bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping drinking water and quality of life aspects in urban settings: an application of the urban exposome
Authors: Andrianou Xanthi D. , der Lek Chava van , Charisiadis Pantelis , Ioannou Solomon , Fotopoulou Kalliopi N. , Papapanagiotou Zoe , Botsaris George , Beumer Carijn , Makris Konstantinos C. 
Published: August 2018

AbstractCities face rapid changes leading to increasing inequalities and emerging public health issues that require cost-effective interventions. The urban exposome framework constitutes a novel approach in tackling city-wide challenges, such as those of drinking water quality and quality of life. In this proof-of-concept study, we presented part of the urban exposome of Limassol (Cyprus) focusing on chemical and microbial drinking water quality parameters and their association with urban neighborhood indicators. A perceptions study and an urban population study was conducted. We mapped the water quality parameters and participants’ opinions on city life (i.e. neighborhood life, health care and green space access) using quarters (small administrative areas) as the reference unit of the city. In an exploratory environment-wide association study analysis, we used all variables (questionnaire responses and water quality metrics) to describe correlations between them accounting, also, for self-reported health status. Overall, urban drinking-water quality using conventional indicators of chemical (disinfection byproducts-trihalomethanes) and microbial (coliforms, E. coli, and Enterococci) quality did not raise particular concerns. The general health and chronic health status of the urban participants were significantly (all >FDR corrected p value of 0.1) associated with different health conditions such as hypertension and asthma, or having financial issues in access to dental care. Additionally, correlations between trihalomethanes and participant characteristics (e.g. household cleaning, drinking water habits) were documented. This proof-of-concept study showed the potential of using integrative approaches to develop urban exposomic profiles and identifying within-city differentiated environmental and health indicators. The characterization of the urban exposome of Limassol will be expanded via the inclusion of biomonitoring tools and untargeted metabolomics platforms.
Genetic structure of invasive baby’s breath (Gypsophila paniculata) populations in a freshwater Michigan dune system
Authors: Leimbach – Maus Hailee B. , Parks Syndell R. , Partridge Charlyn G. 
Published: August 2018

ABSTRACTCoastal sand dunes are dynamic ecosystems with elevated levels of disturbance, and as such they are highly susceptible to plant invasions. One such invasion that is of major concern to the Great Lakes dune systems is that of perennial baby’s breath (Gypsophila paniculata). The invasion of baby’s breath negatively impacts native species such as the federal threatened Pitcher’s thistle (Cirsium pitcheri) that occupy the open sand habitat of the Michigan dune system. Our research goals were to (1) quantify the genetic diversity of invasive baby’s breath populations in the Michigan dune system, and (2) estimate the genetic structure of these invasive populations. We analyzed 12 populations at 14 nuclear and 2 chloroplast microsatellite loci. We found strong genetic structure among populations of baby’s breath sampled along Michigan’s dunes (global FST= 0.228), and also among two geographic regions that are separated by the Leelanau peninsula. Pairwise comparisons using the nSSR data among all 12 populations yielded significant FSTvalues. Results from a Bayesian clustering analysis suggest two main population clusters. Isolation by distance was found over all 12 populations (R = 0.755, P < 0.001) and when only cluster 2 populations were included (R = 0.523, P = 0.030); populations within cluster 1 revealed no significant relationship (R = 0.205, P = 0.494). Private nSSR alleles and cpSSR haplotypes within each cluster suggest the possibility of at least two separate introduction events to Michigan.
Human Epigenetic Aging is Logarithmic with Time across the Entire LifeSpan
Authors: Snir Sagi , Pellegrini Matteo 
Published: August 2018

AbstractIt is well established that organisms undergo epigenetic changes both during development and aging. Developmental changes have been extensively studied to characterize the differentiation of stem cells into diverse lineages. Epigenetic changes during aging have been characterized by multiple epigenetic clocks, that allow the prediction of chronological age based on methylation status. Despite their accuracy and utility, epigenetic age biomarkers leave many questions about epigenetic aging unanswered. Specifically, they do not permit the unbiased characterization of non-linear epigenetic aging trends across entire life spans, a critical question underlying this field of research. Here we a provide an integrated framework to address this question. Our model, inspired from evolutionary models, is able to account for acceleration/deceleration in epigenetic changes by fitting an individuals model age, theepigenetic age, which is related to chronological age in a non-linear fashion. We have devised a two stage procedure leveraging these model ages to infer aging trends over the entire lifespan of a population. Application of this procedure to real data measured across broad age ranges, from before birth to old age, and from two tissue types, suggests a universal logarithmic trend characterizes epigenetic aging across entire lifespans. This observation may have important implications for the development and application of future, more accurate, aging biomarkers.
Metabolic Flux Hierarchy Prioritizes the Entner-Doudoroff Pathway for Carbohydrate Co-Utilization inPseudomonas protegensPf-5
Authors: Wilkes Rebecca A. , Mendonca Caroll M. , Aristilde Ludmilla 
Published: August 2018

ABSTRACTThe genetic characterization ofPseudomonas protegensPf-5 was recently completed. However, the inferred metabolic network structure has not yet been evaluated experimentally. Here we employed13C-tracers and quantitative flux analysis to investigate the intracellular network for carbohydrate metabolism. Similar to otherPseudomonasspecies,P. protegensPf-5 relied primarily on the Entner-Doudoroff (ED) pathway to connect initial glucose catabolism to downstream metabolic pathways. Flux quantitation determined that, in lieu of the direct phosphorylation of glucose by glucose kinase, phosphorylation of oxidized products of glucose (gluconate and 2-ketogluconate) towards the ED pathway accounted for over 90% of consumed glucose and greater than 35% of consumed glucose was secreted as gluconate and 2-ketogluconate. Consistent with the lack of annotated pathways for the initial catabolism of pentoses and galactose inP. protegensPf-5, only glucose was assimilated into intracellular metabolites in the presence of xylose, arabinose, or galactose. However, when glucose was fed simultaneously with fructose or mannose, co-uptake of the hexoses was evident but glucose was preferred over fructose (3 to 1) and over mannose (4 to 1). Despite gene annotation of mannose catabolism toward fructose 6-phosphate, metabolite labeling patterns revealed that mannose-derived carbons specifically entered central carbon metabolism via fructose-1,6-bisphosphate, similarly to fructose catabolism. Remarkably, carbons from mannose and fructose were found to cycle backward through the upper Emden-Meyerhof-Parnas pathway to feed into the ED pathway. Therefore, the operational metabolic network for processing carbohydrates inP. protegensPf-5 prioritizes flux through the ED pathway to channel carbons to downstream metabolic pathways.IMPORTANCESpecies of thePseudomonasgenus thrive in various nutritional environments and have strong biocatalytic potential due to their diverse metabolic capabilities. Carbohydrate substrates are ubiquitous both in environmental matrices and in feedstocks for engineered bioconversion. Here we investigated the metabolic network for carbohydrate metabolism inP. protegensPf-5. Metabolic flux quantitation revealed the relative involvement of different catabolic routes in channeling carbohydrate carbons through the network. We also uncovered that mannose catabolism was similar to fructose catabolism, despite the gene annotation of two different pathways in the genome. Elucidation of the constitutive metabolic network inP. protegensis important for understanding its innate carbohydrate processing, thus laying the foundation for targeting metabolic engineering of this untappedPseudomonasspecies.
Dissecting differential signals in high-throughput data from complex tissues
Authors: Li Ziyi , Wu Zhijin , Jin Peng , Wu Hao 
Published: August 2018

AbstractSamples from clinical practices are often mixtures of different cell types. The high-throughput data obtained from these samples are thus mixed signals. The cell mixture brings complications to data analysis, and will lead to biased results if not properly accounted for. We develop a method to model the high-throughput data from mixed, heterogeneous samples, and to detect differential signals. Our method allows flexible statistical inference for detecting a variety of cell-type specific changes. Extensive simulation studies and analyses of two real datasets demonstrate the favorable performance of our proposed method compared with existing ones serving similar purpose.
Assessment of population differentiation and linkage disequilibrium in Solanum pimpinellifolium using genome-wide high-density SNP markers
Authors: Lin Ya-Ping , Liu Chu-Yin , Chen Kai-Yi 
Published: August 2018

ABSTRACTTo mine new favorable alleles for tomato breeding, we investigated the feasibility of utilizing Solanum pimpinellifolium as a diverse panel of genome-wide association study through the restriction site-associated DNA sequencing technique. Previous attempts to conduct genome-wide association study using S. pimpinellifolium were impeded by an inability to correct for population stratification and by lack of high-density markers to address the issue of rapid linkage disequilibrium decay. In the current study, a set of 24,330 SNPs was identified using 99 S. pimpinellifolium accessions from the Tomato Genetic Resource Center. Approximately 84% PstI site-associated DNA sequencing regions were located in the euchromatic regions, resulting in the tagging of most SNPs on or near genes. Our genotypic data suggested that the optimum number of S. pimpinellifolium ancestral subpopulations was three, and accessions were classified into seven groups. In contrast to the SolCAP SNP genotypic data of previous studies, our SNP genotypic data consistently confirmed the population differentiation, achieving a relatively uniform correction of population stratification. Moreover, as expected, rapid linkage disequilibrium decay was observed in S. pimpinellifolium, especially in euchromatic regions. Approximately two-thirds of the flanking SNP markers did not display linkage disequilibrium. Our result suggests that higher density of molecular markers and more accessions are required to conduct the genome-wide association study utilizing the Solanum pimpinellifolium collection.
Climatic stability and resource availability explains dung beetles (Scarabaeinae) richness patternon the Americas
Authors: Medina Anderson Matos 
Published: August 2018

AbstractClimatic conditions are the main driver of species richness. Specifically, the increase in climatic instability may reduce species richness directly and indirectly by reducing resources available. This hypothesis is evaluated here using a producer-consumer interaction to explain dung beetle richness on a continental scale (America) using mammal richness as resource proxy and temperature and precipitation seasonality as a proxy for climatic instability. A spatial path analysis was built in order to evaluate this hypothesis while controlling for spatial autocorrelation and differences in the sampling effort and abundance of each study (n=115) gathered from the literature. Dung beetle richness was directly explained by temperature seasonality, precipitation seasonality, and mammal richness, whereas only precipitation seasonality had an effect modulated by mammal richness. This result reinforces the notion that species richness can be explained by climatic conditions, but also reveals the importance of biotic interactions in order to understand the mechanisms behind such patterns.
Structures in multiple conformations reveal distinct transition metal and proton pathways in an Nramp transporter
Authors: Bozzi Aaron T. , Zimanyi Christina M. , Nicoludis John M. , Lee Brandon K. , Zhang Casey H. , Gaudet Rachelle 
Published: August 2018

AbstractNramp family transporters—expressed in organisms from bacteria to humans—enable uptake of essential divalent transition metals via an alternating-access mechanism that includes proton co-transport. We present high-resolution structures ofDeinococcus radiodurans(Dra)Nramp at complementary stages of its transport cycle to provide a thorough description of the Nramp transport cycle by identifying the key intramolecular rearrangements and changes to the metal coordination sphere. Strikingly, while metal transport requires cycling from outward-to inward-open states, efficient proton transport still occurs in outward-locked (but not inward-locked) DraNramp. We propose a model in which metal and proton enter the transporter via the same external pathway to the binding site, but follow separate routes to the cytoplasm, thus resolving the electrostatic dilemma of using a cation co-substrate to drive a cation primary substrate. Our results illustrate the flexibility of the LeuT fold to support a broad range of co-substrate coupling and conformational change mechanisms.
Convergent evolution of bird-mammal shared characteristics for adapting to nocturnality
Authors: Wu Yonghua , Wang Haifeng 
Published: August 2018

AbstractThe diapsid lineage (birds) and synapsid lineage (mammals), share a suite of functionally similar characteristics (e.g., endothermy) that are considered to be a result of their convergent evolution, but the candidate selections leading to this convergent evolution are still under debates. Here, we used a newly developed molecular phyloecological approach to reconstruct the diel activity pattern of the common ancestors of living birds. Our results strongly suggest that they had adaptations to nocturnality during their early evolution, which is remarkably similar to that of ancestral mammals. Given their similar adaptation to nocturnality, we propose that the shared traits in birds and mammals may have evolved as a result of the convergent evolution of their early ancestors adapting to ecological factors (e.g., low ambient temperature) associated with nocturnality. Finally, a conceptually unifying ecological model on the evolution of endothermy in diverse organisms with an emphasis on low ambient temperature is proposed. We reason that endothermy may evolve as an adaptive strategy to enable organisms to effectively implement various life cycle activities under relatively low-temperature environments. In particular, a habitat shift from high-temperature to relatively low-temperature environments is identified as a common factor underlying the evolution of endothermy.
Selective volume illumination microscopy offers synchronous volumetric imaging with high contrast
Authors: Truong Thai V. , Holland Daniel B. , Madaan Sara , Andreev Andrey , Troll Josh V. , Koo Daniel E. S. , Keomanee-Dizon Kevin , McFall-Ngai Margaret J. , Fraser Scott E. 
Published: August 2018

AbstractLight field microscopy provides an efficient means to collect 3D images in a single acquisition, as its plenoptic detection captures an extended image volume in one snapshot. The ability of light field microscopy to simultaneously capture image data from a volume of interest, such as a functioning brain or a beating heart, is compromised by inadequate contrast and effective resolution, due, in large part, to light scattering by the tissue. Surprisingly, a major contribution to the image degradation is the signal scattered into the volume of interest by the typical wide-field illumination that excites the sample region outside the volume of interest. Here, we minimize this degradation by employing selective volume illumination, using a modified light sheet approach to illuminate preferentially the volume of interest. This minimizes the unavoidable background generated when extraneous regions of the sample are illuminated, dramatically enhancing the contrast and effective resolution of the captured and reconstructed images. Light Field Selective Volume Illumination Microscopy (LF-SVIM, SVIM for short) dramatically improves the performance of light field microscopy, and offers an unprecedented combination of synchronous z-depth coverage, lateral and axial resolution, and imaging speed.
Efficient implementation of penalized regression for genetic risk prediction
Authors: Privé Florian , Aschard Hugues , Blum Michael G.B. 
Published: August 2018

AbstractPolygenic Risk Scores (PRS) consist in combining the information across many single-nucleotide polymorphisms (SNPs) in a score reflecting the genetic risk of developing a disease. PRS might have a major impact on public health, possibly allowing for screening campaigns to identify high-genetic risk individuals for a given disease. The “Clumping+Thresholding” (C+T) approach is the most common method to derive PRS. C+T uses only univariate genome-wide association studies (GWAS) summary statistics, which makes it fast and easy to use. However, previous work showed that jointly estimating SNP effects for computing PRS has the potential to significantly improve the predictive performance of PRS as compared to C+T.In this paper, we present an efficient method to jointly estimate SNP effects, allowing for practical application of penalized logistic regression (PLR) on modern datasets including hundreds of thousands of individuals. Moreover, our implementation of PLR directly includes automatic choices for hyper-parameters. The choice of hyper-parameters for a predictive model is very important since it can dramatically impact its predictive performance. As an example, AUC values range from less than 60% to 90% in a model with 30 causal SNPs, depending on the p-value threshold in C+T.We compare the performance of PLR, C+T and a derivation of random forests using both real and simulated data. PLR consistently achieves higher predictive performance than the two other methods while being as fast as C+T. We find that improvement in predictive performance is more pronounced when there are few effects located in nearby genomic regions with correlated SNPs; for instance, AUC values increase from 83% with the best prediction of C+T to 92.5% with PLR. We confirm these results in a data analysis of a case-control study for celiac disease where PLR and the standard C+T method achieve AUC of 89% and of 82.5%.In conclusion, our study demonstrates that penalized logistic regression can achieve more discriminative polygenic risk scores, while being applicable to large-scale individual-level data thanks to the implementation we provide in the R package bigstatsr.
FRMPD2: a novel GluN2A-interacting scaffold protein in synaptic excitatory transmission
Authors: Lu Xi , Zhang Haiqing , Tian Xin , Wang Xuefeng 
Published: August 2018

AbstractThe scaffold proteins FRMPD2 is localized at the basolateral membranes of polarized epithelial cells and associated with tight junction formation. But the expression and function of FRMPD2 in vivo remain unknown. Here, we found that postsynaptic FRMPD2 effectively alters the neuronal excitability by regulating NMDARs-component excitatory synaptic transmission in adult hippocampus. FRMPD2 anchors the NMDAR subunit GluN2A at the synapses without changing the total NMDAR expression. By using of Co-IP, Pull Down and SPR, the second PDZ (PDZ2) domain of FRMPD2 direct and binds to the C-terminus of GluN2A. Our study discover that a novel scaffold protein FRMPD2 regulates synaptic excitatory in a PDZ2 domain-dependent manner in adult hippocampus.
Anatomical and physiological foundations of cerebello-hippocampal interactions
Authors: Watson TC , Obiang P , Torres-Herraez A , Wattilliaux A , Coulon P , Rochefort C , Rondi-Reig L 
Published: August 2018

AbstractMultiple lines of evidence suggest that functionally intact cerebello-hippocampal interactions are required for appropriate spatial processing. However, how the cerebellum anatomically and physiologically engages with the hippocampus to sustain such interactions remains unknown. Using rabies virus as retrograde transneuronal tracer, we reveal that the dorsal hippocampus receives input from topographically restricted and disparate regions of the cerebellum. By simultaneously recording local field potential from both the dorsal hippocampus and anatomically connected cerebellar regions, we additionally demonstrate that the two structures interact, in a behaviorally dynamic manner, through subregion-specific synchronization of neuronal oscillations in the 6-12Hz frequency range. Together, these results reveal a novel neural network macro-architecture through which we can understand how a brain region classically associated with motor control, the cerebellum, may influence hippocampal neuronal activity and related functions, such as spatial navigation.
Autoantibodies and anti-microbial antibodies: Homology of the protein sequences of human autoantigens and the microbes with implication of microbial etiology in autoimmune diseases
Authors: Zhang Peilin 
Published: August 2018

AbstractAutoimmune disease is a group of diverse clinical syndromes with defining autoantibodies within the circulation. The pathogenesis of autoantibodies in autoimmune disease is poorly understood. In this study, human autoantigens in all known autoimmune diseases were examined for the amino acid sequences in comparison to the microbial proteins including bacterial and fungal proteins by searching Genbank protein databases. Homologies between the human autoantigens and the microbial proteins were ranked high, medium, and low based on the default search parameters at the NCBI protein databases. Totally 64 human protein autoantigens important for a variety of autoimmune diseases were examined, and 26 autoantigens were ranked high, 19 ranked medium to bacterial proteins (69%) and 27 ranked high and 16 ranked medium to fungal proteins (66%) in their respective amino acid sequence homologies. There are specific autoantigens highly homologous to specific bacterial or fungal proteins, implying potential pathogenic roles of these microbes in specific autoimmune diseases. The computational examination of the primary amino acid sequences of human autoantigens in comparison to the microbial proteins suggests that the environmental exposure to the commensal or pathogenic microbes is potentially important in pathogenesis of a majority of autoimmune diseases, providing a new direction for further experimental investigation in searching for new diagnostic and therapeutic targets for autoimmune diseases.