bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced microwave‐absorbing property of precursor infiltration and pyrolysis derived SiCf/SiC composites at X band: Role of carbon‐rich interphase
Authors: Yang Lingwei , Liu Haitao , Zu Mei
Published: February 2018

Ceramic matrix composites (CMCs) can be microwave‐absorbent when endowing the composite constituents with proper dielectric properties. In this work, we report a new method to enhance the microwave‐absorbing property of CMCs by in situ fabrication of a carbon‐rich interphase at the fiber/matrix interface. This was achieved in a SiC fiber reinforced SiC matrix (SiCf/SiC) composite fabricated by precursor infiltration and pyrolysis (PIP). We found that as the PIP temperature increased from 800 to 1000°C, the microwave‐absorbing property of the SiCf/SiC composite was significantly enhanced at X band, which also surpassed those of the SiC fiber and monolithic SiC ceramic fabricated at the same temperature. The dominant mechanism was studied by decoupling the effect of individual SiC fibers, SiC matrix, and fiber/matrix interface. The results showed that the SiC fiber and SiC matrix were barely microwave‐absorbent, due to their low dielectric losses. The microwave‐absorbing mechanism was finally ascribed to the fiber/matrix interface, which was carbon‐rich, containing Si and O elements. The interphase showed a conductivity that was superior to that of the fiber and the matrix, and mainly dominated the dielectric property of the overall composite. The results highlight the role of carbon‐rich interphase on the microwave‐absorbing property of CMCs.
Effects of composition and solidification rate on growth striations in laser floating zone melted Al2O3/GdAlO3 eutectic ceramics
Authors: Ma Weidan , Su Haijun , Zhang Jun , Ren Qun , Liu Haifang , Wang Enyuan , Ren Junfei , Lu Ze , Liu Lin , Fu Hengzhi
Published: February 2018

Growth striations with a period of 283 seconds are observed in Al2O3/GdAlO3 (GAP) directionally solidified eutectic ceramics prepared by laser floating zone melting (LFZM) process. The effects of composition and solidification rate on the microstructure of growth striations are investigated, aiming to reveal the formation mechanism of growth striations. The results show that a number of coarse primary Al2O3 phases are produced preferentially at growth striations in hypoeutectic ceramics and primary GAP phases segregate in hypereutectic ceramics. Simultaneously, homogeneous “Chinese script” eutectic microstructures are formed between two adjacent growth striations in Al2O3/GAP eutectic ceramics, affected very few by the composition segregations at growth striations. Moreover, it is also found that the interval of periodic growth striations has a liner relationship with solidification rate, but has no relevance with composition. The width of growth striations, however, mainly depends on composition that the larger the composition deviates from eutectic composition, the coarser the phases precipitate at growth striations. Based on the detailed examinations of solid‐liquid interface right at growth striations, the growth striations induced by Marangoni convection are strongly affected by constitutional undercooling in Al2O3/GAP off‐eutectic ceramics.
Relation of serum uric acid to an exaggerated systolic blood pressure response to exercise testing in men with normotension
Authors: Jae Sae Young , Bunsawat Kanokwan , Choi Yoon‐Ho , Kim Yeon Soo , Touyz Rhian M. , Park Jeong Bae , Franklin Barry A.
Published: February 2018

The authors investigated the hypothesis that high serum uric acid concentrations may be related to an exaggerated systolic blood pressure (SBP) response to maximal exercise testing in men with normotension, independent of potential confounding variables. In 4640 healthy men with normotension who underwent maximal treadmill exercise testing and fasting blood chemistry studies, including serum uric acid concentrations, an exaggerated SBP response, defined as SBP ≥ 210 mm Hg, was detected in 152 men (3.3%). After adjusting for potential confounders, participants in the highest quartile of serum uric acid (>6.6 mg/dL) had a higher odds ratio of demonstrating an exaggerated SBP to maximal exercise (odds ratio, 2.19; 95% confidence interval, 1.24–3.86) compared with participants in the lowest quartile of serum uric acid (<5.1 mg/dL). High serum uric acid concentrations are associated with an exaggerated SBP response to maximal exercise testing in men with normotension, independent of established coronary risk factors.
Margin Requirements and the Security Market Line
Authors: JYLHÄ PETRI
Published: February 2018

Between 1934 and 1974, the Federal Reserve changed the initial margin requirement for the U.S. stock market 22 times. I use this variation to show that investors' leverage constraints affect the pricing of risk. Consistent with earlier theoretical predictions, I find that tighter leverage constraints result in a flatter relation between betas and expected returns. My results provide strong empirical support for the idea that the constraints investors face may help explain the empirical failure of the capital asset pricing model.
Seasonal acclimatization of thallus proline contents of Mastocarpus stellatus and Chondrus crispus: intertidal rhodophytes that differ in freezing tolerance
Authors: Harris Jonathan P. , Logan Barry A.
Published: February 2018

Mastocarpus stellatus and Chondrus crispus often co‐occur in the lower intertidal of Northern Atlantic rocky shorelines. At our field site along the Maine coast (USA), Mastocarpus stellatus thalli possessed greater contents of proline when compared with thalli of Chondrus crispus. In addition, M. stellatus thalli acclimated to colder growth conditions in winter/early spring by increasing proline content several fold; no seasonal acclimation in proline content was observed in C. crispus. Proline accumulates in the tissues of a broad diversity of freezing‐tolerant organisms and is among the most common cryoprotectant molecules. Thus, our observations provide a basis for the previously well‐documented greater freezing tolerance of Mastocarpus stellatus when compared with Chondrus crispus.
Development of a multiroute physiologically based pharmacokinetic model for orbifloxacin in rabbits
Authors: Yang F. , Yang F. , Shi W. , Si H. , Kong T. , Wang G. , Zhang J.
Published: February 2018

To predict the orbifloxacin concentrations in rabbits after multiple routes of administration, a flow‐limited multiroute physiologically based pharmacokinetic (PBPK) model was developed. Three routes of administration (IV, IM, and PO) were incorporated into this model. Physiological parameters including tissue weights and blood flows through different tissues were obtained from the literature. The tissue/plasma partition coefficients (PXs) for noneliminating tissues were calculated according to the area method, while the PXs for kidney and the rest of the body compartment, together with other parameters for absorption and elimination, were optimized based on the published concentrations. The comparisons between predicted and observed orbifloxacin concentrations proved its validity, and the present model predicted available concentration data well, including those in liver, kidney, muscle, lung, heart, and plasma after oral, intravenous, or intramuscular administration. A local sensitivity analysis was also performed, which showed that the parameters for oral absorption were most influential on the orbifloxacin concentrations. This model was used to predict plasma and tissue concentrations after multiple oral or intramuscular administration. This study demonstrated the feasibility of predicting drug residues in minor species after multiple routes of administration in the extra‐label manner using the PBPK modeling.
Diagnosis, presentation and initial severity of Autoimmune Hepatitis (AIH) in patients attending 28 hospitals in the UK
Authors: Gordon Victoria , Adhikary Ratul , Appleby Victoria , Das Debasis , Day James , Delahooke Toby , Dixon Selena , Elphick David , Hardie Claire , Hoeroldt Barbara , Hooper Patricia , Hutchinson John , Jones Rebecca , Khan Faisal , Aithal Guruprasad P. , McGonigle John , Nelson Andrew , Nkhoma Alick , Pelitari Stavroula , Prince Martin , Prosser Annell , Sathanarayana Vinay , Savva Sophia , Shah Naina , Saksena Sushma , Thayalasekaran Sreedhari , Vani Deven , Yeoman Andrew , Gleeson Dermot ,   The UK Multi‐Centre AIH Audit Group
Published: February 2018

Background & Aims

There is limited information regarding patients with AIH outside relatively few large centres. We describe here the presenting features of patients with AIH, collected as part of an audit involving 28 UK hospitals.

Methods

Patients (incident since 1/1/2007 or prevalent since 1/1/2000) were ≥18 years and either met 1999 International AIH Group (IAIHG) diagnostic criteria (n = 1164), or received immunosuppressive therapy for clinically diagnosed AIH (n = 103).

Results

Of 1267 patients (80% women, 91% Caucasian, age (median(range)) 55(8‐86) years, 0.5% had acute viral hepatitis (CMV/EBV/HEV); 2% were taking Nitrofurantoin and 0.7% Khat. Twenty‐one percent had clinical decompensation and/or a MELD score of >15. Time from first abnormal liver tests to diagnosis was ≥1 year in 19% and was longer in jaundiced vs non‐jaundiced patients. HBV and HCV serology were undocumented in 4%, serum immunoglobulins in 31% and autoantibodies in 11%‐27%. When documented, ≥1 antibody was present in 83%. LKM‐1‐positive and autoantibody‐negative patients had more severe disease. Histological cirrhosis was reported in 23%, interface hepatitis 88%, predominant lymphocytes/plasma cells 75%, rosettes 19% and emperipolesis 0.4%. Only 65% of those meeting 1999 IAIHG criteria also met simplified IAIHG criteria. University Hospitals compared to District General Hospitals, were more likely to report histological features of AIH.

Conclusions

This cohort from across the UK is older than other multicentre AIH cohorts. One‐fifth had decompensation or MELD >15. Diagnosis was delayed in 19%, diagnostic testing was incomplete in one‐third and rosettes and emperipolesis were infrequently reported.
Strict local martingales and optimal investment in a Black–Scholes model with a bubble
Authors: Herdegen Martin , Herrmann Sebastian
Published: February 2018

There are two major streams of literature on the modeling of financial bubbles: the strict local martingale framework and the Johansen–Ledoit–Sornette (JLS) financial bubble model. Based on a class of models that embeds the JLS model and can exhibit strict local martingale behavior, we clarify the connection between these previously disconnected approaches. While the original JLS model is never a strict local martingale, there are relaxations that can be strict local martingales and that preserve the key assumption of a log‐periodic power law for the hazard rate of the time of the crash. We then study the optimal investment problem for an investor with constant relative risk aversion in this model. We show that for positive instantaneous expected returns, investors with relative risk aversion above one always ride the bubble.
Effectiveness of Rlm7 resistance against Leptosphaeria maculans (phoma stem canker) in UK winter oilseed rape cultivars
Authors: Mitrousia G. K. , Huang Y. J. , Qi A. , Sidique S. N. M. , Fitt B. D. L.
Published: February 2018

The Rlm7 gene in Brassica napus is an important source of resistance for control of phoma stem canker on oilseed rape caused by the fungus Leptosphaeria maculans. This study shows the first report of L. maculans isolates virulent against Rlm7 in the UK. Leptosphaeria maculans isolates virulent against Rlm7 represented 3% of the pathogen population when cultivars with the Rlm7 gene represented 5% of the UK oilseed rape area in 2012/13. However, the Rlm7 gene has been widely used since then, representing >15% of the UK oilseed rape area in 2015/16. Winter oilseed rape field experiments included cultivars with the Rlm7 gene, with the Rlm4 gene or without Rlm genes and took place at five sites in the UK over four cropping seasons. An increase in phoma leaf spotting severity on Rlm7 cultivars in successive seasons was observed. Major resistance genes played a role in preventing severe phoma leaf spotting at the beginning of the cropping season and, in addition, quantitative resistance (QR) in the cultivars examined made an important contribution to control of phoma stem canker development at the end of the cropping season. Deployment of the Rlm7 resistance gene against L. maculans in cultivars with QR in combination with sustainable disease management practices will prolong the use of this gene for effective control of phoma stem canker epidemics.
Event‐related potentials of emotional and neutral memories: The role of encoding position and delayed testing
Authors: Wirkner Janine , Ventura‐Bort Carlos , Schulz Paul , Hamm Alfons O. , Weymar Mathias
Published: February 2018

Previous research found that memory is not only better for emotional information but also for neutral information that has been encoded in the context of an emotional event. In the present ERP study, we investigated two factors that may influence memory for neutral and emotional items: temporal proximity between emotional and neutral items during encoding, and retention interval (immediate vs. delayed). Forty‐nine female participants incidentally encoded 36 unpleasant and 108 neutral pictures (36 neutral pictures preceded an unpleasant picture, 36 followed an unpleasant picture, and 36 neutral pictures were preceded and followed by neutral pictures) and participated in a recognition memory task either immediately (N = 24) or 1 week (N = 25) after encoding. Results showed better memory for emotional pictures relative to neutral pictures. In accordance, enhanced centroparietal old/new differences (500–900 ms) during recognition were observed for unpleasant compared to neutral pictures, most pronounced for the 1‐week interval. Picture position effects, however, were only subtle. During encoding, late positive potentials for neutral pictures were slightly lower for neutral pictures following unpleasant ones, but only at trend level. To summarize, we could replicate and extend previous ERP findings showing that emotionally arousing events are better recollected than neutral events, particularly when memory is tested after longer retention intervals. Picture position during encoding, however, had only small effects on elaborative processing and no effects on memory retrieval.
Nutrition education in the care of patients with chronic kidney disease and end‐stage renal disease
Authors: Anderson Cheryl A. M. , Nguyen Hoang Anh
Published: February 2018

Diet counseling and nutrition education are recommended in the prevention and management of chronic kidney disease (CKD) and end‐stage renal disease (ESRD). The importance of effectively addressing nutrition with patients has grown given the increasing prevalence of obesity, hypertension, and diabetes; conditions which influence CKD/ESRD. Dietary advice for individuals with CKD/ESRD can be seen as complex; and successful dietary management requires careful planning, periodic assessment of nutritional status, as well as monitoring of dietary compliance. In spite of recommendations and pressing need, formal training in nutrition and adequate preparation for providers is limited; and for physicians the lack of nutrition education has been acknowledged, repeatedly, as an area for improvement in medical training curricula. It has also been suggested that dietitians have an essential role in management of CKD in the primary care setting; however, dietitians who do not practice renal education daily may need training on the specific challenges in CKD/ESRD. The objectives of this chapter were to: characterize select nutrition education resources for providers who care for patients with CKD/ESRD; summarize key dietary components emphasized in the care of patients with CKD/ESRD; and address practical considerations in educational efforts focused on nutrition and CKD/ESRD.
Oxidative capacity varies along the length of healthy human tibialis anterior
Authors: Boss Andreas , Heskamp Linda , Breukels Vincent , Bains Lauren J , van Uden Mark J. , Heerschap Arend
Published: February 2018

Key points

During exercise skeletal muscles use the energy buffer phosphocreatine.

The post‐exercise recovery of phosphocreatine is a measure of the oxidative capacity of muscles and is traditionally assessed by 31P magnetic resonance spectroscopy of a large tissue region, assuming homogeneous energy metabolism.

To test this assumption, we collected spatially resolved spectra along the length of human tibialis anterior using a home‐built array of 31P detection coils, and observed a striking gradient in the recovery rate of phosphocreatine, decreasing along the proximo‐distal axis of the muscle.

A similar gradient along this muscle was observed in signal changes recorded by 1H muscle functional MRI.

These findings identify intra‐muscular variation in the physiology of muscles in action and highlight the importance of localized sampling for any methodology investigating oxidative metabolism of this, and potentially other muscles.

The rate of phosphocreatine (PCr) recovery (kPCr) after exercise, characterizing muscle oxidative capacity, is traditionally assessed with unlocalized 31P magnetic resonance spectroscopy (MRS) using a single surface coil. However, because of intramuscular variation in fibre type and oxygen supply, kPCr may be non‐uniform within muscles. We tested this along the length of the tibialis anterior (TA) muscle in 10 male volunteers. For this purpose, we employed a 3T MR system with a 31P/1H volume transmit coil combined with a home‐built 31P phased‐array receive probe, consisting of five coil elements covering the TA muscle length. Mono‐exponential kPCr was determined for all coil elements after 40 s of submaximal isometric dorsiflexion (SUBMAX) and incremental exercise to exhaustion (EXH). In addition, muscle functional MRI (1H mfMRI) was performed using the volume coil after another 40 s of SUBMAX. A strong gradient in kPCr was observed along the TA (P < 0.001), being two times higher proximally vs. distally during SUBMAX and EXH. Statistical analysis showed that this gradient cannot be explained by pH variations. A similar gradient was seen in the slope of the initial post‐exercise 1H mfMRI signal change, which was higher proximally than distally in both the TA and the extensor digitorum longus (P < 0.001) and strongly correlated with kPCr. The pronounced differences along the TA in functional oxidative capacity identify regional variation in the physiological demand of this muscle during everyday activities and have implications for the bio‐energetic assessment of interventions to modify its performance and of neuromuscular disorders involving the TA.
Amblyomma tick species infesting amphibians and reptiles in the seasonally dry Amazon forest, with new host records for Amblyomma rotundatum (Acari: Ixodida: Ixodidae)
Authors: Oda Fabrício Hiroiuki , Kitagawa Clóvis , Noronha Janaina Da Costa , Rodrigues Domingos De Jesus , Martins Thiago Fernandes , Valadão Marisa Caixeta , Carvalho Lorendane Millena de , Campos Artur Kanadani
Published: February 2018

Our study yielded a list of ticks found on amphibians and reptiles at five sites within seasonally dry Amazon forest in Mato Grosso State, central Brazil, in addition to new host records for A. rotundatum. We collected 431 tick specimens: 79 larvae, 115 nymphs, 38 females, and 199 males belonging to A. humerale, A. rotundatum, and Amblyomma sp., on 39 anurans and 21 reptiles. The toads R. guttatus and R. margaritifera and the frog L. pentadactylus are new hosts for A. rotundatum.
Verapamil Targets Membrane Energetics in Mycobacterium tuberculosis
Authors: Chen Chao , Gardete Susana , Jansen Robert Sander , Shetty Annanya , Dick Thomas , Rhee Kyu Y. , Dartois Véronique
Published: February 2018

Mycobacterium tuberculosis
kills more people than any other bacterial pathogen and is becoming increasingly untreatable due to the emergence of resistance. Verapamil, an FDA-approved calcium channel blocker, potentiates the effect of several antituberculosis (anti-TB) drugs
in vitro
and
in vivo
. This potentiation is widely attributed to inhibition of the efflux pumps of
M. tuberculosis
, resulting in intrabacterial drug accumulation. Here, we confirmed and quantified verapamil's synergy with several anti-TB drugs, including bedaquiline (BDQ) and clofazimine (CFZ), but found that the effect is not due to increased intrabacterial drug accumulation. We show that, consistent with its
in vitro
potentiating effects on anti-TB drugs that target or require oxidative phosphorylation, the cationic amphiphile verapamil disrupts membrane function and induces a membrane stress response similar to those seen with other membrane-active agents. We recapitulated these activities
in vitro
using inverted mycobacterial membrane vesicles, indicating a direct effect of verapamil on membrane energetics. We observed bactericidal activity against nonreplicating “persister”
M. tuberculosis
that was consistent with such a mechanism of action. In addition, we demonstrated a pharmacokinetic interaction whereby human-equivalent doses of verapamil caused a boost of rifampin exposure in mice, providing a potential explanation for the observed treatment-shortening effect of verapamil in mice receiving first-line drugs. Our findings thus elucidate the mechanistic basis for verapamil's potentiation of anti-TB drugs
in vitro
and
in vivo
and highlight a previously unrecognized role for the membrane of
M. tuberculosis
as a pharmacologic target.
The Gills of Reef Fish Support a Distinct Microbiome Influenced by Host-Specific Factors
Authors: Pratte Zoe A. , Besson Marc , Hollman Rebecca D. , Stewart Frank J.
Published: February 2018

Teleost fish represent the most diverse of the vertebrate groups and play important roles in food webs, as ecosystem engineers, and as vectors for microorganisms. However, the microbial ecology of fishes remains underexplored for most host taxa and for certain niches on the fish body. This is particularly true for the gills, the key sites of respiration and waste exchange in fishes. Here we provide a comprehensive analysis of the gill microbiome. We focus on ecologically diverse taxa from coral reefs around Moorea, sampling the gills and intestines of adults and juveniles representing 15 families. The gill microbiome composition differed significantly from that of the gut for both adults and juveniles, with fish-associated niches having lower alpha diversity values and higher beta diversity values than those for seawater, sediment, and alga-associated microbiomes. Of ∼45,000 operational taxonomic units (OTUs) detected across all samples, 11% and 13% were detected only in the gill and the intestine, respectively. OTUs most enriched in the gill included members of the gammaproteobacterial genus
Shewanella
and the family
Endozoicimonaceae
. In adult fish, both gill and intestinal microbiomes varied significantly among host species grouped by diet category. Gill and intestinal microbiomes from the same individual were more similar to one another than to gill and intestinal microbiomes from different individuals. These results demonstrate that distinct body sites are jointly influenced by host-specific organizing factors operating at the level of the host individual. The results also identify taxonomic signatures unique to the gill and the intestine, confirming fish-associated niches as distinct reservoirs of marine microbial diversity.

IMPORTANCE
Fish breathe and excrete waste through their gills. The gills are also potential sites of pathogen invasion and colonization by other microbes. However, we know little about the microbial communities that live on the gill and the factors shaping their diversity. Focusing on ecologically distinct types of coral reef fish, we provide a comprehensive analysis of the fish gill microbiome. By comparison to microbiomes of the gut and the surrounding environment, we identify microbes unique to the gill niche. These microbes may be targets for further studies to determine the contribution of the microbiome to waste exchange or host immunity. We also show that despite exhibiting a unique taxonomic signature, the gill microbiome is influenced by factors that also influence the gut microbiome. These factors include the specific identity of the host individual. These results suggest basic principles describing how association with fishes structures the composition of microbial communities.
Integrated Metabolomics and Morphogenesis Reveal Volatile Signaling of the Nematode-Trapping Fungus Arthrobotrys oligospora
Authors: Wang Bai-Le , Chen Yong-Hong , He Jia-Ning , Xue Hua-Xi , Yan Ni , Zeng Zhi-Jun , Bennett Joan W. , Zhang Ke-Qin , Niu Xue-Mei
Published: February 2018

The adjustment of metabolic patterns is fundamental to fungal biology and plays vital roles in adaptation to diverse ecological challenges. Nematode-trapping fungi can switch their lifestyle from saprophytic to pathogenic by developing specific trapping devices induced by nematodes to infect their prey as a response to nutrient depletion in nature. However, the chemical identity of the specific fungal metabolites used during the switch remains poorly understood. We hypothesized that these important signal molecules might be volatile in nature. Gas chromatography-mass spectrometry was used to carry out comparative analysis of fungal metabolomics during the saprophytic and pathogenic lifestyles of the model species
Arthrobotrys oligospora
. Two media commonly used in research on this species, cornmeal agar (CMA) and potato dextrose agar (PDA), were chosen for use in this study. The fungus produced a small group of volatile furanone and pyrone metabolites that were associated with the switch from the saprophytic to the pathogenic stage.
A. oligospora
fungi grown on CMA tended to produce more traps and employ attractive furanones to improve the utilization of traps, while fungi grown on PDA developed fewer traps and used nematode-toxic furanone metabolites to compensate for insufficient traps. Another volatile pyrone metabolite, maltol, was identified as a morphological regulator for enhancing trap formation. Deletion of the gene
AOL_s00079g496
in
A. oligospora
led to increased amounts of the furanone attractant (2-fold) in mutants and enhanced the attractive activity (1.5-fold) of the fungus, while it resulted in decreased trap formation. This investigation provides new insights regarding the comprehensive tactics of fungal adaptation to environmental stress, integrating both morphological and metabolomic mechanisms.

IMPORTANCE
Nematode-trapping fungi are a unique group of soil-living fungi that can switch from the saprophytic to the pathogenic lifestyle once they come into contact with nematodes as a response to nutrient depletion. In this study, we investigated the metabolic response during the switch and the key types of metabolites involved in the interaction between fungi and nematodes. Our findings indicate that
A. oligospora
develops multiple and flexible metabolic tactics corresponding to different morphological responses to nematodes.
A. oligospora
can use similar volatile furanone and pyrone metabolites with different ecological functions to help capture nematodes in the fungal switch from the saprophytic to the pathogenic lifestyle. Furthermore, studies with
A. oligospora
mutants with increased furanone and pyrone metabolites confirmed the results. This investigation reveals the importance of volatile signaling in the comprehensive tactics used by nematode-trapping fungi, integrating both morphological and metabolomic mechanisms.
Plant-Microbe and Abiotic Factors Influencing Salmonella Survival and Growth on Alfalfa Sprouts and Swiss Chard Microgreens
Authors: Reed Elizabeth , Ferreira Christina M. , Bell Rebecca , Brown Eric W. , Zheng Jie
Published: February 2018

Microgreens, like sprouts, are relatively fast-growing products and are generally consumed raw. Moreover, as observed for sprouts, microbial contamination from preharvest sources may also be present in the production of microgreens. In this study, two
Salmonella enterica
serovars (Hartford and Cubana), applied at multiple inoculation levels, were evaluated for survival and growth on alfalfa sprouts and Swiss chard microgreens by using the most-probable-number (MPN) method. Various abiotic factors were also examined for their effects on
Salmonella
survival and growth on sprouts and microgreens. Community-level physiological profiles (CLPPs) of sprout/microgreen rhizospheres with different levels of
S. enterica
inoculation at different growth stages were characterized by use of Biolog EcoPlates. In the seed contamination group, the ability of
S. enterica
to grow on sprouting alfalfa seeds was affected by both seed storage time and inoculation level but not by serovar. However, the growth of
S. enterica
on Swiss chard microgreens was affected by serovar and inoculation level. Seed storage time had little effect on the average level of
Salmonella
populations in microgreens. In the irrigation water contamination group, the growth of
Salmonella
on both alfalfa sprouts and microgreens was largely affected by inoculation level. Surprisingly, the growth medium was found to play an important role in
Salmonella
survival and growth on microgreens. CLPP analysis showed significant changes in the microbial community metabolic diversity during sprouting for alfalfa sprouts, but few temporal changes were seen with microgreens. The data suggest that the change in rhizosphere bacterial functional diversity was dependent on the host but independent of
Salmonella
contamination.

IMPORTANCE
Sprouts and microgreens are considered “functional foods,” i.e., foods containing health-promoting or disease-preventing properties in addition to normal nutritional values. However, the microbial risk associated with microgreens has not been well studied. This study evaluated
Salmonella
survival and growth on microgreens compared to those on sprouts, as well as other abiotic factors that could affect
Salmonella
survival and growth on microgreens. This work provides baseline data for risk assessment of microbial contamination of sprouts and microgreens. Understanding the risks of
Salmonella
contamination and its effects on rhizosphere microbial communities enables a better understanding of host-pathogen dynamics in sprouts and microgreens. The data also contribute to innovative preventive control strategies for
Salmonella
contamination of sprouts and microgreens.
Phenazines Regulate Nap-Dependent Denitrification in Pseudomonas aeruginosa Biofilms
Authors: Lin Yu-Cheng , Sekedat Matthew D. , Cornell William Cole , Silva Gustavo M. , Okegbe Chinweike , Price-Whelan Alexa , Vogel Christine , Dietrich Lars E. P.
Published: February 2018

Microbes in biofilms face the challenge of substrate limitation. In particular, oxygen often becomes limited for cells inPseudomonas aeruginosabiofilms growing in the laboratory or during host colonization. Previously we found that phenazines, antibiotics produced byP. aeruginosa, balance the intracellular redox state of cells in biofilms. Here, we show that genes involved in denitrification are induced in phenazine-null (Δphz) mutant biofilms grown under an aerobic atmosphere, even in the absence of nitrate. This finding suggests that resident cells employ a bet-hedging strategy to anticipate the potential availability of nitrate and counterbalance their highly reduced redox state. Consistent with our previous characterization of aerobically grown colonies supplemented with nitrate, we found that the pathway that is induced in Δphzmutant colonies combines the nitrate reductase activity of the periplasmic enzyme Nap with the downstream reduction of nitrite to nitrogen gas catalyzed by the enzymes Nir, Nor, and Nos. This regulatory relationship differs from the denitrification pathway that functions under anaerobic growth, with nitrate as the terminal electron acceptor, which depends on the membrane-associated nitrate reductase Nar. We identified the sequences in the promoter regions of thenapandniroperons that are required for the effects of phenazines on expression. We also show that specific phenazines have differential effects onnapgene expression. Finally, we provide evidence that individual steps of the denitrification pathway are catalyzed at different depths within aerobically grown biofilms, suggesting metabolic cross-feeding between community subpopulations.

IMPORTANCEAn understanding of the unique physiology of cells in biofilms is critical to our ability to treat fungal and bacterial infections. Colony biofilms of the opportunistic pathogenPseudomonas aeruginosagrown under an aerobic atmosphere but without nitrate express a denitrification pathway that differs from that used for anaerobic growth. We report that the components of this pathway are induced by electron acceptor limitation and that they are differentially expressed over the biofilm depth. These observations suggest that (i)P. aeruginosaexhibits “bet hedging,” in that it expends energy and resources to prepare for nitrate availability when other electron acceptors are absent, and (ii) cells in distinct biofilm microniches may be able to exchange substrates to catalyze full denitrification.
Reduced Chronic Lymphocyte Activation following Interferon Alpha Blockade during the Acute Phase of Simian Immunodeficiency Virus Infection in Rhesus Macaques
Authors: Carnathan Diane , Lawson Benton , Yu Joana , Patel Kalpana , Billingsley James M. , Tharp Gregory K. , Delmas Olivia M. , Dawoud Reem , Wilkinson Peter , Nicolette Charles , Cameron Mark J. , Sekaly Rafick-Pierre , Bosinger Steven E. , Silvestri Guido , Vanderford Thomas H.
Published: February 2018

Pathogenic human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection of humans and rhesus macaques (RMs) induces persistently high production of type I interferon (IFN-I), which is thought to contribute to disease progression. To elucidate the specific role of interferon alpha (IFN-α) in SIV pathogenesis, 12 RMs were treated prior to intravenous (i.v.) SIV
mac239
infection with a high or a low dose of an antibody (AGS-009) that neutralizes most IFN-α subtypes and were compared with six mock-infused, SIV-infected controls. Plasma viremia was measured postinfection to assess the effect of IFN-α blockade on virus replication, and peripheral blood and lymphoid tissue samples were analyzed by immunophenotypic staining. Consistent with the known antiviral effect of IFN-I, high-dose AGS-009 treatment induced a modest increase in acute-phase viral loads versus controls. Four out of 6 RMs receiving a high dose of AGS-009 also experienced an early decline in CD4
+
T cell counts that was associated with progression to AIDS. Interestingly, 50% of the animals treated with AGS-009 (6/12) developed AIDS within 1 year of infection compared with 17% (1/6) of untreated controls. Finally, blockade of IFN-α decreased the levels of activated CD4
+
and CD8
+
T cells, as well as B cells, as measured by PD-1 and/or Ki67 expression. The lower levels of activated lymphocytes in IFN-α-blockaded animals supports the hypothesis that IFN-α signaling contributes to lymphocyte activation during SIV infection and suggests that this signaling pathway is involved in controlling virus replication during acute infection. The potential anti-inflammatory effect of IFN-α blockade should be explored as a strategy to reduce immune activation in HIV-infected individuals.

IMPORTANCE
Interferon alpha (IFN-α) is a member of a family of molecules (type I interferons) that prevent or limit virus infections in mammals. However, IFN-α production may contribute to the chronic immune activation that is thought to be the primary cause of immune decline and AIDS in HIV-infected patients. The study presented here attempts to understand the contribution of IFN-α to the natural history and progression of SIV infection of rhesus macaques, the primary nonhuman primate model system for testing hypotheses about HIV infection in humans. Here, we show that blockade of IFN-α action promotes lower chronic immune activation but higher early viral loads, with a trend toward faster disease progression. This study has significant implications for new treatments designed to impact the type I interferon system.
Ethanolamine Utilization in Bacteria
Authors: Kaval Karan Gautam , Garsin Danielle A.
Published: February 2018

Ethanolamine (EA) is a valuable source of carbon and/or nitrogen for bacteria capable of its catabolism. Because it is derived from the membrane phospholipid phosphatidylethanolamine, it is particularly prevalent in the gastrointestinal tract, which is membrane rich due to turnover of the intestinal epithelium and the resident microbiota. Intriguingly, many gut pathogens carry the
eut
(ethanolamine utilization) genes. EA utilization has been studied for about 50 years, with most of the early work occurring in just a couple of species of
Enterobacteriaceae
. Once the metabolic pathways and enzymes were characterized by biochemical approaches, genetic screens were used to map the various activities to the
eut
genes. With the rise of genomics, the diversity of bacteria containing the
eut
genes and surprising differences in
eut
gene content were recognized. Some species contain nearly 20 genes and encode many accessory proteins, while others contain only the core catabolic enzyme. Moreover, the
eut
genes are regulated by very different mechanisms, depending on the organism and the
eut
regulator encoded. In the last several years, exciting progress has been made in elucidating the complex regulatory mechanisms that govern
eut
gene expression. Furthermore, a new appreciation for how EA contributes to infection and colonization in the host is emerging. In addition to providing an overview of EA-related biology, this minireview will give special attention to these recent advances.
Microbial Functional Gene Diversity Predicts Groundwater Contamination and Ecosystem Functioning
Authors: He Zhili , Zhang Ping , Wu Linwei , Rocha Andrea M. , Tu Qichao , Shi Zhou , Wu Bo , Qin Yujia , Wang Jianjun , Yan Qingyun , Curtis Daniel , Ning Daliang , Van Nostrand Joy D. , Wu Liyou , Yang Yunfeng , Elias Dwayne A. , Watson David B. , Adams Michael W. W. , Fields Matthew W. , Alm Eric J. , Hazen Terry C. , Adams Paul D. , Arkin Adam P. , Zhou Jizhong
Published: February 2018

Contamination from anthropogenic activities has significantly impacted Earth’s biosphere. However, knowledge about how environmental contamination affects the biodiversity of groundwater microbiomes and ecosystem functioning remains very limited. Here, we used a comprehensive functional gene array to analyze groundwater microbiomes from 69 wells at the Oak Ridge Field Research Center (Oak Ridge, TN), representing a wide pH range and uranium, nitrate, and other contaminants. We hypothesized that the functional diversity of groundwater microbiomes would decrease as environmental contamination (e.g., uranium or nitrate) increased or at low or high pH, while some specific populations capable of utilizing or resistant to those contaminants would increase, and thus, such key microbial functional genes and/or populations could be used to predict groundwater contamination and ecosystem functioning. Our results indicated that functional richness/diversity decreased as uranium (but not nitrate) increased in groundwater. In addition, about 5.9% of specific key functional populations targeted by a comprehensive functional gene array (GeoChip 5) increased significantly (
P
< 0.05) as uranium or nitrate increased, and their changes could be used to successfully predict uranium and nitrate contamination and ecosystem functioning. This study indicates great potential for using microbial functional genes to predict environmental contamination and ecosystem functioning.

IMPORTANCE
Disentangling the relationships between biodiversity and ecosystem functioning is an important but poorly understood topic in ecology. Predicting ecosystem functioning on the basis of biodiversity is even more difficult, particularly with microbial biomarkers. As an exploratory effort, this study used key microbial functional genes as biomarkers to provide predictive understanding of environmental contamination and ecosystem functioning. The results indicated that the overall functional gene richness/diversity decreased as uranium increased in groundwater, while specific key microbial guilds increased significantly as uranium or nitrate increased. These key microbial functional genes could be used to successfully predict environmental contamination and ecosystem functioning. This study represents a significant advance in using functional gene markers to predict the spatial distribution of environmental contaminants and ecosystem functioning toward predictive microbial ecology, which is an ultimate goal of microbial ecology.
Comparative activity of antimicrobials againstPseudomonas aeruginosa,Achromobacter xylosoxidansandStenotrophomonas maltophiliakeratitis isolates
Authors: Spierer Oriel , Miller Darlene , O’Brien Terrence P
Published: February 2018

Background/aims

Achromobacter xylosoxidansandStenotrophomonas maltophiliaare emerging corneal pathogens, which are closely related toPseudomonas aeruginosa, and have intrinsic resistance to many commonly available antimicrobials. The purpose of this study is to compare the in vitro efficacy of 12 antimicrobial agents againstA. xylosoxidans,S. maltophiliaandP. aeruginosaisolates recovered from clinical cases of keratitis.

Methods

Recovered corneal isolates (n=58) were identified and extracted from the Microbiology Data Bank of the Bascom Palmer Eye Institute. Comparative in vitro minimum inhibitory concentration (MIC) susceptibility profiles for fluoroquinolones, aminoglycosides, beta-lactams and miscellaneous antibiotics were recorded using the E-test methodology. Pharmacodynamic indices (Cmax/MIC) were calculated.

Results

A. xylosoxidansandS. maltophiliaisolates were resistant to fluoroquinolones, aminoglycosides and ceftazidime (susceptibility rate ranging from 0% to 30%) whileP. aeruginosaisolates showed a susceptibility rate of 95%–100% to these antimicrobials (P<0.00001 for the various antimicrobials). Exception was moxifloxacin with 80% of susceptibility rate toS. maltophiliaisolates and Cmax/MIC=10.19. Ninety to 100% susceptibility rates were found for minocycline and trimethoprim/sulfamethoxazole for bothA. xylosoxidansandS. maltophilia. One hundred per cent of theA. xylosoxidansisolates were susceptible to piperacillin/tazobactam and ticarcillin/clavulanic acid.

Conclusions

There is a significant difference in susceptibility patterns betweenA. xylosoxidans,S. maltophiliaandP. aeruginosa. Fluoroquinolones and aminoglycosides may not be effective againstA. xylosoxidansandS. maltophilia. Antibiotics that are not commercially available as eye drops, such as beta-lactams forA. xylosoxidans, and trimethoprim/sulfamethoxazole and minocycline for bothA. xylosoxidansandS. maltophiliashould be considered.
Convergent molecular defects underpin diverse neurodegenerative diseases
Authors: Tofaris George K , Buckley Noel J
Published: February 2018

In our ageing population, neurodegenerative disorders carry an enormous personal, societal and economic burden. Although neurodegenerative diseases are often thought of as clinicopathological entities, increasing evidence suggests a considerable overlap in the molecular underpinnings of their pathogenesis. Such overlapping biological processes include the handling of misfolded proteins, defective organelle trafficking, RNA processing, synaptic health and neuroinflammation. Collectively but in different proportions, these biological processes in neurons or non-neuronal cells lead to regionally distinct patterns of neuronal vulnerability and progression of pathology that could explain the disease symptomology. With the advent of patient-derived cellular models and novel genetic manipulation tools, we are now able to interrogate this commonality despite the cellular complexity of the brain in order to develop novel therapeutic strategies to prevent or arrest neurodegeneration. Here, we describe broadly these concepts and their relevance across neurodegenerative diseases.
Republished: Transfemoral thrombectomy in the cavernous sinus and superior ophthalmic vein
Authors: Bauer Justin , Kansagra Kartik , Chao Kuo H , Feng Lei
Published: February 2018

Cavernous sinus thrombosis (CST) is a rare condition that can cause death, neurologic disability, and visual loss. A pre-teen with septic CST leading to ocular hypertension and acute visual loss was treated at our institution with thrombectomy and thrombolysis of the cavernous sinuses and superior ophthalmic veins. Successful recanalization of the bilateral cavernous sinuses and superior ophthalmic veins was achieved in two separate procedures without complication. The patient showed immediate symptomatic relief. He was neurologically intact without visual deficits at the 2 month follow-up. This is the first report in the literature showing the feasibility of cavernous sinus thrombectomy using current devices and techniques. Early endovascular therapy may help preserve vision in patients with acute CST.
Impact of provision of time in therapeutic range value on anticoagulation management in atrial fibrillation patients on warfarin
Authors: Huang Duo , Wong Chi-Lap , Cheng Kwan-Wa , Chan Pak-Hei , Yue Wen-Sheng , Wong Chun-Ka , Ho Chi-Wai , Wong Ian C K , Chan Esther W , Siu Chung Wah
Published: February 2018

Introduction

The importance of time in therapeutic range (TTR) in patients prescribed warfarin therapy for stroke prevention in atrial fibrillation (AF) cannot be overemphasised.

Aim

To evaluate the impact of provision of TTR results during clinic visits on anticoagulation management.

Design

Single-centred, randomised controlled study.

Setting

Fifteen arrhythmia clinics in Hong Kong.

Patients

AF patients prescribed warfarin.

Interventions

Provision of TTR or no provision of TTR.

Main outcome measures

A documented discussion between doctors and patients about switching warfarin to a non-vitamin K oral anticoagulant (NOAC).

Results

Four hundred and eighty one patients with AF prescribed warfarin were randomly assigned to (1) a TTR provision group or (2) control. Their mean age was 73.6±12.0 years and 60.7% were men. The mean CHA2DS2-VASc score was 3.2±1.6 and the mean HASBLED score was 1.7±1.2. The mean TTR was 63.9%±29.9%. At the index clinic visit, 71 of 481 patients (14.8%) had a documented discussion about switching warfarin to a NOAC. Patients with provision of TTR results were more likely to discuss switching warfarin to a NOAC than controls (19.1% vs 10.6%, P=0.03), especially those with a TTR <65% (35.2% vs 10.6%, P<0.001). A higher proportion of patients with provision of TTR results switched to a NOAC (5.9% vs 4.1%, P=0.49).

Conclusions

The provision of TTR among patients on warfarin was associated with a discussion about switching from warfarin to a NOAC in those with TTR <65%, but did not result in actual switching to a NOAC, suggesting additional barriers.
Antisense oligonucleotides and other genetic therapies made simple
Authors: Rossor Alexander M , Reilly Mary M , Sleigh James N
Published: February 2018

Many genetic neurological diseases result from the dysfunction of single proteins. Genetic therapies aim to modify these disease-associated proteins by targeting the RNA and DNA precursors. This review provides a brief overview of the main types of genetic therapies, with a focus on antisense oligonucleotides (ASOs) and RNA interference (RNAi). We use examples of new genetic therapies for spinal muscular atrophy, Duchenne muscular dystrophy and familial amyloid polyneuropathy to highlight the different mechanisms of action of ASOs and RNAi.