bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apparent non-canonical trans-splicing is generated by reverse transcriptase in vitro
Authors: Tollervey David , Houseley Jonathan 
Published: July 2019

AbstractTrans-splicing, the in vivo joining of two RNA molecules, is well characterized in several groups of simple organisms but was long thought absent from fungi, plants and mammals. However, recent bioinformatic analyses of expressed sequence tag (EST) databases suggested widespread trans-splicing in mammals^1-2^. Splicing, including the characterised trans-splicing systems, involves conserved sequences at the splice junctions. Our analysis of a yeast non-coding RNA revealed that around 30% of the products of reverse transcription lacked an internal region of 117 nt, suggesting that the RNA was spliced. The junction sequences lacked canonical splice-sites but were flanked by direct repeats, and further analyses indicated that the apparent splicing actually arose because reverse transcriptase can switch templates during transcription^3^. Many newly identified, apparently trans-spliced, RNAs lacked canonical splice sites but were flanked by short regions of homology, leading us to question their authenticity. Here we report that all reported categories of non-canonical splicing could be replicated using an in vitro reverse transcription system with highly purified RNA substrates. We observed the reproducible occurrence of ostensible trans-splicing, exon shuffling and sense-antisense fusions. The latter generate apparent antisense non-coding RNAs, which are also reported to be abundant in humans^4^. Different reverse transcriptases can generate different products of template switching, providing a simple diagnostic. Many reported examples of splicing in the absence of canonical splicing signals may be artefacts of cDNA preparation.
Effects of diamagnetic levitation on bacterial growth in liquid
Authors: Hill Richard , Larkin Oliver , Anthony Paul , Davey Michael , Eaves Laurence , Rees Catherine , Dijkstra Camelia 
Published: July 2019

AbstractDiamagnetic levitation is a technique that uses a strong, spatially-varying magnetic field to levitate diamagnetic materials, such as water and biological cells. This technique has the potential to simulate aspects of weightlessness, on the Earth. In common with all ground-based techniques to simulate weightlessness, however, there are effects introduced by diamagnetic levitation that are not present in space. Since there have been few studies that systematically investigate these differences, diamagnetic levitation is not yet being fully exploited. For the first time, we critically assess the effect of diamagnetic levitation on a bacterial culture in liquid. We used a superconducting magnet to levitate growing bacterial cultures for up to 18 hours, in a series of experiments to determine the effect of diamagnetic levitation on all phases of the bacterial growth cycle. We find that diamagnetic levitation increases the rate of population growth in a liquid culture. The speed of sedimentation of the bacterial cells to the bottom of the container is considerably reduced. Further experiments and microarray gene analysis show that the growth enhancement is due to greater oxygen availability in the magnetically levitated sample. We demonstrate that the magnetic field that levitates the cells also induces convective stirring in the liquid, an effect not present in microgravity. We present a simple theoretical model, showing how the paramagnetic force on dissolved oxygen can cause the liquid to become unstable to convection when the consumption of oxygen by the bacteria generates an oxygen concentration gradient. We propose that this convection enhances oxygen availability by transporting oxygen around the sample. Since convection is absent in space, these results are of significant importance and timeliness to researchers considering using diamagnetic levitation to explore weightless effects on living organisms and a broad range of other topics in the physical and life sciences.
Differential expression analysis for sequence count data
Authors: Anders Simon , Huber Wolfgang 
Published: July 2019

Abstract*Motivation:* High-throughput nucleotide sequencing provides quantitative readouts in assays for RNA expression (RNA-Seq), protein-DNA binding (ChIP-Seq) or cell counting (barcode sequencing). Statistical inference of differential signal in such data requires estimation of their variability throughout the dynamic range. When the number of replicates is small, error modelling is needed to achieve statistical power.
Results:
We propose an error model that uses the negative binomial distribution, with variance and mean linked by local regression, to model the null distribution of the count data. The method controls type-I error and provides good detection power. *Availability:* A free open-source R software package, DESeq, is available from the Bioconductor project and from "http://www-huber.embl.de/users/anders/DESeq":http://www-huber.embl.de/users/anders/DESeq.
Clinical validity assessment of a breast cancer risk model combining genetic and clinical information
Authors: Mealiffe Matthew , Stokowski Renee , Rhees Brian , Prentice Ross , Pettinger Mary , Hinds David 
Published: July 2019

Abstract

Background:

The extent to which common genetic variation can assist in breast cancer (BCa) risk assessment is unclear. We assessed the addition of risk information from a panel of BCa-associated single nucleotide polymorphisms (SNPs) on risk stratification offered by the Gail Model.Methods: We selected 7 validated SNPs from the literature and genotyped them among white women in a nested case-control study within the Women’s Health Initiative Clinical Trial. To model SNP risk, previously published odds ratios were combined multiplicatively. To produce a combined clinical/genetic risk, Gail Model risk estimates were multiplied by combined SNP odds ratios. We assessed classification performance using reclassification tables and receiver operating characteristic (ROC) curves. Results: The SNP risk score was well calibrated and nearly independent of Gail risk, and the combined predictor was more predictive than either Gail risk or SNP risk alone. In ROC curve analysis, the combined score had an area under the curve (AUC) of 0.594 compared to 0.557 for Gail risk alone. For reclassification with 5-year risk thresholds at 1.5% and 2%, the net reclassification index (NRI) was 0.085 (Z = 4.3, P = 1.0 × 10^-5^). Focusing on women with Gail 5-year risk of 1.5-2% results in an NRI of 0.195 (Z = 3.8, P = 8.6 × 10^−5^).

Conclusions:

Combining clinical risk factors and validated common genetic risk factors results in improvement in classification of BCa risks in white, postmenopausal women. This may have implications for informing primary prevention and/or screening strategies. Future research should assess the clinical utility of such strategies.
Evolution of 11[beta]-Hydroxysteroid Dehydrogenase-Type 1 and 11[beta]-Hydroxysteroid Dehydrogenase-type 3
Authors: Baker Michael 
Published: July 2019

AbstractA key regulator of glucocorticoid action is 11[beta]-hydroxysteroid dehydrogenase type-1 (11[beta]-HSD1), which catalyzes the conversion of cortisone to cortisol, the biologically active glucocorticoid. 11[beta]-HSD1 is a paralog of 11[beta]-HSD3, whose physiological function remains unclear. As reported here, 11[beta]-HSD3 has orthologs in sea urchin, amphioxus and Ciona, while 11[beta]-HSD1 first appears in sharks. Thus, 11[beta]HSD3 arose before the evolution of glucocorticoid signaling, suggesting different ancestral function(s) for 11[beta]-HSD3. Four perplexing findings arise from this evolutionary analysis: 1) 11[beta]-HSD1 is not present in a ray-finned fish genome, 2) zebrafish and fathead minnow contain two isoforms of 11[beta]-HSD3; 3) neither rat nor mouse contain 11[beta]-HSD3 and 4) amphioxus contains sixteen 11[beta]-HSD3 paralogs.
Snca and Bdnf gene expression in the VTA and raphe nuclei of midbrain in chronically victorious and defeated male mice
Authors: Kudryavtseva Natalia N. , Bondar Natalia P. , Boyarskikh Ul'yana A. , Filipenko Maxim L. 
Published: July 2019

AbstractThe study aimed to analyze the mRNA levels of Snca and Bdnf genes in the ventral tegmental area (VTA) and raphe nuclei of the midbrain in male mice that had each won or defeated 20 encounters in daily agonistic interactions. Groups of animals that had the same winning and losing track record followed by a no-fight period for 14 days were also studied. Snca mRNA levels were increased in the raphe nuclei in the losers and in the VTA of the winners. After fighting deprivation Snca mRNA levels were decreased to the control level in both groups. Snca mRNA levels were similar to the control level in the VTA of the losers and in the raphe nuclei of the winners. However Snca gene expression was increased in these areas after no-fight period in the winners and losers in comparison with respective mRNA levels in the undeprived animals. Significant positive correlations were found between the mRNA levels of Snca and Bdnf genes in the raphe nuclei. It was concluded, that social experience affects Snca gene expression depending on brain areas and functional activity of monoaminergic systems in chronically victorious or defeated mice.
Modelling predicts that heat stress and not drought will limit wheat yield in Europe
Authors: Semenov Mikhail , Shewry Peter 
Published: July 2019

AbstractGlobal warming is characterised by shifts in weather patterns and increases in extreme weather events. New crop cultivars with specific physiological traits will therefore be required if climate change is not to result in losses of yield and food shortages. However, the intrinsic uncertainty of climate change predictions poses a challenge to plant breeders and crop scientists who have limited time and resources and must select the most appropriate traits for improvement. Modelling is, therefore, a powerful tool to identify future threats to crop production and hence targets for improvement. Wheat is the most important crop in temperate zones, including Europe, and is the staple food crop for many millions of humans and their livestock. However, its production is highly sensitive to environmental conditions, with increased temperature and incidence of drought associated with global warming posing potential threats to yield in Europe. We have therefore predicted the future impacts of these environmental changes on wheat yields using a wheat simulation model combined with climate scenarios based on fifteen global climate models from the IPCC AR4 multi-model ensemble. Despite the lower summer precipitation predicted for Europe, the impact of drought on wheat yields is likely to be smaller than at present, because the warmer conditions will result in earlier maturation before drought becomes severe later in the summer. By contrast, the probability of heat stress around flowering is predicted to increase significantly which is likely to result in considerable yield losses for heat sensitive wheat cultivars commonly grown in north Europe. Breeding strategies should therefore focus on the development of wheat varieties which are tolerant to high temperature around flowering, rather than on developing varieties resistant to drought which may be required for other parts of the world.
Molecular and nanostructural mechanisms of deformation, strength and toughness of spider silk fibrils
Authors: Nova Andrea , Keten Sinan , Pugno Nicola , Redaelli Alberto , Buehler Markus 
Published: July 2019

AbstractSpider silk is one of the strongest, most extensible and toughest biological materials known, exceeding the properties of many engineered materials including steel. Silks feature a hierarchical architecture where highly organized, densely H-bonded beta-sheet nanocrystals are arranged within a semi-amorphous protein matrix consisting of 31-helices and beta-turn protein structures. By using a bottom-up molecular-based mesoscale model that bridges the scales from Angstroms to hundreds of nanometers, here we show that the specific combination of a crystalline phase and a semi-amorphous matrix is crucial for the unique properties of silks. Specifically, our results reveal that the superior mechanical properties of spider silk can be explained solely by structural effects, where the geometric confinement of beta-sheet nanocrystals combined with highly extensible semi-amorphous domains with a large hidden length is the key to reach great strength and great toughness, despite the dominance of mechanically inferior chemical interactions such as H-bonding. Our model directly shows that semi-amorphous regions unravel first when silk is being stretched, leading to the large extensibility of silk. Conversely, the large-deformation mechanical properties and ultimate tensile strength of silk is controlled by the strength of beta-sheet nanocrystals, which is directly related to their size, where small beta-sheet nanocrystals are crucial to reach outstanding levels of strength and toughness. Our model agrees well with observations in recent experiments, where it was shown that a significant change in the strength and toughness can be achieved solely by tuning the size of beta-sheet nanocrystals. Our findings unveil the material design strategy that enables silks to achieve superior material performance despite simple and inferior constituents, resulting in a new paradigm in materials design where enhanced functionality is not achieved using complex building blocks, but rather through the utilization of simple repetitive constitutive elements arranged in hierarchical structures.
Biostratigraphy of the Danian/Selandian transition: A case study from Kamestan anticline section, northwest of Izeh city in Khuzestan province, Southern Iran
Authors: Hadavandkhani Nasrin , Sadeghi Abbas 
Published: July 2019

AbstractThe planktonic foraminifera turnover across the Danian-Selandian boundary (early to late Paleocene, ~60 Ma) has been studied in the Kamestan anticline section. The studied interval span planktonic foraminifera zones P2-P3. In this section Danian-Selandian boundary is located in Pabedeh – Gurpi Formations transition. Here, the boundary of Pabeh and Gurpi Formations is a transitional one and identified by with color change of from grey shale to purple shale of Gurpi Formation to Pabdeh Formation .
Co-detection: Ultra-reliable Nanoparticle-Based Electrical Detection of Biomolecules in the Presence of Large Background Interference
Authors: Liu Yang , Alocilja Evangelyn , Chakrabartty Shantanu 
Published: July 2019

AbstractContrary to popular belief, we report that background interference in conductimetric biochips can be exploited using a novel "co-detection" principle to significantly improve the reliability of detecting trace quantities of biomolecules. The technique called "co-detection" exploits the non-linear redundancy amongst synthetically patterned biomolecular logic circuits for deciphering the presence or absence of target biomolecules in a sample. In this paper, we demonstrate the "co-detection" principle on gold-nanoparticle based conductimetric soft-logic circuits which uses a silver-enhancement technique for signal amplification. Using co-detection, we have been able to measure a 1000 times improvement in the reliability of detecting mouse IgG at concentration levels that are 10^5^ lower than the concentration of rabbit IgG which serves as background interference.
Day-length is central to maintaining consistent seasonal diversity in marine bacterioplankton
Authors: Gilbert Jack , Somerfield Paul , Temperton Ben , Huse Susan , Joint Ian , Field Dawn 
Published: July 2019

AbstractMarine bacterial diversity is vast, but seasonal variation in diversity is poorly understood. Here we present the longest bacterial diversity time series consisting of monthly (72) samples from the western English Channel over a 6 year period (2003-2008) using 747,494 16SrDNA-V6 amplicon-pyrosequences. Although there were characteristic cycles for each phylum, the overall community cycle was remarkably stable year after year. The majority of taxa were not abundant, although on occasion these rare bacteria could dominate the assemblage. Bacterial diversity peaked at the winter solstice and showed remarkable synchronicity with day-length, which had the best explanatory power compared to a combination of other variables (including temperature and nutrient concentrations). Day-length has not previously been recognised as a major force in structuring microbial communities.
Proliferating Cell Nuclear Antigen (PCNA) allows the automatic identification of follicles in microscopic images of human ovarian tissue
Authors: Kelsey Tom , Caserta Benedicta , Castillo Luis , Wallace Hamish , Cóppola Gonzálvez Francisco 
Published: July 2019

Abstract
Background:
Human ovarian reserve is defined by the population of non-growing follicles (NGFs) in the ovary. Direct estimation of ovarian reserve involves the identification of NGFs in prepared ovarian tissue. Previous studies involving human tissue have used hematoxylin and eosin (HE) stain, with NGF populations estimated by human examination either of tissue under a microscopic, or of images taken of this tissue. Methods: In this study we replace HE with Proliferating Cell Nuclear Antigen (PCNA), and automate the identification and enumeration of NGFs that appear in the resulting microscopic images. We compared the automated estimates to those obtained by human experts, with the gold standard taken to be the average of the conservative and liberal estimates by three human experts. Results: The automated estimates were within 10% of the gold standard, for images at both 100x and 200x magnifications. Automated analysis took longer than human analysis for several hundred images, not allowing for breaks from analysis needed by humans.

Conclusion:
Our results both replicate and improve on those of previous studies involving rodent ovaries, and demonstrate the viability of large-scale studies of human ovarian reserve using a combination of immunohistochemistry and computational image analysis techniques.
Report on trial of SatScan tray scanner system by SmartDrive Ltd.
Authors: Blagoderov Vladimir , Kitching Ian , Simonsen Thomas , Smith Vincent 
Published: July 2019

AbstractSmartdrive Ltd. has developed a prototype imaging system, SatScan, that captures digitised images of large areas while keeping smaller objects in focus at very high resolution. The system was set up in the Sackler Biodiversity Imaging laboratory of Natural History Museum on March 8, 2010 for a one-month trial. A series of projects imaging parts of the entomological, botanical and palaeoentomological collection were conducted to assess the systems utility for museum collection management and biodiversity research. The technical and practical limitations of the system were investigated as part of this process.
Unlocking biomarker discovery: Large scale application of aptamer proteomic technology for early detection of lung cancer
Authors: Ostroff Rachel , Bigbee William , Franklin Wilbur , Gold Larry , Mehan Mike , Miller York , Pass Harvey , Rom William , Siegfried Jill , Stewart Alex , Walker Jeffrey , Weissfeld Joel , Williams Stephen , Zichi Dom , Brody Edward 
Published: July 2019

AbstractLung cancer is the leading cause of cancer deaths, because ~84% of cases are diagnosed at an advanced stage. Worldwide in 2008, ~1.5 million people were diagnosed and ~1.3 million died – a survival rate unchanged since 1960. However, patients diagnosed at an early stage and have surgery experience an 86% overall 5-year survival. New diagnostics are therefore needed to identify lung cancer at this stage. Here we present the first large scale clinical use of aptamers to discover blood protein biomarkers in disease with our breakthrough proteomic technology. This multi-center case-control study was conducted in archived samples from 1,326 subjects from four independent studies of non-small cell lung cancer (NSCLC) in long-term tobacco-exposed populations. We measured >800 proteins in 15uL of serum, identified 44 candidate biomarkers, and developed a 12-protein panel that distinguished NSCLC from controls with 91% sensitivity and 84% specificity in a training set and 89% sensitivity and 83% specificity in a blinded, independent verification set. Performance was similar for early and late stage NSCLC. This is a significant advance in proteomics in an area of high clinical need.
Aptamer-based multiplexed proteomic technology for biomarker discovery
Authors: Gold Larry , Ayers Deborah , Bertino Jennifer , Bock Christopher , Bock Ashley , Brody Edward , Carter Jeff , Cunningham Virginia , Dalby Andrew , Eaton Bruce , Fitzwater Tim , Flather Dylan , Forbes Ashley , Foreman Trudi , Fowler Cate , Gawande Bharat , Goss Meredith , Gunn Magda , Gupta Shashi , Halladay Dennis , Heil Jim , Heilig Joe , Hicke Brian , Husar Gregory , Janjic Nebojsa , Jarvis Thale , Jennings Susan , Katilius Evaldas , Keeney Tracy , Kim Nancy , Kaske Terese , Koch Tad , Kraemer Stephan , Kroiss Luke , Le Ngan , Levine Daniel , Lindsey Wes , Lollo Bridget , Mayfield Wes , Mehan Mike , Mehler Robert , Nelson Michele , Nelson Sally , Nieuwlandt Dan , Nikrad Malti , Ochsner Urs , Ostroff Rachel , Otis Matt , Parker Thomas , Pietrasiewicz Steve , Resnicow Dan , Rohloff John , Sanders Glenn , Sattin Sarah , Schneider Dan , Singer Britta , Stanton Martin , Sterkel Alana , Stewart Alex , Stratford Suzanne , Vaught Jonathan , Vrkljan Mike , Walker Jeffrey , Watrobka Mike , Waugh Sheela , Weiss Allison , Wilcox Sheri , Wolfson Alexey , Wolk Steve , Zhang Chi , Zichi Dom 
Published: July 2019

AbstractInterrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine.