bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Structural Features of Human Norovirus Capsid
Authors: Devant Jessica , Hofhaus Götz , Hansman Grant S. 
Published: January 2019

ABSTRACTHuman noroviruses are a major cause of gastroenteritis, yet there are still no vaccines or antivirals available. Nevertheless, a number of vaccine candidates that are currently in clinical trials are composed of norovirus virus-like particles (VLPs). These VLPs are recognized as morphologically and antigenically similar to norovirus virions. An X-ray crystal structure of the prototype (GI.1) VLPs showed that the norovirus capsid has a T=3 icosahedral symmetry and is composed of 180 copies of the major capsid protein (VP1) that folds into three quasi-equivalent subunits (A, B, and C). In this study, we determined the cryo-EM structure of VLPs for two GII.4 noroviruses that were detected in 1974 and 2012. We showed that these VLPs had a T=4 symmetry and were composed of 240 copies of VP1. The VP1 on the T=4 VLPs adapted four quasi-equivalent subunits (termed A, B, C, and D), which formed two distinct dimers (A/B and C/D). We found that the T=4 protruding domain was elevated ~21 Å off the capsid shell, which was ~7 Å more than the previously determined for the T=3 GII.10 norovirus. Another interesting feature of the T=4 VLPs was a small cavity and flaplike structure located at the twofold axis. This structural feature was associated with the shell domain (D subunit) and disrupted the contiguous shell. Altogether, we showed that the T=4 VLPs had a number of structural similarities and differences with other noroviruses, but how these structural changes associate with norovirus virions could be important for vaccine studies.IMPORTANCEThe discovery that the GII.4 VLPs (identified in 1974 and 2012, termed CHDC-1974 and NSW-2012, respectively) have a T=4 symmetry is of major significance, since the NSW-2012 is clinically important and previous structural and biochemical studies assumed noroviruses have a T=3 symmetry and are composed of 180 copies of VP1. More importantly, NSW-2012 norovirus shared 96% amino acid identity with a GII.4 vaccine candidate and our data suggests that this vaccine might also have a T=4 symmetry. Although it is not clear if the T=4 VLPs were an artifact of the insect cell expression system, the T=4 VLP vaccines might not recognize equivalent epitopes on T=3 virions, which will be important for future neutralization studies. Finally, further studies with other norovirus genotypes and virions are clearly needed in order to determine the level of this structural diversity.
Cassava planting material movement and grower behaviour in Zambia: implications for disease management
Authors: Szyniszewska Anna Maria , Chiza Chikoti Patrick , Tembo Mathias , Mulenga Rabson , van den Bosch Frank , Finn McQuaid Christopher 
Published: January 2019

AbstractCassava is an important food crop for most small-holder growers across sub-Saharan Africa, where production is largely limited by the presence of two viral diseases: cassava mosaic disease (CMD) and cassava brown streak disease (CBSD), both propagated by a vector whitefly and via human-mediated movement of infected cassava stems. Despite its importance, there is limited knowledge of growers’ behaviour related to planting material movement, as well as growers’ perception and knowledge of cassava diseases, which have major implications for disease spread and control. This study was conducted to address this knowledge gap by surveying small-holder growers in Zambia. A total of 96 subsistence cassava growers across five provinces were surveyed between 2015 and 2017. Most growers interviewed used planting materials from their own fields (94%) or those of nearby (<10 km) family and friends, although some large transactions with markets, middlemen, and NGOs occurred over longer distances. At the same time, information related to cassava diseases and uninfected planting material only reached 48% of growers, where those with access to information were more concerned about the disease. These data provide a basis for future planning of cassava clean seed systems to control virus diseases, emphasising the critical role of grower knowledge, and consequently education, in success of these systems. In particular, we highlight the importance of extension workers in this education process, as well as farmer’s groups and the media.
An evaluation of the Air Quality Health Index Program on respiratory diseases in Hong Kong: an interrupted time series analysis
Authors: Mason Tonya G. , Schooling C. Mary , Chan King Pan , Tian Linwei 
Published: January 2019

AbstractBackgroundOn December 30th, 2013, the Hong Kong government implemented the Air Quality Health Index (AQHI) to reduce short-term impacts of air pollution on the population. However, whether air quality alert programs, such as the AQHI, reduce morbidity is still questionable. Using a quasi-experimental design, we conducted the first evaluation of the AQHI in Hong Kong focusing on respiratory morbidity.MethodInterrupted time series with Poisson segmented regression from 2010 to 2016 were used to detect any sudden or gradual changes in emergency respiratory hospital admissions, adjusted for air pollutants (NO2, SO2, PM10, O3), temperature and humidity, when the AQHI policy was implemented. Findings were validated using three false policy periods. We also assessed changes by specific respiratory diseases (respiratory tract infections (RTI), asthma, chronic obstructive pulmonary disease and pneumonia) and by age.ResultsFrom January 1st, 2010-December 31st, 2016, 10576.98 deseasonalized, age- and sex-standardized hospital admissions for respiratory diseases occurred in Hong Kong. On implementation of the AQHI, RTI admissions immediately dropped by 14% (relative risk (RR) 0.86 95% confidence interval (CI) 0.76-0.98). In age specific analysis, immediate reductions in hospital admissions, were only apparent in children for RTI (RR 0.84, 95% CI 0.74-0.96) and pneumonia (RR 0.88, 95% CI 0.60-0.96).ConclusionHong Kong’s AQHI helped reduced hospital admissions in children, particularly for RTI and pneumonia. To maximize the health benefits of the policy, at risk groups need to be able to follow the behavioral changes recommended by the AQHI index.
A multidisciplinary approach to a unique Palaeolithic human ichnological record from Italy (Bàsura Cave)
Authors: Romano Marco , Citton Paolo , Salvador Isabella , Arobba Daniele , Rellini Ivano , Firpo Marco , Negrino Fabio , Zunino Marta , Starnini Elisabetta , Avanzini Marco 
Published: January 2019

AbstractBased on the integration of laser scan, sedimentology, geochemistry, archeobotany, geometric morphometries and photogrammetry, here we present evidence testifying a Palaeolithic group that explored a deep cave in northern Italy about 14 ky cal. BP. Ichnological data enable us to shed light on individual and group level behavior, social relationship and mode of exploration of the highly uneven environment. Five individuals, two adults, an adolescent and two children, entered the cave barefoot and with a set of wood chips to illuminate the way. Traces of crawling locomotion are documented for the first time in the global human ichnological record. The anatomic details recognizable in the crawling traces show that no garment was interposed between the limb and the trampled sediments. Our study demonstrate that very young children (the youngest less than three years old) were active members in the Upper Palaeolithic populations, even in seemingly dangerous activities and social ones.
Do clinical investigations predict long-term outcome? A follow-up of paediatric respiratory outpatients
Authors: de Jong Carmen CM. , Pedersen Eva SL. , Goutaki Myrofora , Trachsel Daniel , Barben Juerg , Kuehni Claudia E. 
Published: January 2019

AbstractIntroductionThe contribution of clinical investigations to prediction of long-term outcomes of children investigated for asthma is unclear.AimWe performed a broad range of clinical tests and investigated whether they helped to predict long-term wheeze among children referred for evaluation of possible asthma.MethodsWe studied children aged 6-16 years referred to two Swiss pulmonary outpatient clinics with a history of wheeze, dyspnoea, or cough in 2007. The initial assessment included spirometry, body plethysmography, fractional exhaled nitric oxide, skin prick tests, and bronchial provocation tests (BPT) by exercise, methacholine, and mannitol. Respiratory symptoms were assessed with questionnaires at baseline and at follow-up seven years later. Associations between baseline factors and wheeze at follow-up were investigated by logistic regression.ResultsAt baseline, 111 children were examined in 2007. Seven years after baseline, 85 (77%) completed the follow-up questionnaire, among whom 61 (72%) had wheeze at baseline, while at follow-up 39 (46%) reported wheeze. Adjusting for age and sex, the following characteristics predicted wheeze at adolescence: wheeze triggered by pets (odds ratio 4.2, 95% CI 1.2-14.8), pollen (2.8, 1.1-7.0), and exercise (3.1, 1.2-8.0). Of the clinical tests, only a positive exercise test (3.2, 1.1-9.7) predicted wheeze at adolescence.ConclusionReported exercise-induced wheeze and wheeze triggered by pets or pollen were important predictors of wheeze persistence into adolescence. None of the clinical tests predicted wheeze more strongly than reported symptoms. Clinical tests might be important for asthma diagnosis but medical history is more helpful in predicting prognosis in children referred for asthma.
Ncl1 mediated metabolic rewiring critical during metabolic stress
Authors: Bhat Ajay , Chakraborty Rahul , Adlakha Khushboo , Agam Ganesh , Chakraborty Kausik , Sengupta Shantanu 
Published: January 2019

AbstractNutritional limitation has been vastly studied, however, there is limited knowledge of how cells maintain homeostasis in excess nutrients. In this study, using yeast as a model system, we show that some amino acids are toxic at higher concentrations. With cysteine as a physiologically relevant example, we delineated the pathways/processes that are altered and those that are involved in survival in presence of elevated levels of this amino acid. Using proteomics and metabolomics approach, we found that cysteine upregulates proteins involved in amino acid metabolism, alters amino acid levels, and inhibits protein translation, events that are rescued by leucine supplementation. Through a comprehensive genetic screen we show that leucine mediated effect depends on a tRNA methyltransferase (Ncl1), absence of which decouples cell’s transcription and translation, inhibits the conversation of leucine to ketoisocaproate and leads to TCA cycle block. We therefore, propose a role of Ncl1 in regulating metabolic homeostasis through translational control.
Rice bran supplementation modulates growth, microbiome and metabolome in weaning infants: a clinical trial in Nicaragua and Mali
Authors: Zambrana Luis E. , McKeen Starin , Ibrahim Hend , Zarei Iman , Borresen Erica C. , Doumbia Lassina , Bore Abdoulaye , Cissoko Alima , Douyon Seydou , Kone Karim , Perez Johann , Perez Claudia , Hess Ann , Abdo Zaid , Sangare Lansana , Maiga Ababacar , Becker-Dreps Sylvia , Yuan Lijuan , Koita Ousmane , Vilchez Samuel , Ryan Elizabeth P. 
Published: January 2019

AbstractRice bran supplementation provides nutrients, prebiotics and phytochemicals that enhance gut immunity, reduce enteric pathogens in mice and diarrhea in neonatal pigs, and warranted attention for improvement of environmental enteric dysfunction (EED) in children at risk. EED is a condition that drives childhood stunting via intestinal dysbiosis and impaired nutrient metabolism. This study investigated effects of rice bran supplementation on growth, EED biomarkers, gut microbiome and metabolome in weaning infants from 6 to 12 months old in Nicaragua and Mali. Healthy infants were randomized to a control group or rice bran group that received daily supplementation at increasing doses each month. Stool microbiomes were characterized using 16S rDNA amplicon sequencing. Stool metabolomes were analyzed using ultra-high-performance liquid-chromatography tandem mass-spectrometry. Statistical comparisons were completed at 6, 8, and 12 months of age. Daily consumption of rice bran was safe and feasible for infant growth, decreasing alpha-1 antitrypsin levels, and modulating gut microbiome and metabolome when compared to control. Rice bran merits investigation as a practical intervention strategy that could decrease EED prevalence and risk for children from low- and middle-income countries where rice is grown as a staple food, and bran is used as animal feed or wasted.One Sentence SummaryDietary rice bran supplementation during infant weaning from 6-12 months of age improved growth outcomes, modulated environmental enteric dysfunction biomarkers, and supported metabolism by the gut microbiome.The authors declare no competing financial or non financial interests to disclose as defined by Nature Research. There are also no other interests that might be perceived to influence the results and/or discussion reported in this paper.Correspondence and requests for materials should be addressed to Dr. Elizabeth Ryan (e.p.ryan@colostate.edu).
On the innovation and evolution of predatory tactics
Authors: Gokhale Chaitanya S. , Wignall Anne E. 
Published: January 2019

AbstractPredator-prey systems are ubiquitous across ecological systems. Typical ecological models focus on the dynamics of predator-prey populations. Eco-evolutionary models integrate arms race or Red-Queen like dynamics. The roles of the predator and prey species are always assumed to be static. Nevertheless, sometimes predators can bite off more than they can chew. For example, predators that encounter multiple or dangerous prey types may need to develop new predatory tactics to capture prey. We explore the dynamics of predator-prey dynamics when the prey can injure or kill the predator. This common ecological scenario places pressure on the predator to develop novel predatory tactics to both capture prey and avoid counter-attack from prey. Taking a bottom-up approach, we develop the Holling function mechanistically and then implement it in a model of innovationselection dynamics inspired by economic theory. We show how an interdisciplinary approach can be used to explain the emergence of complex predatory behaviours. Notably, our study shows why predators may hunt dangerous prey even when safe prey are available. In a broader context, we demonstrate how a multidisciplinary approach combining ecology, evolution and economics improves our understanding of a complex behavioural trait.
Thunor: Visualization and Analysis of High-Throughput Dose-response Datasets
Authors: Lubbock Alexander L. R. , Harris Leonard A. , Quaranta Vito , Tyson Darren R. , Lopez Carlos F. 
Published: January 2019

ABSTRACTHigh-throughput cell proliferation assays to quantify drug-response are becoming increasingly common and powerful with the emergence of improved automation and multi-time point analysis methods. However, pipelines for analysis of these datasets that provide reproducible, efficient, and interactive visualization and interpretation are sorely lacking. To address this need, we introduce Thunor, an open-source software platform to manage, analyze, and visualize large, dose-dependent cell proliferation datasets. Thunor supports both end-point and time-based proliferation assays as input. It provides a simple, user-friendly interface with interactive plots and publication-quality images of cell proliferation time courses, dose–response curves, and derived dose–response metrics, e.g. IC50, including across datasets or grouped by tags. Tags are categorical labels for cell lines and drugs, used for aggregation, visualization, and statistical analysis, e.g. cell line mutation or drug class/target pathway. A graphical plate map tool is included to facilitate plate annotation with cell lines, drugs, and concentrations upon data upload. Datasets can be shared with other users via point-and-click access control. We demonstrate the utility of Thunor to examine and gain insight from two large drug response datasets: a large, publicly available cell viability database and an in-house, high-throughput proliferation rate dataset. Thunor is available from www.thunor.net.
Codon clusters with biased synonymous codon usage represent hidden functional domains in protein-coding DNA sequences
Authors: Peng Zhen , Ben-Shahar Yehuda 
Published: January 2019

1.AbstractProtein-coding DNA sequences are thought to primarily affect phenotypes via the peptides they encode. Yet, emerging data suggest that, although they do not affect protein sequences, synonymous mutations can cause phenotypic changes. Previously, we have shown that signatures of selection on gene-specific codons usage bias are common in genomes of diverse eukaryotic species. Thus, synonymous codon usage, just as amino acid usage pattern, is likely a regular target of natural selection. Consequently, here we propose the hypothesis that at least for some protein-coding genes, codon clusters with biased synonymous codon usage patterns might represent “hidden” nucleic-acid-level functional domains that affect the action of the corresponding proteins via diverse hypothetical mechanisms. To test our hypothesis, we used computational approaches to identify over 3,000 putatively functional codon clusters (PFCCs) with biased usage patterns in about 1,500 protein-coding genes in theDrosophila melanogastergenome. Specifically, our data suggest that these PFCCs are likely associated with specific categories of gene function, including enrichment in genes that encode membrane-bound and secreted proteins. Yet, the majority of the PFCCs that we have identified are not associated with previously annotated functional protein domains. Although the specific functional significance of the majority of the PFCCs we have identified remains unknown, we show that in the highly conserved family of voltage-gated sodium channels, the existence of rare-codon cluster(s) in the nucleic-acid region that encodes the cytoplasmic loop that constitutes inactivation gate is conserved across paralogs as well as orthologs across distant animal species. Together, our findings suggest that codon clusters with biased usage patterns likely represent “hidden” nucleic-acid-level functional domains that cannot be simply predicted from the amino acid sequences they encode. Therefore, it is likely that on the evolutionary timescale, protein-coding DNA sequences are shaped by both amino-acid-dependent and codon-usage-dependent selective forces.
Classifying Non-Small Cell Lung Cancer Histopathology Types and Transcriptomic Subtypes using Convolutional Neural Networks
Authors: Yu Kun-Hsing , Wang Feiran , Berry Gerald J. , Ré Christopher , Altman Russ B. , Snyder Michael , Kohane Isaac S. 
Published: January 2019

AbstractNon-small cell lung cancer is a leading cause of cancer death worldwide, and histopathological evaluation plays the primary role in its diagnosis. However, the morphological patterns associated with the molecular subtypes have not been systematically studied. To bridge this gap, we developed a quantitative histopathology analytic framework to identify the gene expression subtypes of non-small cell lung cancer objectively. We processed whole-slide histopathology images of lung adenocarcinoma (n=427) and lung squamous cell carcinoma patients (n=457) in The Cancer Genome Atlas. To establish neural networks for quantitative image analyses, we first build convolutional neural network models to identify tumor regions from adjacent dense benign tissues (areas under the receiver operating characteristic curves (AUC) > 0.935) and recapitulated expert pathologists’ diagnosis (AUC > 0.88), with the results validated in an independent cohort (n=125; AUC > 0.85). We further demonstrated that quantitative histopathology morphology features identified the major transcriptomic subtypes of both adenocarcinoma and squamous cell carcinoma (P < 0.01). Our study is the first to classify the transcriptomic subtypes of non-small cell lung cancer using fully-automated machine learning methods. Our approach does not rely on prior pathology knowledge and can discover novel clinically-relevant histopathology patterns objectively. The developed procedure is generalizable to other tumor types or diseases.
BalticMethanosarcinaandClostridiumcompete for electrons from metallic iron
Authors: Jaramillo Paola Andrea Palacios , Snoeyenbos-West Oona , Löscher Carolin Regina , Thamdrup Bo , Rotaru Amelia-Elena 
Published: January 2019

AbstractMicrobial induced corrosion of steel structures, used for transport or storage of fuels, chemical weapons or waste radionuclides, is an environmental and economic threat. In non-sulfidic environments, the exact role of methanogens in steel corrosion is poorly understood. From the non-sulfidic, methanogenic sediments of the Baltic Sea corrosive communities were enriched using exclusively Fe0as electron donor and CO2as electron acceptor. Methane and acetate production were persistent for three years of successive transfers.MethanosarcinaandClostridiumwere attached to the Fe0, and dominated metagenome libraries. Since prior reports indicatedMethanosarcinawere merely commensals, consuming the acetate produced by acetogens, we investigated whether these methanogens were capable of Fe0corrosion without bacterial partners (inhibited by an antibiotic cocktail). Unassisted, methanogens corroded Fe0to Fe2+at similar rates to the mixed community. Surprisingly, in the absence of competitive bacteria, Baltic-Methanosarcinaproduced six times more methane than they did in the mixed community. This signifies that Baltic-Methanosarcinaachieved better corrosion alone, exclusive of an operative bacterial partner. Our results also show that together with acetogens,Methanosarcinainteract competitively to retrieve electrons from Fe0rather than as commensals as previously assumed.
Identification and characterization of a novelpicgene cluster responsible for picolinic acid degradation inAlcaligenes faecalisJQ135
Authors: Qiu Jiguo , Zhao Lingling , Xu Siqiong , Chen Qing , Chen Le , Liu Bin , Hong Qing , Lu Zhenmei , He Jian 
Published: January 2019

AbstractPicolinic acid (PA) is a natural toxic pyridine derivative. Microorganisms can degrade and utilize PA for growth. However, the full metabolic pathway and its physiological and genetic foundation remain unknown. In this study, we identified thepicgene cluster responsible for the complete degradation of PA fromAlcaligenes faecalisJQ135. PA was initially 6-hydroxylated into 6-hydroxypicolinic acid (6HPA) by PA dehydrogenase (PicA). 6HPA was then 3-hydroxylated by a four-component 6HPA monooxygenase (PicB) to form 3,6-dihydroxypicolinic acid (3,6DHPA), which was then converted into 2,5-dihydroxypyridine (2,5DHP) by a decarboxylase (PicC). The 2,5DHP was further degraded into fumaric acid, through PicD (2,5DHP dioxygenase), PicE (N-formylmaleamic acid deformylase), PicF (maleamic acid amidohydrolase), and PicG (maleic acid isomerase). Homologouspicgene clusters with diverse organizations were found to be widely distributed inα-,β-, andγ-Proteobacteria. Our findings provide new insights into the microbial metabolism of environmental toxic pyridine derivatives.ImportancePicolinic acid is a common metabolite of L-tryptophan and some aromatic compounds and is an important intermediate of industrial concern. Although the microbial degradation/detoxification of picolinic acid has been studied for over 50 years, the underlying molecular mechanisms are still unknown. Here, we show thepicgene cluster responsible for the complete degradation of picolinic acid into the tricarboxylic acid cycle. This gene cluster was found to be widespread in otherα-,β-, andγ-Proteobacteria. These findings provide new perspective for understanding the mechanisms of picolinic acid biodegradation in bacteria.