bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the survival of Zika virus in a vector interconnected sexual contact network
Authors: Ferdousi Tanvir , Cohnstaedt Lee W. , McVey D. S. , Scoglio Caterina M. 
Published: January 2019

ABSTRACTThe recent outbreaks of the insect-vectored Zika virus have demonstrated its potential to be sexually transmitted, which complicates modeling and our understanding of disease dynamics. Autochthonous outbreaks in the US mainland may be a consequence of both modes of transmission, which affect the outbreak size, duration, and virus persistence. We propose a novel individual-based interconnected network model that incorporates both insect-vectored and sexual transmission of this pathogen. This model interconnects a homogeneous mosquito vector population with a heterogeneous human host contact network. The model incorporates the seasonal variation of mosquito abundance and characterizes host dynamics based on age group and gender in order to produce realistic projections. We use a sexual contact network which is generated on the basis of real world sexual behavior data. Our findings suggest that for a high relative transmissibility of asymptomatic hosts, Zika virus shows a high probability of sustaining in the human population for up to 3 months without the presence of mosquito vectors. Zika outbreaks are strongly affected by the large proportion of asymptomatic individuals and their relative transmissibility. The outbreak size is also affected by the time of the year when the pathogen is introduced. Although sexual transmission has a relatively low contribution in determining the epidemic size, it plays a role in sustaining the epidemic and creating potential endemic scenarios.
Determinants of Cancer-specific Quality of Life in Veteran Lung Cancer Survivors Eligible for Long-Term Cure
Authors: Ha Duc , Ries Andrew L. , Swigris Jeffrey J. 
Published: January 2019

AbstractRationale/ObjectiveQuality of life (QoL) is an important issue in lung cancer survivors. We aimed to identify determinants of QoL in lung cancer survivors eligible for long-term cure.MethodsWe performed an exploratory analysis of a cross-sectional study of consecutive lung cancer survivors who completed curative-intent treatment ≥1 month previously. Variables tested included demographic, clinical, physiologic, and symptom-specific patient-reported outcome measures. We defined the primary outcome as a previously-validated cancer-specific QoL measure – the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (C30) summary score. We also verified our findings with the C30 global health status/QoL subscale and a summated score of lung cancer-specific QoL from the EORTC-Lung Cancer Module 13.ResultsIn 75 enrolled participants, measures of fatigue, depression, sleep difficulties, and dyspnea were statistically significant determinants of the C30 summary score in multivariable linear regression analyses. Together, these four symptoms accounted for approximately 85% of the variance in cancer-specific QoL (p<0.001). When we verified our findings with global QoL and lung cancer-specific QoL, fatigue and dyspnea were consistent determinants of QoL.ConclusionsWe found four symptoms – dyspnea, fatigue, depression, and sleep difficulties – that are important determinants of and together accounted for almost all of the variance in cancer-specific QoL in lung cancer survivors eligible for long-term cure. These findings have implications to reduce symptom burden and improve function and QoL in these patients.
The genome of cowpea (Vigna unguiculata[L.] Walp.)
Authors: Lonardi Stefano , Muñoz-Amatriaín María , Liang Qihua , Shu Shengqiang , Wanamaker Steve I. , Lo Sassoum , Tanskanen Jaakko , Schulman Alan H. , Zhu Tingting , Luo Ming-Cheng , Alhakami Hind , Ounit Rachid , Hasan Abid Md. , Verdier Jerome , Roberts Philip A. , Santos Jansen R.P. , Ndeve Arsenio , Doležel Jaroslav , Vrána Jan , Hokin Samuel A. , Farmer Andrew D. , Cannon Steven B. , Close Timothy J. 
Published: January 2019

ABSTRACTCowpea (Vigna unguiculata[L.] Walp.) is a major crop for worldwide food and nutritional security, especially in sub-Saharan Africa, that is resilient to hot and drought-prone environments. A high-quality assembly of the single-haplotype inbred genome of cowpea IT97K-499-35 was developed by exploiting the synergies between single molecule real-time sequencing, optical and genetic mapping, and a novel assembly reconciliation algorithm. A total of 519 Mb is included in the assembled sequences. Nearly half of the assembled sequence is composed of repetitive elements, which are enriched within recombination-poor pericentromeric regions. A comparative analysis of these elements suggests that genome size differences betweenVignaspecies are mainly attributable to changes in the amount ofGypsyretrotransposons. Conversely, genes are more abundant in more distal, high-recombination regions of the chromosomes; there appears to be more duplication of genes within the NBS-LRR and the SAUR-like auxin superfamilies compared to other warm-season legumes that have been sequenced. A surprising outcome of this study is the identification of a chromosomal inversion of 4.2 Mb among landraces and cultivars, which includes a gene that has been associated in other plants with interactions with the parasitic weedStriga gesnerioides. The genome sequence also facilitated the identification of a putative syntelog for multiple organ gigantism in legumes. A new numbering system has been adopted for cowpea chromosomes based on synteny with common bean (Phaseolus vulgaris).
GRep: Gene Set Representation via Gaussian Embedding
Authors: Wang Sheng , Flynn Emily , Altman Russ B. 
Published: January 2019

ABSTRACTMolecular interaction networks are our basis for understanding functional interdependencies among genes. Network embedding approaches analyze these complicated networks by representing genes as low-dimensional vectors based on the network topology. These low-dimensional vectors have recently become the building blocks for a larger number of systems biology applications. Despite the success of embedding genes in this way, it remains unclear how to effectively represent gene sets, such as protein complexes and signaling pathways. The direct adaptation of existing gene embedding approaches to gene sets cannot model the diverse functions of genes in a set. Here, we propose GRep, a novel gene set embedding approach, which represents each gene set as a multivariate Gaussian distribution rather than a single point in the low-dimensional space. The diversity of genes in a set, or the uncertainty of their contribution to a particular function, is modeled by the covariance matrix of the multivariate Gaussian distribution. By doing so, GRep produces a highly informative and compact gene set representation. Using our representation, we analyze two major pharmacogenomics studies and observe substantial improvement in drug target identification from expression-derived gene sets. Overall, the GRep framework provides a novel representation of gene sets that can be used as input features to off-the-shelf machine learning classifiers for gene set analysis.
Motion direction representation in multivariate electroencephalography activity for smooth pursuit eye movements
Authors: Lee Joonyeol , Jeong Woojae , Kim Seolmin , Kim Yee-Joon 
Published: January 2019

AbstractVisually-guided smooth pursuit eye movements are composed of initial open-loop and later steady-state periods. Feedforward sensory information dominates the motor behavior during the open-loop pursuit, and a more complex feedback loop regulates the steady-state pursuit. To understand the neural representations of motion direction during open-loop and steady-state smooth pursuits, we recorded electroencephalography (EEG) responses from human observers while they tracked random dot kinematograms as pursuit targets. We estimated population direction tuning curves from multivariate EEG activity using an inverted encoding model. We found significant direction tuning curves as early as 20 ms from motion onset. Direction tuning responses were generalized to later times during the open-loop smooth pursuit, but they became more dynamic during the later steady-state pursuit. The encoding quality of retinal motion direction information estimated from the early direction tuning curves was predictive of trial-by-trial variation in initial pursuit directions. These results suggest that the movement directions of open-loop smooth pursuit are guided by the representation of the retinal motion present in the multivariate EEG activity.
Targeting tumor-intrinsic metabolic node sensitizes pancreatic cancer to anti-PD1 therapy
Authors: Sharma Nikita S , Gupta Vineet K , Garrido Vanessa T , Hadad Roey , Durden Brittany C , Kesh Kousik , Giri Bhuwan , Ferrantella Anthony , Dudeja Vikas , Saluja Ashok , Banerjee Sulagna 
Published: January 2019

AbstractPancreatic ductal adenocarcinoma (PDAC) is considered to be a highly immunosuppressive and heterogenous neoplasm. Despite improved knowledge regarding the genetic background of the tumor and better understanding of the tumor microenvironment, immune checkpoint inhibitor therapy (targeting CTLA-4, PD-1, PD-L1) has not been very successful against PDAC.The robust desmoplastic stroma, along with an extensive extracellular matrix (ECM) that is rich in hyaluronan, plays an integral role in this immune evasion. Hexosamine biosynthesis pathway (HBP), a shunt pathway of glycolysis, is a metabolic node in cancer cells that can promote survival pathways on one hand and influence the hyaluronan synthesis in the ECM on the other. The rate-limiting enzyme of the pathway, glutamine-fructose amidotransferase (GFAT1), uses glutamine and fructose 6-phosphate to eventually synthesize UDP-GlcNAc.In the current manuscript, we target this glutamine-utilizing enzyme by a small molecule glutamine analog (6-diazo-5-oxo-L-norleucine or DON). Our results show that DON decreases the self-renewal potential and metastatic ability of tumor cell. Further, treatment with DON results in a decrease in hyaluronan and collagen in the tumor microenvironment, leading to an extensive remodeling of the ECM. this in turn, increases CD8+ cytotoxic T-cells infiltration, and makes the tumors tumors more amenable and sensitive to anti-PD1 therapy.
The Imprinted Igf2-Igf2r Axis is Critical for Matching Placental Microvasculature Expansion to Fetal Growth
Authors: Sandovici Ionel , Georgopoulou Aikaterini , Pérez-García Vicente , Hufnagel Antonia , López-Tello Jorge , Lam Brian Y.H. , Schiefer Samira N. , Gaudreau Chelsea , Santos Fátima , Hoelle Katharina , Yeo Giles S.H. , Burling Keith , Reiterer Moritz , Fowden Abigail L. , Burton Graham J. , Branco Cristina M. , Sferruzzi-Perri Amanda N. , Constância Miguel 
Published: January 2019

SUMMARYIn all eutherian mammals, growth of the fetus is dependent upon a functional placenta, but whether and how the latter adapts to putative fetal signals is currently unknown. Here we demonstrate, through fetal, endothelial, hematopoietic and trophoblast-specific genetic manipulations in the mouse, that endothelial and fetus-derived IGF2 is required for the continuous expansion of the feto-placental microvasculature in late pregnancy. The effects of IGF2 on placental microvasculature expansion are mediated, in part, through IGF2R and angiopoietin-Tie2/TEK signalling. Additionally, IGF2 exerts IGF2R-ERK1/2-dependent pro-proliferative and angiogenic effects on primary feto-placental endothelial cells ex vivo. Endothelial and fetus-derived IGF2 also plays an important role in trophoblast morphogenesis, acting through Gcm1 and Synb. Thus, our study reveals a direct role for the imprinted Igf2-Igf2r axis on matching placental development to fetal growth and establishes the principle that hormone-like signals from the fetus play important roles in controlling placental microvasculature and trophoblast morphogenesis.
Using digital organisms to investigate the effect of whole genome duplication in (artificial) evolution
Authors: Yao Yao , Carretero-Paulet Lorenzo , Van de Peer Yves 
Published: January 2019

AbstractThe potential role of whole genome duplication (WGD) in evolution is controversial. Whereas some view WGD mainly as detrimental and an evolutionary ‘dead end’, there is growing evidence that the long-term establishment of polyploidy might be linked to environmental change, stressful conditions, or periods of extinction. However, despite much research, the mechanistic underpinnings of why and how polyploids might be able to outcompete non-polyploids at times of environmental upheaval remain indefinable. Here, we improved our recently developed bio-inspired framework, combining an artificial genome with an agent-based system, to form a population of so-called Digital Organisms (DOs), to examine the impact of WGD on evolution under different environmental scenarios mimicking extinction events of varying strength and frequency. We found that, under stable environments, DOs with non-duplicated genomes formed the majority, if not all, of the population, whereas the numbers of DOs with duplicated genomes increased under dramatically challenging environments. After tracking the evolutionary trajectories of individual artificial genomes in terms of sequence and encoded gene regulatory networks (GRNs), we propose that increased complexity, modularity, and redundancy of duplicated GRNs might provide DOs with increased adaptive potential under extinction events, while ensuring mutational robustness of the whole GRN. Our results confirm the usefulness of our computational simulation in studying the role of WGD in evolution and adaptation, helping to overcome the traditional limitations of evolution experiments with model organisms, and provide some additional insights into how genome duplication might help organisms to compete for novel niches and survive ecological turmoil.
Complete genome screening of clinical MRSA isolates identifies lineage diversity and provides full resolution of transmission and outbreak events
Authors: Sullivan Mitchell J , Altman Deena R , Chacko Kieran I , Ciferri Brianne , Webster Elizabeth , Pak Theodore R. , Deikus Gintaras , Lewis-Sandari Martha , Khan Zenab , Beckford Colleen , Rendo Angela , Samaroo Flora , Sebra Robert , Karam-Howlin Ramona , Dingle Tanis , Hamula Camille , Bashir Ali , Schadt Eric , Patel Gopi , Wallach Frances , Kasarskis Andrew , Gibbs Kathleen , van Bakel Harm 
Published: January 2019

AbstractWhole-genome sequencing (WGS) of Staphylococcus aureus is increasingly used as part of infection prevention practices, but most applications are focused on conserved core genomic regions due to limitations of short-read technologies. In this study we established a long-read technology-based WGS screening program of all first-episode MRSA blood infections at a major urban hospital. A survey of 132 MRSA genomes assembled from long reads revealed widespread gain/loss of accessory mobile genetic elements among established hospital- and community-associated lineages impacting >10% of each genome, and frequent megabase-scale inversions between endogenous prophages. We also characterized an outbreak of a CC5/ST105/USA100 clone among 3 adults and 18 infants in a neonatal intensive care unit (NICU) lasting 7 months. The pattern of changes among complete outbreak genomes provided full spatiotemporal resolution of its origins and progression, which was characterized by multiple sub-transmissions and likely precipitated by equipment sharing. Compared to other hospital strains, the outbreak strain carried distinct mutations and accessory genetic elements that impacted genes with roles in metabolism, resistance and persistence. This included a DNA-recognition domain recombination in the hsdS gene of a Type-I restriction-modification system that altered DNA methylation. RNA-Seq profiling showed that the (epi)genetic changes in the outbreak clone attenuated agr gene expression and upregulated genes involved in stress response and biofilm formation. Overall our findings demonstrate that long-read sequencing substantially improves our ability to characterize accessory genomic elements that impact MRSA virulence and persistence, and provides valuable information for infection control efforts.
Attention Promotes the Neural Encoding of Prediction Errors
Authors: Smout Cooper A. , Tang Matthew F. , Garrido Marta I. , Mattingley Jason B. 
Published: January 2019

AbstractThe human brain is thought to optimise the encoding of incoming sensory information through two principal mechanisms: prediction uses stored information to guide the interpretation of forthcoming sensory events, and attention prioritizes these events according to their behavioural relevance. Despite the ubiquitous contributions of attention and prediction to various aspects of perception and cognition, it remains unknown how they interact to modulate information processing in the brain. A recent extension of predictive coding theory suggests that attention optimises the expected precision of predictions by modulating the synaptic gain of prediction error units. Since prediction errors code for the difference between predictions and sensory signals, this model would suggest that attention increases the selectivity for mismatch information in the neural response to a surprising stimulus. Alternative predictive coding models proposes that attention increases the activity of prediction (or ‘representation’) neurons, and would therefore suggest that attention and prediction synergistically modulate selectivity for feature information in the brain. Here we applied multivariate forward encoding techniques to neural activity recorded via electroencephalography (EEG) as human observers performed a simple visual task, to test for the effect of attention on both mismatch and feature information in the neural response to surprising stimuli. Participants attended or ignored a periodic stream of gratings, the orientations of which could be either predictable, surprising, or unpredictable. We found that surprising stimuli evoked neural responses that were encoded according to the difference between predicted and observed stimulus features, and that attention facilitated the encoding of this type of information in the brain. These findings advance our understanding of how attention and prediction modulate information processing in the brain, and support the theory that attention optimises precision expectations during hierarchical inference by increasing the gain of prediction errors.
Rcs phosphorelay activation in cardiolipin-deficient Escherichia coli reduces biofilm formation
Authors: Nepper Julia F. , Lin Yin C. , Weibel Douglas B. 
Published: January 2019

AbstractBiofilm formation is a complex process that requires a number of transcriptional, proteomic, and physiological changes to enable bacterial survival. The lipid membrane presents a barrier to communication between the machinery within bacteria and the physical and chemical features of their extracellular environment, and yet little is known about how the membrane influences biofilm development. We found that depleting the anionic phospholipid cardiolipin reduces biofilm formation in Escherichia coli cells by as much as 50%. The absence of cardiolipin activates the Rcs envelope stress response, which represses production of flagella, disrupts initial biofilm attachment, and reduces biofilm growth. We demonstrate that a reduction in the concentration of cardiolipin impairs translocation of proteins across the inner membrane, which we hypothesize activates the Rcs pathway through the outer membrane lipoprotein RcsF. Our study demonstrates a molecular connection between the composition of membrane phospholipids and biofilm formation in E. coli and suggests that altering lipid biosynthesis may be a viable approach for altering biofilm formation and possibly other multicellular phenotypes related to bacterial adaptation and survival.ImportanceThere is a growing interest in the role of lipid membrane composition in the physiology and adaptation of bacteria. We demonstrate that a reduction in the anionic phospholipid cardiolipin impairs biofilm formation in Escherichia coli cells. Depleting cardiolipin reduced protein translocation across the inner membrane and activated the Rcs envelope stress response. Consequently, cardiolipin depletion produced cells lacking assembled flagella, which impacted their ability to attach to surfaces and seed the earliest stage in biofilm formation. This study provides empirical evidence for the role of anionic phospholipid homeostasis in protein translocation and its effect on biofilm development, and highlights modulation of the membrane composition as a potential method of altering bacterial phenotypes related to adaptation and survival.
CryoAPEX - an electron tomography tool for subcellular localization of membrane proteins
Authors: Sengupta Ranjan , Poderycki Michael J. , Mattoo Seema 
Published: January 2019

AbstractWe describe a method, termed cryoAPEX, that couples chemical fixation and high pressure freezing of cells with peroxidase-tagging (APEX) to allow precise localization of membrane proteins in the context of a well-preserved subcellular membrane architecture. Further, cryoAPEX is compatible with electron tomography. As an example, we apply cryoAPEX to obtain a high-resolution three-dimensional contextual map of the human Fic (filamentation induced by cAMP) protein, HYPE/FicD. HYPE is a single pass membrane protein that localizes to the endoplasmic reticulum (ER) lumen and regulates the unfolded protein response. Alternate cellular locations for HYPE have been suggested. CryoAPEX analysis shows that, under normal/resting conditions, HYPE localizes robustly within the subdomains of the ER and is not detected in the secretory pathway or other organelles. CryoAPEX is broadly applicable for assessing both lumenal and cytosol-facing membrane proteins.Summary statementCryoAPEX couples localization of peroxidase-tagged membrane proteins at high-resolution with 3D structural analysis, within an optimally preserved cellular context.
De novo assembly of the Mongolian gerbil genome and transcriptome
Authors: Cheng Shifeng , Fu Yuan , Zhang Yaolei , Xian Wenfei , Wang Hongli , Grothe Benedict , Liu Xin , Xu Xun , Klug Achim , McCullagh Elizabeth A 
Published: January 2019

AbstractBACKGROUNDThe Mongolian gerbil (Meriones unguiculatus) has historically been used as a model organism for the auditory and visual systems, stroke/ischemia, epilepsy and aging related research since 1935 when laboratory gerbils were separated from their wild counterparts. In this study we report genome sequencing, assembly, and annotation further supported by transcriptome data from 27 different tissues samples.FINDINGSThe genome was assembled using Illumina HiSeq 2000 and resulted in a final genome size of 2.54 Gbp with contig and scaffold N50 values of 31.4 Kbp and 500.0 Kbp, respectively. Based on the k-mer estimated genome size of 2.48 Gbp, the assembly appears to be complete. The genome annotation was supported by transcriptome data that identified 36 019 predicted protein-coding genes across 27 tissue samples. A BUSCO search of 3023 mammalian groups resulted in 86% of curated single copy orthologs present among predicted genes, indicating a high level of completeness of the genome.CONCLUSIONSWe report a de novo assembly of the Mongolian gerbil genome that was further enhanced by annotation of transcriptome data from several tissues. Sequencing of this genome increases the utility of the gerbil as a model organism, opening the availability of now widely used genetic tools.