bluuebunny/crossref_metadata_2025 huggingface dataset:
Locality and harmony: Perspectives from artificial grammar learning
Authors: Finley Sara
Published: January 2017

Harmony is one of the most researched phenomena in phonological theory, mainly due to its iterative, nonlocal nature. In this review, I summarize several of the key issues in harmony that can be addressed using an artificial grammar learning approach, including differences between consonant and vowel harmony, transparent and opaque neutral vowels, computational complexity of attested and unattested harmony patterns, and morphological and phonetic influences on harmony. The review demonstrates how the artificial grammar learning paradigm can offer unique insights into the representation of vowel harmony and provides suggestions for ways in which aspects of harmony can be manipulated to offer further insights into the still unanswered questions on harmony and phonological representations.
Can monetary policy survive policy model mis‐specification? Model uncertainty and the perils of “policy model complacency”
Authors: Setterfield Mark
Published: January 2017

The question addressed in this paper is: can monetary policy succeed in stabilizing the economy even when the policy model on which it is predicated is mis‐specified? Using variants of the 3‐equation macroeconomic model, it is shown that this question can be answered in the affirmative. The purpose of the paper is not to encourage indifference toward model uncertainty, however, but rather to warn against the perils of “policy model complacency.” This arises if the success of policy is misinterpreted as successful understanding of the workings of the economy, which makes the policy maker vulnerable to surprises: events with systematic origins in the “true” model of the economy that are not anticipated by the (mis‐specified) policy model. To safeguard against this problem, policy makers should always entertain eclectic views of the workings of the economy. This task is easily accomplished by paying attention to heterodox macroeconomics, which frequently makes predictions that are very much at variance with those of the dominant policy model.
Gene expression atlas for the food security crop cassava
Authors: Wilson Mark C. , Mutka Andrew M. , Hummel Aaron W. , Berry Jeffrey , Chauhan Raj Deepika , Vijayaraghavan Anupama , Taylor Nigel J. , Voytas Daniel F. , Chitwood Daniel H. , Bart Rebecca S.
Published: January 2017

Cassava (Manihot esculenta) feeds c. 800 million people world‐wide. Although this crop displays high productivity under drought and poor soil conditions, it is susceptible to disease, postharvest deterioration and the roots contain low nutritional content.

Here, we provide molecular identities for 11 cassava tissue/organ types through RNA‐sequencing and develop an open access, web‐based interface for further interrogation of the data.

Through this dataset, we consider the physiology of cassava. Specifically, we focus on identification of the transcriptional signatures that define the massive, underground storage roots used as a food source and the favored target tissue for transgene integration and genome editing, friable embryogenic callus (FEC). Further, we identify promoters able to drive strong expression in multiple tissue/organs.

The information gained from this study is of value for both conventional and biotechnological improvement programs.
Novel in vivo screening design for the rapid and cost‐effective identification of transcriptional regulators
Authors: Hellmann Eva , Swinka Christine , Heyl Alexander
Published: January 2017

Genetic screens are a common tool to identify new modulators in a defined context, e.g. hormonal response or environmental stress. However, most screens are either in vitro or laborious and time‐and‐space inefficient. Here we present a novel in planta screening approach that shortens the time from the actual screening process to the identification of a new modulator and simultaneously reduces space requirements and costs. The basic features of this screening approach are the creation of luciferase reporter plants which enable a non‐invasive readout in a streamlined multiplate reader process, the transformation of those plants with an inducible, Gateway™‐compatible expression vector, and a screening setup, in which whole plants at the seedling stage are screened in 96‐multiwell plates in the first transformed generation without the use of an expensive charge‐coupled device (CCD) camera system. The screening itself and the verification of candidates can be done in as little as 2–3 weeks. The screen enables the analysis of reporter gene activity upon different treatments. Primary positive plants can immediately be selected and grown further. In this study a fast, simple, cost‐ and space‐efficient in planta screening system to detect novel mediators of a given transcriptional response was developed and successfully tested using the cytokinin signal transduction as a test case.
Airflow limitation severity and post‐operative pulmonary complications following extra‐pulmonary surgery in COPD patients
Authors: Shin Beomsu , Lee Hyun , Kang Danbee , Jeong Byeong‐Ho , Kang Hyung Koo , Chon Hae Ri , Koh Won‐Jung , Chung Man Pyo , Guallar Eliseo , Cho Juhee , Park Hye Yun
Published: January 2017

ABSTRACT

Background and objective

The association between airflow limitation severity and post‐operative pulmonary complications (PPCs) among COPD patients undergoing extra‐pulmonary surgery is unknown. We evaluated the association between forced expiratory volume in 1 s (FEV1
) and PPC in COPD patients undergoing extra‐pulmonary surgery.

Methods

Using prospective cohort of PPC evaluation for extra‐pulmonary surgery, we identified 694 COPD patients who conducted PPC evaluation before extra‐pulmonary surgery between March 2014 and January 2015 at a tertiary hospital, Seoul, Korea.

Results

The overall incidence of PPC was 24.4%. The incidence of PPC in quintiles 1–5 of FEV1
(% predicted) was 31.4, 25.8, 23.7, 21.6 and 19.7%, respectively (P for trend: 0.019). In fully adjusted multivariable models, the relative risks (RRs, 95% CI) for PPC comparing participants in quintiles 1–4 of FEV1
(% predicted) with those in quintile 5 were 1.69 (1.03–2.79), 1.41 (0.83–2.37), 1.26 (0.75–2.11) and 1.30 (0.76–2.22), respectively (P for trend: 0.046). The association of severe airflow limitation with respiratory failure and post‐operative exacerbations was stronger in participants who did not use bronchodilators compared with those who did.

Conclusion

We found a progressive and significant relationship between severity of airflow limitation and the incidence of PPC in COPD patients undergoing extra‐pulmonary surgery. Furthermore, perioperative bronchodilator use was associated with a reduced risk of respiratory failure and post‐operative exacerbations in patients with severe airflow limitation.
Polycystic ovary syndrome (PCOS)
Authors: Balen Adam H
Published: January 2017

Key content

The symptoms of polycystic ovary syndrome (PCOS) include menstrual cycle disturbance and features of hyperandrogenism (hirsutism, acne and alopecia), with associated fertility problems, obesity and psychological issues.

There are ethnic variations in expression of PCOS related to differences in insulin metabolism and this may impact upon treatment algorithms.

Obesity has a major impact on the expression of PCOS and the efficacy of the management of all aspects of the syndrome, in particular infertility.

The management of anovulatory infertility involves lifestyle modification and therapies to induce ovulation, namely clomifene citrate, gonadotrophin therapy and laparoscopic ovarian diathermy.

For those who do not wish to conceive the management of menstrual problems requires prevention of endometrial hyperplasia and adenocarcinoma and consideration of the long term metabolic risks.

Learning objectives

To understand the full spectrum of the syndrome that is PCOS to include how to make the diagnosis and differentiate from other causes of menstrual irregularity and androgen excess.

To appreciate the role of insulin resistance and the long‐term health implications for women with PCOS.

To understand how to manage the issues that may affect a woman in different ways at different times in her life, namely menstrual cycle irregularity, hyperandrogenism and infertility.

Ethical issues

A contentious issue is the appropriateness to deny fertility treatment based upon a cut‐off for body mass index (BMI), when BMI is a crude measure of metabolic risk and the risks of conception at a high BMI are not absolute. This also has to be balanced against the decline in fertility with age which may have an additional impact.

To what extent should young women who are found to have polycystic ovaries on ultrasound scan but without any features of the syndrome be advised about the potential for developing problems in the future?

Should relatives of individuals with PCOS be screened for either PCOS or metabolic syndrome (the latter may apply to male relatives too)?
Subunit‐selective proteasome activity profiling uncovers uncoupled proteasome subunit activities during bacterial infections
Authors: Misas‐Villamil Johana C. , van der Burgh Aranka M. , Grosse‐Holz Friederike , Bach‐Pages Marcel , Kovács Judit , Kaschani Farnusch , Schilasky Sören , Emon Asif E.K. , Ruben Mark , Kaiser Markus , Overkleeft Hermen S. , van der Hoorn Renier A.L.
Published: January 2017

The proteasome is a nuclear‐cytoplasmic proteolytic complex involved in nearly all regulatory pathways in plant cells. The three different catalytic activities of the proteasome can have different functions, but tools to monitor and control these subunits selectively are not yet available in plant science. Here, we introduce subunit‐selective inhibitors and dual‐color fluorescent activity‐based probes for studying two of the three active catalytic subunits of the plant proteasome. We validate these tools in two model plants and use this to study the proteasome during plant–microbe interactions. Our data reveal that Nicotiana benthamiana incorporates two different paralogs of each catalytic subunit into active proteasomes. Interestingly, both β1 and β5 activities are significantly increased upon infection with pathogenic Pseudomonas syringae pv. tomato DC3000 lacking hopQ1‐1 [PtoDC3000(ΔhQ)] whilst the activity profile of the β1 subunit changes. Infection with wild‐type PtoDC3000 causes proteasome activities that range from strongly induced β1 and β5 activities to strongly suppressed β5 activities, revealing that β1 and β5 activities can be uncoupled during bacterial infection. These selective probes and inhibitors are now available to the plant science community, and can be widely and easily applied to study the activity and role of the different catalytic subunits of the proteasome in different plant species.
Clearance of plasma ivermectin with single pass lipid dialysis in 2 dogs
Authors: Londoño Leonel A. , Buckley Gareth J. , Bolfer Luiz , Bandt Carsten
Published: January 2017

Objective

To describe the use of single pass lipid dialysis (SPLD) for treatment of ivermectin toxicosis in 2 Australian Shepherd dogs with the ABCB1‐1Δ gene mutation.

Case Series Summary

Two Australian Shepherd dogs were presented for treatment of ivermectin toxicosis. Dogs were initially treated with intravenous lipid emulsion and supportive care, without improvement of clinical signs. They both developed respiratory paralysis and required mechanical ventilation. In order to increase the clearance of circulating ivermectin, SPLD was performed using dialysate containing 5% lipid. Blood samples were obtained immediately before and after dialysis and analyzed for serum ivermectin concentration. Ivermectin reduction ratio was calculated at 29% and 39% for each dog, respectively. When compared to intrinsic total body ivermectin clearance, only the second dog had a relative improvement of plasma clearance following SPLD. Both dogs were confirmed to be homozygous for ABCB1‐1Δ gene mutations. Both dogs remained ventilator dependent for several days and ultimately made a full recovery.

New or Unique Information Provided

SPLD may be an adjunctive detoxification strategy for highly lipophilic toxins such as ivermectin.
Alternatives in blood operations when choosing non‐DEHP bags
Authors: van der Meer P. F. , Devine D. V. ,   the Biomedical Excellence for Safer Transfusion (BEST) Collaborative
Published: January 2017

The use of di‐ethylhexyl‐phthalate (DEHP) in blood bags is under discussion due to toxicity concerns and possible restrictions. A questionnaire among 15 blood centres in nine countries showed that none so far have fully switched to non‐DEHP blood bags. If centres had to change, sites with a 42‐day outdate would choose for a shorter outdating period, while others would allow a higher haemolysis rate (but within current specifications). To improve red cell quality, about half of the centres are willing to move to an alternative red cell storage solution, while the other half would not change for various reasons.
Seroprevalence and Factors Associated with Coxiella burnetii Infection in Small Ruminants in Baringo County, Kenya
Authors: Muema J. , Thumbi S. M. , Obonyo M. , Wanyoike S. , Nanyingi M. , Osoro E. , Bitek A. , Karanja S.
Published: January 2017

To improve estimates of C. burnetii epidemiology in Kenya, a survey was undertaken in small ruminants in Baringo County, where acute cases of Q fever in humans had been reported in 2014. From 140 household herds selected, 508 (60.5%) goats and 332 (39.5%) sheep were included and an indirect ELISA assay for C. burnetii IgG antibodies performed. In addition, epidemiological information at both herd and animal level was collected. Generalized mixed‐effects multivariable logistic model using herd as the random effect was used to determine variables correlated to the outcome. Overall seroprevalence was 20.5% (95% CI: 17.8%, 23.3%). Goats had 26.0% (95% CI: 22.2%, 30.0%) compared to sheep 12.2% (95% CI: 8.7%, 16.0%). Nomadic pastoralism, goats and older animals (>1 year) were associated with greater risk of C. burnetii seropositivity (P = ≤0.05). Heterogeneity in C. burnetii seropositivity was observed across the sublocations (P = 0.028). Evidence of C. burnetii exposure in small ruminants revealed poses a potential risk of exposure to the people living in close proximity to the animals. We recommended integrated animal–human surveillance and socio‐economic studies for C. burnetii, to aid our understanding of the risk of transmission between the animals and humans, and in the design of prevention and control strategies for the disease in the region.
Reviewer Acknowledgements
Authors: Smith Robert
Published: January 2017

Journal of Education and Training Studies (JETS) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this issue. Many authors, regardless of whether JETS publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this issue.Reviewers for Volume 5, Number 2 Anne M. Hornak, Central Michigan University, USABaraka M. Ngussa, University of Arusha, TanzaniaCagla Atmaca, Pamukkale University, TurkeyDonna Smith, The Open University, UKEbrahim Mohammadpour, Mimos Berhad, IranErica D. Shifflet-Chila, Michigan State University, USAHanan Mohamed Soliman, Faculty of Nursing Mansoura University, EgyptJeyavel Sundaramoorthy, Gulbarga University Campus, IndiaJill M. Feldman, Westat, USAJohn Bosco Azigwe, Bolgatanga Polytechnic, GhanaLeonor Thomson, Universidad de la República, UruguayLorna T. Enerva, Polytechnic University of the Philippines, PhilippinesMarcie Zaharee, The MITRE Corporation, USAMaria Pavlis Korres,        Hellenic Open University, GreeceMehmet Inan, Marmara University, TurkeyMeral Seker, Cukurova University, TurkeyNele Kampa, Leibniz-Institute for Science and Mathematics Education (IPN), GermanyNicole Celestine, The University of Western Australia, AustraliaNiveen M. Zayed, MENA College of Management, JordanRichard H. Martin, Indiana University, USARichard Penny, University of Washington Bothell, USASenem Seda Şahenk Erkan, Marmara University, TurkeySimona Savelli, Università degli Studi Guglielmo Marconi, ItalyYalçın Dilekli, Aksaray University, TurkeyYerlan Seisenbekov, Kazakh National Pedagogical University, KazakhstanYi Lu, American Institute for Research, USAYu-Cheng Tang, National Changhua University of Education, TaiwanZachary Wahl-Alexander, Northern Illinois University, USA   Robert SmithEditorial AssistantOn behalf of,The Editorial Board of Journal of Education and Training StudiesRedfame Publishing9450 SW Gemini Dr. #99416Beaverton, OR 97008, USAURL: http://jets.redfame.com
Exploratory assessment of left ventricular strain–volume loops in severe aortic valve diseases
Authors: Hulshof Hugo G. , van Dijk Arie P. , George Keith P. , Hopman Maria T. E. , Thijssen Dick H. J. , Oxborough David L.
Published: January 2017

Key points

Severe aortic valve diseases are common cardiac abnormalities that are associated with poor long‐term survival.

Before any reduction in left ventricular (LV) function, the left ventricle undergoes structural remodelling under the influence of changing haemodynamic conditions.

In this study, we combined temporal changes in LV structure (volume) with alterations in LV functional characteristics (strain, ԑ) into a ԑ–volume loop, in order to provide novel insight into the haemodynamic cardiac consequences of aortic valve diseases in those with preserved LV ejection fraction.

We showed that our novel ԑ–volume loop and the specific loop characteristics provide additional insight into the functional and mechanical haemodynamic consequences of severe aortic valve diseases (with preserved LV ejection fraction).

Finally, we showed that the ԑ–volume loop characteristics provide discriminative capacity compared with conventional measures of LV function.

The purpose of this study was to examine left ventricular (LV) strain (ԑ)–volume loops to provide novel insight into the haemodynamic cardiac consequences of aortic valve stenosis (AS) and aortic valve regurgitation (AR). Twenty‐seven participants were retrospectively recruited: AR (n = 7), AS (n = 10) and control subjects (n = 10). Standard transthoracic echocardiography was used to obtain apical four‐chamber images to construct ԑ–volume relationships, which were assessed using the following parameters: early systolic ԑ (ԑ_ES); slope of ԑ–volume relationship during systole (Sslope); end‐systolic peak ԑ (peak ԑ); and diastolic uncoupling (systolic ԑ–diastolic ԑ at same volume) during early diastole (UNCOUP_ED) and late diastole (UNCOUP_LD). Receiver operating characteristic curves were used to determine the ability to detect impaired LV function. Although LV ejection fraction was comparable between groups, longitudinal peak ԑ was reduced compared with control subjects. In contrast, ԑ_ES and Sslope were lower in both pathologies compared with control subejcts (P < 0.01), but also different between AS and AR (P < 0.05). UNCOUP_ED and UNCOUP_LD were significantly higher in both patient groups compared with control subjects (P < 0.05). Receiver operating characteristic curves revealed that loop characteristics (AUC = 0.99, 1.00 and 1.00; all P < 0.01) were better able then peak ԑ (AUC = 0.75, 0.89 and 0.76; P = 0.06, <0.01 and 0.08, respectively) and LV ejection fraction (AUC = 0.56, 0.69 and 0.69; all P > 0.05) to distinguish AS vs control, AR vs control and AS vs AR groups, respectively. Temporal changes in ԑ–volume characteristics provide novel insight into the haemodynamic cardiac impact of AS and AR. Contrary to traditional measures (i.e. ejection fraction, peak ԑ), these novel measures successfully distinguish between the haemodynamic cardiac impact of AS and AR.
Quasidimensional Modeling of Diesel Combustion Using Detailed Chemical Kinetics
Authors: Dobos Aron P. , Kirkpatrick Allan T.
Published: January 2017

This paper presents an efficient approach to diesel engine combustion simulation that integrates detailed chemical kinetics into a quasidimensional fuel spray model. The model combines a discrete spray parcel concept to calculate fuel-air mixing with a detailed primary reference fuel chemical kinetic mechanism to determine species concentrations and heat release in time. Comparison of predicted pressure, heat release, and emissions with data from diesel engine experiments reported in the literature shows good agreement overall, and suggests that spray combustion processes can be predictively modeled without calibration of empirical burn rate constants at a significantly lower computational cost than standard multidimensional (CFD) tools.
Phosphorylation of Ser
1928
mediates the enhanced activity of the L-type Ca
2+
channel Ca
v
1.2 by the β
2
-adrenergic receptor in neurons
Authors: Qian Hai , Patriarchi Tommaso , Price Jennifer L. , Matt Lucas , Lee Boram , Nieves-Cintrón Madeline , Buonarati Olivia R. , Chowdhury Dhrubajyoti , Nanou Evanthia , Nystoriak Matthew A. , Catterall William A. , Poomvanicha Montatip , Hofmann Franz , Navedo Manuel F. , Hell Johannes W.
Published: January 2017

β-Adrenergic regulation of the L-type calcium channel Ca
v
1.2 exhibits surprising differences in the heart and brain.
Paper of note in
Science Translational Medicine
9 (373)
Authors: Ferrarelli Leslie K.
Published: January 2017

This week’s paper describes a drug that inhibits multiple growth factor pathways and may effectively treat patients with retinopathies.
Penetration of Ciprofloxacin and Amikacin into the Alveolar Epithelial Lining Fluid of Rats with Pulmonary Fibrosis
Authors: Ni Wentao , Yang Deqing , Mei Hekun , Zhao Jin , Liang Beibei , Bai Nan , Chai Dong , Cui Junchang , Wang Rui , Liu Youning
Published: January 2017

We determined the concentration-time profiles of ciprofloxacin and amikacin in serum and alveolar epithelial lining fluid (ELF) of rats with or without pulmonary fibrosis and investigated the effect of pulmonary fibrosis on the capacity for penetration of antimicrobials into the ELF of rats. Pulmonary fibrosis was induced in rats with a single intratracheal instillation of bleomycin. After intravenous injection of ciprofloxacin or amikacin, blood and bronchoalveolar lavage fluid samples were collected. Urea concentrations in serum and lavage fluid were determined using an enzymatic assay. Ciprofloxacin and amikacin concentrations were determined by high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry, respectively. The mean ratio of ELF to plasma concentrations of ciprofloxacin at each time point in the normal group did not significantly differ from that in the pulmonary fibrosis group. However, the ratio of the ciprofloxacin area under the concentration-time curve from 0 to 24 h (AUC
0–24
) in ELF to the AUC
0–24
in plasma was 1.02 in the normal group and 0.76 in the pulmonary fibrosis group. The mean ELF-to-plasma concentration ratios of amikacin at each time point in the normal group were higher than those in the pulmonary fibrosis group, reaching a statistically significant difference at 1, 2, and 4 h. The ratio of the AUC
0–24
in ELF to the AUC
0–24
in plasma was 0.49 in the normal group and 0.27 in the pulmonary fibrosis group. In conclusion, pulmonary fibrosis can influence the penetration of antimicrobials into the ELF of rats and may have a marked effect on the penetration of amikacin than that of ciprofloxacin.
Characterization of Class IIa Bacteriocin Resistance in Enterococcus faecium
Authors: Geldart Kathryn , Kaznessis Yiannis N.
Published: January 2017

Vancomycin-resistant enterococci, particularly resistant
Enterococcus faecium
, pose an escalating threat in nosocomial environments because of their innate resistance to many antibiotics, including vancomycin, a treatment of last resort. Many class IIa bacteriocins strongly target these enterococci and may offer a potential alternative for the management of this pathogen. However,
E. faecium
's resistance to these peptides remains relatively uncharacterized. Here, we explored the development of resistance of
E. faecium
to a cocktail of three class IIa bacteriocins: enterocin A, enterocin P, and hiracin JM79. We started by quantifying the frequency of resistance to these peptides in four clinical isolates of
E. faecium
. We then investigated the levels of resistance of
E. faecium
6E6 mutants as well as their fitness in different carbon sources. In order to elucidate the mechanism of resistance of
E. faecium
to class IIa bacteriocins, we completed whole-genome sequencing of resistant mutants and performed reverse transcription-quantitative PCR (qRT-PCR) of a suspected target mannose phosphotransferase (ManPTS). We then verified this ManPTS's role in bacteriocin susceptibility by showing that expression of the ManPTS in
Lactococcus lactis
results in susceptibility to the peptide cocktail. Based on the evidence found from these studies, we conclude that, in accord with other studies in
E. faecalis
and
Listeria monocytogenes
, resistance to class IIa bacteriocins in
E. faecium
6E6 is likely caused by the disruption of a particular ManPTS, which we believe we have identified.
Management of Multiple Nitrogen Sources during Wine Fermentation by Saccharomyces cerevisiae
Authors: Crépin Lucie , Truong Nhat My , Bloem Audrey , Sanchez Isabelle , Dequin Sylvie , Camarasa Carole
Published: January 2017

During fermentative growth in natural and industrial environments,Saccharomyces cerevisiaemust redistribute the available nitrogen from multiple exogenous sources to amino acids in order to suitably fulfill anabolic requirements. To exhaustively explore the management of this complex resource, we developed an advanced strategy based on the reconciliation of data from a set of stable isotope tracer experiments with labeled nitrogen sources. Thus, quantifying the partitioning of the N compounds through the metabolism network during fermentation, we demonstrated that, contrary to the generally accepted view, only a limited fraction of most of the consumed amino acids is directly incorporated into proteins. Moreover, substantial catabolism of these molecules allows for efficient redistribution of nitrogen, supporting the operativede novosynthesis of proteinogenic amino acids. In contrast, catabolism of consumed amino acids plays a minor role in the formation of volatile compounds. Another important feature is that the α-keto acid precursors required for thede novosyntheses originate mainly from the catabolism of sugars, with a limited contribution from the anabolism of consumed amino acids. This work provides a comprehensive view of the intracellular fate of consumed nitrogen sources and the metabolic origin of proteinogenic amino acids, highlighting a strategy of distribution of metabolic fluxes implemented by yeast as a means of adapting to environments with changing and scarce nitrogen resources.

IMPORTANCEA current challenge for the wine industry, in view of the extensive competition in the worldwide market, is to meet consumer expectations regarding the sensory profile of the product while ensuring an efficient fermentation process. Understanding the intracellular fate of the nitrogen sources available in grape juice is essential to the achievement of these objectives, since nitrogen utilization affects both the fermentative activity of yeasts and the formation of flavor compounds. However, little is known about how the metabolism operates when nitrogen is provided as a composite mixture, as in grape must. Here we quantitatively describe the distribution through the yeast metabolic network of the N moieties and C backbones of these nitrogen sources. Knowledge about the management of a complex resource, which is devoted to improvement of the use of the scarce N nutrient for growth, will be useful for better control of the fermentation process and the sensory quality of wines.
Formulation of Biocides Increases Antimicrobial Potency and Mitigates the Enrichment of Nonsusceptible Bacteria in Multispecies Biofilms
Authors: Forbes Sarah , Cowley Nicola , Humphreys Gavin , Mistry Hitesh , Amézquita Alejandro , McBain Andrew J.
Published: January 2017

The current investigation aimed to generate data to inform the development of risk assessments of biocide usage. Stabilized domestic drain biofilm microcosms were exposed daily over 6 months to increasing concentrations (0.01% to 1%) of the biocide benzalkonium chloride (BAC) in a simple aqueous solution (BAC-s) or in a complex formulation (BAC-f) representative of a domestic cleaning agent. Biofilms were analyzed by culture, differentiating by bacterial functional group and by BAC or antibiotic susceptibility. Bacterial isolates were identified by 16S rRNA sequencing, and changes in biofilm composition were assessed by high-throughput sequencing. Exposure to BAC-f resulted in significantly larger reductions in levels of viable bacteria than exposure to BAC-s, while bacterial diversity greatly decreased during exposure to both BAC-s and BAC-f, as evidenced by sequencing and viable counts. Increases in the abundance of bacteria exhibiting reduced antibiotic or BAC susceptibility following exposure to BAC at 0.1% were significantly greater for BAC-s than BAC-f. Bacteria with reduced BAC and antibiotic susceptibility were generally suppressed by higher BAC concentrations, and formulation significantly enhanced this effect. Significant decreases in the antimicrobial susceptibility of bacteria isolated from the systems before and after long-term BAC exposure were not detected. In summary, dose-dependent suppression of bacterial viability by BAC was enhanced by formulation. Biocide exposure decreased bacterial diversity and transiently enriched populations of organisms with lower antimicrobial susceptibility, and the effects were subsequently suppressed by exposure to 1% BAC-f, the concentration most closely reflecting deployment in formulated products.

IMPORTANCE
Assessment of the risks of biocide use has been based mainly on the exposure of axenic cultures of bacteria to biocides in simple aqueous solutions. The current investigation aimed to assess the effects of formulation on the outcome of biocide exposure in multispecies biofilms. Formulation of the cationic biocide BAC significantly increased antimicrobial potency. Bacteria with lower antimicrobial susceptibility whose populations were enriched after low-level biocide exposure were more effectively suppressed by the biocide at in-use concentrations (1% [wt/vol]) in a formulation than in a simple aqueous solution. These observations underline the importance of simulating normal deployment conditions in considering the risks and benefits of biocide use.
Adaptive Evolution of Extreme Acidophile Sulfobacillus thermosulfidooxidans Potentially Driven by Horizontal Gene Transfer and Gene Loss
Authors: Zhang Xian , Liu Xueduan , Liang Yili , Guo Xue , Xiao Yunhua , Ma Liyuan , Miao Bo , Liu Hongwei , Peng Deliang , Huang Wenkun , Zhang Yuguang , Yin Huaqun
Published: January 2017

Recent phylogenomic analysis has suggested that three strains isolated from different copper mine tailings around the world were taxonomically affiliated with
Sulfobacillus
thermosulfidooxidans
. Here, we present a detailed investigation of their genomic features, particularly with respect to metabolic potentials and stress tolerance mechanisms. Comprehensive analysis of the
Sulfobacillus
genomes identified a core set of essential genes with specialized biological functions in the survival of acidophiles in their habitats, despite differences in their metabolic pathways. The
Sulfobacillus
strains also showed evidence for stress management, thereby enabling them to efficiently respond to harsh environments. Further analysis of metabolic profiles provided novel insights into the presence of genomic streamlining, highlighting the importance of gene loss as a main mechanism that potentially contributes to cellular economization. Another important evolutionary force, especially in larger genomes, is gene acquisition via horizontal gene transfer (HGT), which might play a crucial role in the recruitment of novel functionalities. Also, a successful integration of genes acquired from archaeal donors appears to be an effective way of enhancing the adaptive capacity to cope with environmental changes. Taken together, the findings of this study significantly expand the spectrum of HGT and genome reduction in shaping the evolutionary history of
Sulfobacillus
strains.

IMPORTANCE
Horizontal gene transfer (HGT) and gene loss are recognized as major driving forces that contribute to the adaptive evolution of microbial genomes, although their relative importance remains elusive. The findings of this study suggest that highly frequent gene turnovers within microorganisms via HGT were necessary to incur additional novel functionalities to increase the capacity of acidophiles to adapt to changing environments. Evidence also reveals a fascinating phenomenon of potential cross-kingdom HGT. Furthermore, genome streamlining may be a critical force in driving the evolution of microbial genomes. Taken together, this study provides insights into the importance of both HGT and gene loss in the evolution and diversification of bacterial genomes.
In Vivo
Single-Cell Fluorescence and Size Scaling of Phytoplankton Chlorophyll Content
Authors: Álvarez Eva , Nogueira Enrique , López-Urrutia Ángel
Published: January 2017

In unicellular phytoplankton, the size scaling exponent of chlorophyll content per cell decreases with increasing light limitation. Empirical studies have explored this allometry by combining data from several species, using average values of pigment content and cell size for each species. The resulting allometry thus includes phylogenetic and size scaling effects. The possibility of measuring single-cell fluorescence with imaging-in-flow cytometry devices allows the study of the size scaling of chlorophyll content at both the inter- and intraspecific levels. In this work, the changing allometry of chlorophyll content was estimated for the first time for single phytoplankton populations by using data from a series of incubations with monocultures exposed to different light levels. Interspecifically, our experiments confirm previous modeling and experimental results of increasing size scaling exponents with increasing irradiance. A similar pattern was observed intraspecifically but with a larger variability in size scaling exponents. Our results show that size-based processes and geometrical approaches explain variations in chlorophyll content. We also show that the single-cell fluorescence measurements provided by imaging-in-flow devices can be applied to field samples to understand the changes in the size dependence of chlorophyll content in response to environmental variables affecting primary production.

IMPORTANCE
The chlorophyll concentrations in phytoplankton register physiological adjustments in cellular pigmentation arising mainly from changes in light conditions. The extent of these adjustments is constrained by the size of the phytoplankton cells, even within single populations. Hence, variations in community chlorophyll derived from photoacclimation are also dependent on the phytoplankton size distribution.
Differential Gene Expression by Lactobacillus plantarum WCFS1 in Response to Phenolic Compounds Reveals New Genes Involved in Tannin Degradation
Authors: Reverón Inés , Jiménez Natalia , Curiel José Antonio , Peñas Elena , López de Felipe Félix , de las Rivas Blanca , Muñoz Rosario
Published: January 2017

Lactobacillus plantarum
is a lactic acid bacterium that can degrade food tannins by the successive action of tannase and gallate decarboxylase enzymes. In the
L. plantarum
genome, the gene encoding the catalytic subunit of gallate decarboxylase (
lpdC
, or
lp_2945
) is only 6.5 kb distant from the gene encoding inducible tannase (
L. plantarum
tanB
[

tanB
Lp

], or
lp_2956
). This genomic context suggests concomitant activity and regulation of both enzymatic activities. Reverse transcription analysis revealed that subunits B (
lpdB
, or
lp_0271
) and D (
lpdD
, or
lp_0272
) of the gallate decarboxylase are cotranscribed, whereas subunit C (
lpdC
, or
lp_2945
) is cotranscribed with a gene encoding a transport protein (
gacP
, or
lp_2943
). In contrast, the tannase gene is transcribed as a monocistronic mRNA. Investigation of knockout mutations of genes located in this chromosomal region indicated that only mutants of the gallate decarboxylase (subunits B and C), tannase, GacP transport protein, and TanR transcriptional regulator (
lp_2942
) genes exhibited altered tannin metabolism. The expression profile of genes involved in tannin metabolism was also analyzed in these mutants in the presence of methyl gallate and gallic acid. It is noteworthy that inactivation of
tanR
suppresses the induction of all genes overexpressed in the presence of methyl gallate and gallic acid. This transcriptional regulator was also induced in the presence of other phenolic compounds, such as kaempferol and myricetin. This study complements the catalog of
L. plantarum
expression profiles responsive to phenolic compounds, which enable this bacterium to adapt to a plant food environment.

IMPORTANCE
Lactobacillus plantarum
is a bacterial species frequently found in the fermentation of vegetables when tannins are present.
L. plantarum
strains degrade tannins to the less-toxic pyrogallol by the successive action of tannase and gallate decarboxylase enzymes. The genes encoding these enzymes are located close to each other in the chromosome, suggesting concomitant regulation. Proteins involved in tannin metabolism and regulation, such GacP (gallic acid permease) and TanR (tannin transcriptional regulator), were identified by differential gene expression in knockout mutants with mutations in genes from this region. This study provides insights into the highly coordinated mechanisms that enable
L. plantarum
to adapt to plant food fermentations.
Identification of Mycobacterial RplJ/L10 and RpsA/S1 Proteins as Novel Targets for CD4+T Cells
Authors: Johnson Alison J. , Kennedy Steven C. , Lindestam Arlehamn Cecilia S. , Goldberg Michael F. , Saini Neeraj K. , Xu Jiayong , Paul Sinu , Hegde Subray S. , Blanchard John S. , Chan John , Jacobs William R. , Sette Alessandro , Porcelli Steven A.
Published: January 2017

Tuberculosis (TB) due toMycobacterium tuberculosisremains a major global infectious disease problem, and a more efficacious vaccine is urgently needed for the control and prevention of disease caused by this organism. We previously reported that a genetically modified strain ofMycobacterium smegmatiscalled IKEPLUS is a promising TB vaccine candidate. Since protective immunity induced by IKEPLUS is dependent on antigen-specific CD4+T cell memory, we hypothesized that the specificity of the CD4+T cell response was a critical feature of this protection. Usingin vitroassays of interferon gamma production (enzyme-linked immunosorbent spot [ELISPOT] assays) by splenocytes from IKEPLUS-immunized C57BL/6J mice, we identified an immunogenic peptide within the mycobacterial ribosomal large subunit protein RplJ, encoded by the Rv0651 gene. In a complementary approach, we generated major histocompatibility complex (MHC) class II-restricted T cell hybridomas from IKEPLUS-immunized mice. Screening of these T cell hybridomas against IKEPLUS and ribosomes enriched from IKEPLUS suggested that the CD4+T cell response in IKEPLUS-immunized mice was dominated by the recognition of multiple components of the mycobacterial ribosome. Importantly, CD4+T cells specific for mycobacterial ribosomes accumulate to significant levels in the lungs of IKEPLUS-immunized mice following aerosol challenge with virulentM. tuberculosis, consistent with a role for these T cells in protective host immunity in TB. The identification of CD4+T cell responses to defined ribosomal protein epitopes expands the range of antigenic targets for adaptive immune responses toM. tuberculosisand may help to inform the design of more effective vaccines against tuberculosis.
A previously unrecognized high-temperature impactite from the Steen River impact structure, Alberta, Canada
Authors: Walton E. , Hughes A. , MacLagan E. , Herd C.D.K. , Dence M.
Published: January 2017

Here, we report a previously unrecognized impactite from the Steen River impact structure in Alberta, Canada, which was intersected by continuous diamond drill core into the allochthonous proximal deposits of this buried 25-km-diameter complex crater. A suite of high-temperature minerals defines the matrix, formed by grain growth in a solid state by static recrystallization of an originally clastic matrix, deposited at temperatures ≥800 °C. This rock type is predominantly a result of the recrystallization of target material driven by the acceleration of hot gasses from volatilized sedimentary cover mixed with variably shocked crystalline basement. Approximately one-third of terrestrial impact structures occur in mixed target rocks; therefore, this type of impactite may be more common than previously realized. Contact metamorphism between entrained sedimentary target rocks and the juxtaposed hot matrix resulted in carbonate decomposition to form a rare spinel-group mineral, magnesioferrite. In crater environments, magnesioferrite has been found in the distal Chicxulub (Mexico) ejecta and may prove a novel indicator mineral for impact into carbonate-bearing target rocks.
Seismic array constraints on reach-scale bedload transport
Authors: Schmandt B. , Gaeuman D. , Stewart R. , Hansen S.M. , Tsai V.C. , Smith J.
Published: January 2017

Measurements and mechanical models of heterogeneous bedload transport in rivers remain basic challenges for studies of landscape evolution and watershed management. A 700 m reach of the Trinity River (northern California, USA), a large gravel-bed river, was instrumented with an array of 76 seismographs during a dam-controlled flood and gravel augmentation to investigate the potential for out-of-stream monitoring. The temporal response to gravel augmentation during constant discharge provides strong evidence of seismic sensitivity to bedload transport and aids in identification of the seismic frequencies most sensitive to bedload in the study area. Following gravel augmentations, the seismic array reveals a period of enhanced transport that spans most or all of the reach for ∼7–10 h. Neither the duration nor the downstream extent of enhanced transport would have been constrained without the seismic array. Sensitivity to along-stream transport variations is further demonstrated by seismic amplitudes that decrease between the upper and lower halves of the reach consistent with decreased bedload flux constrained by time-lapse bathymetry. Insight into the magnitude of impact energy that reaches the bed is also gained from the seismic array. Observed peak seismic power is ∼1%–5% of that predicted by a model of saltation over exposed bedrock. Our results suggest that dissipation of impact energy due to cover effects needs to be considered to seismically constrain bedload transport rates, and that noninvasive constraints from seismology can be used to test and refine mechanical models of bedload transport.
Successful treatment of tumour-induced osteomalacia after resection of an oral peripheral ossifying fibroma
Authors: Sandoval Mark Anthony Santiago , Palermo Majorie Amoroto , Carrillo Ryner , Bundoc Rafael , Carnate Jose Ma , Galsim Romelito Jose
Published: January 2017

Tumour-induced osteomalacia is a paraneoplastic syndrome wherein bone is affected by a hormone from a tumour that causes renal phosphate wasting and hypophosphataemia. Here, we present the case of a 31-year-old man who has been suffering from generalised bone pains and a spine deformity that led to loss of height. Pertinent findings are low serum phosphorus, low vitamin D and decreased bone mineral density. These findings led to a diagnosis of osteomalacia. However, the finding of an oral mass raised some questions as to what role it plays in the patient's disease. It was suspected that the oral mass (fibroma) was producing a hormone that led to renal phosphate wasting, hypophosphataemia and then osteomalacia. This hypothesis was proven after surgical removal of the mass led to normalisation of the metabolic derangements and eventually led to a resolution of the bone pains.
Risk of cardiovascular events, arrhythmia and all-cause mortality associated with clarithromycin versus alternative antibiotics prescribed for respiratory tract infections: a retrospective cohort study
Authors: Berni Ellen , de Voogd Hanka , Halcox Julian P , Butler Christopher C , Bannister Christian A , Jenkins-Jones Sara , Jones Bethan , Ouwens Mario , Currie Craig J
Published: January 2017

Objective

To determine whether treatment with clarithromycin for respiratory tract infections was associated with an increased risk of cardiovascular (CV) events, arrhythmias or all-cause mortality compared with other antibiotics.

Design

Retrospective cohort design comparing clarithromycin monotherapy for lower (LRTI) or upper respiratory tract infection (URTI) with other antibiotic monotherapies for the same indication.

Setting

Routine primary care data from the UK Clinical Practice Research Datalink and inpatient data from the Hospital Episode Statistics (HES).

Participants

Patients aged ≥35 years prescribed antibiotic monotherapy for LRTI or URTI 1998–2012 and eligible for data linkage to HES.

Main outcome measures

The main outcome measures were: adjusted risk of first-ever CV event, within 37 days of initiation, in commonly prescribed antibiotics compared with clarithromycin. Secondarily, adjusted 37-day risks of first-ever arrhythmia and all-cause mortality.

Results

Of 700 689 treatments for LRTI and eligible for the CV analysis, there were 2071 CV events (unadjusted event rate: 29.6 per 10 000 treatments). Of 691 998 eligible treatments for URTI, there were 688 CV events (9.9 per 10 000 treatments). In LRTI and URTI, there were no significant differences in CV risk between clarithromycin and all other antibiotics combined: OR=1.00 (95% CI 0.82 to 1.22) and 0.82 (0.54 to 1.25), respectively. Adjusted CV risk in LRTI versus clarithromycin ranged from OR=1.42 (cefalexin; 95% CI 1.08 to 1.86) to 0.92 (doxycycline; 0.64 to 1.32); in URTI, from 1.17 (co-amoxiclav; 0.68 to 2.01) to 0.67 (erythromycin; 0.40 to 1.11). Adjusted mortality risk versus clarithromycin in LRTI ranged from 0.42 to 1.32; in URTI, from 0.75 to 1.43. For arrhythmia, adjusted risks in LRTI ranged from 0.68 to 1.05; in URTI, from 0.70 to 1.22.

Conclusions

CV events were more likely after LRTI than after URTI. When analysed by specific indication, CV risk associated with clarithromycin was no different to other antibiotics.