bluuebunny/crossref_metadata_2025_split huggingface dataset:
A generalized observation confirmation model to account for false positive error in species detection-nondetection data
Authors: Clare John D. J. , Zuckerberg Benjamin , Townsend Philip A. 
Published: September 2018

AbstractSpatially-indexed repeated detection-nondetection data is widely collected by ecologists interested in estimating parameters associated with species distribution, relative abundance, phenology, and more while accounting for imperfect detection. Recent model development has focused on accounting for false positive error as well, given growing recognition that misclassification is common across many sampling protocols. To date, however, the development of model-based solutions to false positive error has been largely restricted to occupancy models. We describe a general form of the observation confirmation protocol originally described for occupancy estimation that permits investigators to flexibly and intuitively extend several models for detection-nondetection data to account for false positive error. Simulation results demonstrate that estimators for relative abundance and arrival time exhibit relative bias greater than 20% under realistic levels of false positive prevalence (e.g., 5% of detections are false positive). Bias increases as true and false positives occur in more distinct places or times, but can also be sensitive to the values of the state variables of interest, sampling design, and sampling efficiency. Results from an empirical study focusing on patterns of gray fox relative abundance across Wisconsin, USA suggest that false positive error can also distort estimated spatial patterns often used to guide decision-making. The extended estimators described within typically improve performance at any level of confirmation, and when false positive error occurs at random and constitutes less than 10% of all detections, the estimators are essentially unbiased when more than 50 observations can be confirmed as true or false positives. The generalized form of the observation-confirmation protocol is a flexible model-based solution to false positive error useful for researchers collecting data with sampling devices like trail or smartphone cameras, acoustic recorders, or other techniques where classifications can be reviewed post-hoc.
Detection of residual disease after neoadjuvant therapy in breast cancer using personalized circulating tumor DNA analysis
Authors: McDonald Bradon R. , Contente-Cuomo Tania , Sammut Stephen-John , Odenheimer-Bergman Ahuva , Ernst Brenda , Perdigones Nieves , Chin Suet-Feung , Farooq Maria , Cronin Patricia A. , Anderson Karen S. , Kosiorek Heidi E. , Northfelt Donald W. , McCullough Ann E. , Patel Bhavika K. , Caldas Carlos , Pockaj Barbara A. , Murtaza Muhammed 
Published: September 2018

AbstractAccurate detection of minimal residual disease (MRD) can guide individualized management of early stage cancer patients, but current diagnostic approaches lack adequate sensitivity. Circulating tumor DNA (ctDNA) analysis has shown promise for recurrence monitoring but MRD detection immediately after neoadjuvant therapy or surgical resection has remained challenging. We have developed TARgeted DIgital Sequencing (TARDIS) to simultaneously analyze multiple patient-specific cancer mutations in plasma and improve sensitivity for minute quantities of residual tumor DNA. In 77 reference samples at 0.03%-1% mutant allele fraction (AF), we observed 93.5% sensitivity. Using TARDIS, we analyzed ctDNA in 34 samples from 13 patients with stage II/III breast cancer treated with neoadjuvant therapy. Prior to treatment, we detected ctDNA in 12/12 patients at 0.002%-1.04% AF (0.040% median). After completion of neoadjuvant therapy, we detected ctDNA in 7/8 patients with residual disease observed at surgery and in 1/5 patients with pathological complete response (odds ratio, 18.5, Fisher’s exact p=0.032). These results demonstrate high accuracy for a personalized blood test to detect residual disease after neoadjuvant therapy. With additional clinical validation, TARDIS could identify patients with molecular complete response after neoadjuvant therapy who may be candidates for nonoperative management.One Sentence SummaryA personalized ctDNA test achieves high accuracy for residual disease.
Continuous and discrete quantity discrimination in tortoises
Authors: Gazzola Andrea , Vallortigara Giorgio , Pellitteri-Rosa Daniele 
Published: September 2018

AbstractThe ability to estimate quantity, which is crucially important in several aspects of animal behaviour (e.g., foraging), has been extensively investigated in most taxa, with the exception of reptiles. The few studies available, in lizards, report lack of spontaneous discrimination of quantity, which may suggest that reptiles could represent an exception in numerical abilities among vertebrates. We investigated the spontaneous ability of Hermann’s tortoises (Testudo hermanni) to select the larger quantity of food items. Tortoises showed able to choose the larger food item when exposed with two options differing in size (0.25, 0.50, 0.67 and 0.75 ratio) and when presented with two groups differing in numerousness (1 versus 4, 2 versus 4, 2 versus 3 and 3 versus 4 items). The tortoises succeeded in both size and numerousness discrimination, and their performance appeared to depend on the ratio of items to be discriminated (thus following Weber’s Law). These findings in chelonians provide evidence of an ancient system for the extrapolation of numerical magnitudes from given sets of elements, shared among vertebrates.
Preventions of oral self-mutilation in patients with Lesch-Nyhan syndrome
Authors: de Carvalho Lorevanda V. , de Oliveira Luan F. , Chaves Tiago F. 
Published: September 2018

ABSTRACTLesch-Nyhan syndrome (LNS) is a rare genetic disorder linked to the X chromosome that implies an inborn error of metabolism, due to deficiency in the purine metabolic pathway, affected individuals present neurological symptoms, such as cognitive and motor impairment, besides behavioral changes such as self and hetero-aggression. This characteristic aggressive behavior leads to insults and self-mutilation, thus requiring methods of self-protection, some invasive and permanent, such as tooth extraction. Noninvasive methods, such as the use of oral protectors, pharmacological therapies and botulinum toxin A applications, are also employed to decrease discomfort and the implications of such behavior. We describe briefly the methods of prevention against oral self-mutilation in patients with Lesch-Nyhan syndrome found in the literature.
Visualizing metabolic network dynamics through time-series metabolomics data
Authors: Buchweitz Lea F. , Yurkovich James T. , Blessing Christoph M. , Kohler Veronika , Schwarzkopf Fabian , King Zachary A. , Yang Laurence , Jóhannsson Freyr , Sigurjónsson Ólafur E. , Rolfsson Óttar , Heinrich Julian , Dräger Andreas 
Published: September 2018

ABSTRACTNew technologies have given rise to an abundance of -omics data, particularly metabolomics data. The scale of these data introduces new challenges for the interpretation and extraction of knowledge, requiring the development of new computational visualization methodologies. Here, we present a new method for the visualization of time-course metabolomics data within the context of metabolic network maps. We demonstrate the utility of this method by examining previously published data for two cellular systems—the human platelet and erythrocyte under cold storage for use in transfusion medicine.The results comprise two animated videos that allow for new insights into the metabolic state of both cell types. In the case study of the platelet metabolome during storage, the new visualization technique elucidates a nicotinamide accumulation which mirrors that of hypoxanthine and might, therefore, reflect similar pathway usage. This visual analysis provides a possible explanation for why the salvage reactions in purine metabolism exhibit lower activity during the first few days of the storage period. The second case study displays drastic changes in specific erythrocyte metabolite pools at different times during storage at different temperatures.In conclusion, this new visualization technique introduced in this article constitutes a well-suitable approach for large-scale network exploration and advances hypothesis generation. This method can be applied to any system with data and a metabolic map to promote visualization and understand physiology at the network level. More broadly, we hope that our approach will provide the blueprints for new visualizations of other longitudinal -omics data types.AUTHOR SUMMARYProfiling the dynamic state of a metabolic network through the use of time-course metabolomics technologies allows insights into cellular biochemistry. Interpreting these data together at the systems level provides challenges that can be addressed through the development of new visualization approaches. Here, we present a new method for the visualization of time-course metabolomics data that integrates data into an existing metabolic network map. In brief, the metabolomics data are visualized directly on a network map with dynamic elements (nodes that either change size, fill level, or color corresponding with the concentration) while the user controls the time series (i.e., which time point is being displayed) through a graphical interface. We provide short videos that illustrate the utility of this method through its application to existing data sets for the human platelet and erythrocyte. The results presented here give blueprints for the development of visualization methods for other time-course -omics data types that attempt to understand systems-level physiology.
Rapid and stable microbial community assembly in the headwaters of third-order stream
Authors: Teachey Morgan E. , McDonald Jacob M. , Ottesen Elizabeth A. 
Published: September 2018

AbstractSmall streams and their headwaters are a key source of microbial diversity in fluvial systems and serve as an entry point for bacteria from the surrounding landscape. Community assembly processes occurring in these streams shape downstream population structure and nutrient cycles. To elucidate the development and stability of microbial communities along the length of a first through third order stream, fine-scale temporal and spatial sampling regimes were employed along McNutt Creek in Athens, Georgia, USA. 16S rRNA gene libraries were constructed from samples collected on a single day from 19 sites spanning the first 16.76 km of the stream. Selected sites at the upper, mid, and lower reaches of the stream were sampled daily for 11 days to evaluate community variability over time. In a second study, sites at and near the creek’s headwaters were sampled daily for 11 days to understand the initial stages of bacterioplankton community assembly. In all studies, we observed decreasing alpha and beta diversity with increasing downstream distance. These trends were accompanied by the enrichment of a small fraction of taxa found at low abundance in the furthest-upstream environments. Similar sets of taxa consistently increased significantly in relative abundance in downstream samples over time scales ranging from 1 day to 1 year, many of which belong to microbial clades known to be abundant in freshwater environments. These results underpin the importance of headwaters as the site of rapid in-stream selection that results in the reproducible establishment of a highly stable community of freshwater riverine bacteria.ImportanceHeadwater streams are critical introduction points of microbial diversity for larger connecting rivers and play key roles in the establishment of taxa that partake in in-stream nutrient cycling. We examined microbial community composition of a first- through third-order stream using fine-scale temporal and spatial regimes. Our results show that the bacterioplankton community develops rapidly and predictably from the headwater population with increasing total stream length. Along the length of the stream, the microbial community exhibits substantial diversity loss and enriches repeatedly for select taxa across days and years, although the relative abundances of individual taxa vary over time and space. This repeated enrichment of a stable stream community likely contributes to the stability and flexibility of downstream communities.
A multi-omics data simulator for complex disease studies and its application to evaluate multi-omics data analysis methods for disease classification
Authors: Chung Ren-Hua , Kang Chen-Yu 
Published: September 2018

AbstractAn integrative multi-omics analysis approach that combines multiple types of omics data including genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiomics, has become increasing popular for understanding the pathophysiology of complex diseases. Although many multi-omics analysis methods have been developed for complex disease studies, there is no simulation tool that simulates multiple types of omics data and models their relationships with disease status. Without such a tool, it is difficult to evaluate the multi-omics analysis methods on the same scale and to estimate the sample size or power when planning a new multi-omics disease study. We developed a multi-omics data simulator OmicsSIMLA, which simulates genomics (i.e., SNPs and copy number variations), epigenomics (i.e., whole-genome bisulphite sequencing), transcriptomics (i.e., RNA-seq), and proteomics (i.e., normalized reverse phase protein array) data at the whole-genome level. Furthermore, the relationships between different types of omics data, such as meQTLs (SNPs influencing methylation), eQTLs (SNPs influencing gene expression), and eQTM (methylation influencing gene expression), were modeled. More importantly, the relationships between these multi-omics data and the disease status were modeled as well. We used OmicsSIMLA to simulate a multi-omics dataset for breast cancer under a hypothetical disease model, and used the data to compare the performance among existing multi-omics analysis methods in terms of disease classification accuracy and run time. Our results demonstrated that complex disease mechanisms can be simulated by OmicsSIMLA, and a random forest-based method showed the highest prediction accuracy when the multi-omics data were properly normalized.
The requirement for the amino acid co-germinant duringC. difficilespore germination is influenced by mutations inyabGandcspA
Authors: Shrestha Ritu , Sorg Joseph A. 
Published: September 2018

AbstractClostridium difficilespore germination is critical for the transmission of disease.C. difficilespores germinate in response to cholic acid derivatives, such as taurocholate (TA), and amino acids, such as glycine or alanine. Although the bile acid germinant receptor is known, the amino acid germinant receptor has remained elusive. Here, we used EMS mutagenesis to generate mutants with altered requirements for the amino acid co-germinant, similar to the strategy used previously to identify the bile acid receptor, CspC. Surprisingly, we identified strains that do not require amino acids as co-germinants, and the mutant spores germinated in response to TA alone. Upon sequencing these mutants, we identified different mutations inyabG.InC. difficile, yabGexpression is required for the processing of CspBA to CspB and CspA and preproSleC to proSleC during spore formation. A definedyabGmutant exacerbated the EMS mutant phenotype. Moreover, we found that various mutations incspAcaused spores to germinate in the presence of TA alone without the requirement of an amino acid. Thus, our study provides evidence that apart from regulating the CspC levels in the spore, CspA is important for recognition of amino acids as co-germinants duringC. difficilespore germination and that two pseudoproteases (CspC and CspA) function as theC. difficilegerminant receptors.
Unexpected mutual regulation underlies paralogue functional diversification and promotes maturation of a protective epithelial tissue
Authors: Gurska Daniela , Vargas Jentzsch Iris M. , Panfilio Kristen A. 
Published: September 2018

ABSTRACTInsectHox3/zengenes represent an evolutionary hotspot for changes in function and copy number. Single orthologues are required either for early specification or late morphogenesis of the extraembryonic tissues, which protect the embryo. The tandemly duplicatedzenparalogues of the beetleTribolium castaneumpresent a unique opportunity to investigate both functions in a single species. We dissect the paralogues’ expression dynamics (transcript and protein) and transcriptional targets (RNA-seq after RNAi) throughout embryogenesis. We identify an unexpected role of Tc-Zen2 in repression ofTc-zen1, generating a negative feedback loop that promotes developmental progression. Tc-Zen2 regulation is dynamic, including within co-expressed multigene loci. We also show that extraembryonic development is the major event within the transcriptional landscape of late embryogenesis and provide a global molecular characterization of the extraembryonic serosal tissue. Altogether, we propose that paralogue mutual regulation arose progressively and drove multiple instances ofzensubfunctionalization, leading to complementary extant roles.
Universal Light-Sheet Generation with Field Synthesis
Authors: Chang Bo-Jui , Kittisopikul Mark , Dean Kevin M. , Roudot Philippe , Welf Erik , Fiolka Reto 
Published: September 2018

AbstractWe introduce Field Synthesis, a theorem that can be used to synthesize any scanned or dithered light-sheet, including those used in lattice light-sheet microscopy (LLSM), from an incoherent superposition of one-dimensional intensity distributions. This user-friendly and modular approach offers a drastically simplified optical design, higher light-throughput, simultaneous multicolor illumination, and a 100% spatial duty cycle, thereby providing uncompromised biological imaging with decreased rates of photobleaching.
Multiplex transcriptional characterizations across diverse and hybrid bacterial cell-free expression systems
Authors: Yim Sung Sun , Johns Nathan I. , Park Jimin , Gomes Antonio L.C. , McBee Ross M. , Richardson Miles , Ronda Carlotta , Chen Sway P. , Garenne David , Noireaux Vincent , Wang Harris H. 
Published: September 2018

AbstractCell-free expression systems enable rapid prototyping of genetic programs in vitro. However, current throughput of cell-free measurements is often limited by the use of single-channel reporter assays. Here, we describe DNA Regulatory element Analysis by cell-Free Transcription and Sequencing (DRAFTS), a rapid and robust in vitro approach for multiplexed measurement of transcriptional activities from thousands of regulatory sequences in a single reaction. We employed this method in active cell lysates developed from ten diverse bacterial species. Interspecies analysis of transcriptional profiles from >1,000 diverse regulatory sequences revealed functional differences in gene expression that could be predictively modeled. Finally, we constructed and examined the transcriptional capacities of dual-species “hybrid” cell lysates that can simultaneously harness gene expression properties of multiple organisms. We expect that this cell-free multiplex transcriptional measurement approach will improve genetic circuit prototyping in new bacterial chassis for synthetic biology.
Greater strength of selection and higher proportion of beneficial amino acid changing mutations in humans compared to mice andDrosophila melanogaster
Authors: Zhen Ying , Huber Christian D. , Davies Robert W. , Lohmueller Kirk E. 
Published: September 2018

ABSTRACTQuantifying and comparing the amount of adaptive evolution among different species is key to understanding evolutionary processes. Previous studies have shown differences in adaptive evolution across species; however, their specific causes remain elusive. Here, we use improved modeling of weakly deleterious mutations and the demographic history of the outgroup species and ancestral population and estimate that at least 20% of nonsynonymous substitutions between humans and an outgroup species were fixed by positive selection. This estimate is much higher than previous estimates, which did not correct for the sizes of the outgroup species and ancestral population. Next, we directly estimate the proportion and selection coefficients (p+ands+, respectively) of newly arising beneficial nonsynonymous mutations in humans, mice, andDrosophila melanogasterby examining patterns of polymorphism and divergence. We develop a novel composite likelihood framework to test whether these parameters differ across species. Overall, we reject a model with the samep+ands+of beneficial mutations across species, and estimate that humans have a higherp+s+compared toD. melanogasterand mice. We demonstrate that this result cannot be caused by biased gene conversion or hypermutable CpG sites. In summary, we find the proportion of beneficial mutations to be higher in humans than inD. melanogasteror mice, suggesting that organismal complexity, which increases the number of steps required in adaptive walks, may be a key predictor of the amount of adaptive evolution within a species.
Effectiveness of physical inactivation methods of dengue virus: heat-versus UV-inactivation
Authors: Idris Fakhriedzwan , Muharram Siti Hanna , Zaini Zainun , Diah Suwarni 
Published: September 2018

AbstractIntroductionComplete inactivation of virus is crucial before samples are manipulated outside of biological containment areas or general cleaning. There are several control methods that could decrease the risk from viral contamination on surfaces, which include chemical disinfectants, heating sterilisation, and ultraviolet germicidal irradiation depending on the nature and properties of the materials to be sterilised. To date, there are limited studies reporting the effectiveness of physical inactivation methods of dengue virus. Therefore, this study was designed to evaluate the effectiveness of two physical inactivation methods, which are heat- and ultraviolet-inactivation, against dengue virus.Material and methodsAll dengue virus serotypes were subjected to heat treatment at various temperatures and exposed to UV light (wavelength of 250-270 nm) at a distance of approximately 75 cm in a Class II Biosafety cabinet (ESCO) at room temperature. The effectiveness of inactivation methods was tested using viability testing on Vero cells and immunofluorescence assay.ResultsDengue virus can be effectively inactivated by heat treatment at 56°C for at least 30 minutes or at higher temperature. On the other hand, the virus required 45 minutes or longer of ultraviolet light exposure at 75 cm distance from the source to be completely inactivated.ConclusionThe results indicated that DENV can be effectively inactivated using high temperature, i.e. 56°C or above, and UV light irradiation. This result would serve as guidelines in proper decontamination and control of dengue virus in laboratory settings, provided proper conditions are met.
The High-throughput WAFFL System for Treating and Monitoring Individual Drosophila melanogaster Adults
Authors: Jaime Maria D.L.A. , Karott Sean , Salem Ghadi H. , Krynitsky Jonathan , Garmendia-Cedillos Marcial , Anderson Sarah , Harbison Susan , Pohida Thomas J. , Oliver Brian 
Published: September 2018

AbstractNon-mammalian model organisms have been essential for our understanding of the mechanisms and control of development, disease, and physiology, but are underutilized in pharmacological phenotypic screening assays due to low throughput compared to cell-based systems. To increase the utility of using Drosophila melanogaster in screening, we have designed the whole animal feeding flat (WAFFL), a novel, flexible, and complete system for feeding, monitoring, and assaying flies in a high throughput format. Our system was conceived keeping in mind the use of off-the-shelf, commercial, 96-well consumables and equipment in order to be amenable to experimental needs. Here we provide an overview of the design and 3-D printing manufacture specifications.