bluuebunny/crossref_metadata_2025 huggingface dataset:
Wo geht die Reise hin?
Authors: Schöfl Martin , Schönbauer Regina , Weber Christoph , Holzinger Daniel
Published: August 2017

Zusammenfassung. Die vorliegende Studie geht zwei Fragen nach: (1) Wie gestalten sich Verläufe der häufig vorkommenden Störungen der Aufmerksamkeit/Hyperaktivität-Impulsivität und der Sprachentwicklung vom Grundschulalter hin zum Sekundarschulalter? (2) Welche Variablen können diese Verläufe am besten vorhersagen? Zur Beantwortung der Fragen wurden Kinder, die im Alter von 6 bis 10 Jahren die Diagnose einer Sprachschwäche und/oder ADHS erhalten hatten, 5 Jahre später wieder einer umfangreichen und multiprofessionellen Untersuchungsreihe zugeführt. Basis der Analysen stellten Tests (Intelligenz, Sprache), Fragebogenverfahren (BRIEF, CBCL), Beobachtung und explorative Daten dar. Ausgehend von einer Stichprobe von 81 Kindern konnten 67% (n = 55) wieder untersucht werden. Für Sprachschwächen zeigte sich ein tendenziell positiveres Entwicklungsbild (bei 43% der Kinder wurde die Diagnose nicht erneut gestellt) als bei ADHS (stabile Diagnose bei 78%). Für beide Störungsbilder konnten auch Kinder beschrieben werden, deren Symptomatik erstmals im Sekundarschulalter auffällig wurde. Die Anzahl war wiederum für ADHS höher (23%), bei Sprachschwächen betraf diese Verschlechterung nur ein einziges Kind. Als potentielle Prädiktoren erwiesen sich neben der bereits gestellten Diagnose im Grundschulalter weiters das Vorliegen von internalisierenden Symptomen (ADHS) sowie das Geschlecht, die nonverbale Intelligenz und die Inanspruchnahme von logopädischer Therapie zwischen den Testzeitpunkten (Sprachschwäche).
A Silenced Population
Authors: Gryglewicz Kim , Bozzay Melanie , Arthur-Jordon Brittany , Romero Gabriela D. , Witmeier Melissa , Chapple Reshawna , Karver Marc S.
Published: August 2017

Abstract. Background: Given challenges that exceed the normal developmental requirements of adolescence, deaf and hard-of-hearing (DHH) youth are believed to be at elevated risk for engaging in suicide-related behavior (SRB). Unfortunately, little is known about the mechanisms that put these youth potentially at risk. Aims: To determine whether peer relationship difficulties are related to increased risk of SRB in DHH youth. Method: Student records (n = 74) were retrieved from an accredited educational center for deaf and blind students in the United States. Results: Peer relationship difficulties were found to be significantly associated with engagement in SRB but not when accounting for depressive symptomatology. Limitations: The restricted sample limits generalizability. Conclusions regarding risk causation cannot be made due to the cross-sectional nature of the study. Conclusion: These results suggest the need for future research that examines the mechanisms of the relationship between peer relationship difficulties, depression, and suicide risk in DHH youth and potential preventive interventions to ameliorate the risks for these at-risk youth.
Clinical-grade human umbilical cord-derived mesenchymal stem cells reverse cognitive aging via improving synaptic plasticity and endogenous neurogenesis
Authors: Cao Ning , Liao Tuling , Liu Jiajing , Fan Zeng , Zeng Quan , Zhou Junnian , Pei Haiyun , Xi Jiafei , He Lijuan , Chen Lin , Nan Xue , Jia Yali , Yue Wen , Pei Xuetao
Published: August 2017

Cognitive aging is a leading public health concern with the increasing aging population, but there is still lack of specific interventions directed against it. Recent studies have shown that cognitive function is intimately affected by systemic milieu in aging brain, and improvement of systemic environment in aging brain may be a promising approach for rejuvenating cognitive aging. Here, we sought to study the intervention effects of clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on cognitive aging in a murine model of aging. The conventional aging model in mice induced by d-galactose (d-gal) was employed here. Mice received once every two weeks intraperitoneal administration of hUC-MSCs. After 3 months of systematical regulation of hUC-MSCs, the hippocampal-dependent learning and memory ability was effectively improved in aged mice, and the synaptic plasticity was remarkably enhanced in CA1 area of the aged hippocampus; moreover, the neurobiological substrates that could impact on the function of hippocampal circuits were recovered in the aged hippocampus reflecting in: dendritic spine density enhanced, neural sheath and cytoskeleton restored, and postsynaptic density area increased. In addition, the activation of the endogenic neurogenesis which is beneficial to stabilize the neural network in hippocampus was observed after hUC-MSCs transplantation. Furthermore, we demonstrated that beneficial effects of systematical regulation of hUC-MSCs could be mediated by activation of mitogen-activated protein kinase (MAPK)-ERK-CREB signaling pathway in the aged hippocampus. Our study provides the first evidence that hUC-MSCs, which have the capacity of systematically regulating the aging brain, may be a potential intervention for cognitive aging.
P53-dependent downregulation of hTERT protein expression and telomerase activity induces senescence in lung cancer cells as a result of pterostilbene treatment
Authors: Chen Rong-Jane , Wu Pei-Hsuan , Ho Chi-Tang , Way Tzong-Der , Pan Min-Hsiung , Chen Hsiu-Min , Ho Yuan-Soon , Wang Ying-Jan
Published: August 2017

Cellular senescence is characterized by permanent cell cycle arrest, triggered by a variety of stresses, such as telomerase inhibition, and it is recognized as a tumor-suppressor mechanism. In recent years, telomerase has become an important therapeutic target in several cancers; inhibition of telomerase can induce senescence via the DNA damage response (DDR). Pterostilbene (PT), a dimethyl ether analog of resveratrol, possesses a variety of biological functions, including anticancer effects; however, the molecular mechanisms underlying these effects are not fully understood. In this study, we investigated the possible mechanisms of PT-induced senescence through telomerase inhibition in human non-small cell lung cancer cells and delineated the role of p53 in senescence. The results indicated that PT-induced senescence is characterized by a flattened morphology, positive staining for senescence-associated-β galactosidase activity, and the formation of senescence-associated heterochromatic foci. Telomerase activity and protein expression was significantly decreased in H460 (p53 wild type) cells compared with H1299 (p53 null) cells and p53 knockdown H460 cells (H460-p53-). A more detailed mechanistic study revealed that PT-induced senescence partially occurred via a p53-dependent mechanism, triggering inhibition of telomerase activity and protein expression, and leading to the DDR, S phase arrest and, finally, cellular senescence. This study is the first to explore the novel anticancer mechanism of PT senescence induction via the inhibition of telomerase in lung cancer cells.
PDI is an essential redox-sensitive activator of PERK during the unfolded protein response (UPR)
Authors: Kranz Philip , Neumann Fabian , Wolf Alexandra , Classen Fabian , Pompsch Mosche , Ocklenburg Tobias , Baumann Jennifer , Janke Kirsten , Baumann Melanie , Goepelt Kirsten , Riffkin Helena , Metzen Eric , Brockmeier Ulf
Published: August 2017

Endoplasmic reticulum (ER) stress leads to activation of the unfolded protein response (UPR) that results in transient suppression of protein translation to allow recovery but leads to cell death when stress cannot be resolved. Central to initiation of the UPR is the activation of the ER transmembrane kinase protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). Here we report that the thiol oxidoreductase ERp57 and protein disulfide isomerase-A1 (PDI), which belong to the same family of luminal ER oxidoreductases, have strikingly opposing roles in the regulation of PERK function. In HCT116 colon carcinoma cells, lentiviral depletion of ERp57 resulted in oxidation of PDI and activation of PERK, whereas depletion or chemical inhibition of PDI reduced PERK signaling and sensitized the cancer cells to hypoxia and ER stress. We conclude that oxidized PDI acts as a PERK activator, whereas ERp57 keeps PDI in a reduced state in the absence of ER stress. Thus, our study defines a new interface between metabolic redox signaling and PERK-dependent activation of the UPR and has the potential to influence future cancer therapies that target PERK signaling.
Loss of PHD3 in myeloid cells dampens the inflammatory response and fibrosis after hind-limb ischemia
Authors: Beneke Angelika , Guentsch Annemarie , Hillemann Annette , Zieseniss Anke , Swain Lija , Katschinski Dörthe M
Published: August 2017

Macrophages are essential for the inflammatory response after an ischemic insult and thereby influence tissue recovery. For the oxygen sensing prolyl-4-hydroxylase domain enzyme (PHD) 2 a clear impact on the macrophage-mediated arteriogenic response after hind-limb ischemia has been demonstrated previously, which involves fine tuning a M2-like macrophage population. To analyze the role of PHD3 in macrophages, we performed hind-limb ischemia (ligation and excision of the femoral artery) in myeloid-specific PHD3 knockout mice (PHD3−/−) and analyzed the inflammatory cell invasion, reperfusion recovery and fibrosis in the ischemic muscle post-surgery. In contrast to PHD2, reperfusion recovery and angiogenesis was unaltered in PHD3−/−compared to WT mice. Macrophages from PHD3−/−mice showed, however, a dampened inflammatory reaction in the affected skeletal muscle tissues compared to WT controls. This was associated with a decrease in fibrosis and an anti-inflammatory phenotype of the PHD3−/−macrophages, as well as decreased expression of Cyp2s1 and increased PGE2-secretion, which could be mimicked by PHD3−/−bone marrow-derived macrophages in serum starvation.
The triterpenoid CDDO-imidazolide ameliorates mouse liver ischemia-reperfusion injury through activating the Nrf2/HO-1 pathway enhanced autophagy
Authors: Xu Dongwei , Chen Lili , Chen Xiaosong , Wen Yankai , Yu Chang , Yao Jufang , Wu Hailong , Wang Xin , Xia Qiang , Kong Xiaoni
Published: August 2017

Nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated induction of antioxidants has been implicated to have protective roles in ischemia-reperfusion (I/R) injury in many animal models. However, the in vivo effects of CDDO-imidazole (CDDO-Im) (1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole), a Nrf2 activator, in hepatic I/R injury is lacking and its exact molecular mechanisms are still not very clear. The goals of this study were to determine whether CDDO-Im can prevent liver injury induced by I/R in the mouse, and to elucidate the molecular target of drug action. Mice were randomly equally divided into two groups and administered intraperitoneally with either DMSO control or CDDO-Im (2 mg/kg) 3 h before subjected to 90-min hepatic 70% ischemia followed by reperfusion. Subsequently, the Liver and blood samples of these mice were collected to evaluate liver injury. CDDO-Im pretreatment markedly improve hepatic I/R injury by attenuating hepatic necrosis and apoptosis, reducing reactive oxygen species (ROS) levels and inflammatory responses, and ameliorating mitochondrial dysfunction. Mechanistically, by using Nrf2 Knockout mice and hemeoxygenase 1 (HO-1) inhibitor, we found that these CDDO-Im protection effects are attributed to enhanced autophagy, which is mediated by activating Nrf2/HO-1 pathway. By accelerating autophagy and clearance of damaged mitochondria, CDDO-Im reduced the mtDNA release and ROS overproduction, and in turn decreased damage-associated molecular patterns induced inflammatory responses and the following secondary liver injury. These results indicate that by enhancing autophagy, CDDO-Im-mediated activation of Nrf2/HO-1 signaling could be a novel therapeutic strategy to minimize the adverse effects of hepatic I/R injury.
Specialized odorant receptors in social insects that detect cuticular hydrocarbon cues and candidate pheromones
Authors: Pask Gregory M. , Slone Jesse D. , Millar Jocelyn G. , Das Prithwiraj , Moreira Jardel A. , Zhou Xiaofan , Bello Jan , Berger Shelley L. , Bonasio Roberto , Desplan Claude , Reinberg Danny , Liebig Jürgen , Zwiebel Laurence J. , Ray Anandasankar
Published: August 2017

Eusocial insects use cuticular hydrocarbons as components of pheromones that mediate social behaviours, such as caste and nestmate recognition, and regulation of reproduction. In ants such as Harpegnathos saltator, the queen produces a pheromone which suppresses the development of workers’ ovaries and if she is removed, workers can transition to a reproductive state known as gamergate. Here we functionally characterize a subfamily of odorant receptors (Ors) with a nine-exon gene structure that have undergone a massive expansion in ants and other eusocial insects. We deorphanize 22 representative members and find they can detect cuticular hydrocarbons from different ant castes, with one (HsOr263) that responds strongly to gamergate extract and a candidate queen pheromone component. After systematic testing with a diverse panel of hydrocarbons, we find that most Harpegnathos saltator Ors are narrowly tuned, suggesting that several receptors must contribute to detection and discrimination of different cuticular hydrocarbons important in mediating eusocial behaviour.
Tree height strongly affects estimates of water-use efficiency responses to climate and CO2 using isotopes
Authors: Brienen R. J. W. , Gloor E. , Clerici S. , Newton R. , Arppe L. , Boom A. , Bottrell S. , Callaghan M. , Heaton T. , Helama S. , Helle G. , Leng M. J. , Mielikäinen K. , Oinonen M. , Timonen M.
Published: August 2017

Various studies report substantial increases in intrinsic water-use efficiency (W
i
), estimated using carbon isotopes in tree rings, suggesting trees are gaining increasingly more carbon per unit water lost due to increases in atmospheric CO2. Usually, reconstructions do not, however, correct for the effect of intrinsic developmental changes in W
i
as trees grow larger. Here we show, by comparing W
i
across varying tree sizes at one CO2 level, that ignoring such developmental effects can severely affect inferences of trees’ W
i
. W
i
doubled or even tripled over a trees’ lifespan in three broadleaf species due to changes in tree height and light availability alone, and there are also weak trends for Pine trees. Developmental trends in broadleaf species are as large as the trends previously assigned to CO2 and climate. Credible future tree ring isotope studies require explicit accounting for species-specific developmental effects before CO2 and climate effects are inferred.
Multi-laboratory assessment of reproducibility, qualitative and quantitative performance of SWATH-mass spectrometry
Authors: Collins Ben C. , Hunter Christie L. , Liu Yansheng , Schilling Birgit , Rosenberger George , Bader Samuel L. , Chan Daniel W. , Gibson Bradford W. , Gingras Anne-Claude , Held Jason M. , Hirayama-Kurogi Mio , Hou Guixue , Krisp Christoph , Larsen Brett , Lin Liang , Liu Siqi , Molloy Mark P. , Moritz Robert L. , Ohtsuki Sumio , Schlapbach Ralph , Selevsek Nathalie , Thomas Stefani N. , Tzeng Shin-Cheng , Zhang Hui , Aebersold Ruedi
Published: August 2017

Quantitative proteomics employing mass spectrometry is an indispensable tool in life science research. Targeted proteomics has emerged as a powerful approach for reproducible quantification but is limited in the number of proteins quantified. SWATH-mass spectrometry consists of data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics (accuracy, sensitivity, and selectivity) of targeted proteomics at large scale. While previous SWATH-mass spectrometry studies have shown high intra-lab reproducibility, this has not been evaluated between labs. In this multi-laboratory evaluation study including 11 sites worldwide, we demonstrate that using SWATH-mass spectrometry data acquisition we can consistently detect and reproducibly quantify >4000 proteins from HEK293 cells. Using synthetic peptide dilution series, we show that the sensitivity, dynamic range and reproducibility established with SWATH-mass spectrometry are uniformly achieved. This study demonstrates that the acquisition of reproducible quantitative proteomics data by multiple labs is achievable, and broadly serves to increase confidence in SWATH-mass spectrometry data acquisition as a reproducible method for large-scale protein quantification.
Landscape of submitochondrial protein distribution
Authors: Vögtle F.-Nora , Burkhart Julia M. , Gonczarowska-Jorge Humberto , Kücükköse Cansu , Taskin Asli Aras , Kopczynski Dominik , Ahrends Robert , Mossmann Dirk , Sickmann Albert , Zahedi René P. , Meisinger Chris
Published: August 2017

The mitochondrial proteome comprises ~1000 (yeast)–1500 (human) different proteins, which are distributed into four different subcompartments. The sublocalization of these proteins within the organelle in most cases remains poorly defined. Here we describe an integrated approach combining stable isotope labeling, various protein enrichment and extraction strategies and quantitative mass spectrometry to produce a quantitative map of submitochondrial protein distribution in S. cerevisiae. This quantitative landscape enables a proteome-wide classification of 986 proteins into soluble, peripheral, and integral mitochondrial membrane proteins, and the assignment of 818 proteins into the four subcompartments: outer membrane, inner membrane, intermembrane space, or matrix. We also identified 206 proteins that were not previously annotated as localized to mitochondria. Furthermore, the protease Prd1, misannotated as intermembrane space protein, could be re-assigned and characterized as a presequence peptide degrading enzyme in the matrix.
Giant onsite electronic entropy enhances the performance of ceria for water splitting
Authors: Naghavi S. Shahab , Emery Antoine A. , Hansen Heine A. , Zhou Fei , Ozolins Vidvuds , Wolverton Chris
Published: August 2017

Previous studies have shown that a large solid-state entropy of reduction increases the thermodynamic efficiency of metal oxides, such as ceria, for two-step thermochemical water splitting cycles. In this context, the configurational entropy arising from oxygen off-stoichiometry in the oxide, has been the focus of most previous work. Here we report a different source of entropy, the onsite electronic configurational entropy, arising from coupling between orbital and spin angular momenta in lanthanide f orbitals. We find that onsite electronic configurational entropy is sizable in all lanthanides, and reaches a maximum value of ≈4.7 kB per oxygen vacancy for Ce4+/Ce3+ reduction. This unique and large positive entropy source in ceria explains its excellent performance for high-temperature catalytic redox reactions such as water splitting. Our calculations also show that terbium dioxide has a high electronic entropy and thus could also be a potential candidate for solar thermochemical reactions.
Mass production of bulk artificial nacre with excellent mechanical properties
Authors: Gao Huai-Ling , Chen Si-Ming , Mao Li-Bo , Song Zhao-Qiang , Yao Hong-Bin , Cölfen Helmut , Luo Xi-Sheng , Zhang Fu , Pan Zhao , Meng Yu-Feng , Ni Yong , Yu Shu-Hong
Published: August 2017

Various methods have been exploited to replicate nacre features into artificial structural materials with impressive structural and mechanical similarity. However, it is still very challenging to produce nacre-mimetics in three-dimensional bulk form, especially for further scale-up. Herein, we demonstrate that large-sized, three-dimensional bulk artificial nacre with comprehensive mimicry of the hierarchical structures and the toughening mechanisms of natural nacre can be facilely fabricated via a bottom-up assembly process based on laminating pre-fabricated two-dimensional nacre-mimetic films. By optimizing the hierarchical architecture from molecular level to macroscopic level, the mechanical performance of the artificial nacre is superior to that of natural nacre and many engineering materials. This bottom-up strategy has no size restriction or fundamental barrier for further scale-up, and can be easily extended to other material systems, opening an avenue for mass production of high-performance bulk nacre-mimetic structural materials in an efficient and cost-effective way for practical applications.
Evidence that Listeria innocua modulates its membrane’s stored curvature elastic stress, but not fluidity, through the cell cycle
Authors: Furse Samuel , Jakubec Martin , Rise Frode , Williams Huw E. , Rees Catherine E. D. , Halskau Øyvind
Published: August 2017

This paper reports that the abundances of endogenous cardiolipin and phosphatidylethanolamine halve during elongation of the Gram-positive bacterium Listeria innocua. The lyotropic phase behaviour of model lipid systems that describe these modulations in lipid composition indicate that the average stored curvature elastic stress of the membrane is reduced on elongation of the cell, while the fluidity appears to be maintained. These findings suggest that phospholipid metabolism is linked to the cell cycle and that changes in membrane composition can facilitate passage to the succeding stage of the cell cycle. This therefore suggests a means by which bacteria can manage the physical properties of their membranes through the cell cycle.
Genetic predisposition to lung cancer: comprehensive literature integration, meta-analysis, and multiple evidence assessment of candidate-gene association studies
Authors: Wang Junjun , Liu Qingyun , Yuan Shuai , Xie Weijia , Liu Yuan , Xiang Ying , Wu Na , Wu Long , Ma Xiangyu , Cai Tongjian , Zhang Yao , Sun Zhifu , Li Yafei
Published: August 2017

More than 1000 candidate-gene association studies on genetic susceptibility to lung cancer have been published over the last two decades but with few consensuses for the likely culprits. We conducted a comprehensive review, meta-analysis and evidence strength evaluation of published candidate-gene association studies in lung cancer up to November 1, 2015. The epidemiological credibility of cumulative evidence was assessed using the Venice criteria. A total of 1018 publications with 2910 genetic variants in 754 different genes or chromosomal loci were eligible for inclusion. Main meta-analyses were performed on 246 variants in 138 different genes. Twenty-two variants from 21 genes (APEX1 rs1130409 and rs1760944, ATM rs664677, AXIN2 rs2240308, CHRNA3 rs6495309, CHRNA5 rs16969968, CLPTM1L rs402710, CXCR2 rs1126579, CYP1A1 rs4646903, CYP2E1 rs6413432, ERCC1 rs11615, ERCC2 rs13181, FGFR4 rs351855, HYKK rs931794, MIR146A rs2910164, MIR196A2 rs11614913, OGG1 rs1052133, PON1 rs662, REV3L rs462779, SOD2 rs4880, TERT rs2736098, and TP53 rs1042522) showed significant associations with lung cancer susceptibility with strong cumulative epidemiological evidence. No significant associations with lung cancer risk were found for other 150 variants in 98 genes; however, seven variants demonstrated strong cumulative evidence. Our findings provided the most updated summary of genetic risk effects on lung cancer and would help inform future research direction.
A Flexible Electret Membrane with Persistent Electrostatic Effect and Resistance to Harsh Environment for Energy Harvesting
Authors: Huiming Xiao , Gangjin Chen , Xumin Chen , Zhi Chen
Published: August 2017

A novel flexible electret membrane, exhibiting persistent electrostatic effect, distinctive temperature stability and outstanding capability of resistance to harsh environment and fatigue, is demonstrated by experiment. Its excellent electret performance is correlated to the synergy of three factors, which are space charge injection, dipole orientation and interfacial polarization according to the analysis of charge storage mechanism. This electret membrane is provided with sandwich configuration PTFE/THV/PTFE, prepared by hot pressing method and thermal charging technology. After wiped its surface with alcohol, its surface potential declines to zero from −550 V, then recovers rapidly to −310 V and finally maintains constant for 800 hours, which shows that its electret performance distinctly precedes traditional electret material such as single PTFE, FEP electret membrane. The measurement of thermal stimulating potentials displays that its surface potential reaches maximum about 5 times initial value at 125 °C. A micro-vibration energy harvester is assembled with this membrane. Its maximum output power reaches 4.66 μW at tapping frequency 5 Hz and keeps stable during over 2000 tapping tests within 100 days, which indicates the long-life service and resistance to harsh environment and fatigue of this electret membrane.
Seasonal total methane depletion in limestone caves
Authors: Waring Chris L. , Hankin Stuart I. , Griffith David W. T. , Kertesz Michael A. , Kobylski Victoria , Wilson Neil L. , Coleman Nicholas V. , Kettlewell Graham , Zlot Robert , Bosse Michael , Bell Graham
Published: August 2017

Methane concentration in caves is commonly much lower than the external atmosphere, yet the cave CH4 depletion causal mechanism is contested and dynamic links to external diurnal and seasonal temperature cycles unknown. Here, we report a continuous 3-year record of cave methane and other trace gases in Jenolan Caves, Australia which shows a seasonal cycle of extreme CH4 depletion, from ambient ~1,775 ppb to near zero during summer and to ~800 ppb in winter. Methanotrophic bacteria, some newly-discovered, rapidly consume methane on cave surfaces and in external karst soils with lifetimes in the cave of a few hours. Extreme bacterial selection due to the absence of alternate carbon sources for growth in the cave environment has resulted in an extremely high proportion 2–12% of methanotrophs in the total bacteria present. Unexpected seasonal bias in our cave CH4 depletion record is explained by a three-step process involving methanotrophy in aerobic karst soil above the cave, summer transport of soil-gas into the cave through epikarst, followed by further cave CH4 depletion. Disentangling cause and effect of cave gas variations by tracing sources and sinks has identified seasonal speleothem growth bias, with implied palaeo-climate record bias.
Virulence and transcriptome profile of multidrug-resistant Escherichia coli from chicken
Authors: Hussain Hafiz I. , Iqbal Zahid , Seleem Mohamed N. , Huang Deyu , Sattar Adeel , Hao Haihong , Yuan Zonghui
Published: August 2017

Numerous studies have examined the prevalence of pathogenic Escherichia coli in poultry and poultry products; however, limited data are available regarding their resistance- and virulence-associated gene expression profiles. This study was designed to examine the resistance and virulence of poultry E. coli strains in vitro and in vivo via antibiotic susceptibility, biofilm formation and adhesion, and invasion and intracellular survivability assays in Caco-2 and Raw 264.7 cell lines as well as the determination of the median lethal dose in two-day old chickens. A clinical pathogenic multidrug-resistant isolate, E. coli 381, isolated from broilers, was found to be highly virulent in cell culture and 1000-fold more virulent in a chicken model than other strains; accordingly, the isolate was subsequently selected for transcriptome analysis. The comparative gene expression profile of MDR E. coli 381 and the reference human strain E. coli ATCC 25922 was completed with Illumina HiSeq. 2500 transcriptome analysis. Differential gene expression analysis indicates that there are multiple pathways involved in the resistance and virulence of this highly virulent strain. The results garnered from this study provide critical information about the highly virulent MDR E. coli strain of poultry origin and warrant further investigation due to its significant threat to public health.
Compound A influences gene regulation of the Dexamethasone-activated glucocorticoid receptor by alternative cofactor recruitment
Authors: Desmet S. J. , Bougarne N. , Van Moortel L. , De Cauwer L. , Thommis J. , Vuylsteke M. , Ratman D. , Houtman R. , Tavernier J. , De Bosscher K.
Published: August 2017

The glucocorticoid receptor (GR) is a transcription factor of which the underlying gene regulatory mechanisms are complex and incompletely understood. The non-steroidal anti-inflammatory Compound A (CpdA), a selective GR modulating compound in various cell models, has been shown to favour GR-mediated gene repression but not GR-mediated gene activation. Shifting balances towards only a particular subset of GR gene regulatory events may be of benefit in the treatment of inflammatory diseases. We present evidence to support that the combination of CpdA with Dexamethasone (DEX), a classic steroidal GR ligand, can shape GR function towards a unique gene regulatory profile in a cell type-dependent manner. The molecular basis hereof is a changed GR phosphorylation status concomitant with a change in the GR cofactor recruitment profile. We subsequently identified and confirmed the orphan nuclear receptor SHP as a coregulator that is specifically enriched at GR when CpdA and DEX are combined. Combining CpdA with DEX not only leads to stronger suppression of pro-inflammatory gene expression, but also enhanced anti-inflammatory GR target gene expression in epithelial cells, making ligand combination strategies in future a potentially attractive alternative manner of skewing and fine-tuning GR effects towards an improved therapeutic benefit.
TaiNi: Maximizing research output whilst improving animals’ welfare in neurophysiology experiments
Authors: Jiang Zhou , Huxter John R. , Bowyer Stuart A. , Blockeel Anthony J. , Butler James , Imtiaz Syed A. , Wafford Keith A. , Phillips Keith G. , Tricklebank Mark D. , Marston Hugh M. , Rodriguez-Villegas Esther
Published: August 2017

Understanding brain function at the cell and circuit level requires representation of neuronal activity through multiple recording sites and at high sampling rates. Traditional tethered recording systems restrict movement and limit the environments suitable for testing, while existing wireless technology is still too heavy for extended recording in mice. Here we tested TaiNi, a novel ultra-lightweight (<2 g) low power wireless system allowing 72-hours of recording from 16 channels sampled at ~19.5 KHz (9.7 KHz bandwidth). We captured local field potentials and action-potentials while mice engaged in unrestricted behaviour in a variety of environments and while performing tasks. Data was synchronized to behaviour with sub-second precision. Comparisons with a state-of-the-art wireless system demonstrated a significant improvement in behaviour owing to reduced weight. Parallel recordings with a tethered system revealed similar spike detection and clustering. TaiNi represents a significant advance in both animal welfare in electrophysiological experiments, and the scope for continuously recording large amounts of data from small animals.
Drosophila protease ClpXP specifically degrades DmLRPPRC1 controlling mitochondrial mRNA and translation
Authors: Matsushima Yuichi , Hirofuji Yuta , Aihara Masamune , Yue Song , Uchiumi Takeshi , Kaguni Laurie S. , Kang Dongchon
Published: August 2017

ClpXP is the major protease in the mitochondrial matrix in eukaryotes, and is well conserved among species. ClpXP is composed of a proteolytic subunit, ClpP, and a chaperone-like subunit, ClpX. Although it has been proposed that ClpXP is required for the mitochondrial unfolded protein response, additional roles for ClpXP in mitochondrial biogenesis are unclear. Here, we found thatDrosophilaleucine-rich pentatricopeptide repeat domain-containing protein 1 (DmLRPPRC1) is a specific substrate of ClpXP. Depletion or introduction of catalytically inactive mutation of ClpP increases DmLRPPRC1 and causes non-uniform increases of mitochondrial mRNAs, accumulation of some unprocessed mitochondrial transcripts, and modest repression of mitochondrial translation inDrosophilaSchneider S2 cells. Moreover, DmLRPPRC1 over-expression induces the phenotypes similar to those observed when ClpP is depleted. Taken together, ClpXP regulates mitochondrial gene expression by changing the protein level of DmLRPPRC1 inDrosophilaSchneider S2 cells.
Invisible Trojan-horse attack
Authors: Sajeed Shihan , Minshull Carter , Jain Nitin , Makarov Vadim
Published: August 2017

We demonstrate the experimental feasibility of a Trojan-horse attack that remains nearly invisible to the single-photon detectors employed in practical quantum key distribution (QKD) systems, such as Clavis2 from ID Quantique. We perform a detailed numerical comparison of the attack performance against Scarani-Ac´ın-Ribordy-Gisin (SARG04) QKD protocol at 1924 nm versus that at 1536 nm. The attack strategy was proposed earlier but found to be unsuccessful at the latter wavelength, as reported in N. Jain et al., New J. Phys. 16, 123030 (2014). However at 1924 nm, we show experimentally that the noise response of the detectors to bright pulses is greatly reduced, and show by modeling that the same attack will succeed. The invisible nature of the attack poses a threat to the security of practical QKD if proper countermeasures are not adopted.
Projected climate change impacts in rainfall erosivity over Brazil
Authors: Almagro André , Oliveira Paulo Tarso S. , Nearing Mark A. , Hagemann Stefan
Published: August 2017

The impacts of climate change on soil erosion may bring serious economic, social and environmental problems. However, few studies have investigated these impacts on continental scales. Here we assessed the influence of climate change on rainfall erosivity across Brazil. We used observed rainfall data and downscaled climate model output based on Hadley Center Global Environment Model version 2 (HadGEM2-ES) and Model for Interdisciplinary Research On Climate version 5 (MIROC5), forced by Representative Concentration Pathway 4.5 and 8.5, to estimate and map rainfall erosivity and its projected changes across Brazil. We estimated mean values of 10,437 mm ha−1 h−1 year−1 for observed data (1980–2013) and 10,089 MJ mm ha−1 h−1 year−1 and 10,585 MJ mm ha−1 h−1 year−1 for HadGEM2-ES and MIROC5, respectively (1961–2005). Our analysis suggests that the most affected regions, with projected rainfall erosivity increases ranging up to 109% in the period 2007–2040, are northeastern and southern Brazil. Future decreases of as much as −71% in the 2071–2099 period were estimated for the southeastern, central and northwestern parts of the country. Our results provide an overview of rainfall erosivity in Brazil that may be useful for planning soil and water conservation, and for promoting water and food security.
Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners
Authors: Gemperle Jakub , Hexnerová Rozálie , Lepšík Martin , Tesina Petr , Dibus Michal , Novotný Marian , Brábek Jan , Veverka Václav , Rosel Daniel
Published: August 2017

CAS is a docking protein downstream of the proto-oncogene Src with a role in invasion and metastasis of cancer cells. The CAS SH3 domain is indispensable for CAS-mediated signaling, but structural aspects of CAS SH3 ligand binding and regulation are not well understood. Here, we identified the consensus CAS SH3 binding motif and structurally characterized the CAS SH3 domain in complex with ligand. We revealed the requirement for an uncommon centrally localized lysine residue at position +2 of CAS SH3 ligands and two rather dissimilar optional anchoring residues, leucine and arginine, at position +5. We further expanded the knowledge of CAS SH3 ligand binding regulation by manipulating tyrosine 12 phosphorylation and confirmed the negative role of this phosphorylation on CAS SH3 ligand binding. Finally, by exploiting the newly identified binding requirements of the CAS SH3 domain, we predicted and experimentally verified two novel CAS SH3 binding partners, DOK7 and GLIS2.
Delivery of large transgene cassettes by foamy virus vector
Authors: Sweeney Nathan Paul , Meng Jinhong , Patterson Hayley , Morgan Jennifer E. , McClure Myra
Published: August 2017

Viral vectors are effective tools in gene therapy, but their limited packaging capacity can be restrictive. Larger clinically-relevant vectors are needed. Foamy viruses have the largest genomes among mammalian retroviruses and their vectors have shown potential for gene therapy in preclinical studies. However, the effect of vector genome size on titre has not been determined. We inserted increasing lengths of the dystrophin open reading frame in a foamy virus vector and quantified packaged vector RNA and integrated DNA. For both measures, a semi-logarithmic reduction in titre was observed as genome size increased. Concentrated titres were reduced 100-fold to approximately 106 transducing units per ml when vector genomes harboured a 12 kb insert, approximately twice that reported for lentivirus vectors in a comparable study. This potential was applied by optimising foamy virus vectors carrying the full-length dystrophin open-reading frame for transduction of human muscle derived cells. Full-length dystrophin protein was expressed and transduced cells remained able to form myotubes in vitro. Foamy virus vectors are well-suited for stable delivery of large transgene cassettes and warrant further investigation for development as a therapy for Duchenne or Becker muscular dystrophy.
Adaptive simulations, towards interactive protein-ligand modeling
Authors: Lecina Daniel , Gilabert Joan F. , Guallar Victor
Published: August 2017

Modeling the dynamic nature of protein-ligand binding with atomistic simulations is one of the main challenges in computational biophysics, with important implications in the drug design process. Although in the past few years hardware and software advances have significantly revamped the use of molecular simulations, we still lack a fast and accurateab initiodescription of the binding mechanism in complex systems, available only for up-to-date techniques and requiring several hours or days of heavy computation. Such delay is one of the main limiting factors for a larger penetration of protein dynamics modeling in the pharmaceutical industry. Here we present a game-changing technology, opening up the way for fast reliable simulations of protein dynamics by combining an adaptive reinforcement learning procedure with Monte Carlo sampling in the frame of modern multi-core computational resources. We show remarkable performance in mapping the protein-ligand energy landscape, being able to reproduce the full binding mechanism in less than half an hour, or the active site induced fit in less than 5 minutes. We exemplify our method by studying diverse complex targets, including nuclear hormone receptors and GPCRs, demonstrating the potential of using the new adaptive technique in screening and lead optimization studies.
Symmetry in the open-system dynamics of quantum correlations
Authors: Lyyra Henri , Karpat Göktuğ , Li Chuan-Feng , Guo Guang-Can , Piilo Jyrki , Maniscalco Sabrina
Published: August 2017

We study the symmetry properties in the dynamics of quantum correlations for two-qubit systems in one-sided noisy channels, with respect to a switch in the location of noise from one qubit to the other. We consider four different channel types, namely depolarizing, amplitude damping, bit-flip, and bit-phase-flip channel, and identify the classes of initial states leading to symmetric decay of entanglement, non-locality and discord. Our results show that the symmetric decay of quantum correlations is not directly linked to the presence or absence of symmetry in the initial state, while it does depend on the type of correlation considered as well as on the type of noise. We prove that asymmetric decay can be used to infer, in certain cases, characteristic properties of the channel. We also show that the location of noise may lead to dramatic changes in the persistence of phenomena such as entanglement sudden death and time-invariant discord.
Associations between serum homocysteine levels and anxiety and depression among children and adolescents in Taiwan
Authors: Chung Kuo-Hsuan , Chiou Hung-Yi , Chen Yi-Hua
Published: August 2017

Although evidence suggests that homocysteine levels are elevated in severe mental illness in children, findings regarding homocysteine levels in youth with anxiety and depression are scarce. Therefore, this study examined the association of homocysteine levels with anxiety and depression in a community sample of students aged 6–13 years. In total, 649 students were selected from the first, fourth, and seventh grades of schools in Taipei, Taiwan, in 2010. These students completed a hospital-based health examination, which included physical examination, blood sample collection, and questionnaire administration. The data were analysed through multiple linear regression. Among the seventh-grade boys, both depression (adjusted β = 0.044, 95% confidence interval (CI) = 0.004–0.084) and anxiety (adjusted β = 0.052, 95% CI = 0.013–0.091) were independently associated with increased homocysteine levels. In further dichotomisation, compared with students with low anxiety levels, those with moderate to high anxiety levels were significantly positively associated with elevated serum homocysteine levels (adjusted β = 0.091, 95% CI = 0.003–0.180). Our results suggest that increased depression and anxiety may be positively associated with higher serum homocysteine levels in older boys. Our results provide essential data on the biological aspects underlying anxiety and depression in the studied population.
A new horned and long-necked herbivorous stem-archosaur from the Middle Triassic of India
Authors: Sengupta Saradee , Ezcurra Martín D. , Bandyopadhyay Saswati
Published: August 2017

The early evolution of archosauromorphs (bird- and crocodile-line archosaurs and stem-archosaurs) represents an important case of adaptive radiation that occurred in the aftermath of the Permo-Triassic mass extinction. Here we enrich the early archosauromorph record with the description of a moderately large (3–4 m in total length), herbivorous new allokotosaurian, Shringasaurus indicus, from the early Middle Triassic of India. The most striking feature of Shringasaurus indicus is the presence of a pair of large supraorbital horns that resemble those of some ceratopsid dinosaurs. The presence of horns in the new species is dimorphic and, as occurs in horned extant bovid mammals, these structures were probably sexually selected and used as weapons in intraspecific combats. The relatively large size and unusual anatomy of Shringasaurus indicus broadens the morphological diversity of Early–Middle Triassic tetrapods and complements the understanding of the evolutionary mechanisms involved in the early archosauromorph diversification.
NLRP3 inflammasome activation results in liver inflammation and fibrosis in mice infected with Schistosoma japonicum in a Syk-dependent manner
Authors: Lu Ya-Qi , Zhong Shan , Meng Nan , Fan Yin-Ping , Tang Wang-Xian
Published: August 2017

Granulomatous and fibrosing inflammation in response to soluble egg antigen (SEA) from Schistosoma japonicum (S. japonicum) is the main pathological process of S. japonicum infection. Inflammasome activation has recently been implicated in the pathogenesis of liver disease. However, the role of inflammasome activation in schistosomiasis-associated liver fibrosis (SSLF) has not been extensively studied. In this study, it is demonstrated that the NLRP3 inflammasome is markedly activated in mouse HSCs both in vivo and in vitro during S. japonicum infection. Furthermore, it is demonstrated that inhibition of NLRP3 inflammasome significantly alleviates the liver inflammation and collagen deposition that are induced by infection with S. japonicum. The mechanism of SEA-induced NLRP3 inflammasome activation is studied in isolated, cultured mouse HSCs and it is shown that SEA-induced NLRP3 inflammasome activation in HSCs is dependent upon the activities of spleen tyrosine kinase (Syk), an enzyme usually associated with a pathogen recognition receptor for fungal pathogens. Moreover, it is demonstrated that Dectin-1 and JNK signaling are also involved in SEA-induced NLRP3 inflammasome activation in HSCs. These data shed new light on the mechanisms of NLRP3 inflammasome activation during an infection with S. japonicum, and further characterize its role in schistosomiasis-associated liver fibrosis (SSLF).
Rapid replacement by non-vaccine pneumococcal serotypes may mitigate the impact of the pneumococcal conjugate vaccine on nasopharyngeal bacterial ecology
Authors: Kwambana-Adams Brenda , Hanson Blake , Worwui Archibald , Agbla Schadrac , Foster-Nyarko Ebenezer , Ceesay Fatima , Ebruke Chinelo , Egere Uzochukwu , Zhou Yanjiao , Ndukum Maze , Sodergren Erica , Barer Michael , Adegbola Richard , Weinstock George , Antonio Martin
Published: August 2017

There is growing concern that interventions that alter microbial ecology can adversely affect health. We characterised the impact of the seven-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal carriage and the bacterial component of the nasopharyngeal microbiome during infancy. Newborns were recruited into three groups as follows: Group1 (n = 33) was the control group and comprised infants who received PCV7 after 6 months and came from unvaccinated communities. Group 2 (n = 30) came from unvaccinated communities and Group 3 (n = 39) came from vaccinated communities. Both group 2 and 3 received PCV7 at 2, 3 and 4 months. Culture and 16 S rRNA gene sequencing were performed on nasopharyngeal specimens collected at regular intervals from infants. Nasopharyngeal carriage of PCV7 serotypes in Group 1 was significantly higher than in Group 2 and 3 (p < 0.01). However, pneumococcal carriage remained comparable due to an expansion of non-vaccine serotypes in Groups 2 and 3. Determination of phylogenetic dis(similarities) showed that the bacterial community structures were comparable across groups. A mixed effects model showed no difference in community richness (p = 0.15) and Shannon α-diversity (p = 0.48) across the groups. Immediate replacement of pneumococcal vaccine serotypes with non-vaccine serotypes may mitigate the impact of PCV7 on nasopharyngeal bacterial community structure and ecology.
Magnetic microsphere-based portable solid phase extraction device for on-site pre-concentration of organics from large-volume water samples
Authors: Yao Zhijian , Zhao Qingqing , Ma Yan , Wang Wei , Zhou Qing , Li Aimin
Published: August 2017

In this research a new magnetic material called M88 was fully synthetized and characterized for the extraction of pharmaceutical and personal care products in water samples. In addition, a portable prototype of magnetic solidphase extraction (MSPE) device was developed for the onsite preconcentration. The MSPE coupling with high performance liquid chromatography-Diode array detector (HPLC-DAD) method was developed and validated for simultaneous analysis of 11 PPCPs (mefenamic acid, chloroamphenicol, ketoprofen, clofibric acid, indometacin, acetylsalicylic acid, bisphenol A, phenylphenol, gemfibrozil, triclosan, and ibuprofen) in environmental water samples. Experimental parameters affecting the extraction efficiencies, such as the amount of M88, desorption solvent, extraction time, and solution pH and sample volume were investigated. Under the optimal conditions, the limits of detection (LODs, S/N = 3) for the selected PPCPs were found to be in the range of 0.7–9.4 ng/L, with good linear correlation coefficients. It is also shown that the extraction efficiency of M88 was comparable to that of the commercial Oasis HLB and was evidently higher than that of the C18 cartridge. The optimised method was further verified by performing spiking experiments in water samples from Taihu Lake, with good recovery and reproducibility for all the compounds.