bluuebunny/crossref_metadata_2025 huggingface dataset:
Decontamination of an Extracorporeal Membrane Oxygenator Contaminated With Mycobacterium chimaera
Authors: Garvey Mark I. , Phillips Natalie , Bradley Craig W. , Holden Elisabeth
Published: August 2017

Water samples taken from extracorporeal membrane oxygenator (ECMO) devices used at University Hospitals Birmingham yielded high total viable counts (TVCs) containing a variety of microorganisms, including M. chimaera. Disinfection resulted in the reduction of TVCs and eradication of Mycobacterium chimaera. Weekly disinfection and water sampling are required to manage the water quality in these devices.

Infect Control Hosp Epidemiol 2017;38:1244–1246
Collapse of a neutrally buoyant suspension column: from Newtonian to apparent non-Newtonian flow regimes
Authors: Bougouin A. , Lacaze L. , Bonometti T.
Published: August 2017

Experiments on the collapse of non-colloidal and neutrally buoyant particles suspended in a Newtonian fluid column are presented, in which the initial volume fraction of the suspension $\unicode[STIX]{x1D719}$, the viscosity of the interstitial fluid $\unicode[STIX]{x1D707}_{f}$, the diameter of the particles $d$ and the mixing protocol, i.e. the initial preparation of the suspension, are varied. The temporal evolution of the slumping current highlights two main regimes: (i) an inertial-dominated regime followed by (ii) a viscous-dominated regime. The inertial regime is characterized by a constant-speed slumping which is shown to scale as in the case of a classical inertial dam-break. The viscous-dominated regime is observed as a decreasing-speed phase of the front evolution. Lubrication models for Newtonian and power-law fluids describe most of situations encountered in this regime, which strongly depends on the suspension parameters. The temporal evolution of the propagating front is used to extract the rheological parameters of the fluid models. At the early stages of the viscous-dominated regime, a constant effective shear viscosity, referred to as an apparent Newtonian viscous regime, is found to depend only on $\unicode[STIX]{x1D719}$ and $\unicode[STIX]{x1D707}_{f}$ for each mixing protocol. The obtained values are shown to be well fitted by the Krieger–Dougherty model whose parameters involved, say a critical volume fraction $\unicode[STIX]{x1D719}_{m}$ and the exponent of divergence, depend on the mixing protocol, i.e. the microscale interaction between particles. On a longer time scale which depends on $\unicode[STIX]{x1D719}$, the front evolution is shown to slightly deviate from the apparent Newtonian model. In this apparent non-Newtonian viscous regime, the power-law model, indicating both shear-thinning and shear-thickening behaviours, is shown to be more appropriate to describe the front evolution. The present experiments indicate that the mixing protocol plays a crucial role in the selection of a shear-thinning or shear-thickening type of collapse, while the particle diameter $d$ and volume fraction $\unicode[STIX]{x1D719}$ play a significant role in the shear-thickening case. In all cases, the normalized effective consistency of the power-law fluid model is found to be a unique function of $\unicode[STIX]{x1D719}$. Finally, an apparent viscoplastic regime, characterized by a finite length spreading reached at finite time, is observed at high $\unicode[STIX]{x1D719}$. This regime is mostly observed for volume fractions larger than $\unicode[STIX]{x1D719}_{m}$ and up to a volume fraction $\unicode[STIX]{x1D719}_{M}$ close to the random close packing fraction at which the initial column remains undeformed on opening the gate.
Be well: A systems-based wellness intervention using mindfulness in the workplace – A case study
Authors: Levett Kate M , Coughlan Sharyn , Longridge Sharon , Roumeliotis Violet , Adams Jon
Published: August 2017

Introduction: Healthy work environments are essential in determining improved well-being of Australians. Job stress has been identified as a significant factor in psychological distress. This study evaluated the effect of introducing a systems-based workplace wellness programme using mindfulness in the workplace. Methods: The programme ‘Be Well’ was introduced as part of a systems-based approach to workplace health promotion, and evaluated using sick leave as a proxy for workplace stress, and the stress satisfaction offset score to determine the degree of change in stress and satisfaction. Results: There was significant reduction in sick leave (2014 vs. 2012) (p<.001), and significant improvement in stress satisfaction offset score (p<.05). Logistic regression analysis identified the programme components most predictive of reduced stress and higher job satisfaction. Conclusion: The impacts of a systems-based mindfulness workplace wellness intervention, show significant improvements in workers’ sick leave and changes to stress and satisfaction scores. This study has implications for sector-wide policy change in the workplace.
Dental eruption sequence and hypsodonty index of a Pleistocene macraucheniid from the Brazilian Intertropical Region
Authors: Souza Lobo Leonardo , Lessa Gisele , Cartelle Cástor , Romano Pedro S. R.
Published: August 2017

Litopterna is represented in the Pleistocene of the Brazilian Intertropical Region by a monospecific genus of Macraucheniidae, Xenorhinotherium. Although most of the knowledge about this family is derived from the dentition, some dental features still remain unknown. This study describes the eruption sequence of permanent dentition and classifies the hypsodonty status of X. bahiense. The specimens studied are from Toca dos Ossos, a limestone cave located in Bahia State. We perform qualitative macroscopic analysis to describe the eruption dental sequence. Additionally, we perform quantitative analysis to determine the hypsodonty index. The dental eruption sequence of the juvenile specimen is M1, M2, I1, I2, M3, I3, P1, P2, P3, and P4. In addition, the analysis of tooth wear in adult specimens provides similar results. The hypsodonty index assigns a mesodont tooth crown for X. bahiense. The dental eruption sequence is most similar to a rapid-growth extant mammal. Moreover, our results do not support afrotherian-like delayed dental eruption to Litopterna. The hypsodonty index can be related to data on vegetation of the Brazilian Intertropical Region and the shape of the premaxilla of X. bahiense, both of which suggest a browsing diet for this macraucheniid.
The Rise of Professors of Economics and Business Studies in Switzerland
Authors: Rossier Thierry , Bühlmann Felix , Mach André
Published: August 2017

This paper studies the rise of professors of economics and business studies in the second half of the 20th century in Switzerland. It focuses on three types of power resources: positions in the university hierarchy, scientific reputation and extra-academic positions in the economic and political spheres. Based on a biographical database of N = 487 professors, it examines how these resources developed from 1957 to 2000. We find that professors of economic sciences were increasingly and simultaneously successful on all three studied dimensions – especially when compared to disciplines such as law, social sciences or humanities. This evolution seems to challenge the notorious trade-off between scientific and society poles of the academic field: professors of economics and business increased their scientific reputation while becoming more powerful in worldly positions. However, zooming in on their individual endowment with capital, we see that the same professors rarely hold simultaneously a significant amount of scientific and institutional capital.
A NEW UPPER BOUND FOR THE SUM OF DIVISORS FUNCTION
Authors: AXLER CHRISTIAN
Published: August 2017

Robin’s criterion states that the Riemann hypothesis is true if and only if $\unicode[STIX]{x1D70E}(n)<e^{\unicode[STIX]{x1D6FE}}n\log \log n$ for every positive integer $n\geq 5041$. In this paper we establish a new unconditional upper bound for the sum of divisors function, which improves the current best unconditional estimate given by Robin. For this purpose, we use a precise approximation for Chebyshev’s $\unicode[STIX]{x1D717}$-function.
Variation in bacterial endosymbionts associated with the date palm hopper,Ommatissus lybicuspopulations
Authors: Karimi S. , Izadi H. , Askari Seyahooei M. , Bagheri A. , Khodaygan P.
Published: August 2017

The date palm hopper,Ommatissus lybicus, is a key pest of the date palm, which is expected to be comprised of many allopatric populations. The current study was carried out to determine bacterial endosymbiont diversity in the different populations of this pest. Ten date palm hopper populations were collected from the main date palm growing regions in Iran and an additional four samples from Pakistan, Oman, Egypt and Tunisia for detection of primary and secondary endosymbionts using polymerase chain reaction (PCR) assay with their specific primers. The PCR products were directly sequenced and edited using SeqMan software. The consensus sequences were subjected to a BLAST similarity search. The results revealed the presence of ‘CandidatusSulcia muelleri’ (primary endosymbiont) andWolbachia,ArsenophonusandEnterobacter(secondary endosymbionts) in all populations. This assay failed to detect ‘CandidatusNasuia deltocephalinicola’ andSerratiain these populations. ‘Ca. S. muelleri’ exhibited a 100% infection frequency in populations andWolbachia,ArsenophonusandEnterobacterdemonstrated 100, 93.04 and 97.39% infection frequencies, respectively. The infection rate ofArsenophonusandEnterobacterranged from 75 to 100% and 62.5 to 100%, respectively, in different populations of the insect. The results demonstrated multiple infections by ‘Ca. Sulcia muelleri’,Wolbachia,ArsenophonusandEnterobacterin the populations and may suggest significant roles for these endosymbionts on date palm hopper population fitness. This study provides an insight to endosymbiont variation in the date palm hopper populations; however, further investigation is needed to examine how these endosymbionts may affect host fitness.
Tournament-Based Incentives, Corporate Cash Holdings, and the Value of Cash
Authors: Phan Hieu V. , Simpson Thuy , Nguyen Hang T.
Published: August 2017

This research examines the relations between tournament-based incentives and corporate cash holdings and the value of cash. We find robust evidence that tournament-based incentives are positively related to cash holdings and the value of cash. Moreover, the effect of tournament-based incentives on the value of cash is stronger for financially constrained firms. Our evidence indicates that as tournament-based incentives motivate riskier corporate policy choices that lead to not only larger expected shareholder value but also greater cash-flow uncertainty, firms increase cash holdings to cushion potential liquidity shortfalls that may cause underinvestment.
Valuations in Corporate Takeovers and Financial Constraints on Private Targets
Authors: Greene Daniel
Published: August 2017

I examine acquisitions of private firms by public acquirers to better understand the effects of financial constraints on the division of economic gains in takeovers. Empirical tests exploit interstate bank branching deregulation, which relaxes financial constraints on private firms and can strengthen their bargaining position in an acquisition. Using a proxy for the degree to which targets depend on acquirers for financing, I find that private targets depend less on acquirers as a result of interstate bank branching deregulation. Relaxing financial constraints on private targets leads to an increase in target valuation multiples and a decrease in acquirer wealth gains.
Beyond payments for ecosystem services: considerations of trust, livelihoods and tenure security in community-based conservation projects
Authors: Davis Alicia , Goldman Mara J.
Published: August 2017

In the search for successful community-based conservation models there has been a substantial focus on payment for ecosystem services. Such payments are measurable inputs that are often associated with conservation success. A closer look suggests a more complex, historically and culturally contingent picture. We argue that a focus on payment for ecosystem services as a defining factor for success in community conservation risks overlooking other, more significant processes. In particular, we argue for the importance of (1) tenure and livelihood security and (2) relations of trust, communication and respect. We draw on case studies from East Africa, but the findings are relevant for global community-based conservation endeavours.
Adult children stepping in? Long-term care reforms and trends in children's provision of household support to impaired parents in the Netherlands
Authors: VAN DEN BROEK THIJS , DYKSTRA PEARL A. , VAN DER VEEN ROMKE J.
Published: August 2017

Recent long-term care (LTC) reforms in the Netherlands are illustrative of those taking place in countries with a universalistic LTC model based on extensive provision of state-supported services. They entail a shift from de-familialisation, in which widely available state-supported LTC services relieve family members from the obligations to care for relatives in need, to supported familialism, in which family involvement in care-giving is fostered through support and recognition for families in keeping up their caring responsibilities. Using data from four waves of the Netherlands Kinship Panel Study (N = 2,197), we show that between 2002 and 2014 the predicted probability that adult children provide occasional household support to impaired parents rose substantially. Daughters more often provided household support to parents than did sons, but no increase in the gender gap over time was found. We could not attribute the increase in children's provision of household support to drops in the use of state-supported household services. The finding that more and more adult children are stepping in to help their ageing parents fits a more general trend in the Netherlands of increasing interactions in intergenerational families.
Generalised Cogrowth series, random walks, and the group determinant
Authors: HUMPHRIES STEPHEN P.
Published: August 2017

We associate to a groupGa series that generalises the cogrowth series ofGand is related to a random walk onG. We show that the series is rational if and only ifGis finite, generalizing a result of Kouksov [Kou]. We show that whenGis finite, the series determinesG. There are naturally occurring ideals and varieties that are acted on by Aut(G). We study these and generalize this to the context ofS-rings over finite groups. There is an associated representation of Aut(G) and we characterize when this is irreducible.
High distance tangles and tunnel number of knots
Authors: SAITO TOSHIO
Published: August 2017

We show that for any integers ti ⩾ 0 (i = 1, 2) and n ⩾ 2, there is a knot K in the 3-sphere with an n-tangle decomposition K = T1∪T2 such that tnl(Ti) = ti (i = 1, 2) and that tnl(K) = tnl(T1) + tnl(T2) + 2n − 1, where tnl(⋅) is the tunnel number. This contains an affirmative answer to an unsolved problem asked by Morimoto.
Minimizing the Number of Triangular Edges
Authors: GRUSLYS VYTAUTAS , LETZTER SHOHAM
Published: August 2017

We consider the problem of minimizing the number of edges that are contained in triangles, among n-vertex graphs with a given number of edges. For sufficiently large n, we prove an exact formula for this minimum, which partially resolves a conjecture of Füredi and Maleki.
Single Rescuer Ventilation Using a Bag Valve Mask with Removable External Handle: A Randomized Crossover Trial
Authors: Reed Paul , Zobrist Baruch , Casmaer Monica , Schauer Steven G. , Kester Nurani , April Michael D.
Published: August 2017

Introduction

Ventilation with a bag valve mask (BVM) is a challenging but critical skill for airway management in the prehospital setting.

Hypothesis

Tidal volumes received during single rescuer ventilation with a modified BVM with supplemental external handle will be higher than those delivered using a standard BVM among health care volunteers in a manikin model.

Methods

This study was a randomized crossover trial of adult health care providers performing ventilation on a manikin. Investigators randomized participants to perform single rescuer ventilation, first using either a BVM modified by addition of a supplemental external handle or a standard unmodified BVM (Spur II BVM device; Ambu; Ballerup, Denmark). Participants performed mask placement and delivery of 10 breaths per minute for three minutes, as guided by a metronome. After a three-minute rest period, they performed ventilation using the alternative device. The primary outcome measure was mean received tidal volume as measured by the manikin (IngMar RespiTrainer model; IngMar Medical; Pittsburgh, Pennsylvania USA). Secondary outcomes included subject device preference.

Results

Of 70 recruited participants, all completed the study. The difference in mean received tidal volume between ventilations performed using the modified BVM with external handle versus standard BVM was 20 ml (95% CI, -16 to 56 ml; P=.28). There were no significant differences in mean received tidal volume based on the order of study arm allocation. The proportion of participants preferring the modified BVM over the standard BVM was 47.1% (95% CI, 35.7 to 58.6%).

Conclusions

The modified BVM with added external handle did not result in greater mean received tidal volume compared to standard BVM during single rescuer ventilation in a manikin model.

ReedP, ZobristB, CasmaerM, SchauerSG, KesterN, AprilMD. Single rescuer ventilation using a bag valve mask with removable external handle: a randomized crossover trial. Prehosp Disaster Med. 2017;32(6):625–630.
Lower education predicts poor response to dietary intervention in pregnancy, regardless of neighbourhood affluence: secondary analysis from the ROLO randomised control trial
Authors: O’Brien Eileen C , Alberdi Goiuri , Geraghty Aisling A , McAuliffe Fionnuala M
Published: August 2017

Objective

To determine if response to a low glycaemic index (GI) dietary intervention, measured by changes in dietary intake and gestational weight gain, differed across women of varying socio-economic status (SES).

Design

Secondary data analysis of the ROLO randomised control trial. The intervention consisted of a two-hour low-GI dietary education session in early pregnancy. Change in GI was measured using 3 d food diaries pre- and post-intervention. Gestational weight gain was categorised as per the 2009 Institute of Medicine guidelines. SES was measured using education and neighbourhood deprivation.

Setting

The National Maternity Hospital, Dublin, Ireland.

Subjects

Women (n 625) recruited to the ROLO randomised control trial.

Results

The intervention significantly reduced GI and excess gestational weight gain (EGWG) among women with third level education residing in both disadvantaged (GI, mean (sd), intervention v. control: −3·30 (5·15) v. −0·32 (4·22), P=0·024; EGWG, n (%), intervention v. control: 7 (33·6) v. 22 (67·9); P=0·022) and advantaged areas (GI: −1·13 (3·88) v. 0·06 (3·75), P=0·020; EGWG: 41 (34·1) v. 58 (52·6); P=0·006). Neither GI nor gestational weight gain differed between the intervention and control group among women with less than third level education, regardless of neighbourhood deprivation.

Conclusions

A single dietary education session was not effective in reducing GI or gestational weight gain among less educated women. Multifaceted, appropriate and practical approaches are required in pregnancy interventions to improve pregnancy outcomes for less educated women.
Current dietary supplement use of Australian military veterans of Middle East operations
Authors: van der Pols Jolieke C , Kanesarajah Jeeva , Bell Alison , Lui Chi-Wai
Published: August 2017

Objective

To assess patterns and levels of dietary supplement use among Australian Defence Forces, previously deployed to the Middle East Area of Operations.

Design

A cross-sectional study. Participants of a large survey self-completed questions about dietary supplement use, health status, personal and job-related characteristics, and lifestyle factors. Frequency of current use of supplements was assessed in three categories (bodybuilding, energy and weight loss).

Setting

Middle East Area of Operations post-deployment health survey.

Subjects

Current and ex-serving Australian Defence Force personnel (n14 032) who deployed to the Middle East between 2001 and 2009.

Results

Bodybuilding supplements were used by 17·5 % of participants, energy supplements by 24·5 % and weight-loss supplements by 7·6 %. Overall, 32·3 % of participants used any of these supplements. Bodybuilding and energy supplements were more often used by men, younger persons and those in the Army, while weight-loss supplements were more commonly used by women and Navy personnel. Supplements in all three categories were more commonly used by persons in lower ranks, active service and combat roles. Users of bodybuilding supplements had healthier lifestyles and better health status, while users of energy and weight-loss supplements had less healthy lifestyles and poorer mental and physical health status. Overall, 11·7 % of participants used supplements containing caffeine and 3·6 % used a creatine-containing product.

Conclusions

Use of dietary supplements among Australian Defence Force personnel is common, and patterned by lifestyle factors and health status.
Solar storms may trigger sperm whale strandings: explanation approaches for multiple strandings in the North Sea in 2016
Authors: Vanselow Klaus Heinrich , Jacobsen Sven , Hall Chris , Garthe Stefan
Published: August 2017

The Earth's atmosphere and the Earth's magnetic field protects local life by shielding us against Solar particle flows, just like the sun's magnetic field deflects cosmic particle radiation. Generally, magnetic fields can affect terrestrial life such as migrating animals. Thus, terrestrial life is connected to astronomical interrelations between different magnetic fields, particle flows and radiation. Mass strandings of whales have often been documented, but their causes and underlying mechanisms remain unclear. We investigated the possible reasons for this phenomenon based on a series of strandings of 29 male, mostly bachelor, sperm whales (Physeter macrocephalus) in the southern North Sea in early 2016. Whales’ magnetic sense may play an important role in orientation and migration, and strandings may thus be triggered by geomagnetic storms. This approach is supported by the following: (1) disruptions of the Earth's magnetic field by Solar storms can last about 1 day and lead to short-term magnetic latitude changes corresponding to shifts of up to 460 km; (2) many of these disruptions are of a similar magnitude to more permanent geomagnetic anomalies; (3) geomagnetic anomalies in the area north of the North Sea are 50–150 km in diameter; and (4) sperm whales swim about 100 km day−1, and may thus be unable to distinguish between these phenomena. Sperm whales spend their early, non-breeding years in lower latitudes, where magnetic disruptions by the sun are weak and thus lack experience of this phenomenon. ‘Naïve’ whales may therefore become disoriented in the southern Norwegian Sea as a result of failing to adopt alternative navigation systems in time and becoming stranded in the shallow North Sea.
Cancer treatment experiences among survivors of childhood sexual abuse: A qualitative investigation of triggers and reactions to cumulative trauma
Authors: Schnur Julie B. , Dillon Matthew J. , Goldsmith Rachel E. , Montgomery Guy H.
Published: August 2017

Objective:

Some 25% of women and 8% of men in the United States have experienced childhood sexual abuse (CSA) before the age of 18. For these individuals, healthcare visits and interactions can be retraumatizing due to perceived similarities to past abuse (e.g., pain, undressing, lack of control). However, no prior studies have provided formal qualitative analyses regarding CSA survivors' reactions to cancer treatment. Therefore, our study's objective was to identify key themes pertaining to CSA survivors' cancer treatment experiences.

Method:

Male and female members of the Amazon Mechanical Turk (N= 159, mean age = 44.27 years,SD= 10.02) participated in an anonymous online survey study. The inclusion criteria included reporting: history of CSA; a diagnosis of colorectal, gynecological, breast, or skin cancer; and experience of triggers and/or difficulties during cancer treatment. Participants' responses to open-ended questions were analyzed using inductive thematic analysis.

Results:

We identified two primary themes describing CSA survivors' experiences: Theme 1: treatment-related triggers (key subthemes: procedure-related, provider-related, and emotional triggers); and Theme 2: questioning the meaning of cumulative trauma (e.g., “Why me again?”).

Significance of results:

For CSA survivors, cancer and its treatment can trigger thoughts and emotions associated with the original abuse as well as negative evaluations of themselves, the world, and their future. Our findings are consistent with past research on CSA survivors' experiences in non-cancer healthcare settings and add to the literature by highlighting their struggles during cancer treatment. The present results can inform further research on trauma survivors' reactions to cancer treatment and give cancer care providers the context they need to understand and sensitively serve a substantial yet often overlooked patient group.
Breakfast Skipping Is an Independent Predictor of Obesity but not Overweight Among Children in a Southeastern European Population
Authors: Burazeri Genc , Hyska Jolanda , Mone Iris , Roshi Enver
Published: August 2017

Abstract. Aim: To assess the association of breakfast skipping with overweight and obesity among children in Albania, a post-communist country in the Western Balkans, which is undergoing a long and difficult political and socioeconomic transition towards a market-oriented economy. Methods: A nationwide cross-sectional study was carried out in Albania in 2013 including a representative sample of 5810 children aged 7.0 – 9.9 years (49.5% girls aged 8.4 ± 0.6 years and 51.5% boys aged 8.5 ± 0.6 years; overall response rate: 97%). Children were measured for height and weight, and body mass index (BMI) calculated. Cut-off BMI values of the World Health Organization (WHO) and the International Obesity Task Force (IOTF) were used to define overweight and obesity in children. Demographic data were also collected. Results: Upon adjustment for age, sex, and place of residence, breakfast skipping was positively related to obesity (WHO criteria: OR = 1.5, 95% CI = 1.3–1.9; IOTF criteria: OR = 1.9, 95% CI = 1.4–2.5), but not overweight (OR = 1.1, 95% CI = 0.9–1.3 and OR = 1.1, 95% CI = 0.9–1.4, respectively). Furthermore, breakfast skipping was associated with a higher BMI (multivariable-adjusted OR = 1.05, 95% CI = 1.02–1.07). Conclusions: Our findings point to a strong and consistent positive relationship between breakfast skipping and obesity, but not overweight, among children in this transitional southeastern European population. Future studies in Albania and other transitional settings should prospectively examine the causal role of breakfast skipping in the development of overweight and obesity.
Gearing Up for Fall Semester
Authors: Cartier Kimberly
Published: August 2017

Geoscience professors explain how they use their summertime to get ready for teaching, researching, and mentoring when the school year begins again.
Grape pomace compost harbors organohalide-respiring Dehalogenimonas species with novel reductive dehalogenase genes
Authors: Yang Yi , Higgins Steven A , Yan Jun , Şimşir Burcu , Chourey Karuna , Iyer Ramsunder , Hettich Robert L , Baldwin Brett , Ogles Dora M , Löffler Frank E
Published: August 2017

Organohalide-respiring bacteria have key roles in the natural chlorine cycle; however, most of the current knowledge is based on cultures from contaminated environments. We demonstrate that grape pomace compost without prior exposure to chlorinated solvents harbors a Dehalogenimonas (Dhgm) species capable of using chlorinated ethenes, including the human carcinogen and common groundwater pollutant vinyl chloride (VC) as electron acceptors. Grape pomace microcosms and derived solid-free enrichment cultures were able to dechlorinate trichloroethene (TCE) to less chlorinated daughter products including ethene. 16S rRNA gene amplicon and qPCR analyses revealed a predominance of Dhgm sequences, but Dehalococcoides mccartyi (Dhc) biomarker genes were not detected. The enumeration of Dhgm 16S rRNA genes demonstrated VC-dependent growth, and 6.55±0.64 × 108 cells were measured per μmole of chloride released. Metagenome sequencing enabled the assembly of a Dhgm draft genome, and 52 putative reductive dehalogenase (RDase) genes were identified. Proteomic workflows identified a putative VC RDase with 49 and 56.1% amino acid similarity to the known VC RDases VcrA and BvcA, respectively. A survey of 1,173 groundwater samples collected from 111 chlorinated solvent-contaminated sites in the United States and Australia revealed that Dhgm 16S rRNA genes were frequently detected and outnumbered Dhc in 65% of the samples. Dhgm are likely greater contributors to reductive dechlorination of chlorinated solvents in contaminated aquifers than is currently recognized, and non-polluted environments represent sources of organohalide-respiring bacteria with novel RDase genes.
Function-related replacement of bacterial siderophore pathways
Authors: Bruns Hilke , Crüsemann Max , Letzel Anne-Catrin , Alanjary Mohammad , McInerney James O , Jensen Paul R , Schulz Stefan , Moore Bradley S , Ziemert Nadine
Published: August 2017

Bacterial genomes are rife with orphan biosynthetic gene clusters (BGCs) associated with secondary metabolism of unrealized natural product molecules. Often up to a tenth of the genome is predicted to code for the biosynthesis of diverse metabolites with mostly unknown structures and functions. This phenomenal diversity of BGCs coupled with their high rates of horizontal transfer raise questions about whether they are really active and beneficial, whether they are neutral and confer no advantage, or whether they are carried in genomes because they are parasitic or addictive. We previously reported that Salinispora bacteria broadly use the desferrioxamine family of siderophores for iron acquisition. Herein we describe a new and unrelated group of peptidic siderophores called salinichelins from a restricted number of Salinispora strains in which the desferrioxamine biosynthesis genes have been lost. We have reconstructed the evolutionary history of these two different siderophore families and show that the acquisition and retention of the new salinichelin siderophores co-occurs with the loss of the more ancient desferrioxamine pathway. This identical event occurred at least three times independently during the evolution of the genus. We surmise that certain BGCs may be extraneous because of their functional redundancy and demonstrate that the relative evolutionary pace of natural pathway replacement shows high selective pressure against retention of functionally superfluous gene clusters.
Nucleolar expansion and elevated protein translation in premature aging
Authors: Buchwalter Abigail , Hetzer Martin W.
Published: August 2017

Premature aging disorders provide an opportunity to study the mechanisms that drive aging. In Hutchinson-Gilford progeria syndrome (HGPS), a mutant form of the nuclear scaffold protein lamin A distorts nuclei and sequesters nuclear proteins. We sought to investigate protein homeostasis in this disease. Here, we report a widespread increase in protein turnover in HGPS-derived cells compared to normal cells. We determine that global protein synthesis is elevated as a consequence of activated nucleoli and enhanced ribosome biogenesis in HGPS-derived fibroblasts. Depleting normal lamin A or inducing mutant lamin A expression are each sufficient to drive nucleolar expansion. We further show that nucleolar size correlates with donor age in primary fibroblasts derived from healthy individuals and that ribosomal RNA production increases with age, indicating that nucleolar size and activity can serve as aging biomarkers. While limiting ribosome biogenesis extends lifespan in several systems, we show that increased ribosome biogenesis and activity are a hallmark of premature aging.
Protein nanovaccine confers robust immunity against Toxoplasma
Authors: El Bissati Kamal , Zhou Ying , Paulillo Sara Maria , Raman Senthil Kumar , Karch Christopher P. , Roberts Craig W. , Lanar David E. , Reed Steve , Fox Chris , Carter Darrick , Alexander Jeff , Sette Alessandro , Sidney John , Lorenzi Hernan , Begeman Ian J. , Burkhard Peter , McLeod Rima
Published: August 2017

We designed and produced a self-assembling protein nanoparticle. This self-assembling protein nanoparticle contains five CD8+HLA-A03-11 supertypes-restricted epitopes from antigens expressed duringToxoplasma gondii’s lifecycle, the universal CD4+T cell epitope PADRE, and flagellin as a scaffold and TLR5 agonist. These CD8+T cell epitopes were separated by N/KAAA spacers and optimized for proteasomal cleavage. Self-assembling protein nanoparticle adjuvanted with TLR4 ligand-emulsion GLA-SE were evaluated for their efficacy in inducing IFN-γ responses and protection of HLA-A*1101 transgenic mice againstT. gondii. Immunization, using self-assembling protein nanoparticle-GLA-SE, activated CD8+T cells to produce IFN-γ. Self-assembling protein nanoparticle-GLA-SE also protected HLA-A*1101 transgenic mice against subsequent challenge with Type II parasites. Hence, combining CD8+T cell-eliciting peptides and PADRE into a multi-epitope protein that forms a nanoparticle, administered with GLA-SE, leads to efficient presentation by major histocompatibility complex Class I and II molecules. Furthermore, these results suggest that activation of TLR4 and TLR5 could be useful for development of vaccines that elicit T cells to prevent toxoplasmosis in humans.
A defined subunit vaccine that protects against vector-borne visceral leishmaniasis
Authors: Duthie Malcolm S. , Pereira Lais , Favila Michelle , Hofmeyer Kimberly A. , Reed S. Jim , Metangmo Sonia , Townsend Shannon , Laurance John D. , Picone Alessandro , Misquith Ayesha , Hossain Faria , Ghosh Prakash , Khan Md Anik Ashfaq , Guderian Jeffery , Bailor H. Remy , Liang Hong , Vergara Julie , Oliveira Fabiano , Howard Randall F. , Kamhawi Shaden , Mondal Dinesh , Coler Rhea N. , Valenzuela Jesus G. , Reed Steven G.
Published: August 2017

Vaccine development for vector-borne pathogens may be accelerated through the use of relevant challenge models, as has been the case for malaria. Because of the demonstrated biological importance of vector-derived molecules in establishing natural infections, incorporating natural challenge models into vaccine development strategies may increase the accuracy of predicting efficacy under field conditions. Until recently, however, there was no natural challenge model available for the evaluation of vaccine candidates against visceral leishmaniasis. We previously demonstrated that a candidate vaccine against visceral leishmaniasis containing the antigen LEISH-F3 could provide protection in preclinical models and induce potent T-cell responses in human volunteers. In the present study, we describe a next generation candidate, LEISH-F3+, generated by adding a third antigen to the LEISH-F3 di-fusion protein. The rationale for adding a third component, derived from cysteine protease (CPB), was based on previously demonstrated protection achieved with this antigen, as well as on recognition by human T cells from individuals with latent infection. Prophylactic immunization with LEISH-F3+formulated with glucopyranosyl lipid A adjuvant in stable emulsion significantly reduced both Leishmania infantum and L. donovani burdens in needle challenge mouse models of infection. Importantly, the data obtained in these infection models were validated by the ability of LEISH-F3+/glucopyranosyl lipid A adjuvant in stable emulsion to induce significant protection in hamsters, a model of both infection and disease, following challenge by L. donovani–infected Lutzomyia longipalpis sand flies, a natural vector. This is an important demonstration of vaccine protection against visceral leishmaniasis using a natural challenge model.
Dysivillosins A–D, Unusual Anti-allergic Meroterpenoids from the Marine Sponge Dysidea villosa
Authors: Jiao Wei-Hua , Cheng Bao-Hui , Shi Guo-Hua , Chen Guo-Dong , Gu Bin-Bin , Zhou Yong-Jun , Hong Li-Li , Yang Fan , Liu Zhi-Qiang , Qiu Shu-Qi , Liu Zhi-Gang , Yang Ping-Chang , Lin Hou-Wen
Published: August 2017

Four unusual meroterpenoids, dysivillosins A–D (1–4), were isolated from an organic extract of the marine sponge Dysidea villosa collected from the South China Sea. Their planar structures were determined by 1D and 2D NMR and HRESIMS techniques, while the relative and absolute configurations were elucidated by NOESY experiments and comparison between the calculated and experimental ECD spectra. To the best of our knowledge, dysivillosins A–D are the first examples of terpene-polyketide-pyridine hybrid metabolites from the nature. Anti-allergic activity evaluation showed that compounds 1–4 potently inhibited the release of β-hexosaminidase, a marker of degranulation, in a dose-dependent manner with IC50 values of 8.2–19.9 μM. Additionally, the four meroterpenoids could downregulate the production of lipid mediator leukotrienes B4 (LTB4) and pro-inflammatory cytokine interleukin-4 (IL-4) in the antigen-stimulated RBL-2H3 mast cells. Further biological investigations revealed that dysivillosin A (1) could suppress the phosphorylation of Syk and PLCγ1 in IgE/FcɛRI/Syk signaling pathway, which resulted in the inhibition of degranulation and the downregulation of LTB4 and IL-4 production in mast cells.
Nei-like 1 (NEIL1) excises 5-carboxylcytosine directly and stimulates TDG-mediated 5-formyl and 5-carboxylcytosine excision
Authors: Slyvka Anton , Mierzejewska Karolina , Bochtler Matthias
Published: August 2017

Thymine DNA glycosylase (TDG) and Nei-like 1 (NEIL1) have both been implicated in the base excision repair step of active DNA demethylation. The robust glycosylase activity of TDG on DNA substrates containing 5-formylcytosine (5fC) or 5-carboxylcytosine (5caC) is universally accepted, but the mode of action of NEIL1 is still debated. Based on genetic experiments, it has been suggested that NEIL1 acts redundantly with TDG and excises 5fC and 5caC directly. However, this result has been disputed, and it was suggested instead that NEIL1 is recruited by the monofunctional TDG for the 2′-deoxyribose excision step. Using purified human NEIL1 and its catalytically impaired P2T and E3Q variants as controls, we detect NEIL1 activity on 5caC, but not a 5fC containing dsDNA substrate. We confirm direct NEIL1 TDG binding and NEIL1 mediated 2′-deoxyribose excision downstream of TDG glycosylase activity. NEIL1 acts not only downstream of TDG, but also enhances TDG activity on 5fC or 5caC containing DNA. NEIL1 mediated enhancement of the TDG glycosylase activity is substrate specific and does not occur for dsDNA with a T/G mismatch.
A multi-parametric analysis of Trypanosoma cruzi infection: common pathophysiologic patterns beyond extreme heterogeneity of host responses
Authors: Santi-Rocca Julien , Fernandez-Cortes Fernando , Chillón-Marinas Carlos , González-Rubio María-Luisa , Martin David , Gironès Núria , Fresno Manuel
Published: August 2017

The extreme genetic diversity of the protozoan Trypanosoma cruzi has been proposed to be associated with the clinical outcomes of the disease it provokes: Chagas disease (CD). To address this question, we analysed the similarities and differences in the CD pathophysiogenesis caused by different parasite strains. Using syngeneic mice infected acutely or chronically with 6 distant parasite strains, we integrated simultaneously 66 parameters: parasite tropism (7 parameters), organ and immune responses (local and systemic; 57 parameters), and clinical presentations of CD (2 parameters). While the parasite genetic background consistently impacts most of these parameters, they remain highly variable, as observed in patients, impeding reliable one-dimensional association with phases, strains, and damage. However, multi-dimensional statistics overcame this extreme intra-group variability for each individual parameter and revealed some pathophysiological patterns that accurately allow defining (i) the infection phase, (ii) the infecting parasite strains, and (iii) organ damage type and intensity. Our results demonstrated a greater variability of clinical outcomes and host responses to T. cruzi infection than previously thought, while our multi-parametric analysis defined common pathophysiological patterns linked to clinical outcome of CD, conserved among the genetically diverse infecting strains.
Sodium Hyaluronate in the Treatment of Dry Eye Syndrome: A Systematic Review and Meta-Analysis
Authors: Ang Bryan Chin Hou , Sng James Jie , Wang Priscilla Xin Hui , Htoon Hla Myint , Tong Louis Hak Tien
Published: August 2017

This systematic review and meta-analysis compares sodium hyaluronate (HY) with non-HY based artificial tears in the treatment of dry eye syndrome. A literature search for clinical trials comparing HY against non-HY preparations was conducted across PubMed, Cochrane Central Register of Controlled Trials and Scopus databases from inception up to May 2016. Majority of the 18 studies selected for review showed superiority of HY in improving ocular staining and symptoms. Randomized controlled trials (RCTs) examining Schirmer’s I (SH) and tear breakup time (TBUT) underwent further meta-analyses with calculation of pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs). 7 RCTs including 383 eyes randomized to HY and 596 eyes to non-HY preparations underwent meta-analysis for SH. 9 RCTs including 458 eyes randomized to HY and 651 eyes to non-HY preparations underwent meta-analysis for TBUT. By fixed-effects modelling, HY demonstrated greater improvement of SH compared to non-HY preparations (SMD, 0.238; 95% CI, 0.107 to 0.369; p < 0.001). By random-effects modelling, HY demonstrated less improvement of TBUT (SMD, −0.566; 95% CI, −1.099 to −0.0336; p = 0.037). In summary, neither preparation was shown to be consistently superior across all outcome measures. The difference in effect between preparations on SH and TBUT was not clinically significant.
Transcriptional control of motility enables directional movement of Escherichia coli in a signal gradient
Authors: Ravichandar Jayamary Divya , Bower Adam G. , Julius A. Agung , Collins Cynthia H.
Published: August 2017

Manipulation of cellular motility using a target signal can facilitate the development of biosensors or microbe-powered biorobots. Here, we engineered signal-dependent motility in Escherichia coli via the transcriptional control of a key motility gene. Without manipulating chemotaxis, signal-dependent switching of motility, either on or off, led to population-level directional movement of cells up or down a signal gradient. We developed a mathematical model that captures the behaviour of the cells, enables identification of key parameters controlling system behaviour, and facilitates predictive-design of motility-based pattern formation. We demonstrated that motility of the receiver strains could be controlled by a sender strain generating a signal gradient. The modular quorum sensing-dependent architecture for interfacing different senders with receivers enabled a broad range of systems-level behaviours. The directional control of motility, especially combined with the potential to incorporate tuneable sensors and more complex sensing-logic, may lead to tools for novel biosensing and targeted-delivery applications.
Windows of opportunity for Ebola virus infection treatment and vaccination
Authors: Nguyen Van Kinh , Hernandez-Vargas Esteban A.
Published: August 2017

Ebola virus (EBOV) infection causes a high death toll, killing a high proportion of EBOV-infected patients within 7 days. Comprehensive data on EBOV infection are fragmented, hampering efforts in developing therapeutics and vaccines against EBOV. Under this circumstance, mathematical models become valuable resources to explore potential controlling strategies. In this paper, we employed experimental data of EBOV-infected nonhuman primates (NHPs) to construct a mathematical framework for determining windows of opportunity for treatment and vaccination. Considering a prophylactic vaccine based on recombinant vesicular stomatitis virus expressing the EBOV glycoprotein (rVSV-EBOV), vaccination could be protective if a subject is vaccinated during a period from one week to four months before infection. For the case of a therapeutic vaccine based on monoclonal antibodies (mAbs), a single dose might resolve the invasive EBOV replication even if it was administrated as late as four days after infection. Our mathematical models can be used as building blocks for evaluating therapeutic and vaccine modalities as well as for evaluating public health intervention strategies in outbreaks. Future laboratory experiments will help to validate and refine the estimates of the windows of opportunity proposed here.
Metabolic unhealthiness is an important predictor for the development of advanced colorectal neoplasia
Authors: Kim Tae Jun , Kim Eun Ran , Hong Sung Noh , Kim Young-Ho , Chang Dong Kyung , Ji Jaehwan , Kim Jee Eun , Kim Hye Seung , Kim Kyunga , Son Hee Jung
Published: August 2017

Obesity is a well-known risk factor for colorectal neoplasia. Yet, the associations of both metabolic and obesity status with metachronous colorectal neoplasia remain unclear. We conducted a cohort study of 9,331 adults who underwent screening colonoscopy and surveillance colonoscopy. Participants were classified as metabolically healthy if they had no metabolic syndrome component. Participants were categorized into four groups according to body mass index and metabolic status: metabolically healthy non-obese (MHNO; n = 2,745), metabolically abnormal non-obese (MANO; n = 3,267), metabolically healthy obese (MHO; n = 707), and metabolically abnormal obese (MAO; n = 2,612). MAO individuals [n = 159 advanced colorectal neoplasia (AN) cases, 6.1%] and MANO individuals (n = 167 AN cases, 5.1%) had a higher incidence of AN compared with MHNO individuals (n = 79 AN cases, 2.9%). In a multivariable model, the risk of metachronous AN was higher in MANO (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.12–1.84) and MAO (HR 1.52, 95% CI 1.18–1.96) than in MHNO. In contrast, the risk of metachronous AN was not significantly elevated in MHO. In subgroup analyses, with or without adenoma at baseline, MAO was a risk group for metachronous AN, and MHO was not. Our findings suggest that metabolic unhealthiness is a significant predictor for metachronous AN.
Label-free in vivo Raman microspectroscopic imaging of the macromolecular architecture of oocytes
Authors: Heraud Philip , Marzec Katarzyna Maria , Zhang Qing‒Hua , Yuen Wai Shan , Carroll John , Wood Bayden R.
Published: August 2017

Confocal Raman spectroscopy (CRS) can provide information about oocyte competency through measurement of changes in the macromolecular architecture during oocyte development and maturation. Hitherto most spectroscopic studies have been limited to fixed oocytes due to the inherent difficulties working with live cells. Here we report the first three-dimensional images of living murine oocytes using CRS. We show that fixation induces significant changes in the macromolecular chemistry compared to living oocytes. A band at 1602 cm−1, assigned to a marker for mitochondria function was found in living oocytes but absent from fixed oocytes providing an in vivo marker. Fixation resulted in significant changes in protein and nucleic acid bands and the spatial distribution of organelles. Raman imaging of Metaphase I and II (MI, MII) and germinal vesicle stage oocytes showed changes in nuclear organisation and cytoplasm macromolecular architecture during these development and maturation stages related to changes in chromosome condensation, mitochondria aggregation and lipid droplet numbers.