bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients
Authors: Michalovich David , Rodriguez-Perez Noelia , Smolinska Sylwia , Pirozynski Michal , Mayhew David , Uddin Sorif , Van Horn Stephanie , Sokolowska Milena , Altunbulakli Can , Eljaszewicz Andrzej , Pugin Benoit , Barcik Weronika , Kurnik-Lucka Magdalena , Saunders Ken A. , Simpson Karen D. , Schmid-Grendelmeier Peter , Ferstl Ruth , Frei Remo , Sievi Noriane , Kohler Malcolm , Gajdanowicz Pawel , Graversen Katrine B. , Lindholm Bøgh Katrine , Jutel Marek , Brown James R. , Akdis Cezmi A. , Hessel Edith M. , O’Mahony Liam
Published: December 2019

In order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma. Similarly, obesity or asthma induced changes in the composition of the microbiota, while an additive effect is observed in obese asthma patients. Asthma disease severity is negatively correlated with fecal Akkermansia muciniphila levels. Administration of A. muciniphila to murine models significantly reduces airway hyper-reactivity and airway inflammation. Changes in immunological processes and microbiota composition are accentuated in obese asthma patients due to the additive effects of both disease states, while A. muciniphila may play a non-redundant role in patients with a severe asthma phenotype.
Publisher Correction: Automatic Choroid Layer Segmentation from Optical Coherence Tomography Images Using Deep Learning
Authors: Masood Saleha , Fang Ruogu , Li Ping , Li Huating , Sheng Bin , Mathavan Akash , Wang Xiangning , Yang Po , Wu Qiang , Qin Jing , Jia Weiping
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The effect of ω-3 polyunsaturated fatty acids on the liver lipidome, proteome and bile acid profile: parenteral versus enteral administration
Authors: Bechynska Kamila , Daskova Nikola , Vrzackova Nikola , Harant Karel , Heczková Marie , Podzimkova Katerina , Bratova Miriam , Dankova Helena , Berkova Zuzana , Kosek Vit , Zelenka Jaroslav , Hajslova Jana , Sedlacek Radislav , Suttnar Jiri , Hlavackova Alzbeta , Bartonova Lenka , Cahova Monika
Published: December 2019

Parenteral nutrition (PN) is often associated with the deterioration of liver functions (PNALD). Omega-3 polyunsaturated fatty acids (PUFA) were reported to alleviate PNALD but the underlying mechanisms have not been fully unraveled yet. Using omics´ approach, we determined serum and liver lipidome, liver proteome, and liver bile acid profile as well as markers of inflammation and oxidative stress in rats administered either ω-6 PUFA based lipid emulsion (Intralipid) or ω-6/ω-3 PUFA blend (Intralipid/Omegaven) via the enteral or parenteral route. In general, we found that enteral administration of both lipid emulsions has less impact on the liver than the parenteral route. Compared with parenterally administered Intralipid, PN administration of ω-3 PUFA was associated with 1. increased content of eicosapentaenoic (EPA)- and docosahexaenoic (DHA) acids-containing lipid species; 2. higher abundance of CYP4A isoenzymes capable of bioactive lipid synthesis and the increased content of their potential products (oxidized EPA and DHA); 3. downregulation of enzymes involved CYP450 drug metabolism what may represent an adaptive mechanism counteracting the potential negative effects (enhanced ROS production) of PUFA metabolism; 4. normalized anti-oxidative capacity and 5. physiological BAs spectrum. All these findings may contribute to the explanation of ω-3 PUFA protective effects in the context of PN.
Development of Aedes aegypti (Diptera: Culicidae) mosquito larvae in high ammonia sewage in septic tanks causes alterations in ammonia excretion, ammonia transporter expression, and osmoregulation
Authors: Durant Andrea C. , Donini Andrew
Published: December 2019

Larvae of the disease vector mosquito, Aedes aegypti (L.) readily develop in ammonia rich sewage in the British Virgin Islands. To understand how the larvae survive in ammonia levels that are lethal to most animals, an examination of ammonia excretory physiology in larvae collected from septic-water and freshwater was carried out. A. aegypti larvae were found to be remarkably plastic in dealing with high external ammonia through the modulation of NH4+ excretion at the anal papillae, measured using the scanning ion-selective electrode technique (SIET), and NH4+ secretion in the primary urine by the Malpighian tubules when developing in septicwater. Ammonia transporters, Amt and Rh proteins, are expressed in ionoregulatory and excretory organs, with increases in Rh protein, Na+-K+-ATPase, and V-type-H+-ATPase expression observed in the Malpighian tubules, hindgut, and anal papillae in septic-water larvae. A comparative approach using laboratory A. aegypti larvae reared in high ammonia septic-water revealed similar responses to collected A. aegypti with regard to altered ammonia secretion and hemolymph ion composition. Results suggest that the observed alterations in excretory physiology of larvae developing in septic-water is a consequence of the high ammonia levels and that A. aegypti larvae may rely on ammonia transporting proteins coupled to active transport to survive in septic-water.
Genetic variations in olfactory receptor gene OR2AG2 in a large multigenerational family with asthma
Authors: Chakraborty Samarpana , Dakle Pushkar , Sinha Anirban , Vishweswaraiah Sangeetha , Nagori Aditya , Salimath Shivalingaswamy , Prakash Y. S. , Lodha R. , Kabra S. K. , Ghosh Balaram , Faruq Mohammed , Mahesh P. A. , Agrawal Anurag
Published: December 2019

It is estimated from twin studies that heritable factors account for at-least half of asthma-risk, of which genetic variants identified through population studies explain only a small fraction. Multi-generation large families with high asthma prevalence can serve as a model to identify highly penetrant genetic variants in closely related individuals that are missed by population studies. To achieve this, a four-generation Indian family with asthma was identified and recruited for examination and genetic testing. Twenty subjects representing all generations were selected for whole genome genotyping, of which eight were subjected to exome sequencing. Non-synonymous and deleterious variants, segregating with the affected individuals, were identified by exome sequencing. A prioritized deleterious missense common variant in the olfactory receptor gene OR2AG2 that segregated with a risk haplotype in asthma, was validated in an asthma cohort of different ethnicity. Phenotypic tests were conducted to verify expected deficits in terms of reduced ability to sense odors. Pathway-level relevance to asthma biology was tested in model systems and unrelated human lung samples. Our study suggests that OR2AG2 and other olfactory receptors may contribute to asthma pathophysiology. Genetic studies on large families of interest can lead to efficient discovery.
17α Estradiol promotes plasticity of spared inputs in the adult amblyopic visual cortex
Authors: Sengupta Deepali C. , Lantz Crystal L. , Rumi M. A. Karim , Quinlan Elizabeth M.
Published: December 2019

The promotion of structural and functional plasticity by estrogens is a promising approach to enhance central nervous system function in the aged. However, how the sensitivity to estrogens is regulated across brain regions, age and experience is poorly understood. To ask if estradiol treatment impacts structural and functional plasticity in sensory cortices, we examined the acute effect of 17α-Estradiol in adult Long Evans rats following chronic monocular deprivation, a manipulation that reduces the strength and selectivity of deprived eye vision. Chronic monocular deprivation decreased thalamic input from the deprived eye to the binocular visual cortex and accelerated short-term depression of the deprived eye pathway, but did not change the density of excitatory synapses in primary visual cortex. Importantly, we found that the classical estrogen receptors ERα and ERβ were robustly expressed in the adult visual cortex, and that a single dose of 17α-Estradiol reduced the expression of the calcium-binding protein parvalbumin, decreased the integrity of the extracellular matrix and increased the size of excitatory postsynaptic densities. Furthermore, 17α-Estradiol enhanced experience-dependent plasticity in the amblyopic visual cortex, by promoting response potentiation of the pathway served by the non-deprived eye. The promotion of plasticity at synapses serving the non-deprived eye may reflect selectivity for synapses with an initially low probability of neurotransmitter release, and may inform strategies to remap spared inputs around a scotoma or a cortical infarct.
Selective synthesis of spirobiindanes, alkenyl chlorides, and monofluoroalkenes from unactivated gem-difluoroalkanes controlled by aluminum-based Lewis acids
Authors: Wang Jiandong , Ogawa Yuta , Shibata Norio
Published: December 2019

The highly selective synthesis of spirobiindanes, alkenyl chlorides, and monofluoroalkenes via the cleavage of inert C(sp3)–F bonds in unactivated gem-difluoroalkanes using readily available and inexpensive aluminum-based Lewis acids of low toxicity is reported. The selectivity of this reaction can be controlled by modifying the substituents on the central aluminum atom of the promoter. An intramolecular cascade Friedel-Crafts alkylation of unactivated gem-difluorocarbons can be achieved using a stoichiometric amount of AlCl3. The subsequent synthesis of alkenyl chlorides via F/Cl exchange followed by an elimination can be accomplished using AlEt2Cl as a fluoride scavenger and halogen source. The defluorinative elimination of acyclic and cyclic gem-difluorocarbons to give monofluoroalkenes can be achieved using AlEt3.
Tunable High Spatio-Spectral Purity Undulator Radiation from a Transported Laser Plasma Accelerated Electron Beam
Authors: Ghaith A. , Oumbarek D. , Roussel E. , Corde S. , Labat M. , André T. , Loulergue A. , Andriyash I. A. , Chubar O. , Kononenko O. , Smartsev S. , Marcouillé O. , Kitégi C. , Marteau F. , Valléau M. , Thaury C. , Gautier J. , Sebban S. , Tafzi A. , Blache F. , Briquez F. , Tavakoli K. , Carcy A. , Bouvet F. , Dietrich Y. , Lambert G. , Hubert N. , El Ajjouri M. , Polack F. , Dennetière D. , Leclercq N. , Rommeluère P. , Duval J.-P. , Sebdaoui M. , Bourgoin C. , Lestrade A. , Benabderrahmane C. , Vétéran J. , Berteaud P. , De Oliveira C. , Goddet J. P. , Herbeaux C. , Szwaj C. , Bielawski S. , Malka V. , Couprie M.-E.
Published: December 2019

Undulator based synchrotron light sources and Free Electron Lasers (FELs) are valuable modern probes of matter with high temporal and spatial resolution. Laser Plasma Accelerators (LPAs), delivering GeV electron beams in few centimeters, are good candidates for future compact light sources. However the barriers set by the large energy spread, divergence and shot-to-shot fluctuations require a specific transport line, to shape the electron beam phase space for achieving ultrashort undulator synchrotron radiation suitable for users and even for achieving FEL amplification. Proof-of-principle LPA based undulator emission, with strong electron focusing or transport, does not yet exhibit the full specific radiation properties. We report on the generation of undulator radiation with an LPA beam based manipulation in a dedicated transport line with versatile properties. After evidencing the specific spatio-spectral signature, we tune the resonant wavelength within 200–300 nm by modification of the electron beam energy and the undulator field. We achieve a wavelength stability of 2.6%. We demonstrate that we can control the spatio-spectral purity and spectral brightness by reducing the energy range inside the chicane. We have also observed the second harmonic emission of the undulator.
A reporter mouse for non-invasive detection of toll-like receptor ligands induced acute phase responses
Authors: Huang Chun-Fang , Chiu Shang-Yi , Huang Hung-Wen , Cheng Bing-Ho , Pan Hsiu-Min , Huang Wei-Lun , Chang Hsiao-Hui , Liao Chia-Chi , Jiang Si-Tse , Su Yu-Chia
Published: December 2019

The acute phase response (APR) is a systemic first-line defense against challenges including infection, trauma, stress, and neoplasia. Alteration of acute phase protein (APP) levels in plasma is the most important change during acute phase response. C-reactive protein (CRP), which increases dramatically during inflammation onset, is an indicator of inflammation. To monitor the process of APR, we generated human CRP promoter-driven luciferase transgenic (hCRP-Luc) mice to quantify the hCRP promoter activationin vivo. The naïve female hCRP-Luc mice express low basal levels of liver bioluminescence, but the naïve male hCRP-Luc mice do not. Thus, female hCRP-Luc mice are suitable for monitoring the process of APR. The liver bioluminescence of female hCRP-Luc mice can be induced by several toll-like receptor (TLR) ligands. The expression of liver bioluminescence was highly sensitive to endotoxin stimulation in a dose-dependent manner. On-off-on bioluminescence response was noted in female hCRP-Luc mice upon two endotoxin stimulations one month apart. The LPS-induced bioluminescence of the female hCRP-Luc mice was IL-6-mediated and associated with APP alpha-1-acid glycoprotein expression. In conclusion, the female hCRP-Luc mouse is a non-invasive, sensitive and reusable reporter tool for APR.
Unsupervised Pre-training of a Deep LSTM-based Stacked Autoencoder for Multivariate Time Series Forecasting Problems
Authors: Sagheer Alaa , Kotb Mostafa
Published: December 2019

Currently, most real-world time series datasets are multivariate and are rich in dynamical information of the underlying system. Such datasets are attracting much attention; therefore, the need for accurate modelling of such high-dimensional datasets is increasing. Recently, the deep architecture of the recurrent neural network (RNN) and its variant long short-term memory (LSTM) have been proven to be more accurate than traditional statistical methods in modelling time series data. Despite the reported advantages of the deep LSTM model, its performance in modelling multivariate time series (MTS) data has not been satisfactory, particularly when attempting to process highly non-linear and long-interval MTS datasets. The reason is that the supervised learning approach initializes the neurons randomly in such recurrent networks, disabling the neurons that ultimately must properly learn the latent features of the correlated variables included in the MTS dataset. In this paper, we propose a pre-trained LSTM-based stacked autoencoder (LSTM-SAE) approach in an unsupervised learning fashion to replace the random weight initialization strategy adopted in deep LSTM recurrent networks. For evaluation purposes, two different case studies that include real-world datasets are investigated, where the performance of the proposed approach compares favourably with the deep LSTM approach. In addition, the proposed approach outperforms several reference models investigating the same case studies. Overall, the experimental results clearly show that the unsupervised pre-training approach improves the performance of deep LSTM and leads to better and faster convergence than other models.
Advanced P Wave Detection in Ecg Signals During Pathology: Evaluation in Different Arrhythmia Contexts
Authors: Maršánová Lucie , Němcová Andrea , Smíšek Radovan , Vítek Martin , Smital Lukáš
Published: December 2019

Reliable P wave detection is necessary for accurate and automatic electrocardiogram (ECG) analysis. Currently, methods for P wave detection in physiological conditions are well-described and efficient. However, methods for P wave detection during pathology are not generally found in the literature, or their performance is insufficient. This work introduces a novel method, based on a phasor transform, as well as innovative rules that improve P wave detection during pathology. These rules are based on the extraction of a heartbeats’ morphological features and knowledge of heart manifestation during both physiological and pathological conditions. To properly evaluate the performance of the proposed algorithm in pathological conditions, a standard database with a sufficient number of reference P wave positions is needed. However, such a database did not exist. Thus, ECG experts annotated 12 chosen pathological records from the MIT-BIH Arrhythmia Database. These annotations are publicly available via Physionet. The algorithm performance was also validated using physiological records from the MIT-BIH Arrhythmia and QT databases. The results for physiological signals were Se = 98.42% and PP = 99.98%, which is comparable to other methods. For pathological signals, the proposed method reached Se = 96.40% and PP = 85.84%, which greatly outperforms other methods. This improvement represents a huge step towards fully automated analysis systems being respected by ECG experts. These systems are necessary, particularly in the area of long-term monitoring.
Differential impedance spectra analysis reveals optimal actuation frequency in bulk mode acoustophoresis
Authors: Vitali Valentina , Core Giulia , Garofalo Fabio , Laurell Thomas , Lenshof Andreas
Published: December 2019

This work reports a method to select the optimal working frequency in transversal bulk resonator acoustophoretic devices by electrical impedance measurements. The impedance spectra of acoustophoretic devices are rich in spurious resonance peaks originating from different resonance modes in the system not directly related to the channel resonance, why direct measurement of the piezoelectric transducer impedance spectra is not a viable strategy. This work presents, for the first time, that the resonance modes of microchip integrated acoustophoresis channels can be identified by sequentially measuring the impedance spectra of the acoustophoretic device when the channel is filled with two different fluids and subsequently calculate the Normalized Differential Spectrum (NDS). Seven transversal bulk resonator acoustophoretic devices of different materials and designs were tested with successful results. The developed method enables a rapid, reproducible and precise determination of the optimal working frequency.
The amount of available food affects diurnal locomotor activity in migratory songbirds during stopover
Authors: Ferretti Andrea , Maggini Ivan , Lupi Sara , Cardinale Massimiliano , Fusani Leonida
Published: December 2019

Migratory passerine birds fly long distances twice a year alternating nocturnal flights with stopovers to rest and replenish energy stores. The duration of each stopover depends on several factors including internal clocks, meteorological conditions, and environmental factors such as availability of food. Foraging entails energetic costs, and if birds need to refuel efficiently, they should modulate their activity in relation to food availability. We investigated how food availability influences locomotor activity in migrating birds of six passerine species at a spring stopover site in the central Mediterranean Sea. We selected birds with low fat scores which we expected to be strongly motivated to refuel. We simulated stopover sites of different quality by providing temporarily caged birds with different amounts of food to simulate scarce to abundant food. We analysed the diurnal locomotory activity as a proxy for food searching effort. Low food availability resulted in an increased diurnal locomotor activity in almost all species, while all birds showed low intensity of nocturnal migratory restlessness. In conclusion, our study shows that food availability in an important determinant of behaviour of migratory birds at stopover sites.
Heat pain modulation with virtual water during a virtual hand illusion
Authors: Käthner Ivo , Bader Thomas , Pauli Paul
Published: December 2019

Immersive virtual reality is a powerful method to modify the environment and thereby influence experience. The present study used a virtual hand illusion and context manipulation in immersive virtual reality to examine top-down modulation of pain. Participants received painful heat stimuli on their forearm and placed an embodied virtual hand (co-located with their real one) under a virtual water tap, which dispensed virtual water under different experimental conditions. We aimed to induce a temperature illusion by a red, blue or white light suggesting warm, cold or no virtual water. In addition, the sense of agency was manipulated by allowing participants to have high or low control over the virtual hand’s movements. Most participants experienced a thermal sensation in response to the virtual water and associated the blue and red light with cool/cold or warm/hot temperatures, respectively. Importantly, the blue light condition reduced and the red light condition increased pain intensity and unpleasantness, both compared to the control condition. The control manipulation influenced the sense of agency, but did not influence pain ratings. The large effects revealed in our study suggest that context effects within an embodied setting in an immersive virtual environment should be considered within VR based pain therapy.
Malaria resurgence after significant reduction by mass drug administration on Ngodhe Island, Kenya
Authors: Kagaya Wataru , Gitaka Jesse , Chan Chim W. , Kongere James , Md Idris Zulkarnain , Deng Changsheng , Kaneko Akira
Published: December 2019

Although WHO recommends mass drug administration (MDA) for malaria elimination, further evidence is required for understanding the obstacles for the optimum implementation of MDA. Just before the long rain in 2016, two rounds of MDA with artemisinin/piperaquine (Artequick) and low-dose primaquine were conducted with a 35-day interval for the entire population of Ngodhe Island (~500 inhabitants) in Lake Victoria, Kenya, which is surrounded by areas with moderate and high transmission. With approximately 90% compliance, Plasmodium prevalence decreased from 3% to 0% by microscopy and from 10% to 2% by PCR. However, prevalence rebounded to 9% by PCR two months after conclusion of MDA. Besides the remained local transmission, parasite importation caused by human movement likely contributed to the resurgence. Analyses of 419 arrivals to Ngodhe between July 2016 and September 2017 revealed Plasmodium prevalence of 4.6% and 16.0% by microscopy and PCR, respectively. Risk factors for infection among arrivals included age (0 to 5 and 11 to 15 years), and travelers from Siaya County, located to the north of Ngodhe Island. Parasite importation caused by human movement is one of major obstacles to sustain malaria elimination, suggesting the importance of cross-regional initiatives together with local vector control.
Prevalence, awareness, treatment, and control of hypertension in southwestern China
Authors: Huang Xiao-Bo , Zhang Yang , Wang Tzung-Dau , Liu Jian-Xiong , Yi Yan-Jing , Liu Ya , Xu Rong-Hua , Hu Yong-Mei , Chen Mao
Published: December 2019

This study investigated the prevalence, awareness, treatment, and control of hypertension and associated factors among urban adults in southwestern China. The study was conducted from 2013–2014 and used a multistage cluster sampling method to select a representative sample of 11,517 people in southwestern China, aged 35–79 years. Hypertension was defined as either systolic blood pressure of 140 mmHg or greater, diastolic blood pressure of 90 mm Hg or greater, or self-reported current treatment for hypertension with antihypertensive medications. In the study population, hypertension prevalence was found to be 38.4%, with rates of 40.0% and 37.5% for men and women, respectively (p = 0.03). Hypertension prevalence increased with age in both men and women (trend p both <0.01). Among hypertensive patients, 47.9% were aware of their hypertension, 40.1% were undergoing antihypertensive treatment, and 10.3% achieved BP control. A multiple-factor analysis revealed that age, male gender, low educational achievement, family history of hypertension, overweight or obesity, abdominal obesity, and hypertriglyceridemia were positively related to hypertension, while physical exercise was negatively related to hypertension. The prevalence of hypertension among urban adults aged 35 to 79 years in southwestern China was high, while levels of awareness, treatment, and control of hypertension were low. Multifaceted interventional measures are needed to solve the unmet needs.
Converging TLR9 and PI3Kgamma signaling induces sterile inflammation and organ damage
Authors: Lima Braulio Henrique Freire , Marques Pedro Elias , Gomides Lindisley Ferreira , Mattos Matheus Silvério , Kraemer Lucas , Queiroz-Junior Celso M. , Lennon Mark , Hirsch Emilio , Russo Remo Castro , Menezes Gustavo Batista , Hessel Edith M. , Amour Augustin , Teixeira Mauro Martins
Published: December 2019

Toll-like receptor 9 (TLR9) and Phosphatidylinositol-3-kinase gamma (PI3Kγ) are very important effectors of the immune response, however, the importance of such crosstalk for disease development is still a matter of discussion. Here we show that PI3Kγ is required for immune responses in which TLR9 is a relevant trigger. We demonstrate the requirement of PI3Kγ for TLR9-induced inflammation in a model of CpG-induced pleurisy. Such requirement was further observed in inflammatory models where DNA sensing via TLR9 contributes to disease, such as silicosis and drug-induced liver injury. Using adoptive transfer, we demonstrate that PI3Kγ is important not only in leukocytes but also in parenchymal cells for the progression of inflammation. We demonstrate this crosstalk between TLR9 and PI3Kγ in vitro using human PBMCs. The inhibition of PI3Kγ in CpG-stimulated PBMCs resulted in reduction of both cytokine production and phosphorylated Akt. Therefore, drugs that target PI3Kγ have the potential to treat diseases mediated by excessive TLR9 signalling.
Impact of Tilapia hepcidin 2-3 dietary supplementation on the gut microbiota profile and immunomodulation in the grouper (Epinephelus lanceolatus)
Authors: Ting Chen-Hung , Pan Chieh-Yu , Chen Yi-Chun , Lin Yu-Chun , Chen Tzong-Yueh , Rajanbabu Venugopal , Chen Jyh-Yih
Published: December 2019

Hepcidin regulates iron homeostasis and host-defense mechanisms, while the hepcidin-like protein, Tilapia hepcidin (TH)2-3, functions as an antimicrobial peptide (AMP). Since AMP dietary supplements may be used as alternatives to antibiotics in livestock, we tested the effects of recombinant (r)TH2-3 as a dietary supplement in grouper aquaculture. rTH2-3 was produced by aPichia pastorisexpression system and exhibited thermostability and broad-spectrum antimicrobial activity. The feed conversion ratio and feed efficiency were determined inEpinephelus lanceolatus(grouper) fed with rTH2-3-supplemented diet for 28 days. In addition, grouper showed enhanced superoxide dismutase (SOD) activity after rTH2-3 feeding compared to regular-diet-fed fish. Gut microbiota analysis revealed that microbial diversity was enhanced by feeding grouper with 1% rTH2-3. After challenging grouper withVibrio alginolyticus, differential regulation of immune-related genes in the liver and spleen was observed between the TH2-3 and regular-diet groups, including for genes associated with antimicrobial and pro-inflammatory functions, complement components, and major histocompatibility complex (Mhc). These findings suggest that overall immunity was improved. Thus, our results suggest long-term supplementation with rTH2-3 may be beneficial for aquacultured grouper. The beneficial effects of the supplement are likely based on changes in the commensal microbial community as well as immunomodulation.
Association between obstructive sleep apnoea and breast cancer: The Korean National Health Insurance Service Data 2007–2014
Authors: Choi Ji Ho , Lee Jae Yong , Han Kyung Do , Lim Young Chang , Cho Jae Hoon
Published: December 2019

Some studies have argued that obstructive sleep apnoea (OSA) increases the risk of breast cancer. However, the results are often conflicting. This study aimed to investigate associations between OSA and breast cancer incidence using the Korea National Health Insurance Service (KNHIS) database. This retrospective cohort study analyzed data from the KNHIS database. A total of 45,699 women (≥20 years of age) newly diagnosed with OSA between 2007 and 2014 were included. The control groups were a 5-fold, age-matched women who had not been diagnosed with OSA. Mean follow-up duration was 3.7 ± 2.3 years. The primary endpoint was newly diagnosed breast cancer. The breast cancer hazard ratio (95% confidence interval) was calculated for patients with OSA and compared with that of the control group. The incidence of breast cancer among patients with OSA was significantly higher than that among the controls (1.20 [1.04–1.39]). In particular, the incidence of breast cancer was higher among patients aged ≥65 years (1.72 [1.10–2.71]). The result suggests that OSA may be a risk factor for breast cancer in women.
Metabolomic Profiles of Bovine Mammary Epithelial Cells Stimulated by Lipopolysaccharide
Authors: Huang Yixin , Shen Liuhong , Jiang Jing , Xu Qipin , Luo Zhengzhong , Luo Qiao , Yu Shumin , Yao Xueping , Ren Zhihua , Hu Yanchun , Yang Yongxin , Cao Suizhong
Published: December 2019

Bovine mammary epithelial cells (bMECs) are the main cells of the dairy cow mammary gland. In addition to their role in milk production, they are effector cells of mammary immunity. However, there is little information about changes in metabolites of bMECs when stimulated by lipopolysaccharide (LPS). This study describes a metabolomics analysis of the LPS-stimulated bMECs to provide a basis for the identification of potential diagnostic screening biomarkers and possible treatments for bovine mammary gland inflammation. In the present study, bMECs were challenged with 500 ng/mL LPS and samples were taken at 0 h, 12 h and 24 h post stimulation. Metabolic changes were investigated using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF MS) with univariate and multivariate statistical analyses. Clustering and metabolic pathway changes were established by MetaboAnalyst. Sixty-three differential metabolites were identified, including glycerophosphocholine, glycerol-3-phosphate, L-carnitine, L-aspartate, glutathione, prostaglandin G2, α-linolenic acid and linoleic acid. They were mainly involved in eight pathways, including D-glutamine and D-glutamic acid metabolism; linoleic acid metabolism; α-linolenic metabolism; and phospholipid metabolism. The results suggest that bMECs are able to regulate pro-inflammatory, anti-inflammatory, antioxidation and energy-producing related metabolites through lipid, antioxidation and energy metabolism in response to inflammatory stimuli.
Altered monocytic phenotypes are linked with systemic inflammation and may be linked to mortality in dialysis patients
Authors: Brandt Sabine , Ewert Lara , Scurt Florian G. , Reichardt Charlotte , Lindquist Jonathan A. , Gorny Xenia , Isermann Berend , Mertens Peter R.
Published: December 2019

The major causes for increased morbidity and mortality among chronic kidney disease patients are cardiovascular diseases and infection. A causal link between an activated immune system and aggravated atherosclerosis has been postulated that skews the system towards inflammatory responses. Previously, we demonstrated a positive association of pro-inflammatory cytokines with monocytic Y-box binding protein-1 (YB-1) expression and vessel wall infiltration in hemodialysis patients. Here, we question whether the responsiveness and cytokine repertoire of monocytes is altered by pre-activation and how this correlates with survival. EDTA whole blood from hemodialysis patients (n = 45) and healthy controls (n = 34) was collected and leukocytes challenged with LPS. The distribution of monocyte subsets, YB-1acetyl content, and serum cytokine levels were determined. Compared to controls, dialysis patients have fewer classical (Mo1) and more intermediate (Mo2) and non-classical (Mo3) monocytes. In response to LPS, the Mo2 subset significantly increases (p < 0.001) in control subjects, but not in hemodialysis patients; increased CD86 expression indicates a positive response to LPS. Based on the changes within Mo2, subjects could be classified as responders or non-responders: 60% non-responders were seen in the dialysis cohort versus only 35% among healthy controls. YB-1 acetylation is higher in dialysis patients, independent of LPS stimulation. In this small cohort with 72 months follow-up period intracellular YB-1acetyl levels, IL-6, uPAR, and IP10 correlated with excess mortality in the dialysis cohort. Changes in YB-1 acetylation and serum cytokines may, at a given time point, possibly predict the long-term outcome and thus provide a legacy effect in hemodialysis patients.
Mapping species richness using opportunistic samples: a case study on ground-floor bryophyte species richness in the Belgian province of Limburg
Authors: Neyens Thomas , Diggle Peter J. , Faes Christel , Beenaerts Natalie , Artois Tom , Giorgi Emanuele
Published: December 2019

In species richness studies, citizen-science surveys where participants make individual decisions regarding sampling strategies provide a cost-effective approach to collect a large amount of data. However, it is unclear to what extent the bias inherent to opportunistically collected samples may invalidate our inferences. Here, we compare spatial predictions of forest ground-floor bryophyte species richness in Limburg (Belgium), based on crowd- and expert-sourced data, where the latter are collected by adhering to a rigorous geographical randomisation and data collection protocol. We develop a log-Gaussian Cox process model to analyse the opportunistic sampling process of the crowd-sourced data and assess its sampling bias. We then fit two geostatistical Poisson models to both data-sets and compare the parameter estimates and species richness predictions. We find that the citizens had a higher propensity for locations that were close to their homes and environmentally more valuable. The estimated effects of ecological predictors and spatial species richness predictions differ strongly between the two geostatistical models. Unknown inconsistencies in the sampling process, such as unreported observer’s effort, and the lack of a hypothesis-driven study protocol can lead to the occurrence of multiple sources of sampling bias, making it difficult, if not impossible, to provide reliable inferences.
Enlarged subarachnoid space on cranial ultrasound in preterm infants: Neurodevelopmental implication
Authors: Yum Sook Kyung , Im Soo Ah , Seo Yu Mi , Sung In Kyung
Published: December 2019

The role of enlarged subarachnoid space (ESS) in preterm infants has not been described in concrete. We aimed to evaluate whether ESS should be considered a risk factor potentially associated with adverse neurodevelopmental outcomes in prematurity. Electronic medical records of 197 preterm infants (median 32.1 weeks' gestation) including cranial ultrasound (cUS) images, head circumferences, and Korean Developmental Screening Tests for Infants and Children (K-DST) results at 18–24 months corrected age were reviewed. The clinical characteristics and K-DST results were compared in infants with and without ESS (sinocortical width > 3.5 mm). A multivariable logistic regression analysis was performed to identify potential risk factors associated with positive K-DST results. At a median corrected age of 39.0 weeks, 81/197 (41.1%) infants presented ESS. A significantly greater percent of infants in the ESS group screened positive on the K-DST than in the no ESS group (27.2% vs 12.1%, p = 0.007). Within the ESS group, micro-/macrocephaly at term-equivalent age was not different with regard to the K-DST results. From the multivariable logistic regression analysis, gestational age (p = 0.016, OR = 0.855, 95% CI = 0.753–0.971) and ESS (p = 0.019, OR = 1.310, 95% CI = 1.046–1.641) were two significant risk factors associated with positive K-DST results. ESS identified on cUS at term-equivalent age in preterm infants is associated with possible developmental delays. Macrocephaly at term-equivalent age does not guarantee a benign prognosis. Future studies are required to verify ESS as a potential marker for neurodevelopmental delay in preterm infants.
Monitoring of sausage products sold in Sichuan Province, China: a first comprehensive report on meat species’ authenticity determination
Authors: Song Qiuchi , Chen Yiwu , Zhao Liming , Ouyang Hongsheng , Song Jun
Published: December 2019

Presently, there is growing concern worldwide regarding the adulteration of meat products. However, no reports on determining meat authenticity have been reported in China. To verify labelling compliance and evaluate the existence of fraudulent practices, 250 sausage samples were purchased from local markets in Sichuan Province and analysed for the presence of chicken, pork, beef, duck and genetically modified soybean DNA using real-time and end-point PCR methods, providing a Chinese case study on the problem of world food safety. In total, 74.4% (186) of the samples were properly labelled, while the other 25.6% (64) were potentially adulterated samples, which involved three illicit practices: product removal, addition and substitution. The most common mislabelling was the illegal addition of, or contamination with, duck. Therefore, meat authenticity monitoring should be routinely conducted. Additionally, the strict implementation of the nation’s food safety laws, along with regular surveillance, should be compulsory to alleviate and deter meat adulteration.
Error associated with estimates of Minimum Infection Rate for Endemic West Nile Virus in areas of low mosquito trap density
Authors: Chakraborty S. , Smith R. L.
Published: December 2019

West Nile Virus (WNV) is a mosquito-borne infection that can cause serious illness in humans. Surveillance for WNV primarily focuses on a measure of infection prevalence in the Culex spp. mosquitos, its primary vectors, known as the Minimum Infection Rate (MIR). The calculation of MIR for a given area considers the number of mosquitos tested, but not the relative effort to collect mosquitos, leading to a potential underestimation of the uncertainty around the estimate. We performed Value of Information analysis on simulated data sets including a range of mosquito trap densities in two well-studied counties in Illinois between 2005 and 2016 to determine the relative error introduced into MIR associated with changing the density of mosquito traps. We found that low trap density increases the potential for error in MIR estimation, and that it does so synergistically with low true MIR values. We propose that these results could be used to better estimate uncertainty in WNV risk.
Bacillus amyloliquefaciens MBI600 differentially induces tomato defense signaling pathways depending on plant part and dose of application
Authors: Dimopoulou Anastasia , Theologidis Ioannis , Liebmann Burghard , Kalantidis Kriton , Vassilakos Nikon , Skandalis Nicholas
Published: December 2019

The success of Bacillus amyloliquefaciens as a biological control agent relies on its ability to outgrow plant pathogens. It is also thought to interact with its plant host by inducing systemic resistance. In this study, the ability of B. amyloliquefaciens MBI600 to elicit defense (or other) responses in tomato seedlings and plants was assessed upon the expression of marker genes and transcriptomic analysis. Spray application of Serifel, a commercial formulation of MBI600, induced responses in a dose-dependent manner. Low dosage primed plant defense by activation of SA-responsive genes. Suggested dosage induced defense by mediating synergistic cross-talk between JA/ET and SA-signaling. Saturation of tomato roots or leaves with MBI600 elicitors activated JA/ET signaling at the expense of SA-mediated responses. The complex signaling network that is implicated in MBI600-tomato seedling interactions was mapped. MBI600 and flg22 (a bacterial flagellin peptide) elicitors induced, in a similar manner, biotic and abiotic stress responses by the coordinated activation of genes involved in JA/ET biosynthesis as well as hormone and redox signaling. This is the first study to suggest the activation of plant defense following the application of a commercial microbial formulation under conditions of greenhouse crop production.
Peptide hormone ELABELA enhances extravillous trophoblast differentiation, but placenta is not the major source of circulating ELABELA in pregnancy
Authors: Georgiadou Danai , Boussata Souad , Ranzijn Willemijn H. M. , Root Leah E. A. , Hillenius Sanne , bij de Weg Jeske M. , Abheiden Carolien N. H. , de Boer Marjon A. , de Vries Johanna I. P. , Vrijkotte Tanja G. M. , Lambalk Cornelis B. , Kuijper Esther A. M. , Afink Gijs B. , van Dijk Marie
Published: December 2019

Preeclampsia is a frequent gestational hypertensive disorder with equivocal pathophysiology. Knockout of peptide hormone ELABELA (ELA) has been shown to cause preeclampsia-like symptoms in mice. However, the role of ELA in human placentation and whether ELA is involved in the development of preeclampsia in humans is not yet known. In this study, we show that exogenous administration of ELA peptide is able to increase invasiveness of extravillous trophoblasts in vitro, is able to change outgrowth morphology and reduce trophoblast proliferation ex vivo, and that these effects are, at least in part, independent of signaling through the Apelin Receptor (APLNR). Moreover, we show that circulating levels of ELA are highly variable between women, correlate with BMI, but are significantly reduced in first trimester plasma of women with a healthy BMI later developing preeclampsia. We conclude that the large variability and BMI dependence of ELA levels in circulation make this peptide an unlikely candidate to function as a first trimester preeclampsia screening biomarker, while in the future administering ELA or a derivative might be considered as a potential preeclampsia treatment option as ELA is able to drive extravillous trophoblast differentiation.
New Class of Crosslinker-Free Nanofiber Biomaterials from Hydra Nematocyst Proteins
Authors: Bentele Theresa , Amadei Federico , Kimmle Esther , Veschgini Mariam , Linke Philipp , Sontag-González Mariana , Tennigkeit Jutta , Ho Anthony D. , Özbek Suat , Tanaka Motomu
Published: December 2019

Nematocysts, the stinging organelles of cnidarians, have remarkable mechanical properties. Hydra nematocyst capsules undergo volume changes of 50% during their explosive exocytosis and withstand osmotic pressures of beyond 100 bar. Recently, two novel protein components building up the nematocyst capsule wall in Hydra were identified. The cnidarian proline-rich protein 1 (CPP-1) characterized by a “rigid” polyproline motif and the elastic Cnidoin possessing a silk-like domain were shown to be part of the capsule structure via short cysteine-rich domains that spontaneously crosslink the proteins via disulfide bonds. In this study, recombinant Cnidoin and CPP-1 are expressed in E. coli and the elastic modulus of spontaneously crosslinked bulk proteins is compared with that of isolated nematocysts. For the fabrication of uniform protein nanofibers by electrospinning, the preparative conditions are systematically optimized. Both fibers remain stable even after rigorous washing and immersion into bulk water owing to the simultaneous crosslinking of cysteine-rich domains. This makes our nanofibers clearly different from other protein nanofibers that are not stable without chemical crosslinkers. Following the quantitative assessment of mechanical properties, the potential of Cnidoin and CPP-1 nanofibers is examined towards the maintenance of human mesenchymal stem cells.
Manipulating rod-shaped bacteria with optical tweezers
Authors: Zhang Zheng , Kimkes Tom E. P. , Heinemann Matthias
Published: December 2019

Optical tweezers have great potential in microbiology for holding and manipulating single cells under a microscope. However, the methodology to use optical tweezers for live cell studies is still at its infancy. In this work, we determined suitable parameters for stable trapping of single Escherichia coli bacteria, and identified the upper limits of IR-exposure that can be applied without affecting viability. We found that the maximum tolerable IR-exposure is 2.5-fold higher when employing oscillating instead of stationary optical trapping (20 J and 8 J, respectively). We found that good stability of cells in an oscillating trap is achieved when the effective trap length is 20% larger than the cell length, the oscillation frequency higher than 100 Hz and the trap oriented perpendicular to the medium flow direction. Further, we show, using an IR power just sufficient for stable holding, that bacteria remain viable during at least 30 min of holding in an oscillating trap. In this work, we established a method for long-term stable handling of single E. coli cells using optical tweezers. This work will pave the way for future use of optical tweezers in microbiology.
Mebendazole augments sensitivity to sorafenib by targeting MAPK and BCL-2 signalling in n-nitrosodiethylamine-induced murine hepatocellular carcinoma
Authors: Younis Nancy S. , Ghanim Amal M. H. , Saber Sameh
Published: December 2019

Sorafenib (SO) is a multi-kinase inhibitor that targets upstream signals in the MAPK pathway. Drug resistance and transient survival benefits are the main obstacles associated with SO treatment in Hepatocellular carcinoma (HCC) patients. Mebendazole (MBZ), an anthelmintic agent, has demonstrated activity against various cancer types. Therefore, we aimed to investigate the possible mechanisms of MBZ other than its anti-tubulin activity. MBZ (100 mg/kg/day, P.O.) was administered to N-nitrosodiethylamine-induced HCC mice as a monotherapeutic agent or in combination with SO. Our results revealed that MBZ decreased AFP levels, improved liver function and histology and increased survival in HCC mice, particularly when administered in combination with SO. MBZ also reduced hepatic inflammation and fibrogenesis as evidenced by reductions in TNF-α and TGF-β1 levels, respectively. Increased hepatic caspases-3 and -9 and decreased BCL-2 levels suggest induced-cell death. In addition, MBZ demonstrated anti-angiogenic, anti-metastatic, and anti-proliferative effects, as indicated by reduced VEGF levels, MMP-2:TIMP-1 ratios, and reduced cyclin D1 levels and Ki67 immunostaining, respectively. Our main finding was that MBZ targeted downstream signal of the MAPK pathway by inhibiting ERK1/2 phosphorylation. Targeting downstream MAPK signalling by MBZ and upstream signalling by SO is a novel approach to minimizing resistance and prolonging survival.