bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Phrase Table pruning for Hindi to English machine translation through syntactic and marker-based filtering and hybrid similarity measurement
Authors: CHATTERJEE NILADRI , GUPTA SUSMITA
Published: October 2018

For a given training corpus of parallel sentences, the quality of the output produced by a translation system relies heavily on the underlying similarity measurement criteria. A phrase-based machine translation system derives its output through a generative process using a Phrase Table comprising source and target language phrases. As a consequence, the more effective the Phrase Table is, in terms of its size and the output that may be derived out of it, the better is the expected outcome of the underlying translation system. However, finding the most similar phrase(s) from a given training corpus that can help generate a good quality translation poses a serious challenge. In practice, often there are many parallel phrase entries in a Phrase Table that are either redundant, or do not contribute to the translation results effectively. Identifying these candidate entries and removing them from the Phrase Table will not only reduce the size of the Phrase Table, but should also help in improving the processing speed for generating the translations. The present paper develops a scheme based on syntactic structure and the marker hypothesis (Green 1979, The necessity of syntax markers: two experiments with artificial languages, Journal of Verbal Learning and Behavior) for reducing the size of a Phrase Table, without compromising much on the translation quality of the output, by retaining the non-redundant and meaningful parallel phrases only. The proposed scheme is complemented with an appropriate similarity measurement scheme to achieve maximum efficiency in terms of BLEU scores. Although designed for Hindi to English machine translation, the overall approach is quite general, and is expected to be easily adaptable for other language pairs as well.
From filmed pleasure to Fun Palace
Authors: Miro Ana Bonet
Published: October 2018

The Fun Palace, a collaborative enterprise initiated by the radical theatre producer Joan Littlewood and architect Cedric Price in early 1960s London articulated a response to the ‘increased leisure’ available to postwar British society. A critical model for cultural production in which civics met pleasure, the Fun Palace project aimed to construct situations for playful exchange conducted through self-directed actions as a way to activate audiences. Pleasure for all – a ‘breakthrough to total enjoyment’, in opposition to what was seen as existing commodified leisure practices – became understood as a critical agenda pitched against the elitist and interventionist Labour government's 1965 White Paper, A Policy for the Arts: The First Steps. Enforcing class-based distinctions between the high arts and popular entertainment, state arts policy failed to address the key role played by the media in the rise of the leisure society. In analysing British communications in the 1960s, the cultural critic Raymond Williams argued that, rather than opposing fine art with popular entertainment, social growth could only be achieved through the circulation of public and independent media, opportunities for which were at the time limited within the corporate structure of British broadcasting and press.
Prevalence thresholds for wasting, overweight and stunting in children under 5 years
Authors: de Onis Mercedes , Borghi Elaine , Arimond Mary , Webb Patrick , Croft Trevor , Saha Kuntal , De-Regil Luz Maria , Thuita Faith , Heidkamp Rebecca , Krasevec Julia , Hayashi Chika , Flores-Ayala Rafael
Published: October 2018

Objective

Prevalence ranges to classify levels of wasting and stunting have been used since the 1990s for global monitoring of malnutrition. Recent developments prompted a re-examination of existing ranges and development of new ones for childhood overweight. The present paper reports from the WHO–UNICEF Technical Expert Advisory Group on Nutrition Monitoring.

Design

Thresholds were developed in relation tosdof the normative WHO Child Growth Standards. The international definition of ‘normal’ (2sdbelow/above the WHO standards median) defines the first threshold, which includes 2·3 % of the area under the normalized distribution. Multipliers of this ‘very low’ level (rounded to 2·5 %) set the basis to establish subsequent thresholds. Country groupings using the thresholds were produced using the most recent set of national surveys.

Setting

One hundred and thirty-four countries.

Subjects

Children under 5 years.

Results

For wasting and overweight, thresholds are: ‘very low’ (<2·5 %), ‘low’ (≈1–2 times 2·5 %), ‘medium’ (≈2–4 times 2·5 %), ‘high’ (≈4–6 times 2·5 %) and ‘very high’ (>≈6 times 2·5 %). For stunting, thresholds are: ‘very low’ (<2·5 %), ‘low’ (≈1–4 times 2·5 %), ‘medium’ (≈4–8 times 2·5 %), ‘high’ (≈8–12 times 2·5 %) and ‘very high’ (>≈12 times 2·5 %).

Conclusions

The proposed thresholds minimize changes and keep coherence across anthropometric indicators. They can be used for descriptive purposes to map countries according to severity levels; by donors and global actors to identify priority countries for action; and by governments to trigger action and target programmes aimed at achieving ‘low’ or ‘very low’ levels. Harmonized terminology will help avoid confusion and promote appropriate interventions.
Regaining In-Group Continuity in Times of Anxiety About the	Group’s Future
Authors: Smeekes Anouk , Jetten Jolanda , Verkuyten Maykel , Wohl Michael J.A. , Jasinskaja-Lahti Inga , Ariyanto Amarina , Autin Frédérique , Ayub Nadia , Badea Constantina , Besta Tomasz , Butera Fabrizio , Costa-Lopes Rui , Cui Lijuan , Fantini Carole , Finchilescu Gillian , Gaertner Lowell , Gollwitzer Mario , Gómez Ángel , González Roberto , Hong Ying Yi , Jensen Dorthe Høj , Karasawa Minoru , Kessler Thomas , Klein Olivier , Lima Marcus , Renvik Tuuli A. , Megevand Laura , Morton Thomas , Paladino Paola , Polya Tibor , Ruza Aleksejs , Shahrazad Wan , Sharma Sushama , Teymoori Ali , Torres Ana R. , van der Bles Anne M.
Published: October 2018

Abstract. Collective nostalgia for the good old days of the country thrives across the world. However, little is known about the social psychological dynamics of this collective emotion across cultures. We predicted that collective nostalgia is triggered by collective angst as it helps people to restore a sense of in-group continuity via stronger in-group belonging and out-group rejection (in the form of opposition to immigrants). Based on a sample (N = 5,956) of individuals across 27 countries, the general pattern of results revealed that collective angst predicts collective nostalgia, which subsequently relates to stronger feelings of in-group continuity via in-group belonging (but not via out-group rejection). Collective nostalgia generally predicted opposition to immigrants, but this was subsequently not related to in-group continuity.
Schizophrenia-related cognitive dysfunction in the Cyclin-D2 knockout mouse model of ventral hippocampal hyperactivity
Authors: Grimm Christina M. , Aksamaz Sonat , Schulz Stefanie , Teutsch Jasper , Sicinski Piotr , Liss Birgit , Kätzel Dennis
Published: October 2018

Elevated activity at the output stage of the anterior hippocampus has been described as a physiological endophenotype of schizophrenia, and its development maps onto the transition from the prodromal to the psychotic state. Interventions that halt the spreading glutamatergic over-activity in this region and thereby the development of overt schizophrenia could be promising therapies. However, animal models with high construct validity to support such pre-clinical development are scarce. The Cyclin-D2 knockout (CD2-KO) mouse model shows a hippocampal parvalbumin-interneuron dysfunction, and its pattern of hippocampal over-activity shares similarities with that seen in prodromal patients. Conducting a comprehensive phenotyping of CD2-KO mice, we found that they displayed novelty-induced hyperlocomotion (a rodent correlate of positive symptoms of schizophrenia), that was largely resistant against D1- and D2-dopamine-receptor antagonism, but responsive to the mGluR2/3-agonist LY379268. In the negative symptom domain, CD2-KO mice showed transiently reduced sucrose-preference (anhedonia), but enhanced interaction with novel mice and objects, as well as normal nest building and incentive motivation. Also, unconditioned anxiety, perseveration, and motor-impulsivity were unaltered. However, in the cognitive domain, CD2-knockouts showed reduced executive function in assays of rule-shift and rule-reversal learning, and also an impairment in working memory, that was resistant against LY379268-treatment. In contrast, sustained attention and forms of spatial and object-related memory that are mediated by short-term habituation of stimulus-specific attention were intact. Our results suggest that CD2-KO mice are a valuable model in translational research targeted at the pharmacoresistant cognitive symptom domain in causal relation to hippocampal over-activity in the prodrome-to-psychosis transition.
Correction to: TRIM50 suppressed hepatocarcinoma progression through directly targeting SNAIL for ubiquitous degradation
Authors: Ma Xiaoxiao , Ma Xiaomin , Qiu Yumin , Zhu Lihui , Lin Yueke , You Yajing , Ma Dapeng , Qin Zhenzhi , Sun Caiyu , Zhao Yunxue , Sun Yanlin , Han Lihui
Published: October 2018

In Table 1, the number of patients with distant metastasis should be 13(16.5%), and the number of patients without distant metastasis should be 12(15.4%). The authors placed these two numbers inversely in the published paper.
Nitazoxanide, an antiprotozoal drug, inhibits late-stage autophagy and promotes ING1-induced cell cycle arrest in glioblastoma
Authors: Wang Xiaoxiong , Shen Chen , Liu Zhendong , Peng Fei , Chen Xin , Yang Guang , Zhang Daming , Yin Zhiqin , Ma Jichao , Zheng Zhixing , Zhao Boxian , Liu Huailei , Wang Ligang , Wu Jianing , Han Dayong , Wang Kaikai , Zhong Chen , Hou Xu , Zhao Wenyang , Shu Mengting , Wang Xinzhuang , Zhao Shiguang
Published: October 2018

Glioblastoma is the most common and aggressive primary brain tumor in adults. New drug design and development is still a major challenge for glioma treatment. Increasing evidence has shown that nitazoxanide, an antiprotozoal drug, has a novel antitumor role in various tumors and exhibits multiple molecular functions, especially autophagic regulation. However, whether nitazoxanide-associated autophagy has an antineoplastic effect in glioma remains unclear. Here, we aimed to explore the underlying molecular mechanism of nitazoxanide in glioblastoma. Our results showed that nitazoxanide suppressed cell growth and induced cell cycle arrest in glioblastoma by upregulating ING1 expression with a favorable toxicity profile. Nitazoxanide inhibited autophagy through blockage of late-stage lysosome acidification, resulting in decreased cleavage of ING1. A combination with chloroquine or Torin1 enhanced or impaired the chemotherapeutic effect of nitazoxanide in glioblastoma cells. Taken together, these findings indicate that nitazoxanide as an autophagy inhibitor induces cell cycle arrest in glioblastoma via upregulated ING1 due to increased transcription and decreased post-translational degradation by late-stage autophagic inhibition.
Automated quantification of bioluminescence images
Authors: Klose Alexander D. , Paragas Neal
Published: October 2018

We developed a computer-aided analysis tool for quantitatively determining bioluminescent reporter distributions inside small animals. The core innovations are a body-fitting animal shuttle and a statistical mouse atlas, both of which are spatially aligned and scaled according to the animal’s weight, and hence provide data congruency across animals of varying size and pose. In conjunction with a multispectral bioluminescence tomography technique capitalizing on the spatial framework of the shuttle, the in vivo biodistribution of luminescent reporters can rapidly be calculated and, thus, enables operator-independent and computer-driven data analysis. We demonstrate its functionality by quantitatively monitoring a bacterial infection, where the bacterial organ burden was determined and validated with the established serial-plating method. In addition, the statistical mouse atlas was validated and compared to existing techniques providing an anatomical reference. The proposed data analysis tool promises to increase data throughput and data reproducibility and accelerate human disease modeling in mice.
Complex virome in feces from Amerindian children in isolated Amazonian villages
Authors: Siqueira Juliana D. , Dominguez-Bello Maria Gloria , Contreras Monica , Lander Orlana , Caballero-Arias Hortensia , Xutao Deng , Noya-Alarcon Oscar , Delwart Eric
Published: October 2018

The number of viruses circulating in small isolated human populations may be reduced by viral extinctions and rare introductions. Here we used viral metagenomics to characterize the eukaryotic virome in feces from healthy children from a large urban center and from three Amerindian villages with minimal outside contact. Numerous human enteric viruses, mainly from the Picornaviridae and Caliciviridae families, were sequenced from each of the sites. Multiple children from the same villages shed closely related viruses reflecting frequent transmission clusters. Feces of isolated villagers also contained multiple viral genomes of unknown cellular origin from the Picornavirales order and CRESS-DNA group and higher levels of nematode and protozoan DNA. Despite cultural and geographic isolation, the diversity of enteric human viruses was therefore not reduced in these Amazonian villages. Frequent viral introductions and/or increased susceptibility to enteric infections may account for the complex fecal virome of Amerindian children in isolated villages.
SHQ1 regulation of RNA splicing is required for T-lymphoblastic leukemia cell survival
Authors: Su Hexiu , Hu Juncheng , Huang Liang , Yang Yang , Thenoz Morgan , Kuchmiy Anna , Hu Yufeng , Li Peng , Feng Hui , Zhou Yu , Taghon Tom , Van Vlierberghe Pieter , Qing Guoliang , Chen Zhichao , Liu Hudan
Published: October 2018

T-acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with complicated heterogeneity. Although expression profiling reveals common elevated genes in distinct T-ALL subtypes, little is known about their functional role(s) and regulatory mechanism(s). We here show that SHQ1, an H/ACA snoRNP assembly factor involved in snRNA pseudouridylation, is highly expressed in T-ALL. Mechanistically, oncogenic NOTCH1 directly binds to the SHQ1 promoter and activates its transcription. SHQ1 depletion induces T-ALL cell death in vitro and prolongs animal survival in murine T-ALL models. RNA-Seq reveals that SHQ1 depletion impairs widespread RNA splicing, and MYC is one of the most prominently downregulated genes due to inefficient splicing. MYC overexpression significantly rescues T-ALL cell death resulted from SHQ1 inactivation. We herein report a mechanism of NOTCH1–SHQ1–MYC axis in T-cell leukemogenesis. These findings not only shed light on the role of SHQ1 in RNA splicing and tumorigenesis, but also provide additional insight into MYC regulation.
Rats adopt the optimal timescale for evidence integration in a dynamic environment
Authors: Piet Alex T. , El Hady Ahmed , Brody Carlos D.
Published: October 2018

Decision making in dynamic environments requires discounting old evidence that may no longer inform the current state of the world. Previous work found that humans discount old evidence in a dynamic environment, but do not discount at the optimal rate. Here we investigated whether rats can optimally discount evidence in a dynamic environment by adapting the timescale over which they accumulate evidence. Using discrete evidence pulses, we exactly compute the optimal inference process. We show that the optimal timescale for evidence discounting depends on both the stimulus statistics and noise in sensory processing. When both of these components are taken into account, rats accumulate and discount evidence with the optimal timescale. Finally, by changing the volatility of the environment, we demonstrate experimental control over the rats’ accumulation timescale. The mechanisms supporting integration are a subject of extensive study, and experimental control over these timescales may open new avenues of investigation.
HIV-1 Tat interactions with cellular 7SK and viral TAR RNAs identifies dual structural mimicry
Authors: Pham Vincent V. , Salguero Carolina , Khan Shamsun Nahar , Meagher Jennifer L. , Brown W. Clay , Humbert Nicolas , de Rocquigny Hugues , Smith Janet L. , D’Souza Victoria M.
Published: October 2018

The HIV Tat protein competes with the 7SK:HEXIM interaction to hijack pTEFb from 7SK snRNP and recruit it to the TAR motif on stalled viral transcripts. Here we solve structures of 7SK stemloop-1 and TAR in complex with Tat’s RNA binding domain (RBD) to gain insights into this process. We find that 7SK is peppered with arginine sandwich motifs (ASM)—three classical and one with a pseudo configuration. Despite having similar RBDs, the presence of an additional arginine, R52, confers Tat the ability to remodel the pseudo configuration, required for HEXIM binding, into a classical sandwich, thus displacing HEXIM. Tat also uses R52 to remodel the TAR bulge into an ASM whose structure is identical to that of the remodeled ASM in 7SK. Together, our structures reveal a dual structural mimicry wherein viral Tat and TAR have co-opted structural motifs present in cellular HEXIM and 7SK for productive transcription of its genome.
The olfactory epithelium as a port of entry in neonatal neurolisteriosis
Authors: Pägelow Dennis , Chhatbar Chintan , Beineke Andreas , Liu Xiaokun , Nerlich Andreas , van Vorst Kira , Rohde Manfred , Kalinke Ulrich , Förster Reinhold , Halle Stephan , Valentin-Weigand Peter , Hornef Mathias W. , Fulde Marcus
Published: October 2018

Bacterial infections of the central nervous system (CNS) remain a major cause of mortality in the neonatal population. Commonly used parenteral infection models, however, do not reflect the early course of the disease leaving this critical step of the pathogenesis largely unexplored. Here, we analyzed nasal exposure of 1-day-old newborn mice to Listeria monocytogenes (Lm). We found that nasal, but not intragastric administration, led to early CNS infection in neonate mice. In particular, upon bacterial invasion of the olfactory epithelium, Lm subsequently spread along the sensory neurons entering the brain tissue at the cribriform plate and causing a significant influx of monocytes and neutrophils. CNS infection required listeriolysin for penetration of the olfactory epithelium and ActA, a mediator of intracellular mobility, for translocation into the brain tissue. Taken together, we propose an alternative port of entry and route of infection for neonatal neurolisteriosis and present a novel infection model to mimic the clinical features of late-onset disease in human neonates.
Modulation of AMPA receptor surface diffusion restores hippocampal plasticity and memory in Huntington’s disease models
Authors: Zhang Hongyu , Zhang Chunlei , Vincent Jean , Zala Diana , Benstaali Caroline , Sainlos Matthieu , Grillo-Bosch Dolors , Daburon Sophie , Coussen Françoise , Cho Yoon , David Denis J. , Saudou Frederic , Humeau Yann , Choquet Daniel
Published: October 2018

Impaired hippocampal synaptic plasticity contributes to cognitive impairment in Huntington’s disease (HD). However, the molecular basis of such synaptic plasticity defects is not fully understood. Combining live-cell nanoparticle tracking and super-resolution imaging, we show that AMPAR surface diffusion, a key player in synaptic plasticity, is disturbed in various rodent models of HD. We demonstrate that defects in the brain-derived neurotrophic factor (BDNF)–tyrosine receptor kinase B (TrkB) signaling pathway contribute to the deregulated AMPAR trafficking by reducing the interaction between transmembrane AMPA receptor regulatory proteins (TARPs) and the PDZ-domain scaffold protein PSD95. The disturbed AMPAR surface diffusion is rescued by the antidepressant drug tianeptine via the BDNF signaling pathway. Tianeptine also restores the impaired LTP and hippocampus-dependent memory in different HD mouse models. These findings unravel a mechanism underlying hippocampal synaptic and memory dysfunction in HD, and highlight AMPAR surface diffusion as a promising therapeutic target.
Tridimensional infiltration of DNA viruses into the host genome shows preferential contact with active chromatin
Authors: Moreau Pierrick , Cournac Axel , Palumbo Gianna Aurora , Marbouty Martial , Mortaza Shogofa , Thierry Agnes , Cairo Stefano , Lavigne Marc , Koszul Romain , Neuveut Christine
Published: October 2018

Whether non-integrated viral DNAs distribute randomly or target specific positions within the higher-order architecture of mammalian genomes remains largely unknown. Here we use Hi-C and viral DNA capture (CHi-C) in primary human hepatocytes infected by either hepatitis B virus (HBV) or adenovirus type 5 (Ad5) virus to show that they adopt different strategies in their respective positioning at active chromatin. HBV contacts preferentially CpG islands (CGIs) enriched in Cfp1 a factor required for its transcription. These CGIs are often associated with highly expressed genes (HEG) and genes deregulated during infection. Ad5 DNA interacts preferentially with transcription start sites (TSSs) and enhancers of HEG, as well as genes upregulated during infection. These results show that DNA viruses use different strategies to infiltrate genomic 3D networks and target specific regions. This targeting may facilitate the recruitment of transcription factors necessary for their own replication and contribute to the deregulation of cellular gene expression.
Author Correction: Clopidogrel as a donor probe and thioenol derivatives as flexible promoieties for enabling H2S biomedicine
Authors: Zhu Yaoqiu , Romero Elkin L. , Ren Xiaodong , Sanca Angel J. , Du Congkuo , Liu Cai , Karim Zubair A. , Alshbool Fatima Z. , Khasawneh Fadi T. , Zhou Jiang , Zhong Dafang , Geng Bin
Published: October 2018

The original version of this Article contained an error in the spelling of the author Bin Geng, which was incorrectly given as Bing Geng. This has been corrected in both the PDF and HTML versions of the Article.
Author Correction: Geometric Control of Cell Migration
Authors: Chen Bo , Kumar Girish , Co Carlos C. , Ho Chia-Chi
Published: October 2018

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Genome-wide identification of geographical segregated genetic markers in Salmonella enterica serovar Typhimurium variant 4,[5],12:i:-
Authors: Palma Federica , Manfreda Gerardo , Silva Mickael , Parisi Antonio , Barker Dillon O. R. , Taboada Eduardo N. , Pasquali Frédérique , Rossi Mirko
Published: October 2018

Salmonella enterica ser. Typhimurium monophasic variant 4,[5],12:i:- has been associated with food-borne epidemics worldwide and swine appeared to be the main reservoir in most of the countries of isolation. However, the monomorphic nature of this serovar has, so far, hindered identification of the source due to expansion of clonal lineages in multiple hosts and food producing systems. Since geographically structured genetic signals can shape bacterial populations, identification of biogeographical markers in S. 1,4,[5],12:i:- genomes can contribute to improving source attribution. In this study, the phylogeographical structure of 148 geographically and temporally related Italian S. 1,4,[5],12:i:- has been investigated. The Italian isolates belong to a large population of clonal S. Typhimurium/1,4,[5],12:i:- isolates collected worldwide in two decades showing up to 2.5% of allele differences. Phylogenetic reconstruction revealed that isolates from the same geographical origin form highly supported monophyletic groups, suggesting discrete geographical segregation. These monophyletic groups are characterized by the gene content of a large sopE-containing prophage. Within this prophage, genome-wide comparison identified several genes overrepresented in strains of Italian origin. This suggests that certain lineages may be characterized by the acquisition of specific accessory genetic markers useful for improving identification of the source in ongoing epidemics.
Prenatal exposure to incubation calls affects song learning in the zebra finch
Authors: Katsis Andrew C. , Davies Mzuri H. , Buchanan Katherine L. , Kleindorfer Sonia , Hauber Mark E. , Mariette Mylene M.
Published: October 2018

Songbirds are important models for understanding the mechanisms and fitness consequences of imitative vocal learning. Although the effects of early-life environmental and social conditions on song learning are well-established, the impact of early sound exposure has received surprisingly little attention. Yet recent evidence hints at auditory sensitivity in songbird embryos, including in the zebra finch (Taeniopygia guttata), a classic model species for song learning. Here, we tested whether prenatal exposure to incubation calls—highly rhythmic parental vocalisations produced on the nest—affected song learning in zebra finches. Embryos were exposed in the egg to either incubation (treatment) or contact (control) calls, and after hatching were reared in a large colony. The playback treatment did not affect song complexity nor the accuracy of song copying from the social father, but instead increased learning of non-paternal song syllables. This, in turn, improved males’ mounting success in mating trials. These effects may be attributable to changes in juvenile social behaviours, as playback also influenced male behaviour during mating trials. Our study provides the first experimental evidence that prenatal acoustic environment affects song learning and courtship behaviour in songbirds, thereby raising interesting questions on the role of innate versus acquired biases for vocal learning.
Recurrent Neural Network for Predicting Transcription Factor Binding Sites
Authors: Shen Zhen , Bao Wenzheng , Huang De-Shuang
Published: October 2018

It is well known that DNA sequence contains a certain amount of transcription factors (TF) binding sites, and only part of them are identified through biological experiments. However, these experiments are expensive and time-consuming. To overcome these problems, some computational methods, based on k-mer features or convolutional neural networks, have been proposed to identify TF binding sites from DNA sequences. Although these methods have good performance, the context information that relates to TF binding sites is still lacking. Research indicates that standard recurrent neural networks (RNN) and its variants have better performance in time-series data compared with other models. In this study, we propose a model, named KEGRU, to identify TF binding sites by combining Bidirectional Gated Recurrent Unit (GRU) network with k-mer embedding. Firstly, DNA sequences are divided into k-mer sequences with a specified length and stride window. And then, we treat each k-mer as a word and pre-trained word representation model though word2vec algorithm. Thirdly, we construct a deep bidirectional GRU model for feature learning and classification. Experimental results have shown that our method has better performance compared with some state-of-the-art methods. Additional experiments about embedding strategy show that k-mer embedding will be helpful to enhance model performance. The robustness of KEGRU is proved by experiments with different k-mer length, stride window and embedding vector dimension.
The dissipation of thiamethoxam and its main metabolite clothianidin during strawberry growth and jam-making process
Authors: Liu Na , Pan Xinglu , Yang Qingxi , Ji Mingshan , Zhang Zhihong
Published: October 2018

Few studies focused on the residue of thiamethoxam and its metabolite clothianidin on strawberry where it is widely used, despite this is essential to assess the potential food risk of thiamethoxam and its main metabolite clothianidin. In this study, the dissipation of thiamethoxam and its metabolite clothianidin during strawberry growth and jam-making process were assessed. The strawberry was sprayed with thiamethoxam based on the field application to investigate the dissipation of thiamethoxam as well as clothianidin formation. The half-life of thiamethoxam in strawberry was 9.0 days and the concentration of clothianidin in strawberry gradually increased from 0.55 to 11 μg/kg within 30 days. In addition, the amount of thiamethoxam decreased by 51.7% and clothianidin decreased by 40.2% during the homogenization process. The processing factor values of whole processing all less than 1 except simmering. This results from this study will not only help to understand the dissipation kinetics of thiamethoxam and clothianidin in the strawberry, but also facilitate to make more accurate risk assessments of them during strawberry jam making process.
A change of perspective in network centrality
Authors: Sciarra Carla , Chiarotti Guido , Laio Francesco , Ridolfi Luca
Published: October 2018

Typing “Yesterday” into the search-bar of your browser provides a long list of websites with, in top places, a link to a video by The Beatles. The order your browser shows its search results is a notable example of the use of network centrality. Centrality measures the importance of the nodes in a network and it plays a crucial role in several fields, ranging from sociology to engineering, and from biology to economics. Many centrality metrics are available. However, these measures are generally based on ad hoc assumptions, and there is no commonly accepted way to compare the effectiveness and reliability of different metrics. Here we propose a new perspective where centrality definition arises naturally from the most basic feature of a network, its adjacency matrix. Following this perspective, different centrality measures naturally emerge, including degree, eigenvector, and hub-authority centrality. Within this theoretical framework, the effectiveness of different metrics is evaluated and compared. Tests on a large set of networks show that the standard centrality metrics perform unsatisfactorily, highlighting intrinsic limitations for describing the centrality of nodes in complex networks. More informative multi-component centrality metrics are proposed as the natural extension of standard metrics.
Evidence for a direct link between PAD4-mediated citrullination and the oxidative burst in human neutrophils
Authors: Zhou Yebin , An Ling-Ling , Chaerkady Raghothama , Mittereder Nanette , Clarke Lori , Cohen Taylor S. , Chen Bo , Hess Sonja , Sims Gary P. , Mustelin Tomas
Published: October 2018

Neutrophils are critical for the defense against pathogens, in part through the extrusion of extracellular DNA traps, phagocytosis, and the production of reactive oxygen species. Neutrophils may also play an important role in the pathogenesis of rheumatoid arthritis (RA) through the activation of protein arginine deiminases (PADs) that citrullinate proteins that subsequently act as autoantigens. We report that PAD4 is physically associated with the cytosolic subunits of the oxidative burst machinery, p47phox (also known as neutrophil cytosol factor 1, NCF1) and p67phox (NCF2). Activation of PAD4 by membranolytic insults that result in high levels of intracellular calcium (higher than physiological neutrophil activation) leads to rapid citrullination of p47phox/NCF1 and p67phox/NCF2, as well as their dissociation from PAD4. This dissociation prevents the assembly of an active NADPH oxidase complex and an oxidative burst in neutrophils stimulated by phorbol-ester or immune complexes. In further support of a substrate-to-inactive enzyme interaction, small-molecule PAD inhibitors also disrupt the PAD4-NCF complex and reduce oxidase activation and phagocytic killing of Staphylococcus aureus. This novel role of PAD4 in the regulation of neutrophil physiology suggests that targeting PAD4 with active site inhibitors for the treatment of RA may have a broader impact on neutrophil biology than just inhibition of citrullination.
Distinct co-expression networks using multi-omic data reveal novel interventional targets in HPV-positive and negative head-and-neck squamous cell cancer
Authors: Costa Raquel L. , Boroni Mariana , Soares Marcelo A.
Published: October 2018

The human papillomavirus (HPV) is present in a significant fraction of head-and-neck squamous cell cancer (HNSCC). The main goal of this study was to identify distinct co-expression patterns between HPV+ and HPV− HNSCC and to provide insights into potential regulatory mechanisms/effects within the analyzed networks. We selected cases deposited in The Cancer Genome Atlas database comprising data of gene expression, methylation profiles and mutational patterns, in addition to clinical information. The intersection among differentially expressed and differentially methylated genes showed the negative correlations between the levels of methylation and expression, suggesting that these genes have their expression levels regulated by methylation alteration patterns in their promoter. Weighted correlation network analysis was used to identify co-expression modules and a systematic approach was applied to refine them and identify key regulatory elements integrating results from the other omics. Three distinct co-expression modules were associated with HPV status and molecular signatures. Validation using independent studies reporting biological experimental data converged for the most significant genes in all modules. This study provides insights into complex genetic and epigenetic particularities in the development and progression of HNSCC according to HPV status, and contribute to unveiling specific genes/pathways as novel therapeutic targets in HNSCC.
Circulating metabolic biomarkers of renal function in diabetic and non-diabetic populations
Authors: Barrios Clara , Zierer Jonas , Würtz Peter , Haller Toomas , Metspalu Andres , Gieger Christian , Thorand Barbara , Meisinger Christa , Waldenberger Melanie , Raitakari Olli , Lehtimäki Terho , Otero Sol , Rodríguez Eva , Pedro-Botet Juan , Kähönen Mika , Ala-Korpela Mika , Kastenmüller Gabi , Spector Tim D. , Pascual Julio , Menni Cristina
Published: October 2018

Using targeted NMR spectroscopy of 227 fasting serum metabolic traits, we searched for novel metabolic signatures of renal function in 926 type 2 diabetics (T2D) and 4838 non-diabetic individuals from four independent cohorts. We furthermore investigated longitudinal changes of metabolic measures and renal function and associations with other T2D microvascular complications. 142 traits correlated with glomerular filtration rate (eGFR) after adjusting for confounders and multiple testing: 59 in diabetics, 109 in non-diabetics with 26 overlapping. The amino acids glycine and phenylalanine and the energy metabolites citrate and glycerol were negatively associated with eGFR in all the cohorts, while alanine, valine and pyruvate depicted opposite association in diabetics (positive) and non-diabetics (negative). Moreover, in all cohorts, the triglyceride content of different lipoprotein subclasses showed a negative association with eGFR, while cholesterol, cholesterol esters (CE), and phospholipids in HDL were associated with better renal function. In contrast, phospholipids and CEs in LDL showed positive associations with eGFR only in T2D, while phospholipid content in HDL was positively associated with eGFR both cross-sectionally and longitudinally only in non-diabetics. In conclusion, we provide a wide list of kidney function–associated metabolic traits and identified novel metabolic differences between diabetic and non-diabetic kidney disease.
Identification of reference genes for RT-qPCR data normalization in Gammarus fossarum (Crustacea Amphipoda)
Authors: Mehennaoui Kahina , Legay Sylvain , Serchi Tommaso , Guérold François , Giamberini Laure , Gutleb Arno C. , Cambier Sébastien
Published: October 2018

Gene expression profiling via RT-qPCR is a robust technique increasingly used in ecotoxicology. Determination and validation of optimal reference genes is a requirement for initiating RT-qPCR experiments. To our best knowledge, this study is the first attempt of identifying a set of reference genes for the freshwater crustacean Gammarus fossarum. Six candidate genes (Actin, TUB, UB, SDH, Clathrin and GAPDH) were tested in order to determine the most stable ones in different stress conditions and to increase the robustness of RT-qPCR data. SDH and Clathrin appeared as the most stable ones. A validation was performed using G. fossarum samples exposed for 15 days to AgNO3, silver nanoparticles (AgNPs) 40 nm and gold nanoparticles (AuNPs) 40 nm. Effects on HSP90 were evaluated and data normalized using Clathrin and SDH. A down-regulation of HSP90 was observed when G. fossarum were exposed to AuNPs 40 nm whereas no effects were observed when G. fossarum were exposed to AgNPs 40 nm. This study highlights the importance of the preliminary determination of suitable reference genes for RT-qPCR experiments. Additionally, this study allowed, for the first time, the determination of a set of valuable genes that can be used in other RT-qPCR studies using G. fossarum as model organism.
Fine-tuning carbapenem resistance by reducing porin permeability of bacteria activated in the selection process of conjugation
Authors: Kong Hoi-Kuan , Pan Qing , Lo Wai-U. , Liu Xuan , Law Carmen O. K. , Chan Ting-fung , Ho Pak-Leung , Lau Terrence Chi-Kong
Published: October 2018

Antibiotic resistance is an emerging public health issue. Plasmids are one of the popular carriers to disseminate resistance genes among pathogens. However, the response of plasmid-carrying bacteria to antibiotic treatment and how these bacteria evolve to increase their resistance remain elusive. In this study, we conjugated plasmid pNDM-HK to E. coli J53 recipient cells and selected survivors using different concentrations of the broad spectrum antibiotic meropenem. After selection, transconjugants conferred varying minimum inhibitory concentrations with respect to carbapenems. We sequenced and compared the transcriptomes of transconjugants that exhibited distinct carbapenem susceptibilities, and found that the loss of outer membrane proteins led to antibiotic resistance. Moreover, we identified a novel mutation, G63S, in transcription factor OmpR which moderates the expression of outer membrane proteins. The loss of porins was due to incapability of phosphorylation, which is essential for porin transcription and carbapenem resistance. We also characterized other genes that are regulated by ompR in this mutant, which contributed to bacterial antibiotic resistance. Overall, our studies suggest antibiotic pressure after conjugation might be an alternative pathway to promote antimicrobial resistance.
Toxic Effects of Size-tunable Gold Nanoparticles on Caenorhabditis elegans Development and Gene Regulation
Authors: Hu Chun-Chih , Wu Gong-Her , Lai Sheng-Feng , Muthaiyan Shanmugam Muniesh , Hwu Y. , Wagner Oliver I. , Yen Ta-Jen
Published: October 2018

We utilized size-tunable gold nanoparticles (Au NPs) to investigate the toxicogenomic responses of the model organism Caenorhabditis elegans. We demonstrated that the nematode C. elegans can uptake Au NPs coated with or without 11-mercaptoundecanoic acid (MUA), and Au NPs are detectable in worm intestines using X-ray microscopy and confocal optical microscopy. After Au NP exposure, C. elegans neurons grew shorter axons, which may have been related to the impeded worm locomotion behavior detected. Furthermore, we determined that MUA to Au ratios of 0.5, 1 and 3 reduced the worm population by more than 50% within 72 hours. In addition, these MUA to Au ratios reduced the worm body size, thrashing frequency (worm mobility) and brood size. MTT assays were employed to analyze the viability of cultured C. elegans primary neurons exposed to MUA-Au NPs. Increasing the MUA to Au ratios increasingly reduced neuronal survival. To understand how developmental changes (after MUA-Au NP treatment) are related to changes in gene expression, we employed DNA microarray assays and identified changes in gene expression (e.g., clec-174 (involved in cellular defense), cut-3 and fil-1 (both involved in body morphogenesis), dpy-14 (expressed in embryonic neurons), and mtl-1 (functions in metal detoxification and homeostasis)).
Facile lipase-catalyzed synthesis of a chocolate fat mimetic
Authors: Ghazani Saeed M. , Marangoni Alejandro G.
Published: October 2018

A cocoa butter equivalent (CBE) was synthesized enzymatically from readily available edible fats with fatty acid and triacylglycerol compositions that closely resemble the fat present in chocolate, cocoa butter. A commercially available immobilized fungal lipase, Lipozyme RM IM, was used as the reaction catalyst. Reaction parameters were a temperature of 65 °C, water activity of 0.11, a 4 h reaction time, and a substrate mass ratio of a commercial enzymatically synthesized shea stearin (SS) to palm mid-fraction (PMF) of 6:4 (w/w). Fractionation was also used after reaction completion to further approach the triacylglycerol composition of cocoa butter by removing trisaturated and unsaturated triacylglycerols. The yield of the triglyceride 1-palmitoyl-2-oleoyl, 3-stearoyl-glycerol (POS) produced was 57.7% (w/w). The amounts of 1,3-dipalmitoyl-2-oleoyl-glycerol (POP), (POS) and 1,3-stearoyl-2-oleoyl-glycerol (SOS) in the final CBE were 11.2%, 36.3%, and 34.8%, respectively. In comparison, the amounts of POP, POS and SOS in the cocoa butter used in this study were 15.2%, 38.2%, and 27.8%, respectively. No significant differences (P > 0.05) in melting point and enthalpy of fusion between CB and the CBE were observed. In comparison, a non-interesterified blend of SS and PMF (60:40 w/w) showed significantly (P < 0.05) higher melting point and lower enthalpy of fusion compared to CB. The crystal polymorphic form V of CB (β2-3L) was similar to that of CBE and SS/PMF (60:40 w/w). The solid fat content (SFC) vs. temperature profile of the CBE generally resembled that of CB, except that the CBE had significantly (P < 0.05) higher SFCs at 5, 10, 15, 20 and 25 °C compared to both CB and SS/PMF (60:40 w/w). Addition of 15% (w/w) CBE to CB did not cause any changes in physical properties (melting point, SFC and crystal polymorphic forms) of the CB. This study demonstrates the potential for synthesizing a CB-like CBE using a green, rapid, straightforward one step enzymatic conversion followed by fractionation from widely available edible fats.
Milk Fat Globule Membrane Supplementation in Formula-fed Rat Pups Improves Reflex Development and May Alter Brain Lipid Composition
Authors: Moukarzel Sara , Dyer Roger A. , Garcia Cyrielle , Wiedeman Alejandra M. , Boyce Guilaine , Weinberg Joanne , Keller Bernd O. , Elango Rajavel , Innis Sheila M.
Published: October 2018

Human milk contains nutritional, immunoprotective and developmental components that support optimal infant growth and development. The milk fat globule membrane (MFGM) is one unique component, comprised of a tri-layer of polar lipids, glycolipids, and proteins, that may be important for brain development. MFGM is not present in most infant formulas. We tested the effects of bovine MFGM supplementation on reflex development and on brain lipid and metabolite composition in rats using the “pup in a cup” model. From postnatal d5 to d18, rats received either formula supplemented with MFGM or a standard formula without MFGM; a group of mother-reared animals was used as reference/control condition. Body and brain weights did not differ between groups. MFGM supplementation reduced the gap in maturation age between mother-reared and standard formula-fed groups for the ear and eyelid twitch, negative geotaxis and cliff avoidance reflexes. Statistically significant differences in brain phospholipid and metabolite composition were found at d13 and/or d18 between mother-reared and standard formula-fed groups, including a higher phosphatidylcholine:phosphatidylethanolamine ratio, and higher phosphatidylserine, glycerol-3 phosphate, and glutamine in mother-reared compared to formula-fed pups. Adding MFGM to formula narrowed these differences. Our study demonstrates that addition of bovine MFGM to formula promotes reflex development and alters brain phospholipid and metabolite composition. Changes in brain lipid metabolism and their potential functional implications for neurodevelopment need to be further investigated in future studies.
A new look at weather-related health impacts through functional regression
Authors: Masselot Pierre , Chebana Fateh , Ouarda Taha B. M. J. , Bélanger Diane , St-Hilaire André , Gosselin Pierre
Published: October 2018

A major challenge of climate change adaptation is to assess the effect of changing weather on human health. In spite of an increasing literature on the weather-related health subject, many aspect of the relationship are not known, limiting the predictive power of epidemiologic models. The present paper proposes new models to improve the performances of the currently used ones. The proposed models are based on functional data analysis (FDA), a statistical framework dealing with continuous curves instead of scalar time series. The models are applied to the temperature-related cardiovascular mortality issue in Montreal. By making use of the whole information available, the proposed models improve the prediction of cardiovascular mortality according to temperature. In addition, results shed new lights on the relationship by quantifying physiological adaptation effects. These results, not found with classical model, illustrate the potential of FDA approaches.
A Prognostic 5-lncRNA Expression Signature for Head and Neck Squamous Cell Carcinoma
Authors: Liu Guancheng , Zheng Jinyang , Zhuang Liming , Lv Yunxia , Zhu Gangcai , Pi Leiming , Wang Junchen , Chen Changhan , Li Zhexuan , Liu Jiangyi , Chen liangjuan , Cai Gengming , Zhang Xin
Published: October 2018

Head and neck squamous cell carcinoma (HNSCC) is a common malignant cancer that accounts for 5–10% of all cancers. This study aimed to identify essential genes associated with the prognosis of HNSCC and construct a powerful prognostic model for the risk assessment of HNSCC. RNAseq expression profile data for the patients with HNSCC were obtained from the TCGA database (GEO). A total of 500 samples with full clinical following-up were randomly divided into a training set and a validation set. The training set was used to screen for differentially expressed lncRNAs. Single-factor survival analysis was performed to obtain lncRNAs that associated with prognosis. A robust likelihood-based survival model was constructed to identify the lncRNAs that are essential for the prognosis of HNSCC. A co-expression network between genes and lncRNAs was also constructed to identify lncRNAs co-expressed with genes to serve as the final signature lncRNAs for prognosis. Finally, the prognostic effect of the signature lncRNAs was tested by multi-factor survival analysis and a scoring model for the prognosis of HNSCC was constructed. Moreover, the results of the validation set and the relative expression levels of the signature lncRNAs in the tumour and the adjacent tissue were consistent with the results of the training set. The 5 lncRNAs were distributed among 3 expression modules. Further KEGG pathway enrichment analysis showed that these 3 co-expressed modules participate in different pathways, and many of these pathways are associated with the development and progression of disease. Therefore, we proposed that the 5 validated lncRNAs can be used to predict the prognosis of HNSCC patients and can be applied in postoperative treatment and follow-up.