bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cryo-OrbiSIMS for 3D molecular imaging of a bacterial biofilm in its native state
Authors: Zhang Junting , Brown James , Scurr David , Bullen Anwen , MacLellan-Gibson Kirsty , Williams Paul , Alexander Morgan R. , Hardie Kim R. , Gilmore Ian S. , Rakowska Paulina D. 
Published: December 2019

AbstractWe describe a method for label-free molecular imaging of biological materials, preserved in a native state, by using an OrbiSIMS instrument equipped with cryogenic sample handling and developing a high-pressure freezing protocol compatible with mass spectrometry. We studied the 3D distribution of quorum sensing signalling molecules, nucleobases and bacterial membrane molecules, in a mature Pseudomonas aeruginosa biofilm, with high spatial-resolution and high mass-resolution.
An Adaptive Cue Selection Model of Allocentric Spatial Reorientation
Authors: Negen James , Bird Laura , Nardini Marko 
Published: December 2019

AbstractAfter becoming disoriented, an organism must use the local environment to reorient and recover vectors to important locations. Debates over how this happens have been extensive. A new theory, Adaptive Combination, suggests that the information from different spatial cues are combined with Bayesian efficiency. To test this further, we modified the standard reorientation paradigm to be more amenable to Bayesian cue combination analyses while still requiring reorientation, still requiring participants to recall goal locations from memory, and focusing on situations that require the use of the allocentric (world-based; not egocentric) frame. 12 adults and 20 children at 5-7 years old were asked to recall locations in a virtual environment after a disorientation. They could use either a pair of landmarks at the North and South, a pair at the East and West, or both. Results were not consistent with Adaptive Combination. Instead, they are consistent with the use of the most useful (nearest) single landmark in isolation. We term this Adaptive Selection. Experiment 2 suggests that adults also use the Adaptive Selection method when they are not disoriented but still required to use a local allocentric frame. This suggests that the process of recalling a location in the allocentric frame is typically guided by the single most useful landmark, rather than a Bayesian combination of landmarks – regardless of whether the use of the allocentric frame is forced by disorientation or another method. These failures to benefit from a Bayesian strategy accord with the broad idea that there are important limits to Bayesian theories of the cognition, particularly for complex tasks such as allocentric recall.
Quantifying subclinical and longitudinal microvascular changes following episcleral plaque brachytherapy (EPB) using spectral-domain OCT angiography
Authors: Green Kyle M. , Toy Brian C. , Ashimatey Bright S. , Mustafi Debarshi , Jennelle Richard L. , Astrahan Melvin A. , Chu Zhongdi , Wang Ruikang K. , Kim Jonathan , Berry Jesse L. , Kashani Amir H. 
Published: December 2019

AbstractBackgroundI-125 episcleral plaque brachytherapy (EPB) is standard-of-care for globe-conserving treatment of medium-sized choroidal melanomas. Radiation retinopathy is a potential consequence of treatment, characterized by deleterious effects on retinal microvasculature. We investigated the application of Optical Coherence Tomography Angiography (OCTA) for detecting and longitudinally monitoring I-125 episcleral plaque brachytherapy induced radiation retinopathy.MethodsHigh resolution OCTA of the central 3×3mm macula were obtained from I-25 episcleral plaque brachytherapy treated and untreated fellow eyes of 62 patients. Capillary density (vessel skeleton density, VSD) and caliber (vessel diameter index, VDI) were quantified using previously validated semi-automated algorithms. Nonperfusion was also quantified as flow impairment regions (FIR). Exams from treated and fellow eyes obtained pre-treatment and at 6-month, 1-year, and 2-year intervals were compared using generalized estimating equation linear models. Dosimetry maps were used to evaluate spatial correlation between radiation dose and microvascular metrics.ResultsMean time from treatment to last follow-up was 10.8 months. Mean±SD and median radiation dose at the fovea were 64.5 ± 76 Gy and 32.0 Gy, respectively. Preoperative logMAR (Snellen) mean visual acuity was 0.26 ± 0.05 (∼20/35) and 0.08 ± 0.02 (∼20/25) in treated and fellow eyes, respectively. At 6 months, treated eyes had significantly lower VSD (0.147 ± 0.003 vs 0.155 ± 0.002;p= 0.023) and higher FIR (1.95 ± 0.176 vs 1.45 ± 0.099;p= 0.018) compared to fellow eyes. There was a significant decrease in VSD and a corresponding increase in FIR even for treated eyes without clinically identifiable retinopathy at 6 months. VDI was significantly higher in treated eyes than in fellow eyes at 2 years (2.93 ± 0.022 vs 2.84 ± 0.016;p= 0.002). Microvascular changes were spatially correlated with a radiation gradient of 85-250 Gy across the fovea.ConclusionsOCTA can be used to quantify and monitor EPB induced radiation, and can detect vascular abnormalities even in the absence of clinically observable retinopathy. OCTA may therefore be useful in investigating treatment interventions that aim to delay EPB-induced radiation retinopathy.
How grazing and other disturbance factors influence biodiversity in Cyprus, with a focus on breeding bird communities
Authors: Hellicar M. A. , Kirschel A. N. G. 
Published: December 2019

AbstractGrazing and browsing by sheep and goats has been an important anthropogenic influence on ecosystems in the Mediterranean region for centuries. This influence has changed significantly in recent decades, with a general shift from free-range grazing to the penning of animals. The intermediate disturbance hypothesis (IDH) proposes that perturbation - including anthropogenic disturbance - is the “norm” for ecosystems, and Mediterranean systems in particular, and that higher species diversity is found under conditions of continuous, low-level perturbation. We used Cyprus as a case study with the aim of assessing the impact of changes in grazing practice on biodiversity, while also taking account of other anthropogenic factors, such as fire. We aimed to test the IDH as it relates to grazing of scrub and open forest habitats in Cyprus, in the context of the general shift away from free-range grazing. Our hypothesis was that a greater diversity of breeding birds and plants would be found at sites subject to continuous low-level grazing perturbation over a long period of time, compared to sites where grazing has recently ceased, overgrazed sites and sites that have never been grazed.We carried out surveys of breeding birds and vegetation at 48 study sites in scrub and open woodland across Cyprus. We estimated relative grazing pressure (past and present) and fire history at these sites, and looked for associations between these factors and birds, and perennial vegetation.Our findings showed the importance of anthropogenic disturbance for biodiversity in scrub and open forest habitats in Cyprus. However, our results relating to the influence of fire and grazing on birds and vegetation suggest that it is not a regime of continuous low-level disturbance, but rather the absence of perturbation – or at least only very low-level perturbation – that benefits biodiversity in these habitats in Cyprus. This suggests the best approach for biodiversity management in scrub and open woodland habitats in Cyprus is to keep grazing to a minimum and avoid fires, though a ‘no grazing’ approach should also be avoided, because absence of grazers would likely increase fire risk.
Cognitive modelling reveals distinct electrophysiological markers of decision confidence and error monitoring
Authors: Rausch Manuel , Zehetleitner Michael , Steinhauser Marco , Maier Martin E. 
Published: December 2019

AbstractIs confidence in perceptual decisions generated by the same brain processes as decision itself, or does confidence require metacognitive processes following up on the decision? In a masked orientation task with varying stimulus-onset-asynchrony, we used EEG and cognitive modelling to trace the timing of the neural correlates of confidence. Confidence as reported by observers increased with stimulus-onset-asynchrony in correct and to a lesser degree in incorrect trials, a pattern incompatible with established models of confidence. Electrophysiological activity in two different time periods was associated with confidence, namely, 350 – 500 ms after stimulus onset and 250 – 350 ms after the response. Cognitive modelling revealed that only the activity following on the stimulus exhibited the same statistical regularities as confidence, while the statistical pattern of the activity following the response was not compatible with confidence. It is argued that electrophysiological markers of decision confidence and error awareness are at least in parts distinct.
Differential Gene Set Enrichment Analysis: A statistical approach to quantify the relative enrichment of two gene sets
Authors: Joly James H. , Lowry William E. , Graham Nicholas A. 
Published: December 2019

AbstractGene Set Enrichment Analysis (GSEA) is an algorithm widely used to identify statistically enriched gene sets in transcriptomic data. However, to our knowledge, there exists no method for examining the enrichment of two gene sets relative to one another. Here, we present Differential Gene Set Enrichment Analysis (DGSEA), an adaptation of GSEA that assesses the relative enrichment of two gene sets. Using the metabolic pathways glycolysis and oxidative phosphorylation as an example, we demonstrate that DGSEA accurately captures the hypoxia-induced shift towards glycolysis. We also show that DGSEA is more predictive than GSEA of the metabolic state of cancer cell lines, including lactate secretion and intracellular concentrations of lactate and AMP. Furthermore, we demonstrate that DGSEA identifies novel metabolic dependencies not found by GSEA in cancer cell lines. Together, these data demonstrate that DGSEA is a novel tool to examine the relative enrichment of two gene sets.
The potential for a released autosomal X-shredder becoming a driving-Y chromosome and invasively suppressing wild populations of malaria mosquitoes
Authors: Alcalay Yehonatan , Fuchs Silke , Galizi Roberto , Bernardini Federica , Haghighat-Khah Roya Elaine , Rusch Douglas B. , Adrion Jeffrey R. , Hahn Matthew W. , Tortosa Pablo , Papathanos Philippos Aris 
Published: December 2019

AbstractSynthetic sex-ratio distorters based on X-chromosome shredding are predicted to be more efficient than sterile males for population suppression of malaria mosquitoes using genetic control. X-chromosome shredding operates through the targeted elimination of X-chromosome-bearing gametes during male spermatogenesis, resulting in males that have a high fraction of male offspring. Strains harboring autosomal constructs containing a modified endonuclease I-PpoI have now been developed in the malaria mosquito Anopheles gambiae, resulting in strong sex-ratio distortion towards males. Data are being gathered for these strains for submission of regulatory dossiers for contained use and subsequent field release in West Africa. Since autosomal X-shredders are transmitted in a Mendelian fashion and can be selected against their frequency in the population is expected to decline once releases are halted. However, any unintended transfer of the X-shredder to the Y-chromosome could theoretically change these dynamics: This could lead to 100% transmission of the newly Y-linked X-shredder to the predominant male-biased offspring and its insulation from negative selection in females, resulting in its potential spread in the population and ultimately to suppression. Here, we analyze plausible mechanisms whereby an autosomal X-shredder could become linked to the Y-chromosome after release and provide data regarding its potential for activity should it become linked to the Y-chromosome. Our results strongly suggest that Y-chromosome linkage through remobilization of the transposon used for the initial genetic transformation is unlikely, and that, in the unexpected event that the X-shredder becomes linked to the Y-chromosome, expression and activity of the X-shredder would likely be inhibited by meiotic sex chromosome inactivation. We conclude that a functioning X-shredding-based Y-drive resulting from a naturally induced transposition or translocation of the transgene onto the Y-chromosome is unlikely.
The Topology of Mutated Driver Pathways
Authors: Dridi Raouf , Alghassi Hedayat , Obeidat Maen , Tayur Sridhar 
Published: December 2019

AbstractMuch progress has been made, and continues to be made, towards identifying candidate mutated driver pathways in cancer. However, no systematic approach to understanding how candidate pathways relate to each other for a given cancer (such as Acute myeloid leukemia), and how one type of cancer may be similar or different from another with regard to their respective pathways (Acute myeloid leukemia vs. Glioblastoma multiforme for instance), has emerged thus far. Our work attempts to contribute to the understanding ofspace of pathwaysthrough a novel topological framework. We illustrate our approach, using mutation data (obtained from TCGA) of two types of tumors: Acute myeloid leukemia (AML) and Glioblastoma multiforme (GBM). We find that the space of pathways for AML is homotopy equivalent to a sphere, while that of GBM is equivalent to a genus-2 surface. We hope to trigger new types of questions (i.e., allow for novel kinds of hypotheses) towards a more comprehensive grasp of cancer.
Genomic characterisation and context of the blaNDM-1 carbapenemase in Escherichia coli ST101
Authors: Ashcroft Melinda M. , Forde Brian M. , Phan Minh-Duy , Peters Kate M. , Henderson Andrew , Hancock Steven J. , Roberts Leah W. , White Rhys T. , Chan Kok-Gan , Chong Teik Min , Yin Wai-Fong , Paterson David L. , Walsh Timothy R. , Schembri Mark A. , Beatson Scott A. 
Published: December 2019

AbstractCarbapenems are last-resort antibiotics; however, the spread of plasmid-encoded carbapenemases such as the New Delhi metallo-β-lactamase 1 (NDM-1) challenges their effectiveness. The rise of NDM-1 has coincided with the emergence of extensively multidrug resistant (MDR) lineages such as Escherichia coli ST101. Here we present a comprehensive genomic analysis of seven E. coli ST101 isolates that carry the blaNDM-1 gene. We determined the complete genomes of two isolates and the draft genomes of five isolates, enabling complete resolution of the plasmid context of blaNDM-1. Comparisons with thirteen previously published ST101 genomes revealed a monophyletic lineage within the B1 phylogroup forming two clades (designated Clade 1 and Clade 2). Most Clade 1 strains are MDR, encoding resistance to at least 9 different antimicrobial classes, including extended spectrum cephalosporins. Additionally, we characterised different pathways for blaNDM-1 carriage and persistence in the ST101 lineage. For IncC plasmids, carriage was associated with recombination and local transposition events within the antibiotic resistance island. In contrast, we revealed recent transfer of a large blaNDM-1 resistance island between F-type plasmids. The complex acquisition pathways characterised here highlight the benefits of long-read Single Molecule Real Time sequencing in revealing evolutionary events that would not be apparent by short-read sequencing alone. These high-quality E. coli ST101 genomes will provide an important reference for further analysis of the role of mobile genetic elements in this emerging multidrug resistant lineage.ImportanceCarbapenem resistant Escherichia coli are urgent priority organisms as they are resistant to our drugs of last resort. E. coli ST101 have been reported as carriers of the New Delhi Metallo-beta-Lactamase 1 gene (blaNDM-1), conferring resistance to carbapenems, however there is limited genomic information available for this lineage. In this study we used long-read genome sequencing to characterise the complete genomes of two E. coli ST101 strains and determine the carriage of blaNDM-1 in a collection of E. coli ST101 strains. We showed that carriage of blaNDM-1 and resistance determinants to eight other antimicrobial classes was confined to a single clade. We also showed two different pathways for the carriage of blaNDM-1, which was dependent on the type of plasmid. Long-read sequencing allowed us to show the full complexities of these resistance regions and highlighted how strains from an emerging E. coli lineage have become resistant to nearly all available antimicrobials.
Cellular proteostasis decline in human senescence
Authors: Sabath Niv , Levy-Adam Flonia , Younis Amal , Rozales Kinneret , Meller Anatoly , Hadar Shani , Soueid-Baumgarten Sharon , Shalgi Reut 
Published: December 2019

AbstractProteostasis collapse, the diminished ability to maintain protein homeostasis, has been established as a hallmark of nematode aging. However, whether proteostasis collapse occurs in humans has remained unclear. Here we demonstrate that proteostasis decline is intrinsic to human senescence. Using transcriptome-wide characterization of gene expression, splicing and translation, we found a significant deterioration in the transcriptional activation of the heat shock response in stressed senescent cells. Furthermore, phosphorylated HSF1 nuclear localization and distribution were impaired in senescence. Interestingly, alternative splicing regulation was also dampened. Surprisingly, we found a decoupling between different Unfolded Protein Response (UPR) branches in stressed senescent cells. While young cells initiated UPR-related translational and transcriptional regulatory responses, senescent cells showed enhanced translational regulation and ER stress sensing, however they were unable to trigger UPR-related transcriptional responses. This was accompanied by diminished ATF6 nuclear localization in stressed senescent cells. Finally, we revealed a deterioration of proteasome function in senescence following heat stress, which did not recover upon return to normal temperature. Together, our data unraveled a deterioration in the ability to mount dynamic stress transcriptional programs upon human senescence with broad implications on proteostasis control, and connected proteostasis decline to human aging.SignificanceProtein homeostasis (proteostasis), the balance between protein synthesis, folding, and degradation, is thought to deteriorate with age, and the prevalence of protein misfolding diseases, e.g. Alzheimer’s, Parkinson’s etc., with human aging is increased. However, while in worms this phenomenon has been well established, in humans it remained unclear. Here we show that proteostasis is declined in human senescence, i.e. cellular aging. We found that while stress sensing is enhanced in senescent cells, and their response at the level of protein synthesis is intact, they fail to properly activate multiple programs required for stress adaptation at the level of gene transcription. Our findings support the notion that proteostasis decline may have major implications on human aging.
Fluorescent polysome profiling reveals stress-mediated regulation of HSPA14-ribosome interactions
Authors: Meller Anatoly , Coombs David , Shalgi Reut 
Published: December 2019

AbstractRibosome-associated factors play important roles in regulation of translation in response to various physiological and environmental signals. Here we present fluorescent polysome profiling, a new method that provides simultaneous detection of UV and fluorescence directly from polysome gradients. We demonstrate the capabilities of the method by following the polysome incorporation of different fluorescently tagged ribosomal proteins in human cells. Furthermore, we used fluorescent polysome profiling to examine chaperone-ribosome interactions, and characterized their changes in response to proteotoxic stress conditions. We revealed dynamic regulation of HSPA14-polysome association in response to heat shock, with a marked heat shock-mediated increase in the polysome-association of HSPA14. Our data suggest a model whereby HSPA14 dimerization is increased upon heat shock. We therefore established fluorescent polysome profiling as a streamlined method, that can enhance and facilitate the broad exploration of ribosome-associated factors and their regulation.
Versatile simulations of admixture and accurate local ancestry inference withmixnmatchandancestryinfer
Authors: Schumer Molly , Powell Daniel L. , Corbett-Detig Russ 
Published: December 2019

AbstractIt is now clear that hybridization between species is much more common than previously recognized. As a result, we now know that the genomes of many modern species, including our own, are a patchwork of regions derived from past hybridization events. Increasingly researchers are interested in disentangling which regions of the genome originated from each parental species using local ancestry inference methods. Due to the diverse effects of admixture, this interest is shared across disparate fields, from human genetics to research in ecology and evolutionary biology. However, local ancestry inference methods are sensitive to a range of biological and technical parameters which can impact accuracy. Here we present paired simulation and ancestry inference pipelines,mixnmatchandancestryinfer, to help researchers plan and execute local ancestry inference studies.mixnmatchcan simulate arbitrarily complex demographic histories in the parental and hybrid populations, selection on hybrids, and technical variables such as coverage and contamination.ancestryinfertakes as input sequencing reads from simulated or real individuals, and implements an efficient local ancestry inference pipeline. We perform a series of simulations withmixnmatchto pinpoint factors that influence accuracy in local ancestry inference and highlight useful features of the two pipelines. Together,mixnmatchandancestryinferare powerful tools for predicting the performance of local ancestry inference methods on real data.
On the challenges ahead of spatial scientometrics focusing on the city level
Authors: Csomós György 
Published: December 2019

PurposeSpatial bibliometrics and scientometrics have traditionally focused on examining both country and regional levels; however, in recent years, numerous spatial analyses on the city level have been carried out. While city-level scientometric analyses have gained popularity among policymakers and statistical/economic research organizations, researchers in the field of bibliometrics are divided regarding whether it is possible to observe the spatial unit “city” through bibliometric and scientometric tools. The purpose of this paper is to reveal the most significant challenges ahead of spatial scientometrics focusing on the city level by examining relevant scientometric studies.Design/methodology/approachThis analysis involves the most significant spatial scientometric studies focusing on the city level and carefully examines how they collect bibliometric and/or scientometric data, what methodologies they employ to process bibliometric data and most importantly, how they approach the spatial unit “city”.FindingsAfter systematically scrutinizing relevant studies in the field, three major problems have been identified: there is no standardized method of how cities should be defined and how metropolitan areas should be delineated; there is no standardized method of how bibliometric and scientometric data on the city level should be collected and processed; and it is not clearly defined how cities can profit from the results of bibliometric and scientometric analysis focusing on them.Originality/valueThis is the first study that compiles a “database” of scientometric studies focusing on the city level. The paper not only reveals major challenges ahead of city level spatial analysis but recommends some possible solution as well.