. In the present study, lifetime measurements are done for single and double layered electron beam physical vapor deposition (EB-PVD) GdZ and DySZ samples by thermal-cycling tests. The double layered TBCs consisted of a thin 7YSZ layer and, on top, the new candidate material. Both single and double layered samples of GdZ and DySZ have shown similar or better lifetimes than the standard 7YSZ samples. However, single layered TBCs showed better lifetime results than the respective double layers. In this study, changes in the microstructure, diffusion of elements and sintering of the TBC materials with aging are observed.
Smooth MgO films grown on graphite and graphene by pulsed laser deposition
Authors: Stuart Sean C. , Satchet Edward , Sandin Andreas , Maria Jon-Paul , Rowe John E. (Jack) , Dougherty Daniel B. , Ulrich Marc
Published: August 2013

Pulsed laser deposition was used to grow thin (1–100 nm) magnesium oxide films directly on graphite and epitaxial graphene on SiC(0001). The authors observe very smooth (typical rms roughness of ∼0.4 nm) film morphologies that are nearly independent of film thickness and conformal to the substrate for films grown on room temperature substrates. Surface roughness is less than 1 nm for thicknesses up to 100 nm and is independent of oxygen background pressure during growth. X-ray diffraction shows no evidence of crystallinity for films grown on room temperature substrates but shows ⟨100⟩ texture for films grown on heated substrates that also have very rough surface morphologies. X-ray photoelectron spectroscopy shows hydroxylation of films due to air exposure that can only be partially removed by annealing, indicating the presence of atomic defects in the films.
Simulation of the transient heat transfer between two coaxial cylinders
Authors: Graur Irina , Ho Minh Tuan , Wuest Martin
Published: August 2013

The transient heat flux between two coaxial cylinders is studied on the basis of the numerical solution of the nonlinear unsteady S-model kinetic equation. A large range of the gas rarefaction and two temperature ratios between the cylinders' walls are considered. The time evolutions of the averaged over the distance between the cylinders heat flux, pressure, and bulk velocity are analyzed. The steady state time, as a time of steady state flow establishment, is introduced. This time depends on the characteristic time of the system and on the gas rarefaction. It is found that this steady state time for the averaged heat flux varies approximately 18 times from the near free molecular to the hydrodynamic flow regime. In the slip flow regime, the analytical expression for the steady state temperature distribution between two cylinders is obtained. It is found that the transient heat flux evolution derived from the energy balance allows to estimate the time of steady state flow establishment in the slip flow regime.
Inductively coupled plasma–reactive ion etching of c- and a-plane AlGaN over the entire Al composition range: Effect of BCl3 pretreatment in Cl2/Ar plasma chemistry
Authors: Shah Amit P. , Laskar Masihhur R. , Azizur Rahman A. , Gokhale Maheshwar R. , Bhattacharya Arnab
Published: August 2013

Inductively coupled plasma (ICP)–reactive ion etching (RIE) patterning is a standard processing step for UV and optical photonic devices based on III-nitride materials. There is little research on ICP-RIE of high Al-content AlGaN alloys and for nonpolar nitride orientations. The authors present a comprehensive study of the ICP-RIE of c- and a-plane AlGaN in Cl2/Ar plasma over the entire Al composition range. The authors find that the etch rate decreases in general with increasing Al content, with different behavior for c- and a-plane AlGaN. They also study the effect of BCl3 deoxidizing plasma pretreatment. An ICP deoxidizing BCl3 plasma with the addition of argon is more efficient in removal of surface oxides from AlxGa1−xN than RIE alone. These experiments show that AlxGa1−xN etching is affected by the higher binding energy of AlN and the higher affinity of oxygen to aluminum compared to gallium, with oxides on a-plane AlGaN more difficult to etch as compared to oxides on c-plane AlGaN, specifically for high Al composition materials. The authors achieve reasonably high etch rate (∼350 nm/min) for high Al-content materials with a smooth surface morphology at a low DC bias of ∼−45 VDC.
Nutrient Regulation of Immunity: O-GlcNAcylation Regulates Stimulus-Specific NF-κB–Dependent Transcription
Authors: Hart Gerald W.
Published: August 2013

Posttranslational modification of a shared transcription factor enables distinct stimuli to elicit the expression of different target genes.
HIV Detection Is a (c)GAS
Authors: Mueller Kristen L.
Published: August 2013

Cell culture experiments suggest that detection of retroviral DNA activates cellular defense systems.
Dissecting Dystrophies
Authors: Hurtley Stella M.
Published: August 2013

An atypical kinase genetically associated with muscular dystrophies recognizes a unique trisaccharide structure.
Homeostasis of Glutathione Is Associated with Polyamine-Mediated β-Lactam Susceptibility in Acinetobacter baumannii ATCC 19606
Authors: Kwon Dong H. , Hekmaty Saboor , Seecoomar Gomattie
Published: August 2013

Glutathione is a tripeptide (
l
-γ-glutamyl–
l
-cysteinyl–glycine) thiol compound existing in many bacteria and maintains a proper cellular redox state, thus protecting cells against toxic substances such as reactive oxygen species. Polyamines (spermine and spermidine) are low-molecular-weight aliphatic polycations ubiquitously presenting in all living cells and modulate many cellular functions. We previously reported that exogenous polyamines significantly enhanced β-lactam susceptibility of β-lactam-associated multidrug-resistant
Acinetobacter baumannii
. In this study, three genes differentially associated with the polyamine effects on β-lactam susceptibility were identified by transposon mutagenesis of
A. baumannii
ATCC 19606. All three genes encoded components of membrane transport systems. Inactivation of one of the genes encoding a putative glutathione transport ATP-binding protein increased the accumulation of intracellular glutathione (∼150 to ∼200%) and significantly decreased the polyamine effects on β-lactam susceptibility in
A. baumannii
ATCC 19606. When the cells were grown with polyamines, the levels of intracellular glutathione in
A. baumannii
ATCC 19606 significantly decreased from ∼0.5 to ∼0.2 nmol, while the levels of extracellular glutathione were correspondingly increased. However, the levels of total glutathione (intra- plus extracellular) were unchanged when the cells were grown with or without polyamines. Overall, these results suggest that exogenous polyamines induce glutathione export, resulting in decreased levels of intracellular glutathione, which may produce an improper cellular redox state that is associated with the polyamine-mediated β-lactam susceptibility of
A. baumannii
. This finding may provide a clue for development of new antimicrobial agents and/or novel strategies to treat multidrug-resistant
A. baumannii
.
Effects of Bacteriocins on Methicillin-Resistant Staphylococcus aureus Biofilm
Authors: Okuda Ken-ichi , Zendo Takeshi , Sugimoto Shinya , Iwase Tadayuki , Tajima Akiko , Yamada Satomi , Sonomoto Kenji , Mizunoe Yoshimitsu
Published: August 2013

Control of biofilms formed by microbial pathogens is an important subject for medical researchers, since the development of biofilms on foreign-body surfaces often causes biofilm-associated infections in patients with indwelling medical devices. The present study examined the effects of different kinds of bacteriocins, which are ribosomally synthesized antimicrobial peptides produced by certain bacteria, on biofilms formed by a clinical isolate of methicillin-resistant
Staphylococcus aureus
(MRSA). The activities and modes of action of three bacteriocins with different structures (nisin A, lacticin Q, and nukacin ISK-1) were evaluated. Vancomycin, a glycopeptide antibiotic used in the treatment of MRSA infections, showed bactericidal activity against planktonic cells but not against biofilm cells. Among the tested bacteriocins, nisin A showed the highest bactericidal activity against both planktonic cells and biofilm cells. Lacticin Q also showed bactericidal activity against both planktonic cells and biofilm cells, but its activity against biofilm cells was significantly lower than that of nisin A. Nukacin ISK-1 showed bacteriostatic activity against planktonic cells and did not show bactericidal activity against biofilm cells. Mode-of-action studies indicated that pore formation leading to ATP efflux is important for the bactericidal activity against biofilm cells. Our results suggest that bacteriocins that form stable pores on biofilm cells are highly potent for the treatment of MRSA biofilm infections.
Staphylococcus aureus Fatty Acid Auxotrophs Do Not Proliferate in Mice
Authors: Parsons Joshua B. , Frank Matthew W. , Rosch Jason W. , Rock Charles O.
Published: August 2013

Inactivation of acetyl-coenzyme A (acetyl-CoA) carboxylase confers resistance to fatty acid synthesis inhibitors in
Staphylococcus aureus
on media supplemented with fatty acids. The addition of
anteiso
-fatty acids (1 mM) plus lipoic acid supports normal growth of Δ
accD
strains, but supplementation with mammalian fatty acids was less efficient. Mice infected with strain RN6930 developed bacteremia, but bacteria were not detected in mice infected with its Δ
accD
derivative.
S. aureus
bacteria lacking acetyl-CoA carboxylase can be propagated
in vitro
but were unable to proliferate in mice, suggesting that the acquisition of inactivating mutations in this enzyme is not a mechanism for the evasion of fatty acid synthesis inhibitors.
Lack of Pharmacokinetic Interaction between Rilpivirine and Integrase Inhibitors Dolutegravir and GSK1265744
Authors: Ford Susan L. , Gould Elizabeth , Chen Shuguang , Margolis David , Spreen William , Crauwels Herta , Piscitelli Stephen
Published: August 2013

Dolutegravir (DTG) and GSK1265744 are HIV integrase inhibitors (INIs) in clinical development. The oral formulation of rilpivirine (RPV), a nonnucleoside reverse transcriptase inhibitor (NNRTI), has been approved for treatment-naive HIV infection. Long-acting depot injections of GSK1265744 and RPV are also being developed. This study evaluated the potential for drug interactions between RPV and these INIs. This phase 1, open-label, two-cohort, three-period, single-sequence crossover study evaluated oral coadministration of RPV with DTG or GSK1265744. Healthy subjects received DTG (50 mg every 24 h for 5 days) or GSK1265744 (30 mg every 24 h for 12 days) in period 1 followed by a washout, RPV (25 mg every 24 h for 11 or 12 days) in period 2, immediately followed by RPV (25 mg every 24 h) plus DTG (50 mg every 24 h) for 5 days or GSK1265744 (30 mg every 24 h) for 12 days in period 3. Steady-state pharmacokinetic (PK) parameters were estimated using noncompartmental analysis of data collected on the last day of each period. The combinations of RPV and DTG (
n
= 16) and of RPV and GSK1265744 (
n
= 11) were well tolerated; no grade 3 or 4 adverse events (AEs) or AE-related discontinuations were observed. The 90% confidence intervals for the area under the curve from time zero until the end of the dosage interval [AUC
0–τ
] and maximum concentration of drug in serum (
C
max
) geometric mean ratios were within 0.8 to 1.25. Following administration of DTG + RPV, DTG and RPV
C
τ increased by 22% and 21%, respectively. Following administration of GSK1265744 + RPV, RPV
C
τ decreased 8%. DTG and GSK1265744 can be administered with RPV without dosage adjustment for either agent. These results support coadministration of RPV with DTG or GSK1265744 as either oral or long-acting depot injection regimens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01467531.)
Mutational Analysis of Quinolone Resistance Protein QnrB1
Authors: Jacoby George A. , Corcoran Marian A. , Mills Debra M. , Griffin Caitlin M. , Hooper David C.
Published: August 2013

Alanine substitutions and selected deletions have been used to localize amino acids in QnrB essential for its protective activity. Essential amino acids are found at positions i and i
−2
in the pentapeptide repeat module and in the larger of two loops, where deletion of only a single amino acid compromises activity. Deletion of 10 amino acids at the N terminus is tolerated, but removal of 3 amino acids in the C-terminal dimerization unit destroys activity.
Flucytosine Antagonism of Azole Activity versus Candida glabrata: Role of Transcription Factor Pdr1 and Multidrug Transporter Cdr1
Authors: Steier Zoë , Vermitsky John-Paul , Toner Geoffrey , Gygax Scott E. , Edlind Thomas , Katiyar Santosh
Published: August 2013

Infections with the opportunistic yeast
Candida glabrata
have increased dramatically in recent years. Antifungal therapy of yeast infections commonly employs azoles, such as fluconazole (FLC), but
C. glabrata
frequently develops resistance to these inhibitors of ergosterol biosynthesis. The pyrimidine analog flucytosine (5-fluorocytosine [5FC]) is highly active versus
C. glabrata
but is now rarely used clinically due to similar concerns over resistance and, a related concern, the toxicity associated with high doses used to counter resistance. Azole-5FC combination therapy would potentially address these concerns; however, previous studies suggest that 5FC may antagonize azole activity versus
C. glabrata
. Here, we report that 5FC at subinhibitory concentrations antagonized the activity of FLC 4- to 16-fold versus 8 of 8
C. glabrata
isolates tested. 5FC antagonized the activity of other azoles similarly but had only indifferent effects in combination with unrelated antifungals. Since azole resistance in
C. glabrata
results from transcription factor Pdr1-dependent upregulation of the multidrug transporter gene
CDR1
, we reasoned that 5FC antagonism might be similarly mediated. Indeed, 5FC-FLC antagonism was abrogated in
pdr1
Δ and
cdr1
Δ strains. In further support of this hypothesis, 5FC exposure induced
CDR1
expression 6-fold, and this upregulation was Pdr1 dependent. In contrast to azoles, 5FC is not a Cdr1 substrate and so its activation of Pdr1 was unexpected. We observed, however, that 5FC exposure readily induced petite mutants, which exhibit Pdr1-dependent
CDR1
upregulation. Thus, mitochondrial dysfunction resulting in Pdr1 activation is the likely basis for 5FC antagonism of azole activity versus
C. glabrata
.