bluuebunny/crossref_metadata_2025 huggingface dataset:
Eating and Feeding at the Margins of the State: Barriers to Health Care for Undocumented Migrant Women and the “Clinical” Aspects of Food Assistance
Authors: Carney Megan A.
Published: February 2015

In this article, I examine the various meanings of Mexican and Central American migrant women's utilization of private food assistance programs. I present findings from 20 months of ethnographic fieldwork conducted between 2008 and 2011 with migrant women, public health workers, and staff and volunteers of food assistance programs in Santa Barbara County, California. I discuss the barriers undocumented women face in accessing formal health care and the social and moral obligations that underpin these women's role in feeding others. I also document the ways in which private food assistance programs are orienting toward a focus on health in service delivery, and how women depend on provisions from these programs to support feeding practices at home. I argue that these findings are significant for current engagement by critical medical anthropologists in studying framings of “the clinic” and cultural beliefs about “deservingness.”
Iron bioavailability in 8–24‐month‐old Thai children from a micronutrient‐fortified quick‐cooking rice containing ferric ammonium citrate or a mixture of ferrous sulphate and ferric sodium ethylenediaminetetraacetic acid
Authors: Chavasit Visith , Porasuphatana Suparat , Suthutvoravut Umaporn , Zeder Christroph , Hurrell Richard
Published: February 2015

A quick‐cooking rice, produced from broken rice, is a convenient ingredient for complementary foods in Thailand. The rice is fortified with micronutrients including iron during the processing procedure, which can cause unacceptable sensory changes. A quick‐cooking rice fortified with ferric ammonium citrate (FAC) or a mixture of ferrous sulphate (FeSO4) and ferric sodium ethylenediaminetetraacetic acid (NaFeEDTA), with a 2:1 molar ratio of iron from FeSO4 : iron from NaFeEDTA (FeSO4 + NaFeEDTA), gave a product that was organoleptically acceptable. The study compared iron absorption by infants and young children fed with micronutrient‐fortified quick‐cooking rice containing the test iron compounds or FeSO4. Micronutrient‐fortified quick‐cooking rice prepared as a traditional Thai dessert was fed to two groups of 15 8–24‐month healthy Thai children. The iron fortificants were isotopically labelled with 57Fe for the reference FeSO4 or 58Fe for the tested fortificants, and iron absorption was quantified based on erythrocyte incorporation of the iron isotopes 14 days after feeding. The relative bioavailability of FAC and of the FeSO4 + NaFeEDTA was obtained by comparing their iron absorption with that of FeSO4. Mean fractional iron absorption was 5.8% [±standard error (SE) 1.9] from FAC and 10.3% (±SE 1.9) from FeSO4 + NaFeEDTA. The relative bioavailability of FAC was 83% (P = 0.02). The relative bioavailability of FeSO4 + NaFeEDTA was 145% (P = 0.001). Iron absorption from the rice containing FAC or FeSO4 + NaFeEDTA was sufficiently high to be used in its formulation, although iron absorption from FeSO4 + NaFeEDTA was significantly higher (P < 0.00001).
Morphological and cytological data support the independent specific status of Parasenecio delphiniiphyllus (Asteraceae–Senecioneae) from China
Authors: Ren Chen , Luo Jiang‐Ping , Hong Yu , Yang Qin‐Er
Published: February 2015

We demonstrate that the controversial Parasenecio delphiniiphyllus (known from northeastern Yunnan and western Guizhou, China) is not conspecific with P. delphiniifolius (Japan) since these two species are readily distinguishable by inflorescence structure and involucre length, as well as in the length of anther tails and anther collars. The two species also have different chromosome numbers, 2n = 60 in P. delphiniiphyllus and 2n = 52 in P. delphiniifolius. Evidence from gross morphology, floral micro‐morphology, cytology and geographical distribution strongly supports the independent specific status of P. delphiniiphyllus.
Effects of forest fragmentation on the oak–rodent mutualism
Authors: Morán‐López Teresa , Fernández Miguel , Alonso Cesar Luis , Flores‐Rentería Dulce , Valladares Fernando , Díaz Mario
Published: February 2015

Land‐use changes are expected to affect plant–disperser conditional mutualisms through changes in animal behavior. We analyzed the oak–rodent conditional mutualism in Mediterranean fragmented forests at two climatically different locations. We quantified fragmentation effects on seed dispersal effectiveness and assessed if such effects were due to changes in habitat structure and intraspecific competition for acorns in fragmented areas. Fragmentation decreased cover from predators within mouse territories as well as intraspecific competition for acorns. This resulted in lower dispersal effectiveness in small forest fragments. Globally, habitat structure was the main driver in mouse foraging decisions. In small fragments, low shelter availability precluded mouse movements, leading to short mobilization distances and low caching rates. However, as the proportion of cover from predators increased, mice were able to modulate their foraging decisions depending on intraspecific competition for acorns, resulting in higher dispersal quality. In addition to fragmentation effects, delayed breeding in the southern locality caused lower number of rodents during the dispersal season, which reduced acorn mobilization rates. Our study shows that seed dispersal patterns in managed systems can be analyzed as the result of management effects on key environmental factors in dispersers’ foraging decisions.
ORGANIZATIONAL PATHWAYS TO COMPLIANT REFORM IMPLEMENTATION: EVIDENCE FROM MEXICAN CIVIL SERVICE REFORM
Authors: NIETO MORALES FERNANDO , WITTEK RAFAEL , HEYSE LIESBET
Published: February 2015

A technocratic pathway to public management reform stresses the need for committing sizeable resources to reform implementation. Building on an institutional framework, we argue that there are alternative pathways to compliant implementation for government agencies with limited resources. Our comparative study of 55 Mexican government agencies that were the object of the 2003 Civil Service Reform Act reveals the co‐occurrence of both technocratic and institutional pathways to compliant implementation. The common denominator across pathways in organizations with limited resources was the absence of strong oppositional norms (patronage) and the presence of robust interpersonal trust. We conclude that the role played by available resources in compliant reform implementation is far from straightforward, and depends on different combinations of public organizations' endogenous characteristics.
Explaining Disagreement: A Problem for (Some) Hybrid Expressivists
Authors: Eriksson John
Published: February 2015

Hybrid expressivists depart from pure expressivists by claiming that moral sentences express beliefs and desires.DanielBoisvert andMichaelRidge, two prominent defenders of hybrid views, also depart from pure expressivists by claiming that moral sentences express general attitudes rather than an attitude towards the subject of the sentence. This article argues that even if the shift to general attitudes helps solve some of the traditional problems associated with pure expressivism, a view likeRidge's, according to which the descriptive meaning is speaker relative, turns out to have problems explaining moral disagreement.
Successful Treatment of Severe Psoriasis in an Adolescent with Ustekinumab
Authors: AbuHilal Mohn'd , Ho Nhung
Published: February 2015

Psoriasis is a chronic, inflammatory, immune‐mediated disease. Approximately 30% of patients have disease onset before age 18 years. Psoriasis in children and adolescents may be difficult to control, with subsequent poor quality of life and psychosocial consequences. We describe the case of a 12‐year‐old boy with severe, refractory, chronic plaque psoriasis for 6 years. Various therapeutic regimens including different topical corticosteroids, topical vitamin D analogs, phototherapy, photochemotherapy, systemic therapy with methotrexate, cyclosporin, and combination therapies showed only partial or transient responses with frequent relapses. Because anti‐interleukin‐12/23 agents have been successfully used in adults with psoriasis, ustekinumab was initiated and our patient showed a rapid, excellent, sustained response. No recurrence or flares have been observed after 33 months of follow‐up. This case illustrates that ustekinumab may be an effective and safe therapeutic option in adolescents with psoriasis.
Interleukin‐10 and tumour necrosis factor‐alpha serum levels in chronic Chagas disease patients
Authors: Vasconcelos R. H. T. , Azevedo E. de A. N. , Diniz G. T. N. , Cavalcanti M. da G. A. de M. , de Oliveira W. , de Morais C. N. L. , Gomes Y. de M.
Published: February 2015

In Chagas disease, chronically infected individuals may be asymptomatic or may present cardiac or digestive complications, and it is well known that the human immune response is related to different clinical manifestations. Different patterns of cytokine levels have been previously described in different clinical forms of this disease, but contradictory results are reported. Our aim was to evaluate the serum levels of interleukin‐10 and tumour necrosis factor‐alpha in patients with asymptomatic and cardiac Chagas disease. The serum interleukin‐10 levels in patients with cardiomyopathy were higher than those in asymptomatic patients, mainly in those without heart enlargement. Although no significant difference was observed in serum tumour necrosis factor‐alpha levels among the patients, we found that cardiac patients also present high levels of this cytokine, largely those with heart dilatation. Therefore, these cytokines play an important role in chronic Chagas disease cardiomyopathy. Follow‐up investigations of these and other cytokines in patients with chronic Chagas disease need to be conducted to improve the understanding of the immunopathology of this disease.
Late‐life homicide‐suicide: a national case series inNewZealand
Authors: Cheung Gary , Hatters Friedman Susan , Sundram Frederick
Published: March 2015

Homicide‐suicide is a rare event, but it has a significant impact on the family and community of the perpetrator and victim(s). The phenomenon of late‐life homicide‐suicide has not been previously studied inNewZealand, and there is only limited data in the international literature. The aim of this study is to systematically review coroners' records of late‐life homicide‐suicides inNewZealand. After ethics approval was granted, the Coronial Services ofNewZealand was approached to provide records of all closed cases with a suicide verdict (age 65+) over a five‐year period (July 2007–December 2012). Of the 225 suicides, 4 cases of homicide‐suicide were identified (an estimated incidence of 0.12 per 100 000 per persons year). All four perpetrators were men; three had been farmers. Their ages ranged from 65 to 82. One case occurred in the context of an underlying psychiatric illness (psychotic depression in bipolar disorder). Firearms were used in three cases. Two cases were categorized as spousal/consortial subtype, one case as filicide‐suicide, and one case as siblicide‐suicide. The prospect of major social upheaval in the form of losing their homes was present in all four cases. The findings of this case series were consistent with the limited existing literature on homicide‐suicide. Age‐related biopsychosocial issues were highlighted in this case series of late‐life homicide‐suicide. Additionally, evaluating firearm licences in high‐risk groups may represent a prevention strategy.
Resampling (bootstrapping) the mean: A definite do
Authors: Rosenfeld J. Peter , Donchin Emanuel
Published: February 2015

There has been discussion lately about whether bootstrap versus permutations methods are the more appropriate in diagnostic psychophysiology, especially in the context of concealed information tests (CITs), also called guilty knowledge tests (GKTs). We review the use of bootstrapping in most published CIT/GKT studies (where means, or correlations, as opposed to peak amplitudes are estimated) and find them valid and reliable. When bootstrapping and permutations were applied to the same synthesized ERP datasets, they agreed 98.1% of the time, averaged over 24,000 iterations.
A toll‐like receptor 3 single nucleotide polymorphism in Japanese patients with sarcoidosis
Authors: Ikezoe K. , Handa T. , Tanizawa K. , Kubo T. , Ito I. , Sokai A. , Nakatsuka Y. , Nagai S. , Izumi T. , Mishima M.
Published: February 2015

Toll‐like receptor 3 (TLR3) may be associated with T helper 1 immune response. This study aimed to investigate the role of a functional TLR3 single nucleotide polymorphism (SNP) in sarcoidosis. We genotyped 220 Japanese patients with sarcoidosis and 140 controls for TLR3 SNP rs3775291 to analyze its association with susceptibility to sarcoidosis and assessed its relationship to clinical features in 172 patients over 2 years. The TLR3 rs3775291 genotype was not significantly associated with disease susceptibility. However, patients with cardiac sarcoidosis (CS) significantly more frequently had the TT genotype (p < 0.01) or the T allele (p < 0.05) than those patients without CS. We conclude that TLR3 SNP rs3775291 may affect cardiac involvement in Japanese patients with sarcoidosis.
Review: The role of antibodies, autoantigens and food allergens in canine atopic dermatitis
Authors: Pucheu‐Haston Cherie M. , Bizikova Petra , Eisenschenk Melissa N. C. , Santoro Domenico , Nuttall Tim , Marsella Rosanna
Published: February 2015

Background

Canine atopic dermatitis (AD) is considered to be an immunoglobulin E (IgE)‐mediated hypersensitivity response to environmental allergens. The role of other antibody isotypes and nonenvironmental allergens in disease pathogenesis remains unclear.

Objectives

The objective of this review is to provide an update on advances in the understanding of the relevance of specific antibody isotypes, autoallergens and nonenvironmental allergens in the pathogenesis of canineAD.

Methods

Citation databases, abstracts and proceedings from international meetings published between 2001 and 2013 were reviewed. Where necessary, older articles were included for background information.

Results

Neither total nor allergen‐specific IgE necessarily correlates with clinical disease in canineAD. Some dogs exhibit clinical signs that are indistinguishable fromADbut have no demonstrable allergen‐specific IgE (atopic‐like dermatitis). Allergen‐specific immunoglobulin G may be demonstrated in canineAD, but there is no evidence that this isotype plays a role in disease development. Although humans withADmay develop serum IgE against autoallergens, this finding has not been substantiated in the dog. In contrast, adverse food reactions are frequently co‐associated withADin the dog. Ingestion of food and environmental allergens may trigger exacerbations ofAD.

Conclusions and clinical importance

Determination of the role of IgE in the pathogenesis of canineADstill requires clarification. Clinical trials and research studies must distinguish atopic dogs with allergen‐specific IgE or skin test reactivity from those without. There is no convincing evidence demonstrating a pathogenic role for either allergen‐specific immunoglobulin G or autoallergens in canineAD, but food items may be triggers for disease flares in certain individuals.
Modulation of sweet taste sensitivities by endogenous leptin and endocannabinoids in mice
Authors: Niki Mayu , Jyotaki Masafumi , Yoshida Ryusuke , Yasumatsu Keiko , Shigemura Noriatsu , DiPatrizio Nicholas V. , Piomelli Daniele , Ninomiya Yuzo
Published: February 2015

Key points

Potential roles of endogenous leptin and endocannabinoids in sweet taste were examined by using pharmacological antagonists and mouse models including leptin receptor deficient (db/db) and diet‐induced obese (DIO) mice.

Chorda tympani (CT) nerve responses of lean mice to sweet compounds were increased after administration of leptin antagonist (LA) but not affected by administration of cannabinoid receptor antagonist (AM251).

db/db mice showed clear suppression of CT responses to sweet compounds after AM251, increased endocannabinoid levels in the taste organ, and enhanced expression of a biosynthesizing enzyme of endocannabinoids in taste cells.

The effect of LA was gradually decreased and that of AM251 was increased during the course of obesity in DIO mice.

These findings suggest that circulating leptin, but not local endocannabinoids, is a dominant modulator for sweet taste in lean mice and endocannabinoids become more effective modulators of sweet taste under conditions of deficient leptin signalling.

Leptin is an anorexigenic mediator that reduces food intake by acting on hypothalamic receptor Ob‐Rb. In contrast, endocannabinoids are orexigenic mediators that act via cannabinoid CB1 receptors in hypothalamus, limbic forebrain, and brainstem. In the peripheral taste system, leptin administration selectively inhibits behavioural, taste nerve and taste cell responses to sweet compounds. Opposing the action of leptin, endocannabinoids enhance sweet taste responses. However, potential roles of endogenous leptin and endocannabinoids in sweet taste remain unclear. Here, we used pharmacological antagonists (Ob‐Rb: L39A/D40A/F41A (LA), CB1: AM251) and examined the effects of their blocking activation of endogenous leptin and endocannabinoid signalling on taste responses in lean control, leptin receptor deficient db/db, and diet‐induced obese (DIO) mice. Lean mice exhibited significant increases in chorda tympani (CT) nerve responses to sweet compounds after LA administration, while they showed no significant changes in CT responses after AM251. In contrast, db/db mice showed clear suppression of CT responses to sweet compounds after AM251, increased endocannabinoid (2‐arachidonoyl‐sn‐glycerol (2‐AG)) levels in the taste organ, and enhanced expression of a biosynthesizing enzyme (diacylglycerol lipase α (DAGLα)) of 2‐AG in taste cells. In DIO mice, the LA effect was gradually decreased and the AM251 effect was increased during the course of obesity. Taken together, our results suggest that circulating leptin, but not local endocannabinoids, may be a dominant modulator for sweet taste in lean mice; however, endocannabinoids may become more effective modulators of sweet taste under conditions of deficient leptin signalling, possibly due to increased production of endocannabinoids in taste tissue.
Coupled Multi-Disciplinary Simulation of Composite Engine Structures in Propulsion Environment
Authors: Chamis Christos C. , Singhal Surendra N.
Published: March 2015

A computational simulation procedure is described for the coupled response of multi-layered multi-material composite engine structural components which are subjected to simultaneous multi-disciplinary thermal, structural, vibration, and acoustic loadings including the effect of hostile environments. The simulation is based on a 3D finite element analysis technique in conjunction with structural mechanics codes and with the acoustic analysis methods. The composite material behavior is assessed at the various composite scales, i.e., the laminate/ply/fiber and matrix constituents, via a nonlinear material characterization model. Sample cases exhibiting nonlinear geometrical, material, loading, and environmental behavior of aircraft engine fan blades, are presented. Results for deformed shape, vibration frequencies, mode shapes, and acoustic noise emitted from the fan blade, are discussed for their coupled effect in hot and humid environment. Results such as acoustic noise for coupled composite-mechanics/heat transfer/structural/vibration/acoustic analyses demonstrate the effectiveness of coupled multi-disciplinary computational simulation and the various advantages of composite materials compared to metals.
Development of a Gas Turbine Generator On-Board Electric Power Source for MAGLEV Trains
Authors: Washizu Teruo , Morishita Teru , Matsuda Shoji , Terauchi Nobuo
Published: March 2015

We have been jointly developing an on-board electric power source for MAGLEV trains by applying a 30kW generator for gas turbine hybrid passenger cars.

Operating the generator on a test model apparatus simulating the generator installed in a MAGLEV train, we investigated its electrical and mechanical characteristics with the location close to superconducting coils. The effects of magnetic field on the generator’s characteristics are investigated and described in this paper.

MAGLEV trains require about a 50kW on-board power supply per car. At present, we are designing a 50kW gas turbine generator on the basis of the 30kW gas turbine generator.
Integration of Condition Monitoring Technologies for the Health Monitoring of Gas Turbines
Authors: Meher-Homji Cyrus B. , Cullen Jim P.
Published: March 2015

Rapid advancements in gas turbine technology have created a need for advanced condition monitoring systems for critical applications of gas turbines. With a new generation of high temperature and high output engines (150–200 MW) the objectives of attaining a high availability and limiting degradation are of paramount importance. There are several condition monitoring techniques available to gas turbine users. Most publications tend to focus on a specific technique and do not address the need for integration of techniques. Several vibration problems that occur in gas turbines are manifestations of aerodynamic problems. To detect underlying problems of this nature, one is required to integrate performance, vibration and other condition monitoring data. This paper provides a comprehensive review of condition monitoring techniques and presents the thesis that for meaningful condition monitoring one requires the utilization of a variety of condition monitoring techniques coupled with an understanding of gas turbine design and its operational envelope. Case studies are provided to indicate the need for an integrated condition monitoring approach.
Rim Seal Experiments and Analysis of a Rotor-Stator System With Nonaxisymmetric Main Flow
Authors: Hamabe K. , Ishida K.
Published: March 2015

To examine the simplified model to predict the ingress flow rate which was formerly proposed by the authors, the scaling characteristics of a shrouded rotor-stator system with a nonaxisymmetric main flow is studied using gas concentration measurements in the wheel-space. The predicted value for the sealing effectiveness as well as the minimum cooling air flow ratio necessary to prevent ingress is shown to be relatively in good agreement with the test results. It is also found that for the precise prediction of the sealing effectiveness, the circumferential static pressure distribution in the annulus is needed.
A 3-D Inverse Methodology Applied to the Design of Axisymmetric Ducts
Authors: Dedoussis V. , Chaviaropoulos P. , Papailiou K. D.
Published: March 2015

An inverse inviscid potential fully 3-D methodology is introduced. The method is based on a potential function/stream function formulation where the physical space is mapped onto a computational one via a body-fitted coordinate transformation. Potential function and two orthogonal stream functions (vectors) are used as independent variables, whilst the velocity magnitude, the aspect ratio of the elementary streamtubes cross-section and density are the dependent ones. Differential geometry and generalized tensor analysis arguments are employed both to formulate the method and derive the governing differential equations. A reduced version of the general 3-D methodology is applied to the design of axisymmetric ducts. The main advantage of the proposed approach is that the flow and geometry solutions are entirely decoupled. The geometry is computed independently after the flow field has been determined. Results are compared to analytical and numerical solutions of a direct method.
Concentration Fluctuations in Turbulent Cross Jet Mixing
Authors: Andrews G. E. , Abdul Hussain U. S.
Published: March 2015

Concentration fluctuations were investigated using a water tunnel with a separate salt-water solution as a ‘fuel’ tracer flow. A fine electrode was used to detect the concentration of the tracer from the local conductivity. The frequency response of 0.4 by 1 mm probe tip was 10 kHz. An impinging axial/radial jet configuration was studied as this is a key element in some burner and gas turbine low emission combustor designs. Mixing was complete to within 5% by six axial hole diameters, an order of magnitude improvement on single jet mixing. The mixing traverses close to the jets demonstrated the importance of the method of fuel injection on the mixing process. The turbulent scalar mixing results are a suitable data set for CFD code validation of isothermal jet mixing.
Development and Operation of Remotely Controlled Modular Gas Turbine Driven Compressor Stations
Authors: Austin C. J. , Higgins H. C.
Published: March 2015

British Gas is the largest integrated gas company in the western world operating on both sides of the Atlantic. Within the UK, the company’s activities embrace off-shore exploration and production, transmission and distribution together with the retailing and installation of appliances in customers homes.
Comparison of the phase-invariant and mosaic crystal models for dynamical x-ray diffraction from metamorphic InxGa1−xAs/GaAs (001) structures
Authors: Rago Paul B. , Ayers John E.
Published: February 2015

In this paper, the authors present a mosaic crystal model for the calculation of dynamical x-ray rocking curves from metamorphic semiconductor device structures containing dislocations. This model represents an extension of the previously reported phase-invariant model, which is applicable to most metamorphic heterostructures and serves as the basis for their x-ray characterization, allowing determination of the depth profiles of strain, composition, and dislocation density. The new model can be applied similarly but avoids the limitations of the phase invariant model, namely, a loss of accuracy in some structures with closely lattice matched layers and layers containing large dislocation densities. In this paper, the authors present the computational details of the new mosaic crystal model, demonstrate its application to graded InxGa1−xAs/GaAs (001) metamorphic buffers and device structures, and make quantitative comparisons between the results of the phase-invariant and mosaic crystal models.
Education on the Digital Terrain: A Case Study Exploring College Athletes’ Perceptions of Social-Media Training
Authors: Sanderson Jimmy , Browning Blair , Schmittel Annelie
Published: February 2015

College athletes are active on a variety of social-media platforms. As a result, most athletic departments require them to participate in social-media education. Although this practice is becoming more prominent, little research has explored how college athletes perceive such training. This case study explored college athletes’ social-media use and their perceptions about social-media education. Semi structured interviews of 20 college athletes at a Division I university were conducted. Using social-cognitive theory as a framework, analysis revealed that while participants expressed a desire for social-media education, they indicated that most of the messages they receive about social media tend to be forgettable. Consequently, athletic departments need to take a more refexive approach to social-media education that incorporates college athletes’ feedback to optimize this instruction.
Valuing the Media: Access and Autonomy as Functions of Legitimacy for Journalists
Authors: Suggs David Welch
Published: February 2015

Sports reporters depend on access to events and sources as much or more than any other news professional. Over the past few years, some sports organizations have attempted to restrict such access, as well as what reporters can publish via social media. In the digital era, access and publishing autonomy, as institutionalized concepts, are evolving rapidly. Hypotheses tying access and work practices to reporters’ perceptions of the legitimacy they experience are developed and tested via a structural equation model, using responses to a survey of journalists in American intercollegiate athletics and observed dimensions of access and autonomy to measure a latent variable of legitimacy. The model suggests that reporters have mixed views about whether they possess the legitimacy they need to do their jobs.
Science Signaling
Podcast: 24 February 2015
Authors: Venuprasad K , VanHook Annalisa M.
Published: February 2015

The ubiquitin ligase Itch prevents skin inflammation in mice by targeting an activator of p38α for degradation.
Nanocarriers deliver DNA to brain tumors
Authors: Stephan Matthias
Published: February 2015

Nanoparticles can deliver suicide gene therapy to CNS tumors.
Assessment of Minocycline and Polymyxin B Combination against Acinetobacter baumannii
Authors: Bowers Dana R. , Cao Henry , Zhou Jian , Ledesma Kimberly R. , Sun Dongxu , Lomovskaya Olga , Tam Vincent H.
Published: February 2015

Antimicrobial resistance among
Acinetobacter baumannii
is increasing worldwide, often necessitating combination therapy. The clinical utility of using minocycline with polymyxin B is not well established. In this study, we investigated the activity of minocycline and polymyxin B against 1 laboratory isolate and 3 clinical isolates of
A. baumannii
. Minocycline susceptibility testing was performed with and without an efflux pump inhibitor, phenylalanine-arginine β-naphthylamide (PAβN). The intracellular minocycline concentration was determined with and without polymyxin B (0.5 μg/ml). Time-kill studies were performed over 24 h using approximately 10
6
CFU/ml of each strain with clinically relevant minocycline concentrations (2 μg/ml and 8 μg/ml), with and without polymyxin B (0.5 μg/ml). The
in vivo
efficacy of the combination was assessed in a neutropenic murine pneumonia model. Infected animals were administered minocycline (50 mg/kg), polymyxin B (10 mg/kg), or both to achieve clinically equivalent exposures in humans. A reduction in the minocycline MIC (≥4×) was observed in the presence of PAβN. The intracellular concentration and
in vitro
bactericidal effect of minocycline were both enhanced by polymyxin B. With 2 minocycline-susceptible strains, the bacterial burden in lung tissue at 24 h was considerably reduced by the combination compared to monotherapy with minocycline or polymyxin B. In addition, the combination prolonged survival of animals infected with a minocycline-susceptible strain. Polymyxin B increased the intracellular concentration of minocycline in bacterial cells and enhanced the bactericidal activity of minocycline, presumably due to efflux pump disruption. The clinical utility of this combination should be further investigated.
Impacts of Global Transcriptional Regulators on Persister Metabolism
Authors: Mok Wendy W. K. , Orman Mehmet A. , Brynildsen Mark P.
Published: February 2015

Bacterial persisters are phenotypic variants with an extraordinary capacity to tolerate antibiotics, and they are hypothesized to be a main cause of chronic and relapsing infections. Recent evidence has suggested that the metabolism of persisters can be targeted to develop therapeutic countermeasures; however, knowledge of persister metabolism remains limited due to difficulties associated with isolating these rare and transient phenotypic variants. By using a technique to measure persister catabolic activity, which is based on the ability of metabolites to enable aminoglycoside (AG) killing of persisters, we investigated the role of seven global transcriptional regulators (ArcA, Cra, cyclic AMP [cAMP] receptor protein [CRP], DksA, FNR, Lrp, and RpoS) on persister metabolism. We found that removal of CRP resulted in a loss of AG potentiation in persisters for all metabolites tested. These results highlight a central role for cAMP/CRP in persister metabolism, as its perturbation can significantly diminish the metabolic capabilities of persisters and effectively eliminate the ability of AGs to eradicate these troublesome bacteria.
Kidney Injury Associated with Telavancin Dosing Regimen in an Animal Model
Authors: Tam Vincent H. , Ledesma Kimberly R. , Bowers Dana R. , Zhou Jian , Truong Luan D.
Published: February 2015

The elevation of serum creatinine levels is a concern with telavancin therapy. We examined the onset of kidney injury associated with telavancin in an animal model. Urine samples were collected at baseline and daily to determine the concentrations of kidney injury molecule 1 (KIM-1), a marker for early kidney injury. When a clinically relevant exposure of telavancin was given daily to rats, some differences in kidney injury were attributed to the dosing regimen. Further investigations of alternative telavancin dosing regimens are warranted.
A New Fungal Isolate, Penidiella sp. Strain T9, Accumulates the Rare Earth Element Dysprosium
Authors: Horiike Takumi , Yamashita Mitsuo
Published: February 2015

With an aim to develop a highly efficient method for the recovery of rare earth elements (REEs) by using microorganisms, we attempted to isolate dysprosium (Dy)-accumulating microorganisms that grow under acidic conditions from environmental samples containing high concentrations of heavy metals. One acidophilic strain, T9, which was isolated from an abandoned mine, decreased the concentration of Dy in medium that contained 100 mg/liter Dy to 53 mg/liter Dy after 3 days of cultivation at pH 2.5. The Dy content in the cell pellet of the T9 strain was 910 μg/mg of dry cells. The T9 strain also accumulated other REEs. Based on the results of 28S-D1/D2 rRNA gene sequencing and morphological characterization, we designated this fungal strain
Penidiella
sp. T9. Bioaccumulation of Dy was observed on the cell surface of the T9 strain by elemental mapping using scanning electron microscopy-energy dispersive X-ray spectroscopy. Our results indicate that
Penidiella
sp. T9 has the potential to recover REEs such as Dy from mine drainage and industrial liquid waste under acidic conditions.
Simple and Portable Magnetic Immunoassay for Rapid Detection and Sensitive Quantification of Plant Viruses
Authors: Rettcher Stefanie , Jungk Felicitas , Kühn Christoph , Krause Hans-Joachim , Nölke Greta , Commandeur Ulrich , Fischer Rainer , Schillberg Stefan , Schröper Florian
Published: February 2015

Plant pathogens cause major economic losses in the agricultural industry because late detection delays the implementation of measures that can prevent their dissemination. Sensitive and robust procedures for the rapid detection of plant pathogens are therefore required to reduce yield losses and the use of expensive, environmentally damaging chemicals. Here we describe a simple and portable system for the rapid detection of viral pathogens in infected plants based on immunofiltration, subsequent magnetic detection, and the quantification of magnetically labeled virus particles.
Grapevine fanleaf virus
(GFLV) was chosen as a model pathogen. Monoclonal antibodies recognizing the GFLV capsid protein were immobilized onto immunofiltration columns, and the same antibodies were linked to magnetic nanoparticles. GFLV was quantified by immunofiltration with magnetic labeling in a double-antibody sandwich configuration. A magnetic frequency mixing technique, in which a two-frequency magnetic excitation field was used to induce a sum frequency signal in the resonant detection coil, corresponding to the virus concentration within the immunofiltration column, was used for high-sensitivity quantification. We were able to measure GFLV concentrations in the range of 6 ng/ml to 20 μg/ml in less than 30 min. The magnetic immunoassay could also be adapted to detect other plant viruses, including
Potato virus X
and
Tobacco mosaic virus
, with detection limits of 2 to 60 ng/ml.
Protective Efficacy and Pharmacokinetics of Human/Mouse Chimeric Anti-Stx1 and Anti-Stx2 Antibodies in Mice
Authors: Melton-Celsa Angela R. , Carvalho H. M. , Thuning-Roberson Claire , O'Brien A. D.
Published: February 2015

In the United States, Shiga toxin (Stx)-producingEscherichia coli(STEC) is the most frequent infectious cause of hemorrhagic colitis. Hemolytic uremic syndrome (HUS) is a serious sequela that may develop after STEC infection that can lead to renal failure and death in up to 10% of cases. STEC can produce one or more types of Stx, Stx1 and/or Stx2, and Stx1 and Stx2 are responsible for HUS-mediated kidney damage. We previously generated two monoclonal antibodies (MAbs) that neutralize the toxicity of Stx1 or Stx2. In this study, we evaluated the protective efficacy of human/mouse chimeric versions of those monoclonal antibodies, named cαStx1 and cαStx2. Mice given an otherwise lethal dose of Stx1 were protected from death when injected with cαStx1 either 1 h before or 1 h after toxin injection. Additionally, streptomycin-treated mice fed the mouse-lethal STEC strain B2F1 that produces the Stx2 variant Stx2d were protected when given a dose of 0.1 mg of cαStx2/kg of body weight administered up to 72 h post-oral bacterial challenge. Since many STEC strains produce both Stx1 and Stx2 and since either toxin may lead to the HUS, we also assessed the protective efficacy of the combined MAbs. We found that both antibodies were required to protect mice from the presence of both Stx1 and Stx2. Pharmacokinetic studies indicated that cαStx1 and cαStx2 had serum half-lives (t1/2) of about 50 and 145 h, respectively. We propose that cαStx1 and cαStx2, both of which have been tested for safety in humans, could be used therapeutically for prevention or treatment early in the development of HUS.
TleA, a Tsh-Like Autotransporter Identified in a Human Enterotoxigenic Escherichia coli Strain
Authors: Gutiérrez Daniela , Pardo Mirka , Montero David , Oñate Angel , Farfán Mauricio J. , Ruiz-Pérez Fernando , Del Canto Felipe , Vidal Roberto
Published: February 2015

Enterotoxigenic
Escherichia coli
(ETEC), a leading cause of acute diarrhea, colonizes the intestine by means of adhesins. However, 15 to 50% of clinical isolates are negative for known adhesins, making it difficult to identify antigens for broad-coverage vaccines. The ETEC strain 1766a, obtained from a child with watery diarrhea in Chile, harbors the colonization factor CS23 but is negative for other known adhesins. One clone, derived from an ETEC 1766a genomic library (clone G10), did not produce CS23 yet was capable of adhering to Caco-2 cells. The goal of this study was to identify the gene responsible for this capacity. Random transposon-based mutagenesis allowed the identification of a 4,110-bp gene that codes for a homologue of the temperature-sensitive hemagglutinin (Tsh) autotransporter described in avian
E. coli
strains (97% identity, 90% coverage) and that is called TleA (Tsh-like ETEC autotransporter) herein. An isogenic ETEC 1766a strain with a
tleA
mutation showed an adhesion level similar to that of the wild-type strain, suggesting that the gene does not direct attachment to Caco-2 cells. However, expression of
tleA
conferred the capacity for adherence to nonadherent
E. coli
HB101. This effect coincided with the detection of TleA on the surface of nonpermeabilized bacteria, while, conversely, ETEC 1766a seems to secrete most of the produced autotransporter to the medium. On the other hand, TleA was capable of degrading bovine submaxillary mucin and leukocyte surface glycoproteins CD45 and P-selectin glycoprotein ligand 1 (PSGL-1). These results suggest that TleA promotes colonization of the intestinal epithelium and that it may modulate the host immune response.
The IbeA Invasin of Adherent-Invasive Escherichia coli Mediates Interaction with Intestinal Epithelia and Macrophages
Authors: Cieza Roberto J. , Hu Jia , Ross Brittany N. , Sbrana Elena , Torres Alfredo G.
Published: February 2015

Adherent-invasive
Escherichia coli
(AIEC) pathogroup isolates are a group of isolates from the intestinal mucosa of Crohn's disease patients that can invade intestinal epithelial cells (IECs) or macrophages and survive and/or replicate within. We have identified the
ibeA
gene in the genome of AIEC strain NRG857c and report the contribution of IbeA to the interaction of AIEC with IECs and macrophages and colonization of the mouse intestine. An
ibeA
deletion mutant strain (NRG857cΔ
ibeA
) was constructed, and the
in vitro
effect on AIEC adhesion and invasion of nonpolarized and polarized Caco-2 cells, the adhesion and transcytosis of M-like cells, the intracellular survival in THP-1 macrophages, and the contribution to intestinal colonization of the CD-1 murine model of infection were evaluated. A significant reduction in invasion was observed with the
ibeA
mutant in Caco-2 and M-like cells, whereas adhesion was not affected. Complementation of the mutant reestablished Caco-2 invasive phenotype to wild-type levels. Reduction in invasion did not significantly affect transcytosis through M-like cells at early time points. The absence of
ibeA
significantly affected AIEC intramacrophage survival up to 24 h postinfection. No significant changes associated with IbeA were found in AIEC colonization across the murine gastrointestinal tract, but a slight reduction of gamma interferon was observed in the ceca of mice infected with the
ibeA
mutant. In addition, a decrease in the pathology scores was observed in the ilea and ceca of mice infected with the
ibeA
mutant. Our data support the function of IbeA in the AIEC invasion process, macrophage survival, and inflammatory response in the murine intestine.
Acrophialophora, a Poorly Known Fungus with Clinical Significance
Authors: Sandoval-Denis Marcelo , Gené Josepa , Sutton Deanna A. , Wiederhold Nathan P. , Guarro Josep
Published: February 2015

Acrophialophora fusisporais an emerging opportunistic fungus capable of causing human infections. The taxonomy of the genus is not yet resolved and, in order to facilitate identification of clinical specimens, we have studied a set of clinical and environmentalAcrophialophoraisolates by morphological and molecular analyses. This set included the available type strains ofAcrophialophoraspecies and similar fungi, some of which were considered by various authors to be synonyms ofA. fusispora. Sequence analysis of the large subunit (LSU) and internal transcribed spacer (ITS) regions of the nuclear ribosomal DNA and a fragment of the β-tubulin (Tub) gene revealed thatAcrophialophorabelongs in the familyChaetomiaceaeand comprises three different species, i.e.,A. fusispora,Acrophialophora levis, andAcrophialophora seudatica; the latter was previously included in the genusAmpullifera. The most prevalent species among clinical isolates wasA. levis(72.7%), followed byA. fusispora(27.3%), both of which were isolated mostly from respiratory specimens (72.7%), as well as subcutaneous and corneal tissue samples. In general, of the eight antifungal drugs tested, voriconazole had the greatestin vitroactivity, while all other agents showed poorin vitroactivity against these fungi.
Prominent Amphibian (Xenopus laevis) Tadpole Type III Interferon Response to the Frog Virus 3 Ranavirus
Authors: Grayfer Leon , De Jesús Andino Francisco , Robert Jacques
Published: February 2015

Ranaviruses (
Iridoviridae
) are posing an increasing threat to amphibian populations, with anuran tadpoles being particularly susceptible to these viral infections. Moreover, amphibians are the most basal phylogenetic class of vertebrates known to possess both type I and type III interferon (IFN)-mediated immunity. Moreover, little is known regarding the respective roles of the IFN mediators in amphibian antiviral defenses. Accordingly, we transcriptionally and functionally compared the amphibian
Xenopus laevis
type I (IFN) and III (IFN-λ) IFNs in the context of infections by the ranavirus frog virus 3 (FV3).
X. laevis
IFN and IFN-λ displayed distinct tissue expression profiles. In contrast to our previous findings that
X. laevis
tadpoles exhibit delayed and modest type I IFN responses to FV3 infections compared to the responses of adults, here we report that tadpoles mount timely and robust type III IFN gene responses. Recombinant forms of these cytokines (recombinant
X. laevis
IFN [r
Xl
IFN] and r
Xl
IFN-λ) elicited antiviral gene expression in the kidney-derived A6 cell line as well as in tadpole leukocytes and tissues. However, r
Xl
IFN-λ was less effective than r
Xl
IFN in preventing FV3 replication in A6 cells and tadpoles and inferior at promoting tadpole survival. Intriguingly, FV3 impaired A6 cell and tadpole kidney type III IFN receptor gene expression. Furthermore, in A6 cultures r
Xl
IFN-λ conferred equal or greater protection than r
Xl
IFN against recombinant viruses deficient for the putative immune evasion genes, the viral caspase activation and recruitment domain (vCARD) or a truncated vIF-2α gene. Thus, in contrast to previous assumptions, tadpoles possess intact antiviral defenses reliant on type III IFNs, which are overcome by FV3 pathogens.

IMPORTANCE
Anuran tadpoles, including those of
Xenopus laevis
, are particularly susceptible to infection by ranavirus such as FV3. We investigated the respective roles of
X. laevis
type I and type III interferons (IFN and IFN-λ, respectively) during FV3 infections. Notably, tadpoles mounted timely and more robust IFN-λ gene expression responses to FV3 than adults, contrasting with the poorer tadpole type I IFN responses. However, a recombinant
X. laevis
IFN-λ (r
Xl
IFN-λ) conferred less protection to tadpoles and the A6 cell line than r
Xl
IFN, which may be explained by the FV3 impairment of IFN-λ receptor gene expression. The importance of IFN-λ in tadpole anti-FV3 defenses is underlined by the critical involvement of two putative immune evasion genes in FV3 resistance to IFN- and IFN-λ-mediated responses. These findings challenge the view that tadpoles have defective antiviral immunity and suggest, rather, that their antiviral responses are predominated by IFN-λ responses, which are overcome by FV3.