bluuebunny/crossref_metadata_2025 huggingface dataset:
The Core, Periphery, and Beyond: Stock Market Comovements among EU and Non‐EU Countries
Authors: Goldstein Michael A. , McCarthy Joseph , Orlov Alexei G.
Published: January 2019

Using linear and nonlinear correlations, copulas, quantile dependence and lower tail dependence, we find that (1) equity markets of the advanced European Union (EU) countries comove more closely with each other than with the peripheral economies, (2) comovements with non‐EU countries are lower, (3) relative comovement structure before, during, and after the global financial crisis has been very stable, and (4) the level of comovements remained virtually the same between the crisis and post‐crisis periods. Our results are robust to controlling for Fama‐French, U.S. and global risk factors, as well as monetary policy, market interest rates, exchange rates, and uncertainty.
Growth of engineered Pseudomonas putida KT2440 on glucose, xylose, and arabinose: Hemicellulose hydrolysates and their major sugars as sustainable carbon sources
Authors: Wang Yan , Horlamus Felix , Henkel Marius , Kovacic Filip , Schläfle Sandra , Hausmann Rudolf , Wittgens Andreas , Rosenau Frank
Published: January 2019

Lignocellulosic biomass is the most abundant bioresource on earth containing polymers mainly consisting of d‐glucose, d‐xylose, l‐arabinose, and further sugars. In order to establish this alternative feedstock apart from applications in food, we engineered Pseudomonas putida KT2440 as microbial biocatalyst for the utilization of xylose and arabinose in addition to glucose as sole carbon sources. The d‐xylose‐metabolizing strain P. putida KT2440_xylAB and l‐arabinose‐metabolizing strain P. putida KT2440_araBAD were constructed by introducing respective operons from Escherichia coli. Surprisingly, we found out that both recombinant strains were able to grow on xylose as well as arabinose with high cell densities and growth rates comparable to glucose. In addition, the growth characteristics on various mixtures of glucose, xylose, and arabinose were investigated, which demonstrated the efficient co‐utilization of hexose and pentose sugars. Finally, the possibility of using lignocellulose hydrolysate as substrate for the two recombinant strains was verified. The recombinant P. putida KT2440 strains presented here as flexible microbial biocatalysts to convert lignocellulosic sugars will undoubtedly contribute to the economic feasibility of the production of valuable compounds derived from renewable feedstock.
Bioactive compounds, pigments, antioxidant activity and antimicrobial activity of yellow prickly pear peels
Authors: Castro Luís M. G. , Alexandre Elisabete M. C. , Pintado Manuela , Saraiva Jorge A.
Published: January 2019

The main goal of this research was to study the effects of pressure, extraction time and ethanol concentration on antioxidant activity, total phenolics, flavonoids, anthocyanins, carotenoids and betalains compounds extraction from yellow prickly pear peels. A Box–Behnken design and Response Surface Methodology were used to evaluate the effects and estimate the optimum extraction conditions. Antimicrobial activity was evaluated against Escherichia coli and Listeria innocua. Ethanol concentration was the variable that showed the highest effect on extraction yields but high‐pressure increased extraction yields between 6% and 17%. Models showed good fitting and adequacy to the experimental data and the high correlation of models indicated that it can be employed to optimise extraction conditions. The experimental and predicted values differed <10% and the extracts inhibited the growth of both bacteria. High‐pressure could be a promising extraction process to improve extraction of bioactives from prickly pear peels.
Influence of ultra‐high pressure homogenisation on physicochemical and sensorial properties of orange juice in comparison with conventional thermal processing
Authors: Velázquez‐Estrada Rita‐María , Hernández‐Herrero María‐Manuela , Guamis‐López Buenaventura , Roig‐Saguès Artur‐Xavier
Published: January 2019

The effect of different ultra‐high pressure homogenisation (UHPH) treatments on physicochemical and sensorial properties of orange juice was studied in comparison with thermal pasteurisation (90 °C, 1 min). UHPH treatments consisted on combinations of two inlet temperatures (10 or 20 °C) and three pressures (100, 200 and 300 MPa). Effect of treatments was assessed on general quality parameters (colour, pH, °Brix, titratable acidity, reducing sugars and non‐enzymatic browning index), particle size distribution and cloud stability. None of the UHPH treatments caused significant differences in the °Brix, reducing sugars, pH and non‐enzymatic browning index with respect of fresh or pasteurised juice. Only titratable acidity was significantly lower when inlet temperature of UHPH treatments was 20 °C. UHPH treatments significantly reduced the particle size and in consequence the cloudiness and the total colour value (∆E*) increased. The overall consumer acceptability of UHPH and pasteurised juices was similar.
ZnO‐activated formation of phase pure perovskite Pb(In1/2Nb1/2)O3‐Pb(Zn1/3Nb2/3)O3‐PbTiO3 powder
Authors: Brova Michael J. , Watson Beecher H. , R. Kupp Elizabeth , Fanton Mark A. , Meyer Richard J. , Messing Gary L.
Published: January 2019

This paper reports on the phase formation of perovskite Pb(In1/2Nb1/2)O3‐Pb(Zn1/3Nb2/3)O3‐PbTiO3 (PIN‐PZN‐PT) powder when doped with 0.04 to 0.83 mol% ZnO. Air calcination of undoped powder mixtures for 4 hours at 800°C resulted in a mixture of Pb2Zn0.29Nb1.71O6.565 pyrochlore, PIN‐PZN‐PT perovskite, and In2O3. ZnO dopant concentrations as low as 0.04 mol% increased the rate of perovskite formation and resulted in near phase pure perovskite powder of 0.5 μm particle size when heated at 800°C in air. In all cases PbTiO3 and Pb(In1/2Nb1/2)O3 formed prior to PIN‐PZN‐PT formation. ZnO doping promotes perovskite phase formation by increasing the reactivity of the intermediate pyrochlore phase by substituting Zn2+ on Nb5+ sites and forming oxygen vacancies when heated in air. Heating in high resulted in an incomplete reaction and a mixture of perovskite and pyrochlore whereas low resulted in phase separation into a mixture of rhombohedral perovskite, tetragonal perovskite, and pyrochlore. The sensitivity clearly shows that oxygen vacancies due to ZnO‐doping are critical for synthesis of phase pure PIN‐PZN‐PT powder.
Cardiac resynchronization therapy reverses severe dyspnea associated with acceleration‐dependent left bundle branch block in a patient with structurally normal heart
Authors: Prystowsky Eric N. , Padanilam Benzy J.
Published: January 2019

A 55‐year‐old woman presented with severe dyspnea during acceleration‐dependent left bundle branch block (LBBB). Metoprolol initially ameliorated symptoms by preventing the heart rate at which LBBB occurred. Over time LBBB presented at slower heart rates and the patient developed recurrent dyspnea during an activity that correlated with the development of LBBB on event monitors and exercise stress testing. A biventricular pacemaker was implanted, and the patient's symptoms remain resolved after a follow‐up of over 4 years. More research is needed to define the use of cardiac resynchronization therapy in patients with normal heart function.
MicroRNAs as regulators of cell death mechanisms in amyotrophic lateral sclerosis
Authors: Gagliardi Delia , Comi Giacomo P. , Bresolin Nereo , Corti Stefania
Published: January 2019

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons (MNs), resulting in paralysis and precocious death from respiratory failure. Although the causes of ALS are incompletely understood, the role of alterations in RNA metabolism seems central. MicroRNAs (miRNAs) are noncoding RNAs implicated in the regulation of gene expression of many relevant physiological processes, including cell death. The recent model of programmed cell death (PCD) encompasses different mechanisms, from apoptosis to regulated necrosis (RN), in particular necroptosis. Both apoptosis and necroptosis play a significant role in the progressive death of MNs in ALS. In this review, we present key research related to miRNAs that modulate apoptosis and RN pathways in ALS. We also discuss whether these miRNAs represent potential targets for therapeutic development in patients.
Optimal human capital policies under the endogenous choice of educational types
Authors: Obara Takuya
Published: January 2019

This study examines optimal human capital policies under nonlinear labor and capital income taxes in the presence of consumption value of education in a two‐period setting. We show that when individuals can choose educational types differing by the relative importance of consumption value and production value, education subsidies for low‐type individuals should not equal an efficient level that offsets distortions induced by nonlinear taxes on labor and capital income. Our findings imply that education policy does not restore efficiency, or the Diamond–Mirrlees production efficiency theorem fails. Moreover, capital income taxation is optimal, which means that the Atkinson–Stiglitz theorem breaks down.
Phylogeography, population genetics and distribution modelling reveal vulnerability of Scirpus longii (Cyperaceae) and the Atlantic Coastal Plain Flora to climate change
Authors: Spalink Daniel , MacKay Ron , Sytsma Kenneth J.
Published: January 2019

A proactive approach to conservation must be predictive, anticipating how habitats will change and which species are likely to decline or prosper. We use composite species distribution modelling to identify suitable habitats for 18 members of the North American Atlantic Coastal Plain Flora (ACPF) since the Last Glacial Maximum and project these into the future. We then use Scirpus longii (Cyperaceae), a globally imperiled ACPF sedge with many of the characteristics of extinction vulnerability, as a case study. We integrate phylogeographical and population genetic analyses and species distribution modelling to develop a broad view of its current condition and prognosis for conservation. We use genotyping‐by‐sequencing to characterize the genomes of 142 S. longii individuals from 20 populations distributed throughout its range (New Jersey to Nova Scotia). We measure the distribution of genetic diversity in the species and reconstruct its phylogeographical history using the snapp and rase models. Extant populations of S. longii originated from a single refugium south of the Laurentide ice sheet around 25 ka. The genetic diversity of S. longii is exceedingly low, populations exhibit little genetic structure and the species is slightly inbred. Projected climate scenarios indicate that nearly half of extant populations of S. longii will be exposed to unsuitable climate by 2070. Similar changes in suitable habitat will occur for many other northern ACPF species—centres of diversity will shift northward and Nova Scotia may become the last refuges for those species not extinguished.
EEG profiles during general anesthesia in children: A comparative study between sevoflurane and propofol
Authors: Rigouzzo Agnes , Khoy‐Ear Linda , Laude Dominique , Louvet Nicolas , Moutard Marie‐Laure , Sabourdin Nada , Constant Isabelle
Published: January 2019

Background

In this prospective study, we describe the electroencephalographic (EEG) profiles in children anesthetized with sevoflurane or propofol.

Methods

Seventy‐three subjects (11 years, range 5‐18) were included and randomly assigned to two groups according to the anesthetic agent. Anesthesia was performed by target‐controlled infusion of propofol (group P) or by sevoflurane inhalation (group S). Steady‐state periods were performed at a fixed randomized concentration between 2, 3, 4, 5, and 6 μg.ml−1 of propofol in group P and between 1, 2, 3, 4, and 5% of sevoflurane in group S. Remifentanil was continuously administered throughout the study. Clinical data, Bispectral Index (BIS), and raw EEG were continuously recorded. The relationship between BIS and anesthetic concentrations was studied using nonlinear regression. For all steady‐state periods, EEG traces were reviewed to assess the presence of epileptoid signs, and spectral analysis of raw EEG was performed.

Results

Under propofol, BIS decreased monotonically and EEG slowed down as concentrations increased from 2 to 6 μg.ml−1. Under sevoflurane, BIS decreased from 0% to 4% and paradoxically rose from 4% to 5% of expired concentration: this increase in BIS was associated with the occurrence of fast oscillations and epileptoid signs on the EEG trace. Propofol was associated with more delta waves and burst suppression periods compared to sevoflurane.

Conclusion

Under deep anesthesia, the BIS and electroencephalographic profiles differ between propofol and sevoflurane. For high concentrations of sevoflurane, an elevated BIS value may be interpreted as a sign of epileptoid patterns or EEG fast oscillations rather than an insufficient depth of hypnosis.
Efficient Photooxidation of Aryl(hetaryl)pyrazolines by Benzoquinone
Authors: Traven Valery F. , Ivanov Ivan V. , Dolotov Sergei M. , Semakin Artem N. , Cheptsov Dmitriy A. , Mamirgova Zarina Z.
Published: January 2019

Photooxidation of aryl(hetaryl)pyrazolines in the presence of benzoquinone has been studied in organic solvents. This reaction occurs at high rate to provide the corresponding pyrazole in a good yield. The effects of the solvent, pyrazoline structure and oxygen provide definite information on the reaction pathway. It appears that radical species are intermediates in the photooxidation of aryl(hetaryl)pyrazolines in the presence of benzoquinone. A comparison of the new results with the photooxidation of aryl(hetaryl)pyrazolines in the presence of perchloroalkanes is also discussed.
New pattern hair loss in young Turkish women; What's wrong in their daily life?
Authors: Sahin Gokhan , Pancar Gunseli S. , Kalkan Goknur
Published: January 2019

Background

The application of heat, used to straighten the typically coiled hair, has long been hypothesized to play a role in the etiologic factor for central centrifugal cicatricial alopecia (CCCA). The aim of this study was to evaluate the effect of thermal hair straightening on hair loss pattern in Asian women exist.

Materials and methods

Thirty‐five patients with hair loss who have been using hair straightening devices and 25 patients with telogen effluvium were enrolled in this prospective study. Laboratory analysis and dermatoscopic findings were used to compare these groups.

Results

The peripilar white halo around hairs, peripilar dark/gray halo around follicular orifices, the predominance of a single hair perifollicular unit (FU), hair diameter diversity, the thin miniaturized hair, interfollicular pinpoint white dots, and white patches were statistically higher in hair straightener group (P < 0.001). White patches of the scalp increased by the time of the application of these devices (P < 0.01). White patches of vertex region were significantly higher than the midfrontal region (P < 0.01).

Conclusion

The common side effects of thermal hot comb strengtheners’ were summarized as damage to the hair shaft; decreasing in the brightness of the hair, burns, and scars on the scalp; and lastly CCCA‐like hair loss.
Use of contrast‐enhanced ultrasonography in the diagnosis of a liver lobe torsion in a rabbit (Oryctolagus cuniculus)
Authors: Stock Emmelie , Vanderperren Katrien , Moeremans Ilse , de Rooster Hilde , Hermans Katleen , Saunders Jimmy H.
Published: January 2019

A 1‐year‐old male French Lop rabbit (Oryctolagus cuniculus) was presented with a sudden onset of hyporexia. Physical examination revealed cranial abdominal discomfort. Liver enzymes were elevated on serum biochemistry profile. Abdominal radiographs showed diffusely gas‐dilated small intestinal loops. On abdominal ultrasound, a lobe in the right aspect of the liver was hypoechoic with rounded margins and was surrounded by hyperechoic fat and anechoic fluid. Contrast‐enhanced ultrasonography showed complete lack of perfusion in the abnormal right liver lobe. Exploratory laparotomy revealed torsion of the quadrate liver lobe. Diffuse coagulation necrosis was noted on histopathologic examination. The rabbit fully recovered after surgery.
The Role of Self-efficacy on Performance of Sports Skills of Football Players
Authors: Sivrikaya M. Haluk
Published: January 2019

The main goal of this study was to determine effect of self-efficacy on performance of football players in Erzurum city. The present research was practical in terms of purpose and correlation in term of its nature. The statistical population of research was Ataturk University boys students (18-22 yrs old) unfamiliar to football scissors kick, in 2018. So, 52 participants were selected randomly based on Morgan Table from 60 volunteers. In this study, two questionnaires of self-efficacy and Charbonneau sport performance were used to collect data. To test hypotheses, regression test was used. In this research, SPSS 20 software was used in all calculations and tests. The results showed that self-efficacy play a significant role in learning of scissors kick.  Self-efficacy is one of the most important characteristics of a successful athlete.
One-way mixing of collinear waves in an adhesive layer
Authors: Ju Taeho , Achenbach Jan D. , Jacobs Laurence J. , Qu Jianmin
Published: January 2019

This paper studies the one-way collinear mixing of a pair of longitudinal and shear waves in an adhesive layer. The objective is to establish a theoretical framework for developing ultrasonic methods for nondestructively characterizing adhesive bonds by using only one side of the adhesive joint. The adhesive joint is modeled as a nonlinear elastic layer embedded in a linear elastic matrix of infinite extent. First, a solution is developed for the general case where the elastic impedance of the layer is different from that of the surrounding matrix. Then, a nonlinear spring model is developed that yields a reduced order solution for the one-way collinear wave mixing problem at hand. It is shown that in the limit of vanishing layer thickness, the solution to a layer of finite thickness reduces to that of the spring model, provided that a proper relationship is used between the properties of the nonlinear layer and the nonlinear spring. In other words, a very thin layer can be effectively replaced by a nonlinear spring. Finally, numerical analyses show that such effective replacement is valid when the layer thickness is less than a few percent of the shortest wavelength used in the measurement.
Experimental study of the transmission of low-frequency acoustic waves through a water–air interface
Authors: Voloshchenko Alexander P. , Tarasov Sergei P.
Published: January 2019

The effect of the anomalous transparency of the water–air interface on low-frequency acoustic waves is investigated. The effect is an abnormal increase in the amount of energy that passes from water to air. This effect is manifested if the source of the acoustic waves is located at a distance less than the wavelength from the water–air interface. According to the mathematical models of Godin and Brekhovskikh, this effect is based on the properties of inhomogeneous plane waves. The results of the measurement of the pressure transmission coefficient for a spherical source are given in this article, and the conditions of the laboratory experiment are briefly described. Graphs showing the dependence of the transmission coefficient on the frequency of source radiation are provided. Oscillograms that indirectly confirm the presence of inhomogeneous plane waves are also provided. The results of the experiments are in good agreement with the theoretical calculations of Godin and Brekhovskikh. The article briefly discusses possible ways of applying the anomalous transparency effect in two real problems: transferring information from a submarine to an aircraft and monitoring underwater seismic activity.
A Pedometer-Based Physically Active Learning Intervention: The Importance of Using Preintervention Physical Activity Categories to Assess Effectiveness
Authors: Morris Jade L. , Daly-Smith Andy , Defeyter Margaret A. , McKenna Jim , Zwolinsky Steve , Lloyd Scott , Fothergill Melissa , Graham Pamela L.
Published: January 2019

Purpose: To assess physical activity outcomes of a pedometer-based physically active learning (PAL) intervention in primary school children. Methods: Six paired schools were randomly allocated to either a 6-week teacher-led pedometer-based physically active learning intervention or a control (n = 154, female = 60%, age = 9.9 [0.3] y). Accelerometers assessed total daily sedentary time, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). Preintervention mean daily MVPA minutes grouped participants as Low Active (<45 min/d) and High Active (≥45 min/d). Results: From the final sample size, the intervention (n = 52) significantly improved LPA versus control (n = 31, P = .04), by reducing sedentary time. More intervention (+10%) than control (+3%) pupils met the 60 minutes per day guidelines. In both intervention subgroups, pupils spent less time in LPA (P < .05) versus control. The greatest nonsignificant increase was found in the Low Active pupils MVPA levels. Conclusions: Improvements in LPA were statistically significant in the intervention versus control group. In subgroup analysis, Low Active pupils in the intervention showed the greatest beneficial effects and the Most Active pupils may have replaced MVPA and sedentary time with LPA. The intervention group housed clusters of pupils showing variable responsiveness, justifying routine examination of subgroup variability in future studies.
Effects of KPC Variant and Porin Genotype on the
In Vitro
Activity of Meropenem-Vaborbactam against Carbapenem-Resistant
Enterobacteriaceae
Authors: Wilson William R. , Kline Ellen G. , Jones Chelsea E. , Morder Kristin T. , Mettus Roberta T. , Doi Yohei , Nguyen M. Hong , Clancy Cornelius J. , Shields Ryan K.
Published: January 2019

Meropenem-vaborbactam is a new agent with the potential to treat carbapenem-resistant
Enterobacteriaceae
(CRE) infections. We describe the
in vitro
activity of meropenem-vaborbactam against representative CRE genotypes and laboratory-engineered
Escherichia coli
isolates harboring mutant
bla
KPC
genes associated with ceftazidime-avibactam resistance.
Increased Resistance ofSalmonella entericaSerovar Typhimurium andEscherichia coliO157:H7 to 222-Nanometer Krypton-Chlorine Excilamp Treatment by Acid Adaptation
Authors: Kang Jun-Won , Kang Dong-Hyun
Published: January 2019

There is a need for novel, mercury-free UV lamp technology to replace germicidal lamps containing harmful mercury, which are routinely utilized for UV pasteurization of apple juice. In addition, consideration of the changes in response to antimicrobial treatments that may occur when pathogens are adapted to the acid in an apple juice matrix is critical to the practical application of this technology. Based on this, an investigation using 222-nm KrCl excilamp technology, an attractive alternative to mercury lamps, was conducted. Our study demonstrated increased resistance to 222-nm KrCl excilamp treatment as pathogens adapted to acids, and this was due to changes in reactivity to ROS with changes in the fatty acid composition of the cell membrane. Despite increased resistance, the 222-nm KrCl excilamp achieved pathogen reductions of 5 log or more at laboratory scale without affecting apple juice quality. These results provide valuable baseline data for application of 222-nm KrCl excilamps in the apple juice industry.
Genomic Diversity, Virulence, and Antimicrobial Resistance ofKlebsiella pneumoniaeStrains from Cows and Humans
Authors: Yang Yongqiang , Higgins Catherine H. , Rehman Ibraheem , Galvao Klibs N. , Brito Ilana L. , Bicalho Marcela L. , Song Jeongmin , Wang Hongning , Bicalho Rodrigo C.
Published: January 2019

We demonstrate here the genetic diversity ofK. pneumoniaeisolates from dairy cows and the mixed phylogenetic lineages between bovine and human isolates. The ferric uptake operonkfuABCgenes were more prevalent in strains from clinical mastitis cows. Furthermore, we report the emergence of an IncN-type plasmid carrying theblaCTX-M-1andmph(A) genes among dairy farms in the United States. Our study evaluated the genomic diversity of the bovine and human isolates, and the findings uncovered different profiles of virulence determinants among bovine and humanK. pneumoniaeisolates at the genome population level.
Rapid and Simple Universal
Escherichia coli
Genotyping Method Based on Multiple-Locus Variable-Number Tandem-Repeat Analysis Using Single-Tube Multiplex PCR and Standard Gel Electrophoresis
Authors: Caméléna François , Birgy André , Smail Yasmine , Courroux Céline , Mariani-Kurkdjian Patricia , Le Hello Simon , Bonacorsi Stéphane , Bidet Philippe
Published: January 2019

Fast typing methods that can easily and accurately distinguish clonal groups and unrelated isolates are of particular interest for microbiologists confronted with outbreaks or performing epidemiological studies. Highly discriminatory universal methods, like PFGE, optical mapping, or WGS, are expensive and/or time-consuming. MLST is useful for phylogeny but is less discriminatory and requires sequencing facilities. PCR methods, which are fast and easy to perform, also have drawbacks. Random PCRs and REP-PCR are universal but lack reproducibility. Other PCR methods may lack the discriminatory power to differentiate isolates during outbreaks. MLVA combines the advantages of PCR methods with a high discriminatory power but in its standard form requires sequencing capillary electrophoresis. The method that we have developed combines the advantages of standard PCR (simple, fast, and inexpensive) with the high discriminatory power of MLVA and permits the typing of all
E. coli
isolates (either intestinal or extraintestinal pathogenic isolates as well as commensal isolates).
Selectivity among Anti-σ Factors by
Mycobacterium tuberculosis
ClpX Influences Intracellular Levels of Extracytoplasmic Function σ Factors
Authors: Joshi Anuja C. , Kaur Prabhjot , Nair Radhika K. , Lele Deepti S. , Nandicoori Vinay Kumar , Gopal Balasubramanian
Published: January 2019

The ability of
Mycobacterium tuberculosis
to quickly adapt to changing environmental stimuli occurs by maintaining protein homeostasis. Extracytoplasmic function (ECF) σ factors play a significant role in coordinating the transcription profile to changes in environmental conditions. Release of the σ factor from the anti-σ is governed by the ClpXP2P1 assembly.
M. tuberculosis
ECF anti-σ factors have an
ssrA
-like degron for targeted degradation. A point mutation in the degron leads to differences in ClpX-mediated proteolysis and affects the cellular abundance of ECF σ factors. ClpX activity thus synchronizes changes in gene expression with environmental stimuli affecting
M. tuberculosis
physiology.
Natural Inhibitor of Human Cytomegalovirus in Human Seminal Plasma
Authors: Lippold Sina , Braun Berenike , Krüger Franziska , Harms Mirja , Müller Janis A. , Groß Rüdiger , Münch Jan , von Einem Jens
Published: January 2019

The role of semen in sexual transmission of human cytomegalovirus (HCMV) is currently unclear. This is surprising, as HCMV is frequently detected in this body fluid and infection is of high danger for neonates and pregnant women. In this study, we found that seminal plasma (SP) dose dependently inhibited HCMV infection. The infection inhibition was specific for HCMV, as other viruses, such as human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus 2 (HSV-2), were not inhibited by SP. SP must contain a soluble, heat-resistant factor that limits attachment of HCMV particles to cells, probably by interaction with the trimeric glycoprotein complex gH/gL/gO. This novel virus-host interaction could possibly limit transmission of HCMV via semen during sexual intercourse.
The Human CD4+T Cell Response against Mumps Virus Targets a Broadly Recognized Nucleoprotein Epitope
Authors: de Wit Jelle , Emmelot Maarten E. , Poelen Martien C. M. , Lanfermeijer Josien , Han Wanda G. H. , van Els Cécile A. C. M. , Kaaijk Patricia
Published: January 2019

Recent outbreaks of mumps among vaccinated young adults have been reported worldwide. Humoral responses against mumps virus (MuV) are well characterized, although no correlate of protection has been elucidated, stressing the need to better understand cellular MuV-specific immunity. In this study, we identified the first MuV T cell epitope, which is derived from the viral nucleoprotein (MuV-N) and was recognized by a cytotoxic/Th1 CD4+T cell clone that was isolated from a mumps case. Moreover, the epitope was predicted to bind a broad variety of common HLA-DRB1 alleles, which was confirmed by the epitope-specific cytotoxic/Th1 CD4+T cell responses observed in multiple mumps cases with various HLA-DRB1 genotypes. The identified epitope is completely conserved among various mumps strains. These findings qualify this promiscuous MuV T cell epitope as a useful tool for further in-depth exploration of MuV-specific T cell immunity after natural mumps virus infection or induced by vaccination.
Unique Transcriptional Architecture in Airway Epithelial Cells and Macrophages Shapes Distinct Responses following Influenza Virus Infection
Ex Vivo
Authors: Ma Joel Z. , Ng Wy Ching , Zappia Luke , Gearing Linden J. , Olshansky Moshe , Pham Kym , Cheong Karey , Hsu Arthur , Turner Stephen J. , Wijburg Odilia , Londrigan Sarah L. , Brooks Andrew G. , Reading Patrick C.
Published: January 2019

Airway epithelial cells (AEC) and airway macrophages (AM) represent major targets of influenza A virus (IAV) infection in the lung, yet the two cell types respond very differently to IAV infection. We have used RNA sequencing to define the host transcriptional responses in each cell type under steady-state conditions as well as following IAV infection. To do this, different cell subsets isolated from the lungs of mock- and IAV-infected mice were subjected to RNA sequencing. Under steady-state conditions, AM and AEC express distinct transcriptional activities, consistent with distinct physiological roles in the airways. Not surprisingly, these cells also exhibited major differences in transcriptional responses following IAV infection. These studies shed light on how the different transcriptional architectures of airway cells from two different lineages drive transcriptional responses to IAV infection.
US3 Kinase-Mediated Phosphorylation of Tegument Protein VP8 Plays a Critical Role in the Cellular Localization of VP8 and Its Effect on the Lipid Metabolism of Bovine Herpesvirus 1-Infected Cells
Authors: Zhang Kuan , Donovan Tara , Sucharita Soumya , Brownlie Robert , Snider Marlene , Tikoo Suresh K. , van Drunen Littel-van den Hurk Sylvia
Published: January 2019

Nuclear localization signals (NLSs) and nuclear export signals (NESs) are important elements directing VP8 to the desired locations in the BoHV-1-infected cell. In this study, a critical regulator that switches the nuclear and cytoplasmic localization of VP8 in BoHV-1-infected cells was identified. BoHV-1 used viral kinase US3 to regulate the cellular localization of VP8. Early during BoHV-1 infection VP8 was localized in the nucleus, where it performs various functions; once US3 was expressed, phosphorylated VP8 was cytoplasmic and ultimately accumulated in the
cis
-Golgi apparatus, presumably to be incorporated into virions. The Golgi localization of VP8 was only observed in virus-infected cells and not in US3-cotransfected cells, suggesting that this is mediated by other viral factors. Interestingly, VP8 was shown to cause increased cholesterol levels, which is a novel function for VP8 and a potential strategy to supply lipid for viral replication.
Candidalysin Crucially Contributes to Nlrp3 Inflammasome Activation by Candida albicans Hyphae
Authors: Rogiers Ona , Frising Ulrika C. , Kucharíková Soňa , Jabra-Rizk Mary Ann , van Loo Geert , Van Dijck Patrick , Wullaert Andy
Published: January 2019

Candidiasis is a potentially lethal condition that is caused by systemic dissemination of
Candida albicans
, a common fungal commensal residing mostly on mucosal surfaces. The transition of
C. albicans
from an innocuous commensal to an opportunistic pathogen goes hand in hand with its morphological transformation from a fungus to a hyphal appearance. On the one hand, the latter manifestation enables
C. albicans
to penetrate tissues, while on the other hand, the expression of many hypha-specific genes also endows it with the capacity to trigger particular cytokine responses. The Nlrp3 inflammasome is a crucial component of the innate immune system that provokes release of the IL-1β cytokine from myeloid cells upon encountering
C. albicans
hyphae. Our study reveals the peptide candidalysin as one of the hypha-derived drivers of Nlrp3 inflammasome responses in primary macrophages and, thus, contributes to better understanding the fungal mechanisms that determine the pathogenicity of
C. albicans
.
Physical Determinants of Amyloid Assembly in Biofilm Formation
Authors: Andreasen Maria , Meisl Georg , Taylor Jonathan D. , Michaels Thomas C. T. , Levin Aviad , Otzen Daniel E. , Chapman Matthew R. , Dobson Christopher M. , Matthews Steve J. , Knowles Tuomas P. J.
Published: January 2019

Biofilms are generated by bacteria, embedded in the formed extracellular matrix. The biofilm's function is to improve the survival of a bacterial colony through, for example, increased resistance to antibiotics or other environmental stresses. Proteins secreted by the bacteria act as a major structural component of this extracellular matrix, as they self-assemble into highly stable amyloid fibrils, making the biofilm very difficult to degrade by physical and chemical means once formed. By studying the self-assembly mechanism of the fibrils from their monomeric precursors in two unrelated bacteria, our experimental and theoretical approaches shed light on the mechanism of functional amyloid assembly in the context of biofilm formation. Our results suggest that fibril formation may be a rate-limiting step in biofilm formation, which in turn has implications on the protein self-assembly reaction as a target for potential antibiotic drugs.
Nonsteroidal Anti-inflammatory Drugs Alter the Microbiota and Exacerbate
Clostridium difficile
Colitis while Dysregulating the Inflammatory Response
Authors: Maseda Damian , Zackular Joseph P. , Trindade Bruno , Kirk Leslie , Roxas Jennifer Lising , Rogers Lisa M. , Washington Mary K. , Du Liping , Koyama Tatsuki , Viswanathan V. K. , Vedantam Gayatri , Schloss Patrick D. , Crofford Leslie J. , Skaar Eric P. , Aronoff David M.
Published: January 2019

Clostridium difficile
infection (CDI) is a spore-forming anaerobic bacterium and leading cause of antibiotic-associated colitis. Epidemiological data suggest that use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk for CDI in humans, a potentially important observation given the widespread use of NSAIDs. Prior studies in rodent models of CDI found that NSAID exposure following infection increases the severity of CDI, but mechanisms to explain this are lacking. Here we present new data from a mouse model of antibiotic-associated CDI suggesting that brief NSAID exposure prior to CDI increases the severity of the infectious colitis. These data shed new light on potential mechanisms linking NSAID use to worsened CDI, including drug-induced disturbances to the gut microbiome and colonic epithelial integrity. Studies were limited to a single NSAID (indomethacin), so future studies are needed to assess the generalizability of our findings and to establish a direct link to the human condition.
Three
Toxoplasma gondii
Dense Granule Proteins Are Required for Induction of Lewis Rat Macrophage Pyroptosis
Authors: Wang Yifan , Cirelli Kimberly M. , Barros Patricio D. C. , Sangaré Lamba Omar , Butty Vincent , Hassan Musa A. , Pesavento Patricia , Mete Asli , Saeij Jeroen P. J.
Published: January 2019

Inflammasomes are major components of the innate immune system and are responsible for detecting various microbial and environmental danger signals. Upon invasion of Lewis rat macrophages, the parasite rapidly activates the NLRP1 inflammasome, resulting in pyroptosis and elimination of the parasite’s replication niche. The work reported here revealed that
Toxoplasma
GRA35, GRA42, and GRA43 are required for induction of Lewis rat macrophage pyroptosis. GRA42 and GRA43 mediate the correct localization of other GRAs, including GRA35, to the parasitophorous vacuole membrane. These three GRAs were also found to be important for parasite
in vivo
fitness in a
Toxoplasma
-susceptible rat strain, independently of their role in NLRP1 inflammasome activation, suggesting that they perform other important functions. Thus, this study identified three GRAs that mediate the induction of Lewis rat macrophage pyroptosis and are required for pathogenesis of the parasite.
Comparative Metabolomics and Transcriptomics Reveal Multiple Pathways Associated with Polymyxin Killing in Pseudomonas aeruginosa
Authors: Han Mei-Ling , Zhu Yan , Creek Darren J. , Lin Yu-Wei , Gutu Alina D. , Hertzog Paul , Purcell Tony , Shen Hsin-Hui , Moskowitz Samuel M. , Velkov Tony , Li Jian
Published: January 2019

Pseudomonas aeruginosa
has been highlighted by the recent WHO Global Priority Pathogen List due to multidrug resistance. Without new antibiotics, polymyxins remain a last-line therapeutic option for this difficult-to-treat pathogen. The emergence of polymyxin resistance highlights the growing threat to our already very limited antibiotic armamentarium and the urgency to understand the exact mechanisms of polymyxin activity and resistance. Integration of the correlative metabolomics and transcriptomics results in the present study discovered that polymyxin treatment caused significant perturbations in the biosynthesis of lipids, lipopolysaccharide, and peptidoglycan, central carbon metabolism, and oxidative stress. Importantly, lipid A modifications were surprisingly rapid in response to polymyxin treatment at clinically relevant concentrations. This is the first study to reveal the dynamics of polymyxin-induced cellular responses at the systems level, which highlights that combination therapy should be considered to minimize resistance to the last-line polymyxins. The results also provide much-needed mechanistic information which potentially benefits the discovery of new-generation polymyxins.
SAPHO syndrome with enthesopathy
Authors: Su Chin-Fang , Shen Yu-Chuan , Liao Hsien-Tzung , Tsai Chang-Youh
Published: January 2019

Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome was first described as chronic recurrent multifocal osteomyelitis. Because of its rarity, a thorough description of its clinical manifestations is lacking. Herein, we describe the clinical manifestations and imaging features, especially the enthesopathy in bilateral Achilles tendons, of a middle-aged Asian woman with SAPHO syndrome, who improved after diclofenac treatment.
Are dietary patterns differently associated with differentiated levels of mental health problems? Results from a large cross-sectional study among Iranian manufacturing employees
Authors: Heidari Zahra , Feizi Awat , Roohafza Hamidreza , Rabiei Katayoun , Sarrafzadegan Nizal
Published: January 2019

Objectives

The present study aimed to classify participants based on mental health problems profile and to evaluate its relationship with dietary patterns among Iranian manufacturing employees.

Design

Observational study with a cross-sectional design.

Setting

This study was conducted in Esfahan Steel Company, one of the biggest Iranian industrial manufacturing companies.

Participants

Complete data on 2942 manufacturing employees, with a mean (SD) age of 36.68 (7.31) years, were analysed.

Outcome measures

Hospital Anxiety and Depression Scale(HADA) and General Health Questionnaire (GHQ-12) were used to evaluate anxiety and depression and psychological distress, respectively.

Results

Three major dietary patterns, namely ‘western’, ‘healthy’ and ‘traditional’, were extracted using factor analysis. A two-class, one-factor structure was identified from study participants in terms of mental health problems profile based on the factor mixture model. Two identified classes were labelled as ‘low mental health problems’ (2683 manufacturing employees, 91.2%) and ‘high mental health problems’ (259 individuals, 8.8%). After adjusting for the impact of potential confounders, manufacturing employees in the highest tertile of healthy dietary pattern had lower odds of being in the high mental health problems profile class (OR=0.67, 95% CI 0.49 to 0.92). In contrast, greater adherence to Western and traditional dietary patterns was associated with increased odds of being in the high mental health problems class (OR=1.66, 95% CI: 1.18 to 2.35 and OR=1.52, 95% CI :1.10 to 2.11, respectively).

Conclusions

Our study provided informative pathways on the association of dietary patterns and mental health among manufacturing employees. The findings can be used by workplace health promotion policymakers in improving mental health in such study population. Interventional and prospective studies that investigate the effects of change in dietary patterns on the mental health of manufacturing employees are suggested.
Predictive and spatial analysis for estimating the impact of sociodemographic factors on contraceptive use among women living with HIV/AIDS (WLWHA) in Kenya: Implications for policies and practice
Authors: Okoli Menkeoma Laura , Alao Samuel , Ojukwu Somtochukwu , Emechebe Nnadozie C , Ikhuoria Asuelimen , Kip Kevin E
Published: January 2019

Background

Despite the availability and knowledge of various contraceptive methods, consistent utilisation in women living with HIV/AIDS (WLWHA) within the reproductive age group remains below the Sustainable Development Goals (SDGs) and Family Planning 2020 goals. This study examines the association between sociodemographic factors and contraceptive use including the effect of clustering tendencies of these factors on contraceptive usage among WLWHA in Kenya.

Methods

Weighted multivariate logistic regression models were conducted to determine the association of sociodemographic factors on contraception use among WLWHA using the 2008–2009 Kenya Demographic Health Survey. Spatial autocorrelation techniques were used to explore clustering tendencies of these factors on contraception utilisation. Our study population included 304 HIV positive women, aged 15–49 years.

Results

Among 304 HIV-positive women in our study population, 92 (30.3%) reported using one method of contraception. Contraceptive use was significantly associated with wealth and education after adjustment for other sociodemographic variables. Women classified as having low and middle wealth index were less likely to use contraceptives (OR=0.17, 95% CI 0.07 to 0.43; OR=0.33, 95% CI 0.11 to 0.98, respectively) compared with women classified as having high wealth index. Similarly, women with primary education only were less likely to use contraceptives compared with women with secondary or higher education (OR=0.42, 95% CI 0.18 to 0.98). Spatial autocorrelation revealed significant positive clusters with weak clustering tendencies of non-contraceptive use among different levels of wealth index and education within different regions of Kenya.

Conclusion

These findings underscores the need for intervention programmes to further target socially disadvantaged WLWHA, which is necessary for achieving the SDGs.
Burden of heart failure in Flemish general practices: a registry-based study in the Intego database
Authors: Smeets Miek , Vaes Bert , Mamouris Pavlos , Van Den Akker Marjan , Van Pottelbergh Gijs , Goderis Geert , Janssens Stefan , Aertgeerts Bert , Henrard Séverine
Published: January 2019

Objectives

To assess the prevalence and incidence of heart failure (HF) stages A to C/D and their evolution over a 16-year period. Additionally, trends in comorbidities and cardiovascular (CV) treatment in patients with HF were studied in the same period.

Design

Registry-based study.

Setting

Primary care, Flanders, Belgium.

Participants

Data were obtained from Intego, a morbidity registration network in which 111 general practitioners of 48 practices collaborate. In the study period between 2000 and 2015, data from 165 796 unique patients aged 45 years and older were available.

Outcome measures

Prevalence and incidence were calculated for HF stage A, B and C/D by gender. Additionally, the trend in age-standardised prevalence and incidence rates between 2000 and 2015 was analysed with joint-point regression. The same model was used to study trends in comorbidity profiles in incident HF cases and trends in cardiovascular medication in prevalent HF cases.

Results

We found a downward trend in the incidence and prevalence of HF stage C/D in Flemish general practice between 2000 and 2015, whereas the prevalence and incidence of stage A and B increased. The burden of comorbidities in incident HF cases increased during the study period, as shown by an increasing disease count (p<0.001). The prescription of cardiovascular medication such as renin-angiotensin-aldosterone system blockade, β-blockers and statins showed a sharp increase in the first part of the study period (2000–2008).

Conclusion

Age-standardised incidence and prevalence of HF stage C/D showed a slightly downward trend over the past 16 years, probably due to the sharp increase in cardiovascular treatment. However, the increasing age-standardised incidence and prevalence of stage A and B, as precursors of symptomatic HF, together with a rising comorbid burden, highlights the challenges we are still facing.