bluuebunny/crossref_metadata_2025 huggingface dataset:
Faster spring migration in northern wheatears is not explained by an endogenous seasonal difference in refueling rates
Authors: Eikenaar Cas , Tsvey Arseny , Schmaljohann Heiko
Published: May 2015

A widespread phenomenon in migrant birds is that they travel faster in spring than in autumn. During migration birds spend most time at stopover sites and, correspondingly, the faster spring migration is mainly explained by shorter stopovers in spring than autumn. Because a main purpose of stopovers is to replenish the fuel used in flight, a higher rate of fuel deposition (FDR) in spring is thought to explain the shorter stopovers and hence shorter total duration of migration in spring. Critical migratory processes, including the onset and extent of pre‐migratory fueling, are endogenously regulated. It is therefore not unlikely that refueling at stopover sites is, at least partly, also under endogenous control. We here tested whether there is an endogenous seasonal difference in food intake and FDR, which could contribute to shorter stopovers and hence faster migration in spring. We measured daily food intake and daily FDR in two subspecies of the northern wheatear Oenanthe oenanthe, temporarily confined at stopover under identical constant indoor conditions in spring and autumn. The two wheatear subspecies differed markedly in absolute food intake and FDR. Within subspecies, however, food intake and FDR did not differ between spring and autumn, indicating that faster spring migration in northern wheatears is not explained by an endogenously controlled seasonal difference in birds’ motivation to refuel. To further substantiate this claim, similar measurements should be taken at other locations along northern wheatears’ migration routes. Comparable experiments in other species could test the generality of our results.
Effect of specialization on genetic parameters of studbook–entry inspection in Dutch Warmblood horses
Authors: Rovere G. , Madsen P. , Norberg E. , van Arendonk J.A.M. , Ducro B.J.
Published: May 2015

Recent studies on data from the Dutch Warmblood Studbook (KWPN) have shown that the ongoing specialization of horses for either dressage (DH) or show jumping (JH) has led to a decreasing genetic relationship between the two subpopulations. The aim of this study was to analyse the effect of the specialization process on the genetic parameters of traits measured in the studbook–entry inspection of KWPN during the last fifteen years. Data from 18 125 DH and 23 800 JH recorded from 1998 until 2013 were used to analyse 13 traits scored in both DH and JH. Analyses were performed in a Bayesian framework. Firstly, variance components were estimated based on the whole data set. Secondly, genetic correlations between traits measured in DH or JH were estimated using bivariate analyses. Thirdly, three time periods were defined and genetic correlations between subpopulations were estimated within each period. Heritability was moderate (0.17–0.39) for both DH and JH. Genetic correlations between traits measured in DH or JH were not different from one considering the posterior standard deviation of the estimation; however, in most of the traits, a clear trend in reduction of the genetic correlation for traits expressed in DH and JH and an increase in their posterior standard deviation for recent years was observed. These results suggest that specialization could lead to differences in traits measured in DH and JH in the recent years.
Application of Combined Far‐Infrared Radiation and Air Convection for Drying of Instant Germinated Brown Rice
Authors: Nachaisin Mali , Jamradloedluk Jindaporn , Niamnuy Chalida
Published: May 2015

Shorter drying time and reduced energy consumption for instant germinated brown rice drying were evaluated to ensure that the quality of the final product was not compromised. Energy consumption, moisture content, color, morphology, rehydration, texture and sensory evaluation were determined during drying with a combination of far‐infrared radiation and hot air. Far‐infrared intensities from 1 to 5 kW/m2 were combined with a 40C temperature and 1 m/s air velocity. Drying rate increased with far‐infrared intensity, hence reducing the total drying time. The mathematical model was validated by comparing the simulated results with temperature and moisture content to described the drying behavior of instant germinated brown rice (R2 = 0.999). The total color difference (ΔE) varied from 2.9 to 4.2. Increasing far‐infrared intensity decreased hardness, chewiness and gumminess, but increased the rehydration of instant germinated brown rice. The effective moisture diffusivity increased with the far‐infrared intensity varying from 0.39 × 10−11 to 3.6 × 10−10 m2/s. The specific energy consumption at 5 kW/m2 far‐infrared intensity was 2.90 kWh/kg of water removed, resulting in a 66% energy saving when compared to 1 kW/m2 far‐infrared intensity.

Practical Applications

As an excellent source of nutrients, germinated brown rice has gained more attention than white rice. However, information on instant rice obtained from germinated brown rice is scarce. An alternative technique about instant germinated brown rice preparation was therefore proposed in this work. This study gives a method for the preparation for instant germinated brown rice, which would be a good choice for production of instant germinated brown rice in the industry.
Metamorphic imprint of accretion and ridge subduction in the Pan‐African Damara Belt, Namibia
Authors: Cross C. B. , Diener J. F. A. , Fagereng Å.
Published: May 2015

Ridge subduction is an inescapable plate tectonic process, but has only been documented in modern circum‐Pacific environments and not yet been recognized from suture zones associated with supercontinent assembly, likely because its imprint is obliterated by later collision. The formation of the Pan‐African Damara Belt of central Namibia involved northward subduction of the Khomas Sea underneath the Congo Craton, prior to final suturing of the Congo and Kalahari Cratons. The accretionary history of the Belt is preserved in the Southern and Southern Marginal Zones, which consist of turbiditic metasedimentary and intercalcated mafic rocks with MORB affinity. Two localities in the Kuiseb and Gaub canyons reveal that aluminous metapelites contain a fabric‐defining assemblage of fine‐grained muscovite, chlorite, biotite, quartz and graphite that is overprinted by randomly oriented porphyroblasts and poikiloblasts of garnet, staurolite, kyanite and biotite. Associated metamafic rocks consist of hornblende, chlorite, epidote, rutile and quartz, with actinolite cores preserved in amphibole porphyroblasts. Metamorphic conditions for the fabric‐defining assemblage are estimated at ∼10 kbar and 540–560 C, whereas peak metamorphism likely occurred at 10–10.5 kbar and 600 C. Consequently, these rocks preserve a two‐stage prograde metamorphic history, where initial tectonic burial was followed by relatively rapid, near‐isobaric heating without attendant deformation to peak metamorphic conditions. We propose that initial burial occurred through subduction and underplating to the accretionary prism, before ridge subduction and opening of a slab window heated the rocks to peak metamorphic conditions. The exceptional preservation of the tectono‐thermal imprint of the accretionary orogenic stage is due to the relatively soft, largely aborted collision that characterized the Damara orogeny, which can be attributed to the confined extent of the Khomas Sea.
Inhibition of microglial activation contributes to propofol‐induced protection against post‐cardiac arrest brain injury in rats
Authors: Wang Wei , Lu Rui , Feng Da‐yun , Liang Li‐rong , Liu Bing , Zhang Hui
Published: May 2015

It has been suggested that propofol can modulate microglial activity and hence may have potential roles against neuroinflammation following brain ischemic insult. However, whether and how propofol can inhibit post‐cardiac arrest brain injury via inhibition of microglia activation remains unclear. A rat model of asphyxia cardiac arrest (CA) was created followed by cardiopulmonary resuscitation. CA induced marked microglial activation in the hippocampal CA1 region, revealed by increased OX42 and P2 class of purinoceptor 7 (P2X7R) expression, as well as p38 MAPK phosphorylation. Morris water maze showed that learning and memory deficits following CA could be inhibited or alleviated by pre‐treatment with the microglial inhibitor minocycline or propofol. Microglial activation was significantly suppressed likely via the P2X7R/p‐p38 pathway by propofol. Moreover, hippocampal neuronal injuries after CA were remarkably attenuated by propofol. In vitro experiment showed that propofol pre‐treatment inhibited ATP‐induced microglial activation and release of tumor necrosis factor‐α and interleukin‐1β. In addition, propofol protected neurons from injury when co‐culturing with ATP‐treated microglia. Our data suggest that propofol pre‐treatment inhibits CA‐induced microglial activation and neuronal injury in the hippocampus and ultimately improves cognitive function.

image

We proposed a possible mechanism of propofol‐mediated brain protection after cardiac arrest (CA). CA induces P2X7R upregulation and p38 phosphorylation in microglia, which induces release of TNF‐α and IL‐1β and consequent neuronal injury. Propofol could inhibit microglial activation and alleviate neuronal damage. Our results suggest propofol‐induced anti‐inflammatory treatment as a plausible strategy for therapeutic intervention in post‐CA brain injury.
The mechanistic target of rapamycin (mTOR) pathway and S6 Kinase mediate diazoxide preconditioning in primary rat cortical neurons
Authors: Dutta Somhrita , Rutkai Ibolya , Katakam Prasad V. G. , Busija David W.
Published: May 2015

We examined the role of the mechanistic target of rapamycin (mTOR) pathway in delayed diazoxide (DZ)‐induced preconditioning of cultured rat primary cortical neurons. Neurons were treated for 3 days with 500 μM DZ or feeding medium and then exposed to 3 h of continuous normoxia in Dulbecco's modified eagle medium with glucose or with 3 h of oxygen–glucose deprivation (OGD) followed by normoxia and feeding medium. The OGD decreased viability by 50%, depolarized mitochondria, and reduced mitochondrial respiration, whereas DZ treatment improved viability and mitochondrial respiration, and suppressed reactive oxygen species production, but did not restore mitochondrial membrane potential after OGD. Neuroprotection by DZ was associated with increased phosphorylation of protein kinase B (Akt), mTOR, and the major mTOR downstream substrate, S6 Kinase (S6K). The mTOR inhibitors rapamycin and Torin‐1, as well as S6K‐targeted siRNA abolished the protective effects of DZ. The effects of DZ on mitochondrial membrane potential and reactive oxygen species production were not affected by rapamycin. Preconditioning with DZ also changed mitochondrial and non‐mitochondrial oxygen consumption rates. We conclude that in addition to reducing reactive oxygen species (ROS) production and mitochondrial membrane depolarization, DZ protects against OGD by activation of the Akt‐mTOR‐S6K pathway and by changes in mitochondrial respiration.

image

Ischemic strokes have limited therapeutic options. Diazoxide (DZ) preconditioning can reduce neuronal damage. Using oxygen–glucose deprivation (OGD), we studied Akt/mTOR/S6K signaling and mitochondrial respiration in neuronal preconditioning. We found DZ protects neurons against OGD via the Akt/mTOR/S6K pathway and alters the mitochondrial and non‐mitochondrial oxygen consumption rate. This suggests that the Akt/mTOR/S6k pathway and mitochondria are novel stroke targets.
Hypothalamic Agouti‐Related Peptide mRNA is Elevated During Natural and Stress‐Induced Anorexia
Authors: Dunn I. C. , Wilson P. W. , D'Eath R. B. , Boswell T.
Published: May 2015

As part of their natural lives, animals can undergo periods of voluntarily reduced food intake and body weight (i.e. animal anorexias) that are beneficial for survival or breeding, such as during territorial behaviour, hibernation, migration and incubation of eggs. For incubation, a change in the defended level of body weight or ‘sliding set point’ appears to be involved, although the neural mechanisms reponsible for this are unknown. We investigated how neuropeptide gene expression in the arcuate nucleus of the domestic chicken responded to a 60–70% voluntary reduction in food intake measured both after incubation and after an environmental stressor involving transfer to unfamiliar housing. We hypothesised that gene expression would not change in these circumstances because the reduced food intake and body weight represented a defended level in birds with free access to food. Unexpectedly, we observed increased gene expression of the orexigenic peptide agouti‐related peptide (AgRP) in both incubating and transferred animals compared to controls. Also pro‐opiomelanocortin (POMC) mRNA was higher in incubating hens and significantly increased 6 days after exposure to the stressor. Conversely expression of neuropeptide Y and cocaine‐ and amphetamine‐regulated transcript gene was unchanged in both experimental situations. We conclude that AgRP expression remains sensitive to the level of energy stores during natural anorexias, which is of adaptive advantage, although its normal orexigenic effects are over‐ridden by inhibitory signals. In the case of stress‐induced anorexia, increased POMC may contribute to this inhibitory role, whereas, for incubation, reduced feeding may also be associated with increased expression in the hypothalamus of the anorexigenic peptide vasoactive intestinal peptide.
Seclusion experienced by mental health professionals
Authors: Kuosmanen L. , Makkonen P. , Lehtila H. , Salminen H.
Published: May 2015

Accessible summary

Seclusion in psychiatric inpatient care means confining service users in a locked room.

Service users and staff seem to have different opinions on the usefulness of seclusion.

This is possibly the first time when two mental health nurses went voluntarily into seclusion and reported their experiences.

The nurses felt that the seclusion room was inhumane and proposed improvements to seclusion in general and to the seclusion facilities in particular.

Seclusion in psychiatric hospital care refers to isolating a service user from other service users and staff, most often in a locked and unfurnished room. Service users' experiences of seclusion are mostly negative, and although some have seen a rationale for its use, mental health nurses should be encouraged to evaluate current seclusion practices from the service user's perspective. In this small‐scale experiment, two mental health nurses were voluntarily secluded for 24 h. The aim was to explore the experience of being secluded, to understand and evaluate the impact of seclusion in greater detail, and to encourage discussion on one of the controversies in mental health nursing. To the best of our knowledge, this is the first attempt to evaluate the impact of seclusion based on mental health nurses' firsthand experiences. The nurses received usual seclusion treatment and described their experiences of this every 6 h. Based on the nurses' experiences, seclusion, even in voluntary, safe and planned circumstances, may increase anxiety and frustration. Seclusion was viewed negatively and the physical environment was considered inhumane. The nurses offered some practical suggestions for updating seclusion practices and re‐designing seclusion facilities. Mental health nurses, who frequently decide on and invariably implement seclusion, are key to improving seclusion practices.
Legacy effects of no‐analogue disturbances alter plant community diversity and composition in semi‐arid sagebrush steppe
Authors: Ripplinger Julie , Franklin Janet , Edwards Thomas C.
Published: May 2015

Questions

(i) What role does the type of managed disturbance play in structuring sagebrush steppe plant communities? (ii) How does the composition of post‐disturbance plant communities change with time since disturbance? (iii) Does plant community diversity change over time following managed disturbance?

Location

Field study within the sagebrush steppe ecosystem. Rich County, Utah, USA.

Methods

We developed a chronosequence spanning up to 50 yrs post‐treatment to study sagebrush steppe vegetation dynamics. Direct ordination was used to examine plant community composition by managed disturbance type and time since disturbance, and factorial analysis of covariance was used to examine diversity dynamics following disturbance. Indicator species values were calculated in order to identify characteristic species for each disturbance type.

Results

Plant communities experienced a shift toward distinct community composition for each of the three managed disturbance types, and gave no indication of returning to untreated community composition or diversity. Small post‐disturbance increases in the number of non‐native grass species were observed in the treatments relative to reference, with native forb species making the largest contribution to altered composition. On fire‐ and chemically‐treated sites the proportional native forb species richness increased over time since disturbance, while the proportional contribution of non‐native forbs to total species richness decreased. For all three treatment types, native grasses contributed less on average to total richness than on reference sites, while non‐native grasses made up a higher proportion of total richness.

Conclusions

Common shrubland management techniques have legacy effects on the composition and diversity of sagebrush steppe plant communities, and no‐analogue disturbances, such as chemical or mechanical treatments, have more pronounced legacy effects than treatments similar to natural disturbance regimes (fire). This study informs a broader understanding of how management actions affect natural systems by highlighting the importance of long‐term management legacies as drivers of plant community structure and function.
The predictive and incremental validity of the German adaptation of the Static‐2002 in a sexual offender sample released from the prison system
Authors: Martens Ronja , Rettenberger Martin , Eher Reinhard
Published: May 2015

Purpose

The aim of this study was to examine the predictive validity of the German adaptation of the Static‐2002 and to compare it with the results of the Static‐99.

Method

The predictive validity of Static‐2002 was investigated in a sample of n = 452 sexual offenders released from the Austrian Prison System. The instrument was coded retrospectively using file information. Afterwards, the predictive estimates of the Static‐2002 were related to officially documented reconviction data.

Results

The Static‐2002 was found to have large effect sizes for predicting sexual, violent, and general recidivism (area under the receiver operating characteristic curve [AUC] = .78, .75, .75, respectively) for the total offender sample. For the general sexual offender sample, it did not predict reoffence significantly better than the Static‐99 ([AUC] = .77, .72, and .72, respectively). However, the Static‐2002 was found to perform better in the child molesters subsample (AUC = .83, .74, .75, respectively) than in rapists (AUC = .66, .72, .73, respectively), even though these differences did not reach statistical significance. The Static‐2002 was found to have incremental predictive validity beyond the Static‐99, but only for general and not for sexual or violent recidivism.

Conclusions

Although a replacement of the Static‐99 by the Static‐2002 cannot be recommended, it has to be emphasized that the Static‐2002 yielded large effect sizes in predicting general, violent, and sexual recidivism and, therefore, nevertheless represents an excellent measure for capturing the reoffence risk of sexual offenders.
Bile duct‐ligated mice exhibit multiple phenotypic similarities to acute decompensation patients despite histological differences
Authors: O'Brien Alastair , China Louise , Massey Karen A. , Nicolaou Anna , Winstanley Alison , Newson Justine , Hobbs Adrian , Audzevich Tatsiana , Gilroy Derek W.
Published: May 2015

Background & Aims

Patients with decompensated cirrhosis are susceptible to infection. Innate immune dysfunction and development of organ failure are considered to underlie this. A rodent model of liver disease sharing these phenotypic features would assist in vivo study of underlying mechanisms and testing of therapeutics. We evaluated three models to identify which demonstrated the greatest clinical and immunological phenotypic similarity to patients with acutely decompensated (AD) cirrhosis.

Methods

We selected Bile Duct Ligation (BDL) rats at 4 weeks, BDL mice at 14 days and Carbon tetrachloride (CCl4) mice at 10 weeks (with studies performed 7 days after final CCl4 infection). We examined organ dysfunction, inflammatory response to carrageenan‐in‐paw, plasma eicosanoid concentrations, macrophage cytokine production and responses to peritoneal infection.

Results

Bile duct ligation caused sarcopenia, liver, cardiovascular and renal dysfunction whereas CCl4 mice demonstrated no clinical abnormalities. BDL rodents exhibited depressed response to carrageenan‐in‐paw unlike CCl4 mice. BDL rats have slightly elevated plasma eicosanoid levels and plasma showed partial PGE2‐mediated immune suppression whereas CCl4 mice did not. Plasma NOx was elevated in patients with acute or chronic liver failure (AoCLF) compared to healthy volunteers and BDL rodents but not CCl4 mice. Elevated nitric oxide (NO) via inducible nitric oxide synthase (iNOS) mediates defective leucocyte trafficking in BDL rodent models.

Conclusions

We conclude that BDL mice and rats are not simply models of cholestatic liver injury but may be used to study mechanisms underlying poor outcome from infection in AD and have identified elevated NO as a potential mediator of depressed leucocyte trafficking.
Modeling Perfusion Dynamics in the Skin During Iontophoresis of Vasoactive Drugs Using Single‐Pulse and Multiple‐Pulse Protocols
Authors: Iredahl Fredrik , Sadda Veeranjaneyulu , Ward Liam J. , Hackethal Johannes , Farnebo Simon , Tesselaar Erik , Sjöberg Folke
Published: May 2015

Objective

After iontophoresis of vasoactive drugs into the skin, a decrease in perfusion is commonly observed. We delivered vaso‐active drugs by iontophoresis using different delivery protocols to study how these affect this decrease in perfusion as measured using LDF.

Methods

We measured skin perfusion during iontophoresis of (ACh), MCh, and NA using a single pulse or separate pulses at different skin sites, and during repeated delivery of ACh at the same site.

Results

Perfusion half‐life was 6.1 (5.6–6.6) minutes for ACh and 41 (29–69) minutes for MCh (p < 0.001). The maximum response with multiple pulses of ACh iontophoresis was lower than with a single pulse, 30 (22–37) PU vs. 43 (36–50) PU, p < 0.001. Vasoconstriction to NA was more rapid with a single pulse than with multiple pulses. The perfusion half‐life of ACh decreased with repeated delivery of ACh at the same site—first 16 (14–18), second 5.9 (5.1–6–9) and third 3.2 (2.9–3.5) minutes, p < 0.001.

Conclusions

The drug delivery protocol affects microvascular responses to iontophoresis, possibly as a result of differences in the dynamics of local drug concentrations. Perfusion half‐life may be used as a measure to quantify the rate of perfusion recovery after iontophoresis of vasoactive drugs.
Subunits B′γ and B′ζ of protein phosphatase 2A regulate photo‐oxidative stress responses and growth in Arabidopsis thaliana
Authors: Konert Grzegorz , Rahikainen Moona , Trotta Andrea , Durian Guido , Salojärvi Jarkko , Khorobrykh Sergey , Tyystjärvi Esa , Kangasjärvi Saijaliisa
Published: May 2015

Plants survive periods of unfavourable conditions with the help of sensory mechanisms that respond to reactive oxygen species (ROS) as signalling molecules in different cellular compartments. We have previously demonstrated that protein phosphatase 2A (PP2A) impacts on organellar cross‐talk and associated pathogenesis responses in Arabidopsis thaliana. This was evidenced by drastically enhanced pathogenesis responses and cell death in cat2 pp2a‐b′γ double mutants, deficient in the main peroxisomal antioxidant enzyme CATALASE 2 and PP2A regulatory subunit B′γ (PP2A‐B′γ). In the present paper, we explored the impacts of PP2A‐B′γ and a highly similar regulatory subunit PP2A‐B′ζ in growth regulation and light stress tolerance in Arabidopsis. PP2A‐B′γ and PP2A‐B′ζ display high promoter activities in rapidly growing tissues and are required for optimal growth under favourable conditions. Upon acclimation to a combination of high light, elevated temperature and reduced availability of water, however, pp2a‐b′γζ double mutants grow similarly to the wild type and show enhanced tolerance against photo‐oxidative stress. We conclude that by controlling ROS homeostasis and signalling, PP2A‐B′γ and PP2A‐B′ζ may direct acclimation strategies upon environmental perturbations, hence acting as important determinants of defence responses and light acclimation in plants.
Evidence for ACD5 ceramide kinase activity involvement in Arabidopsis response to cold stress
Authors: Dutilleul Christelle , Chavarria Heidy , Rézé Nathalie , Sotta Bruno , Baudouin Emmanuel , Guillas Isabelle
Published: May 2015

Although sphingolipids emerged as important signals for plant response to low temperature, investigations have been limited so far to the function of long‐chain base intermediates. The formation and function of ceramide phosphates (Cer‐Ps) in chilled Arabidopsis were explored. Cer‐Ps were analysed by thin layer chromatography (TLC) following in vivo metabolic radiolabelling. Ceramide kinase activity, gene expression and growth phenotype were determined in unstressed and cold‐stressed wild type (WT) and Arabidopsis ceramide kinase mutant acd5. A rapid and transient formation of Cer‐P occurs in cold‐stressed WT Arabidopsis plantlets and cultured cells, which is strongly impaired in acd5 mutant. Although concomitant, Cer‐P formation is independent of long‐chain base phosphate (LCB‐P) formation. No variation of ceramide kinase activity was measured in vitro in WT plantlets upon cold stress but the activity in acd5 mutant was further reduced by cold stress. At the seedling stage, acd5 response to cold was similar to that of WT. Nevertheless, acd5 seed germination was hypersensitive to cold and abscisic acid (ABA), and ABA‐dependent gene expression was modified in acd5 seeds when germinated at low temperature. Our data involve for the first time Cer‐P and ACD5 in low temperature response and further underline the complexity of sphingolipid signalling operating during cold stress.
How can research on pathogen population biology suggest disease management strategies? The example of barley scald (Rhynchosporium commune)
Authors: McDonald B. A.
Published: May 2015

Barley scald fungus, Rhynchosporium commune, belongs to a host‐specialized species complex infecting grasses. Coalescent analyses of several genes indicate that R. commune originated c. 2500 years ago, after the domestication of barley. Phylogeographical analyses identified a diversity hotspot in Scandinavia, indicating an origin in northern Europe. After its emergence, R. commune became distributed globally on infected seeds, eventually invading the Fertile Crescent and infecting wild barley progenitors. Analyses of gene flow identified historical routes of migration out of Scandinavia and indicate a high degree of modern gene flow among South Africa, Australia and New Zealand. About 76% of global species diversity is found within barley fields, with all field populations showing a genetic structure consistent with sexual recombination. High levels of regional gene flow suggest wind‐dispersed ascospores and movement of infected seed. Quantitative traits, including pathogen aggressiveness, thermal sensitivity and fungicide resistance, showed high heritability and high levels of diversity within nine globally representative populations. Field experiments provided evidence for a fitness cost associated with complex virulence and a trade‐off between pathogenic and saprophytic fitness. All findings indicate that global R. commune populations have significant potential to evolve rapidly in response to environmental changes, including deployment of resistant cultivars, fungicide applications and global warming. Specific recommendations to improve management of barley scald include: (i) focus resistance breeding efforts in northern Europe, which offers the best location to screen germplasm and may provide useful sources of scald resistance; (ii) improve seed treatment, certification and quarantine programmes to limit long distance pathogen movement; (iii) manage barley stubble to decrease pathogen population size, limit production of sexual inoculum and reduce the pathogen's evolutionary potential.
Bedside Ultrasonography for Arteriovenous Fistula Cannulation
Authors: Patel Roshan A. , Stern Aaron S. , Brown Maritza , Bhatti Saad
Published: May 2015

Difficulty in accessing a new arteriovenous fistula (AVF) is a common technical issue in hemodialysis patients, which often leads to interventional radiology and/or vascular surgery referral. As a consequence, the patient who needs dialysis may require a temporary dialysis catheter with its known potential complications. We present a case where bedside ultrasonography facilitated successful cannulation of a difficult AVF. Ultrasonography (US) training in this procedure may allow early cannulation of new AVFs when the venous diameter is large enough (>0.6 cm) but the fistula is too deep (>0.6 cm). Real‐time, US‐guided AVF cannulation may also decrease the number of failed venous punctures per hemodialysis (HD) session minimizing vessel wall damage and subsequent potential hematoma and aneurysm formation.
Subcutaneous infection caused by Blastoschizomyces capitatus post allogeneic hematopoietic transplant and its successful treatment with voriconazole
Authors: Devadas S.K. , Bhat V. , Khattry N.
Published: May 2015

We describe a 33‐year‐old man with relapsed acute myelogenous leukemia who developed subcutaneous nodules >6 months after allogeneic hematopoietic stem cell transplant. These nodules were caused by Blastoschizomyces capitatus. The lesions progressed after treatment with a posaconazole suspension. The lesions resolved after switching to voriconazole, which was given for 21 weeks. B. capitatus is a rare infection affecting immunocompromised patients, which responds to azoles.
Atomic layer deposition precursor step repetition and surface plasma pretreatment influence on semiconductor–insulator–semiconductor heterojunction solar cell
Authors: Talkenberg Florian , Illhardt Stefan , Radnóczi György Zoltán , Pécz Béla , Schmidl Gabriele , Schleusener Alexander , Dikhanbayev Kadyrjan , Mussabek Gauhar , Gudovskikh Alexander , Sivakov Vladimir
Published: May 2015

Semiconductor–insulator–semiconductor heterojunction solar cells were prepared using atomic layer deposition (ALD) technique. The silicon surface was treated with oxygen and hydrogen plasma in different orders before dielectric layer deposition. A plasma-enhanced ALD process was applied to deposit dielectric Al2O3 on the plasma pretreated n-type Si(100) substrate. Aluminum doped zinc oxide (Al:ZnO or AZO) was deposited by thermal ALD and serves as transparent conductive oxide. Based on transmission electron microscopy studies the presence of thin silicon oxide (SiOx) layer was detected at the Si/Al2O3 interface. The SiOx formation depends on the initial growth behavior of Al2O3 and has significant influence on solar cell parameters. The authors demonstrate that a hydrogen plasma pretreatment and a precursor dose step repetition of a single precursor improve the initial growth behavior of Al2O3 and avoid the SiOx generation. Furthermore, it improves the solar cell performance, which indicates a change of the Si/Al2O3 interface states.
Validation of Sensititre Dry-Form Broth Microdilution Panels for Susceptibility Testing of Ceftazidime-Avibactam, a Broad-Spectrum-β-Lactamase Inhibitor Combination
Authors: Jones Ronald N. , Holliday Nicole M. , Krause Kevin M.
Published: May 2015

Ceftazidime-avibactam is a broad-spectrum-β-lactamase inhibitor combination in late-stage clinical development for the treatment of serious infections. In preparation for clinical microbiology laboratory use, a validation experiment was initiated to evaluate a commercial broth microdilution product (Sensititre dried MIC susceptibility system) compared to reference panels using 525 recent clinical isolates. Among 11 pathogen groups, all had Sensititre MIC/reference MIC ratios predominantly at 1 (47.5% to 97.5%), and automated and manual endpoint results did not differ.
Enterobacteriaceae
MIC comparisons showed a modest skewing of Sensititre MIC results toward an elevated MIC (33.9%), but the essential agreement was 98.9% with 100.0% reproducibility. In conclusion, Sensititre panels produced accurate ceftazidime-avibactam MIC results, allowing quality MIC guidance for therapy following regulatory approvals.
Flow Cytometry-Based Method To Detect Persisters in Candida albicans
Authors: Chang Wenqiang , Zhang Ming , Li Ying , Lou Hongxiang
Published: May 2015

Candida albicans
biofilms contain a subpopulation whose members are defined as persisters, displaying great tolerance of fungicides. To directly observe such persisters, an effective method using green fluorescent protein (GFP) strain labeling by mutation of the gene encoding glyceraldehyde-3-phosphate dehydrogenase (
TDH3
), combined with propidium iodide (PI) staining, was established. Amphotericin B-tolerant persisters harbor the characteristics of both GFP positivity [GFP (+)] and propidium iodide (PI) negativity [PI (−)], which are easily visualized using a fluorescence microscope and measured by flow cytometry.
In Vitro
Susceptibility of Leishmania infantum to Artemisinin Derivatives and Selected Trioxolanes
Authors: Cortes Sofia , Albuquerque Andreia , Cabral Lília I. L. , Lopes Liliana , Campino Lenea , Cristiano Maria L. S.
Published: May 2015

Leishmaniasis is among the world's most neglected diseases. Currently available drugs for treatment present drawbacks, urging the need for more effective, safer, and cheaper drugs. A small library of artemisinin-derived trioxanes and synthetic trioxolanes was tested against promastigote and intramacrophage amastigote forms of
Leishmania infantum
. The trioxolanes LC50 and LC95 presented the best activity and safety profiles, showing potential for further studies in the context of leishmanial therapy. Our results indicate that the compounds tested exhibit peroxide-dependent activity.
A Simulation Study Reveals Lack of Pharmacokinetic/Pharmacodynamic Target Attainment in De-escalated Antibiotic Therapy in Critically Ill Patients
Authors: Carlier Mieke , Roberts Jason A. , Stove Veronique , Verstraete Alain G. , Lipman Jeffrey , De Waele Jan J.
Published: May 2015

De-escalation of empirical antibiotic therapy is often included in antimicrobial stewardship programs in critically ill patients, but differences in target attainment when antibiotics are switched are rarely considered. The primary objective of this study was to compare the fractional target attainments of contemporary dosing of empirical broad-spectrum β-lactam antibiotics and narrower-spectrum antibiotics for a number pathogens for which de-escalation may be considered. The secondary objective was to determine whether alternative dosing strategies improve target attainment. We performed a simulation study using published population pharmacokinetic (PK) studies in critically ill patients for a number of broad-spectrum β-lactam antibiotics and narrower-spectrum antibiotics. Simulations were undertaken using a data set obtained from critically ill patients with sepsis without absolute renal failure (
n
= 49). The probability of target attainment of antibiotic therapy for different microorganisms for which de-escalation was applied was analyzed. EUCAST MIC distribution data were used to calculate fractional target attainment. The probability that therapeutic exposure will be achieved was lower for the narrower-spectrum antibiotics with conventional dosing than for the broad-spectrum alternatives and could drastically be improved with higher dosages and different modes of administrations. For a selection of microorganisms, the probability that therapeutic exposure will be achieved was overall lower for the narrower-spectrum antibiotics using conventional dosing than for the broad-spectrum antibiotics.
First Report of OXA-181-Producing Escherichia coli in China and Characterization of the Isolate Using Whole-Genome Sequencing
Authors: Liu Yanbin , Feng Yu , Wu Wenjing , Xie Yi , Wang Xiaohui , Zhang Xiaoxia , Chen Xinchuan , Zong Zhiyong
Published: May 2015

We report the first OXA-181-producing strain in China.
bla
OXA-181
was found in sequence type 410 (ST410)
Escherichia coli
strain WCHEC14828 from a Chinese patient without recent travel history. Genome sequencing and conjugation experiments were performed.
bla
OXA-181
was carried on a 51-kb self-transmissible IncX3 plasmid and was linked with
qnrS1
, a quinolone resistance gene.
bla
OXA-181
was introduced onto the IncX3 plasmid from a ColE2-type plasmid, and IncX3 plasmids have the potential to mediate the dissemination of
bla
OXA-181
.
Heteroresistance to Itraconazole Alters the Morphology and Increases the Virulence of Cryptococcus gattii
Authors: Ferreira Gabriella Freitas , Santos Julliana Ribeiro Alves , Costa Marliete Carvalho da , Holanda Rodrigo Assunção de , Denadai Ângelo Márcio Leite , Freitas Gustavo José Cota de , Santos Áquila Rodrigues Costa , Tavares Priscila Batista , Paixão Tatiane Alves , Santos Daniel Assis
Published: May 2015

Cryptococcus gattii
is the main etiological agent of cryptococcosis in immunocompetent individuals. The triazole drug itraconazole is one of the antifungals used to treat patients with cryptococcosis. Heteroresistance is an adaptive mechanism to counteract the stress of increasing drug concentrations, and it can enhance the ability of a microorganism to survive under antifungal pressure. In this study, we evaluated the ability of 11
C. gattii
strains to develop itraconazole heteroresistance. Heteroresistant clones were analyzed for drug susceptibility, alterations in cell diameter, capsule properties, and virulence in a murine model. Heteroresistance to itraconazole was intrinsic in all of the strains analyzed, reduced both the capsule size and the cell diameter, induced molecular heterogeneity at the chromosomal level, changed the negatively charged cells, reduced ergosterol content, and improved the antioxidant system. A positive correlation between surface/volume ratio of original cells and the level of heteroresistance to itraconazole (LHI) was observed in addition to a negative correlation between capsule size of heteroresistant clones and LHI. Moreover, heteroresistance to itraconazole increased the engulfment of
C. gattii
by macrophages and augmented fungal proliferation inside these cells, which probably accounted for the reduced survival of the mice infected with the heteroresistant clones and the higher fungal burden in lungs and brain. Our results indicate that heteroresistance to itraconazole is intrinsic and increases the virulence of
C. gattii
. This phenomenon may represent an additional mechanism that contributes to relapses of cryptococcosis in patients during itraconazole therapy.
Azole Antifungal Agents To Treat the Human Pathogens Acanthamoeba castellanii and Acanthamoeba polyphaga through Inhibition of Sterol 14α-Demethylase (CYP51)
Authors: Lamb David C. , Warrilow Andrew G. S. , Rolley Nicola J. , Parker Josie E. , Nes W. David , Smith Stephen N. , Kelly Diane E. , Kelly Steven L.
Published: May 2015

In this study, we investigate the amebicidal activities of the pharmaceutical triazole CYP51 inhibitors fluconazole, itraconazole, and voriconazole againstAcanthamoeba castellaniiandAcanthamoeba polyphagaand assess their potential as therapeutic agents againstAcanthamoebainfections in humans. Amebicidal activities of the triazoles were assessed byin vitrominimum inhibition concentration (MIC) determinations using trophozoites ofA. castellaniiandA. polyphaga. In addition, triazole effectiveness was assessed by ligand binding studies and inhibition of CYP51 activity of purifiedA. castellaniiCYP51 (AcCYP51) that was heterologously expressed inEscherichia coli. Itraconazole and voriconazole bound tightly to AcCYP51 (dissociation constant [Kd] of 10 and 13 nM), whereas fluconazole bound weakly (Kdof 2,137 nM). Both itraconazole and voriconazole were confirmed to be strong inhibitors of AcCYP51 activity (50% inhibitory concentrations [IC50] of 0.23 and 0.39 μM), whereas inhibition by fluconazole was weak (IC50, 30 μM). However, itraconazole was 8- to 16-fold less effective (MIC, 16 mg/liter) at inhibitingA. polyphagaandA. castellaniicell proliferation than voriconazole (MIC, 1 to 2 mg/liter), while fluconazole did not inhibitAcanthamoebacell division (MIC, >64 mg/liter)in vitro. Voriconazole was an effective inhibitor of trophozoite proliferation forA. castellaniiandA. polyphaga; therefore, it should be evaluated in trials versus itraconazole for controllingAcanthamoebainfections.
Limited Ability of Posaconazole To Cure both Acute and Chronic Trypanosoma cruzi Infections Revealed by Highly Sensitive
In Vivo
Imaging
Authors: Francisco Amanda Fortes , Lewis Michael D. , Jayawardhana Shiromani , Taylor Martin C. , Chatelain Eric , Kelly John M.
Published: May 2015

The antifungal drug posaconazole has shown significant activity against
Trypanosoma cruzi
in vitro
and in experimental murine models. Despite this, in a recent clinical trial it displayed limited curative potential. Drug testing is problematic in experimental Chagas disease because of difficulties in demonstrating sterile cure, particularly during the chronic stage of infection when parasite burden is extremely low and tissue distribution is ill defined. To better assess posaconazole efficacy against acute and chronic Chagas disease, we have exploited a highly sensitive bioluminescence imaging system which generates data with greater accuracy than other methods, including PCR-based approaches. Mice inoculated with bioluminescent
T. cruzi
were assessed by
in vivo
and
ex vivo
imaging, with cyclophosphamide-induced immunosuppression used to enhance the detection of relapse. Posaconazole was found to be significantly inferior to benznidazole as a treatment for both acute and chronic
T. cruzi
infections. Whereas 20 days treatment with benznidazole was 100% successful in achieving sterile cure, posaconazole failed in almost all cases. Treatment of chronic infections with posaconazole did however significantly reduce infection-induced splenomegaly, even in the absence of parasitological cure. The imaging-based screening system also revealed that adipose tissue is a major site of recrudescence in mice treated with posaconazole in the acute, but not the chronic stage of infection. This
in vivo
screening model for Chagas disease is predictive, reproducible and adaptable to diverse treatment schedules. It should provide greater assurance that drugs are not advanced prematurely into clinical trial.
The Monoterpene Carvacrol Generates Endoplasmic Reticulum Stress in the Pathogenic Fungus Candida albicans
Authors: Chaillot Julien , Tebbji Faiza , Remmal Adnane , Boone Charlie , Brown Grant W. , Bellaoui Mohammed , Sellam Adnane
Published: May 2015

The monoterpene carvacrol, the major component of oregano and thyme oils, is known to exert potent antifungal activity against the pathogenic yeast
Candida albicans
. This monoterpene has been the subject of a considerable number of investigations that uncovered extensive pharmacological properties, including antifungal and antibacterial effects. However, its mechanism of action remains elusive. Here, we used integrative chemogenomic approaches, including genome-scale chemical-genetic and transcriptional profiling, to uncover the mechanism of action of carvacrol associated with its antifungal property. Our results clearly demonstrated that fungal cells require the unfolded protein response (UPR) signaling pathway to resist carvacrol. The mutants most sensitive to carvacrol in our genome-wide competitive fitness assay in the yeast
Saccharomyces cerevisiae
expressed mutations of the transcription factor Hac1 and the endonuclease Ire1, which is required for Hac1 activation by removing a nonconventional intron from the 3′ region of
HAC1
mRNA. Confocal fluorescence live-cell imaging revealed that carvacrol affects the morphology and the integrity of the endoplasmic reticulum (ER). Transcriptional profiling of pathogenic yeast
C. albicans
cells treated with carvacrol demonstrated a bona fide UPR transcriptional signature. Ire1 activity detected by the splicing of
HAC1
mRNA in
C. albicans
was activated by carvacrol. Furthermore, carvacrol was found to potentiate antifungal activity of the echinocandin antifungal caspofungin and UPR inducers dithiothreitol and tunicamycin against
C. albicans
. This comprehensive chemogenomic investigation demonstrated that carvacrol exerts its antifungal activity by altering ER integrity, leading to ER stress and the activation of the UPR to restore protein-folding homeostasis.
Dissemination of IncI2 Plasmids That Harbor the
bla
CTX-M
Element among Clinical Salmonella Isolates
Authors: Wong Marcus Ho-yin , Liu Lizhang , Yan Meiying , Chan Edward Wai-chi , Chen Sheng
Published: May 2015

The extended-spectrum-β-lactamase (ESBL) determinant CTX-M-55 is increasingly prevalent in
Escherichia coli
but remains extremely rare in
Salmonella
. This study reports the isolation of a plasmid harboring the
bla
CTX-M-55
element in a clinical
Salmonella enterica
serotype Typhimurium strain resistant to multiple antibiotics. This plasmid is genetically identical to several known IncI2-type elements harbored by
E. coli
strains recovered from animals. This finding indicates that IncI2 plasmids harboring the
bla
CTX-M
genes may undergo cross-species migration among potential bacterial pathogens, with
E. coli
as the major source of such elements.
Activity of Imipenem with Relebactam against Gram-Negative Pathogens from New York City
Authors: Lapuebla Amabel , Abdallah Marie , Olafisoye Olawole , Cortes Christopher , Urban Carl , Landman David , Quale John
Published: May 2015

Imipenem with relebactam was active against
Escherichia coli
,
Klebsiella pneumoniae
, and
Enterobacter
spp., including
K. pneumoniae
carbapenemase (KPC)-producing isolates. Loss of OmpK36 in KPC-producing
K. pneumoniae
isolates affected the susceptibility of this combination. Enhanced activity was evident against
Pseudomonas aeruginosa
, including isolates with depressed
oprD
and increased
ampC
expression. However, the addition of relebactam to imipenem did not provide added benefit against
Acinetobacter baumannii
. The combination of imipenem with relebactam demonstrated activity against KPC-producing
Enterobacteriaceae
and multidrug-resistant
P. aeruginosa
.
Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management
Authors: Tong Steven Y. C. , Davis Joshua S. , Eichenberger Emily , Holland Thomas L. , Fowler Vance G.
Published: May 2015

Staphylococcus aureus
is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of
S. aureus
infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.