bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Sulcus Sink”: A Compact Binary and Semi-Automated Inverse Dijkstra-based System for Describing Sulcal Trajectories
Authors: Pienaar Rudolph , Hasselgrove Christian , Im Kiho , Kennedy David , Grant P Ellen , Boriel Denise , Tang Lena , Makris Nikos 
Published: February 2020

AbstractWe present a description of a system that uses a compact binary representation to describe and trace sulci on a reconstructed human cortical surface, based on a set of human-generated targets. The inputs to the system were manually created on a training set of 20 normal subjects (11 females, 9 males) with ages 22 – 40 years. T1 weighted MPRAGE images were collected on a Siemens 3T Trio scanner, with TR/TE = 2530/3.3, matrix = 256×256, FOV = 256mm, slice thickness 1.33mm. The resultant images were reconstructed with Freesurfer, and 10 sulci on each hemisphere were traced by an expert human operator and independently assessed for accuracy. Presented with these input trajectories in its training phase, the system attempted to determine a compact binary feature vector of each sulcus on each subject using as descriptor a binary parametrized function of several surface-geometry variables (such as mean curvature, sulcal depth, edge length, etc.). This function was optimized in a supervised learning fashion using a Dijkstra-based graph theory formulation, in which the binary weights were used to define graph edge costs. In the setup phase, the system was presented with sulcal trajectories already defined on surfaces, and then adjusted its parametrized weights in a binary fashion to minimize differences between the training input path and its Dijkstra-generated output path. Once the setup phase was complete and sulci had been described in a per-sulcus, per-subject manner, we generalized the per-sulcus description across all the subjects to construct a template binary word for each specific sulcus. The performance of the system for each subject and each sulcus, and for each template sulcus group was measured against the original human reference in both a quantitative and qualitative manner. Individual subjects generally showed very good optimization to their manually traced training samples across all sulci, with 91% average overlap within 4mm of the human target. Generalized group results, as expected, showed less overlap with the original human targets, but still performed on average with 80% overlap. Quantitatively, the group results were nonetheless for the most part quite acceptable to an independent human evaluator. The parametrized binary weight description that drives the Dijkstra path optimization is presented as a mechanism to succinctly and compactly describe individual human sulci and groups of sulci.
Deep sequencing of nonenzymatic RNA primer extension
Authors: Duzdevich Daniel , Carr Christopher E. , Szostak Jack W. 
Published: February 2020

ABSTRACTLife emerging in an RNA world is expected to propagate RNA as hereditary information, requiring some form of primitive replication without enzymes. Nonenzymatic template-directed RNA primer extension is a model of the polymerisation step in this posited form of replication. The sequence space accessed by primer extension dictates potential pathways to self-replication and, eventually, ribozymes. Which sequences can be accessed? What is the fidelity of the reaction? Does the recently-illuminated mechanism of primer extension affect the distribution of sequences that can be copied? How do sequence features respond to experimental conditions and prebiotically relevant contexts? To help answer these and related questions, we here introduce a deep-sequencing methodology for studying RNA primer extension. We have designed and vetted special RNA constructs for this purpose, honed a protocol for sample preparation and developed custom software that sorts and analyses raw sequencing data. We apply this new methodology to proof-of-concept controls, and demonstrate that it works as expected and reports on key features of the sequences accessed by primer extension.
Sex moderates the relationship between aortic stiffness, cognition and cerebrovascular reactivity in healthy older adults
Authors: Sabra Dalia , Intzandt Brittany , Desjardins-Crepeau Laurence , Langeard Antoine , Steele Christopher J. , Frouin Frédérique , Hoge Richard D. , Bherer Louis , Gauthier Claudine J. 
Published: February 2020

AbstractIt is well established that sex differences exist in the manifestation of cardiovascular diseases. Arterial stiffness (AS) has been associated with changes in cerebrovascular reactivity (CVR) and cognitive decline in aging. Specifically, older adults with increased AS show a decline on executive function (EF) tasks. Interestingly, the relationship between AS and CVR is more complex, where some studies show decreased CVR with increased AS, and others demonstrate preserved CVR despite higher AS. We investigated the possible role of sex and hematocrit (HCT) on these hemodynamic relationships. Acquisitions were completed in 48 older adults. Dual-echo pCASL data were collected during a hypercapnia challenge. Aortic PWV data was acquired using cine phase contrast velocity series. A moderation model test revealed that sex moderated the relationship between PWV and CVR and PWV and EF. In addition, there was a significant effect of HCT on the sex differences observed in the moderation effect on EF. Together, our results indicate that the relationships between PWV, CVR and EF are in part mediated by sex and HCT.HighlightsThis study investigates the role of sex on cerebrovascular measures of brain health and congitionSex moderates the relationship between PWV, cerebrovascular reactivity and cognitionHematocrit influences the sex differences observed
Prevalence and global distribution ofblaKPC-2andblaNDM-1genes inKlebsiella Pneumoniae
Authors: Zhang Xiufeng , Li Fangping , Cui Shiyun , Mao Lisha , Li Xiaohua , Furqan Awan , Lv Weibiao , Zeng Zhenling 
Published: February 2020

AbstractCarbapene-resistantKlebsiella pneumoniaeinfections have caused a major concern and posed a global health threat to public.blaKPC-2andblaNDM-1genes are the most widely reported of carbapenem resistance genes inK. pneumoniae. In this study, we investigated phylogenetic relationships of carbapene-resistantK. pneumoniaefrom a tertiary hospital between 2013 and 2018 in China and analyzed the global epidemiology and distribution ofblaKPC-2andblaNDM-1gene inK. pneumoniaebased on 1579 NGS genomes. We found that 19 carbapene-resistantK. pneumoniaeisolated were divided into five lineages and all had high genotypic and phenotypic resistance. Two lineages (mostly ST11 and ST25) were the major type detected carryingblaKPC-2andblaNDM-1gene, respectively. Among global genomes data, 147 known ST types have been identified and ST11 and ST258 were the globally prevalent clones. Genetic environment analysis showed that theISKpn27-blaKPC-2-ISKpn6andblaNDM-1-ble-trpf-nagAmay be the core structure in the horizontal transfer ofblaKPC-2andblaNDM-1, respectively. In addition, DNA transferase (hin) may be involved in the horizontal transfer or the expression ofblaNDM-1. This study sheds some light on the genetic environment ofblaKPC-2andblaNDM-1and should foster further studies about the mechanism of carbapene-resistantK. pneumoniaedissemination.
Neural network features distinguish chemosensory stimuli inCaenorhabditis elegans
Authors: How Javier J. , Navlakha Saket , Chalasani Sreekanth H. 
Published: February 2020

AbstractNervous systems extract and process information from their environment to alter animal behavior and physiology. Despite progress in understanding how different stimuli are represented by changes in neuronal activity, less is known about how they affect broader neural network properties. We developed a framework to use graph-theoretic features of neural network activity and predict ecologically-relevant stimulus properties – namely, stimulus identity and valence. Specifically, we used the transparent nematode,Caenorhabditis elegans, with its small nervous system, to define neural network features associated with various chemosensory stimuli. We trapped animals using a microfluidic device and exposed their noses to chemical stimuli known to be attractive or repellent, while monitoring changes in neural activity in more than 40 neurons in their heads. We found that repellents trigger higher average neural activity across the network, and that the tastant salt increases neural variability. In contrast, graph-theoretic features, which capture patterns of interactions between neurons, are better suited to decode stimulus identity than measures of neural activity. Furthermore, we show that a simple machine learning classifier trained using graph-theoretic features alone or in combination with neural activity features can accurately predict stimulus identity. These results indicate that graph theory reveals network characteristics that are distinct from neural activity, confirming its utility in extracting stimulus properties from neural population data.Significance StatementChanges in the external environment (stimuli) alter patterns of neural activity in animal nervous systems. A central challenge in computational neuroscience is to identify how stimulus properties alter interactions between neurons. We recorded neural activity data fromC. eleganshead neurons while the animal experienced various chemosensory stimuli. We then used a combination of activity statistics (i.e., average, standard deviation, and several frequency-based measures) and graph-theoretic features of network structure (e.g., modularity – the extent to which a network can be divided into independent clusters) to define neural properties that can accurately predict stimulus identity. Our method is general and can be used across species.
CasRx-mediated RNA targeting prevents choroidal neovascularization in a mouse model of age-related macular degeneration
Authors: Zhou Changyang , Hu Xinde , Tang Cheng , Liu Wenjia , Wang Shaoran , Zhou Yingsi , Zhao Qimeng , Bo Qiyu , Shi Linyu , Sun Xiaodong , Zhou Haibo , Yang Hui 
Published: February 2020

AbstractThe smallest Cas13 family protein, CasRx, has a high cleavage activity and targeting specificity, offering attractive opportunity for therapeutic applications. Here we report that delivery of CasRx by adeno-associated virus via intravitreal injection could efficiently knockdownVegfatranscripts and significantly reduce the area of laser-induced choroidal neovascularization in a mouse model of age-related macular degeneration. Thus, RNA-targeting CRISPR system could be used forin vivogene therapy.
Brain Injury after Transcatheter Aortic Valve Replacement for Bicuspid Versus Tricuspid Aortic Valve Stenosis
Authors: Fan Jiaqi , Fang Xian , Liu Chunhui , Zhu Gangjie , Hou Cody R. , Jiang Jubo , Lin Xinping , Wang Lihan , He Yuxin , Zhu Qifeng , Ng Stella , Chen Zexin , Hu Haitao , Tse Hungfat , Liu Xianbao , Wang Jian’an 
Published: February 2020

AbstractBackgroundsThe risk of brain injury in bicuspid aortic valve (BAV) patients following transcatheter aortic valve replacement (TAVR) is currently unknown.Methods and ResultsA total of 204 consecutive severe aortic stenosis patients who underwent TAVR were enrolled. 83 (40.7%) patients were BAV patients and the other 121 patients were tricuspid aortic valve (TAV) patients. All patients received diffusion-weighted magnetic resonance imaging (DW-MRI) at baseline, 2 to 7 days after TAVR. Mean ages (mean ± SD: 75.8 ± 6.7 years vs. 78.9 ± 6.6 years, p = 0.004) and STS scores (6.0 ± 3.7 vs. 7.1 ± 4.2, p = 0.044) of the BAV and TAV patients were significantly different, while the stroke rates (2.4% vs. 1.7%, p = 0.704) were comparable between two groups. BAV patients were associated with higher number of new lesions (5.69 ± 6.22 vs. 3.50 ± 4.16, p = 0.008), total lesion volume [median(interquartile range): 290(70-930) mm3 vs. 140(35-480) mm3, p = 0.008], and the volume per lesion [70.0(45.0-115.0) mm3 vs. 57.5(24.5-93.0) mm3, p = 0.037] in DW-MRI. Moreover, the proportion of patients with lesions larger than 1cm3 (28.6% vs. 10.9%, p = 0.005) and the number of new lesions in the middle cerebral arteries zone (1.46 ± 2.07 vs. 0.98 ± 1.84, p = 0.039) and intermediate zone between the anterior cerebral and middle cerebral arteries (ACA/MCA) (1.07 ± 1.68 vs. 0.50 ± 1.05, p = 0.007), and between the vertebral artery and basilar artery (VA/BA) (1.01 ± 1.35 vs. 0.77 ± 1.44, p = 0.033) were higher in BAV patients than in TAV patients.ConclusionsBAV patients may encounter more severe brain injuries not only due to greater number of lesions but also due to larger lesion size, especially in the ACA/MCA, MCA and VA/BA lesions zone.
Rewinding the molecular clock in the genusCarabus(Coleoptera: Carabidae) in light of fossil evidence and the Gondwana split: a re-analyses
Authors: Opgenoorth Lars , Hofmann Sylvia , Schmidt Joachim 
Published: February 2020

1AbstractBackgroundMolecular clocks have become powerful tools given increasing sequencing and fossil resources. However, outcome of calibration analyses depend on choosing priors. Here we revisit a seminal dating study of the genusCarabusby Andujar et al. proposing that their prior choices need re-evaluation with the hypothesis that reflecting fossil evidence and the Gondwanan split properly rewinds the molecular clock significantly. We used the same dataset including five mitochondrial and four nuclear DNA fragments with 7888 nt total length. We set the root age based on the fossil evidence of Harpalinae ground beetles in the Upper Cretaceous and introduce the Paleogene divergence of the outgroup taxaCeroglossus(endemic to South-America) andPamborus+Maoripamborus(Australia, New Zealand) as a new prior based on current paleontological and geological literature.ResultsThe ultrametric time-calibrated tree of the extended nd5 dataset resulted in a median TMRCACarabusage of 58.48 Ma (HPD95% 46.61-72.04), roughly 35 Ma older than in the Andujar study. The splits betweenC. rugosusandC. morbillosus(A), betweenC. riffensisfrom the EuropeanMesocarabus(B), and betweenEurycarabusandNesaeocarabus(C) were dated to 19.19 (13.54-25.87), 25.95 (18.8-34.62), and 23.98 (17.28-31.47) Ma and were thus decidedly older than previously reported (7.48, 10.93, and 9.51 Ma). These changes were driven solely by constraining the Carabidae time tree root with Harpalinae amber fossils at ∼99 Ma. Utilizing the nd5 dating results of three well supportedCarabusclades as secondary calibration points for the complete MIT-NUC data set lead to a TMRCA ofCarabusof 53.56 (41.25-67.05) Ma compared to 25.16 (18.41-33.04) in Andujar’s study.ConclusionTaking into account the Gondwanan split as a new prior, together with the fossil evidence of the outgroup taxon Harpalini in the Late Cretaceous, our new approach supports an origin of the genusCarabusin the Paleocene-Early Eocene. Our results are preliminary due to the heavy reliance on the nd5 gene and thus will have to be tested with sufficient set of nuclear markers. In addition, uncertainties arise from dating the root age of the tree based on a single fossil and outgroup taxon which has a major effect on the results. Improvement of the fossil data base particularly in the supertribe Carabitae is thus strongly needed to reduce the currently large uncertainties in datingCarabusphylogeny.
Urethral luminal epithelia are castration-insensitive progenitors of the proximal prostate
Authors: Joseph Diya B. , Henry Gervaise H. , Malewska Alicia , Iqbal Nida S. , Ruetten Hannah M. , Turco Anne E. , Abler Lisa L. , Sandhu Simran K. , Cadena Mark T. , Malladi Venkat S. , Reese Jeffrey C. , Mauck Ryan J. , Gahan Jeffrey C. , Hutchinson Ryan C. , Roehrborn Claus G. , Baker Linda A. , Vezina Chad M. , Strand Douglas W. 
Published: February 2020

AbstractCastration-insensitive epithelial progenitors capable of regenerating the prostate are concentrated in the proximal region close to the urethra, but the identification of these cells has been limited to individual cell surface markers. Here, we use single cell RNA sequencing (scRNA-seq) to obtain a cellular anatomy of the mouse prostate and urethra and create a comparative map with the human. These data reveal that previously identified facultative progenitors marked by TROP2, Sca-1, KRT4, and PSCA are actually luminal epithelia of the urethra that extend into the proximal prostate. These mouse urethral cells are the human equivalent of previously identified club and hillock urethral cells. Castration decreases androgen-dependent prostate luminal epithelia as expected, but TROP2+ urethral luminal epithelia survive and expand into the prostate. Benign prostatic hyperplasia (BPH) has long been considered an ‘embryonic reawakening’, but the cellular origin of peri-urethral growth is unclear. We use scRNA-seq and flow cytometry to demonstrate an increase in urethral luminal epithelia within glandular nodules from patients with BPH, which are further enriched in patients treated with a 5 alpha reductase inhibitor. These data demonstrate that the putative prostate progenitors enriched by castration in the proximal prostate are an expansion of urethral luminal epithelia and that these cells may play an important role in the etiology of human BPH.Significance StatementThe prostate involutes after castration, but regrows to its original size with androgen replenishment. This observation prompted the search for a castration-insensitive prostate progenitor. Here, Josephet al. produce a comparative cellular atlas of the prostate and urethra in the mousevs.human, discovering an equivalent urethral luminal epithelial cell type that extends into the proximal prostatic ducts and expresses previously identified markers of facultative prostate progenitors. Urethral luminal epithelia are established before prostate budding in human and mouse development, and expand after castration in the mouse and after 5 alpha reductase inhibitor treatment in human BPH. These data suggest that luminal epithelia of the urethra are castration-insensitive cells of proximal ducts that may act as progenitors in human BPH.
Input connectivity reveals additional heterogeneity of dopaminergic reinforcement inDrosophila
Authors: Otto Nils , Pleijzier Markus W. , Morgan Isabel C. , Edmondson-Stait Amelia J. , Heinz Konrad J. , Stark Ildiko , Dempsey Georgia , Ito Masayoshi , Kapoor Ishaan , Hsu Joseph , Schlegel Philipp M. , Bates Alexander S. , Feng Li , Costa Marta , Ito Kei , Bock Davi D. , Rubin Gerald M , Jefferis Gregory S. X. E. , Waddell Scott 
Published: February 2020

SummaryDifferent types ofDrosophiladopaminergic neurons (DANs) reinforce memories of unique valence and provide state-dependent motivational control [1]. Prior studies suggest that the compartment architecture of the mushroom body (MB) is the relevant resolution for distinct DAN functions [2, 3]. Here we used a recent electron microscope volume of the fly brain [4] to reconstruct the fine anatomy of individual DANs within three MB compartments. We find the 20 DANs of the γ5 compartment, at least some of which provide reward teaching signals, can be clustered into 5 anatomical subtypes that innervate different regions within γ5. Reconstructing 821 upstream neurons reveals input selectivity, supporting the functional relevance of DAN sub-classification. Only one PAM-γ5 DAN subtype γ5(fb) receives direct recurrent input from γ5β’2a mushroom body output neurons (MBONs) and behavioral experiments distinguish a role for these DANs in memory revaluation from those reinforcing sugar memory. Other DAN subtypes receive major, and potentially reinforcing, inputs from putative gustatory interneurons or lateral horn neurons, which can also relay indirect feedback from MBONs. We similarly reconstructed the single aversively reinforcing PPL1-γ1pedc DAN. The γ1pedc DAN inputs mostly differ from those of γ5 DANs and they cluster onto distinct dendritic branches, presumably separating its established roles in aversive reinforcement and appetitive motivation [5, 6]. Tracing also identified neurons that provide broad input to γ5, β’2a and γ1pedc DANs suggesting that distributed DAN populations can be coordinately regulated. These connectomic and behavioral analyses therefore reveal further complexity of dopaminergic reinforcement circuits between and within MB compartments.HighlightsNanoscale anatomy reveals additional subtypes of rewarding dopaminergic neurons.Connectomics reveals extensive input specificity to subtypes of dopaminergic neurons.Axon morphology implies dopaminergic neurons provide subcompartment-level function.Unique dopaminergic subtypes serve aversive memory extinction and sugar learning.
Museum phylogenomics of extinctOryctesbeetles from the Mascarene Islands
Authors: Latorre Sergio M. , Herrmann Matthias , Paulsen M.J. , Rödelsperger Christian , Dréau Andreea , Röseler Waltraud , Sommer Ralf J. , Burbano Hernán A. 
Published: February 2020

AbstractThe evolution of island systems is characterized by processes that result in extreme morphological diversity, high endemism and high extinction rates. These dynamics can make phylogenetic reconstruction difficult, i.e. the extinct flightless Dodo from Mauritius was assigned to the family of doves only through DNA analysis of subfossils. Many insect species on islands have gone extinct through habitat loss, and face similar challenges to decipher their evolutionary history, however historical specimens have not yet been harnessed for phylogenomic reconstructions. Here, we employed historical museum specimens from the Mascarene Islands to generate the first whole-genome based phylogeny of three presumably extinct species of the rhinoceros beetle genusOryctes. We compared their genomes with those of an extantOryctesspecies from the island of Réunion, as well as a flightless Réunion-based species previously placed into the supposedly unrelated genusMarronus. We found thatMarronus borbonicusbelongs instead to the genusOryctesand that the two Réunion-based species (O. borbonicusandM. borbonicus) are not sister taxa, suggesting two independent colonizations. The divergence time between them (<3Myr) overlaps with the volcanic formation of Réunion, likely indicating thatM. borbonicusbecame flightlessin situ. Our study showcases the power of genomes from insect museum specimens to address evolutionary questions in light of increasing extinction rates.