bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan
Authors: Sakaue Saori , Kanai Masahiro , Karjalainen Juha , Akiyama Masato , Kurki Mitja , Matoba Nana , Takahashi Atsushi , Hirata Makoto , Kubo Michiaki , Matsuda Koichi , Murakami Yoshinori ,   FinnGen, Daly Mark J. , Kamatani Yoichiro , Okada Yukinori 
Published: December 2019

AbstractHuman genetics seeks a way to improve human health on a global scale. Expectations are running high for polygenic risk scores (PRSs) to be translated into clinical practice to predict an inborn susceptibility to health risks. While risk stratification based on PRS is one way to promote population health, a strategy to utilize genetics to prioritize modifiable risk factors and biomarkers driving heath outcome is also warranted. To this end, here we utilized PRSs to comprehensively investigate the association of the genetic susceptibility to complex traits with human lifespan in collaboration with three worldwide biobanks (ntotal = 675,898). First, we conducted genome-wide association studies for 45 quantitative clinical phenotypes, constructed the individual PRSs, and associated them with the age at death of 179,066 participants in BioBank Japan. The PRSs revealed that the genetic susceptibility of high systolic blood pressure (sBP) was strongly associated with a shorter lifespan (hazard ratio [HR] = 1.03, P = 1.4×10-7). Next, we sought to replicate these associations in individuals of European ancestry in UK Biobank (n = 361,194) and FinnGen (n = 135,638). Among the investigated traits, the individuals with higher blood pressure-related PRSs were trans-ethnically associated with a shorter lifespan (HR = 1.03, Pmeta = 3.9×10-13 for sBP) and parental lifespan (HR = 1.06, PUKBB = 2.0×10-86 for sBP). Further, our trans-biobank study identified additional complex traits associated with lifespan (e.g., obesity, height, serum lipids, and platelet counts). Of them, obesity-related traits showed strikingly heterogeneous effects on lifespan between Japanese and European populations (Pheterogeneity = 9.5×10-8 for body mass index). Through trans-ethnic biobank collaboration, we elucidated the novel value of the PRS study in genetics-driven prioritization of risk factors and biomarkers which can be medically intervened to improve population health.
Statistically-estimated tree biomass, stem density, and basal area for the upper Midwestern United States at the time of Euro-American settlement
Authors: Paciorek Christopher J. , Cogbill Charles V. , Peters Jody A. , Goring Simon J. , Williams John W. , Mladenoff David J. , Dawson Andria , McLachlan Jason S. 
Published: December 2019

AbstractWe present gridded 8 km-resolution data products of the estimated biomass, basal area, and stem density of tree taxa at the time of Euro-American settlement of the midwestern United States for the states of Minnesota, Wisconsin, Michigan, Illinois, and Indiana. The data come from settlement-era Public Land Survey (PLS) data (ca. 0.8-km resolution) of trees recorded by land surveyors. The surveyor notes have been transcribed, cleaned, and processed to estimate biomass, basal area, and stem density at individual points on the landscape. The point-level data are then aggregated within grid cells and statistically smoothed using a statistical model that accounts for zero-inflated continuous data with smoothing based on generalized additive modeling techniques and approximate Bayesian uncertainty estimates. We expect this data product to be useful for understanding the state of vegetation in the midwestern United States prior to large-scale Euro-American settlement. In addition to specific regional questions, the data product can serve as a baseline against which to investigate how forests and ecosystems change after intensive settlement. The data products (including both raw and statistically smoothed estimates at the 8-km scale) are being made available at the LTER network data portal as version 1.0.
Studying RNA–DNA interactome by Red-C identifies noncoding RNAs associated with repressed chromatin compartment and reveals transcription dynamics
Authors: Gavrilov Alexey A. , Zharikova Anastasiya A. , Galitsyna Aleksandra A. , Luzhin Artem V. , Rubanova Natalia M. , Golov Arkadiy K. , Petrova Nadezhda V. , Logacheva Maria D. , Kantidze Omar L. , Ulianov Sergey V. , Magnitov Mikhail D. , Mironov Andrey A. , Razin Sergey V. 
Published: December 2019

AbstractNon-coding RNAs (ncRNAs) participate in various biological processes, including regulating transcription and sustaining genome 3D organization. Here, we present a method termed Red-C that exploits proximity ligation to identify contacts with the genome for all RNA molecules present in the nucleus. Using Red-C, we uncovered the RNA–DNA interactome of human K562 cells and identified hundreds of ncRNAs enriched in active or repressed chromatin, including previously undescribed RNAs. We found two microRNAs—MIR3648 and MIR3687 transcribed from the rRNA locus—that are associated with inactive chromatin genome wide. These miRNAs favor bulk heterochromatin over Polycomb-repressed chromatin and interact preferentially with late-replicating genomic regions. Analysis of the RNA–DNA interactome also allowed us to trace the kinetics of messenger RNA production. Our data support the model of co-transcriptional intron splicing, but not the hypothesis of the circularization of actively transcribed genes.
Do deep neural networks see the way we do?
Authors: Jacob Georgin , Pramod R. T. , Katti Harish , Arun S. P. 
Published: December 2019

ABSTRACTDeep neural networks have revolutionized computer vision, and their object representations match coarsely with the brain. As a result, it is widely believed that any fine scale differences between deep networks and brains can be fixed with increased training data or minor changes in architecture. But what if there are qualitative differences between brains and deep networks? Do deep networks even see the way we do? To answer this question, we chose a deep neural network optimized for object recognition and asked whether it exhibits well-known perceptual and neural phenomena despite not being explicitly trained to do so. To our surprise, many phenomena were present in the network, including the Thatcher effect, mirror confusion, Weber’s law, relative size, multiple object normalization and sparse coding along multiple dimensions. However, some perceptual phenomena were notably absent, including processing of 3D shape, patterns on surfaces, occlusion, natural parts and a global advantage. Our results elucidate the computational challenges of vision by showing that learning to recognize objects suffices to produce some perceptual phenomena but not others and reveal the perceptual properties that could be incorporated into deep networks to improve their performance.
Auditory enhancement of illusory contour perception
Authors: Tivadar Ruxandra I. , Gaglianese Anna , Murray Micah M. 
Published: December 2019

AbstractIllusory contours (ICs) are borders that are perceived in the absence of contrast gradients. Until recently, IC processes were considered exclusively visual in nature and presumed to be unaffected by information from other senses. Electrophysiological data in humans indicates that sounds can enhance IC processes. Despite cross-modal enhancement being observed at the neurophysiological level, to date there is no evidence of direct amplification of behavioural performance in IC processing by sounds. We addressed this knowledge gap. Healthy adults (N=15) discriminated instances when inducers were arranged to form an IC from instances when no IC was formed (NC). Inducers were low-constrast and masked, and there was continuous background acoustic noise throughout a block of trials. On half of the trials, i.e. independently of IC vs. NC, a 1000Hz tone was presented synchronously with the inducer stimuli. Sound presence improved the accuracy of indicating when an IC was presented, but had no impact on performance with NC stimuli (significant IC presence/absence × Sound presence/absence interaction). There was no evidence that this was due to general alerting or to a speed-accuracy trade-off (no main effect of sound presence on accuracy rates and no comparable significant interaction on reaction times). Moreover, sound presence increased sensitivity and reduced bias on the IC vs. NC discrimination task. These results demonstrate that multisensory processes augment mid-level visual functions, exemplified by IC processes. Aside from the impact on neurobiological and computational models of vision our findings may prove clinically beneficial for low-vision or sight-restored patients.
A minimal CRISPR-Cas3 system for genome engineering
Authors: Csörgő Bálint , León Lina M. , Chau-Ly Ilea J. , Vasquez-Rifo Alejandro , Berry Joel D. , Mahendra Caroline , Crawford Emily D. , Lewis Jennifer D. , Bondy-Denomy Joseph 
Published: December 2019

AbstractCRISPR-Cas technologies have provided programmable gene editing tools that have revolutionized research. The leading CRISPR-Cas9 and Cas12a enzymes are ideal for programmed genetic manipulation, however, they are limited for genome-scale interventions. Here, we utilized a Cas3-based system featuring a processive nuclease, expressed endogenously or heterologously, for genome engineering purposes. Using an optimized and minimal CRISPR-Cas3 system (Type I-C) programmed with a single crRNA, large deletions ranging from 7 - 424 kb were generated in Pseudomonas aeruginosa with high efficiency and speed. By comparison, Cas9 yielded small deletions and point mutations. Cas3-generated deletion boundaries were variable in the absence of a homology-directed repair (HDR) template, and successfully and efficiently specified when present. The minimal Cas3 system is also portable; large deletions were induced with high efficiency in Pseudomonas syringae and Escherichia coli using an “all-in-one” vector. Notably, Cas3 generated bi-directional deletions originating from the programmed cut site, which was exploited to iteratively reduce a P. aeruginosa genome by 837 kb (13.5%) using 10 distinct crRNAs. We also demonstrate the utility of endogenous Cas3 systems (Type I-C and I-F) and develop an “anti-anti-CRISPR” strategy to circumvent endogenous CRISPR-Cas inhibitor proteins. CRISPR-Cas3 could facilitate rapid strain manipulation for synthetic biological and metabolic engineering purposes, genome minimization, and the analysis of large regions of unknown function.
Differences in berry primary and secondary metabolisms identified by transcriptomic and metabolic profiling of two table grape color somatic variants
Authors: Santibáñez Claudia , Meyer Carlos , Martínez Litsy , Moyano Tomás , Lunn John , Feil Regina , Dai Zhanwu , Carrasco David , Arroyo-García Rosa , Hilbert Ghislaine , Renaud Christel , Delrot Serge , Manke-Nachtigall Fabiane , Gutiérrez Rodrigo , Matus José Tomás , Gomès Eric , Arce-Johnson Patricio 
Published: December 2019

ABSTRACTAnthocyanins are flavonoids responsible for the color of berries in skin-pigmented grapevine (Vitis vinifera L.). Due to the widely adopted vegetative propagation of this species, somatic mutations occurring in meristematic cell layers can be fixed and passed into the rest of the plant when cloned. In this study we focused on the transcriptomic and metabolic differences between two color somatic variants. Using microscopic, metabolic and mRNA profiling analyses we compared the table grape cultivar (cv.) ‘Red Globe’ (RG, with purplish berry skin) and cv. ‘Chimenti Globe’ (CG, with a contrasting reddish berry skin color). As expected, significant differences were found in the composition of flavonoids and other phenylpropanoids, but also in their upstream precursors’ shikimate and phenylalanine. Among primary metabolites, sugar phosphates related with sucrose biosynthesis were less accumulated in cv. ‘CG’. The red-skinned cv. ‘CG’ only contained di-hydroxylated anthocyanins (i.e. peonidin and cyanidin) while the tri-hydroxylated derivatives malvidin, delphinidin and petunidin were absent, in correlation to the reddish cv. ‘CG’ skin coloration. Transcriptomic analysis showed alteration in flavonoid metabolism and terpenoid pathways and in primary metabolism such as sugar content. Eleven flavonoid 3’5’-hydroxylase gene copies were down-regulated in cv. ‘CG’. This family of cytochrome P450 oxidoreductases are key in the biosynthesis of tri-hydroxylated anthocyanins. Many transcription factors appeared down-regulated in cv. ‘CG’ in correlation to the metabolic and transcriptomic changes observed. The use of molecular markers and its confirmation with our RNA-seq data showed the exclusive presence of the null MYBA2 white allele (i.e. homozygous in both L1 and L2 layers) in the two somatic variants. Therefore, the differences in MYBA1 expression seem sufficient for the skin pigmentation differences and the changes in MYBA target gene expression in cv. ‘Chimenti Globe’.
Sex enhances survival inParamecium
Authors: Thind Amarinder Singh , Vitali Valerio , Guarracino Mario R. , Catania Francesco 
Published: December 2019

AbstractThe pervasiveness of sex despite its well-known costs is a long-standing puzzle in evolutionary biology. Current explanations for the success of sex in nature largely rely on the adaptive significance of the new or rare genotypes that sex may generate. Less explored is the possibility that sex-underlying molecular mechanisms can enhance fitness and convey benefits to the individuals that bear the immediate costs of sex. Here we show that self-fertilization can increase stress resistance in the ciliateParamecium tetraurelia. This advantage is independent of new genetic variation, coupled with a reduced nutritional input, and offers fresh insights into the mechanistic origin of sex. In addition to providing evidence that the molecular underpinnings of sexual reproduction and the stress response are linked inP. tetraurelia, these findings supply an explanation for the persistence of self-fertilization in this ciliate.
Conserved and specific genomic features of endogenous polydnaviruses revealed by whole genome sequencing of two ichneumonid wasps
Authors: Legeai Fabrice , Santos Bernardo F. , Robin Stéphanie , Bretaudeau Anthony , Dikow Rebecca B. , Lemaitre Claire , Jouan Véronique , Ravallec Marc , Drezen Jean-Michel , Tagu Denis , Gyapay Gabor , Zhou Xin , Liu Shanlin , Webb Bruce A. , Brady Seán G. , Volkoff Anne-Nathalie 
Published: December 2019

AbstractPolydnaviruses (PDVs) are mutualistic endogenous viruses associated with some lineages of parasitoid wasps that allow successful development of the wasps within their hosts. PDVs include two taxa resulting from independent virus acquisitions in braconid (bracoviruses) and ichneumonid wasps (ichnoviruses). PDV genomes are fully incorporated into the wasp genomes and comprise (1) virulence genes located on proviral segments that are packaged into the viral particle, and (2) genes involved in the production of the viral particles, which are not encapsidated. Whereas the genomic organization of bracoviruses within the wasp genome is relatively well known, the architecture of endogenous ichnoviruses remains poorly understood. We sequenced the genome of two ichnovirus-carrying wasp species,Hyposoter didymatorandCampoletis sonorensis. Complete assemblies with long scaffold sizes allowed identification of the integrated ichnovirus, highlighting an extreme dispersion within the wasp genomes of the viral loci,i.e.isolated proviral segments and clusters of replication genes. Comparing the two wasp species, proviral segments harbor distinct gene content and variable genomic environment, whereas viral machinery clusters show conserved gene content and order, and can be inserted in collinear wasp genomic regions. This distinct architecture is consistent with the biological properties of the two viral elements: proviral segments producing virulence proteins allowing parasitism success are fine-tuned to the host physiology, while an ancestral viral architecture was likely maintained for the genes involved in virus particle production. Finding a distinct genomic architecture of ichnoviruses and bracoviruses highlights different evolutionary trajectories leading to virus domestication in the two wasp lineages.
An Erg driven transcriptional program controls B-lymphopoiesis
Authors: Ng Ashley P. , Coughlan Hannah D. , Hediyeh-zadeh Soroor , Behrens Kira , Johanson Timothy M. , Yuan Low Michael Sze , Bell Charles C. , Gilan Omer , Chan Yih-Chih , Kueh Andrew J. , Boudier Thomas , DiRago Ladina , Hyland Craig D. , Ierino Helen , Mifsud Sandra , Viney Elizabeth , Willson Tracy , Dawson Mark A. , Allan Rhys S. , Herold Marco J. , Rogers Kelly , Tarlinton David M , Smyth Gordon K. , Davis Melissa J. , Nutt Stephen L. , Alexander Warren S. 
Published: December 2019

Summary/AbstractB-cell development is initiated by the stepwise differentiation of hematopoietic stem cells into lineage committed progenitors, ultimately generating the mature B-cells that mediate protective immunity. This highly regulated process also generates clonal immunological diversity via recombination of immunoglobulin genes. While several transcription factors that control B-cell development and V(D)J recombination have been defined, how these processes are initiated and coordinated into a precise regulatory network remains poorly understood. Here, we show that the transcription factor ETS Related Gene (Erg) is essential for the earliest steps in B-cell differentiation. Erg initiates a transcriptional network involving the B-cell lineage defining genes,Ebf1andPax5, that directly promotes the expression of key genes involved in V(D)J recombination and formation of the B-cell receptor. Complementation of the Erg-deficiency with a productively rearranged immunoglobulin gene rescued B-cell development, demonstrating that Erg is an essential and exquisitely stage specific regulator of the gene regulatory network controlling B-lymphopoiesis.
Self-supervised retinal thickness prediction enables deep learning from unlabeled data to boost classification of diabetic retinopathy
Authors: Holmberg Olle G. , Köhler Niklas D. , Martins Thiago , Siedlecki Jakob , Herold Tina , Keidel Leonie , Asani Ben , Schiefelbein Johannes , Priglinger Siegfried , Kortuem Karsten U. , Theis Fabian J. 
Published: December 2019

AbstractAccess to large, annotated samples represents a considerable challenge for training accurate deep-learning models in medical imaging. While current leading-edge transfer learning from pre-trained models can help with cases lacking data, it limits design choices, and generally results in the use of unnecessarily large models. We propose a novel, self-supervised training scheme for obtaining high-quality, pre-trained networks from unlabeled, cross-modal medical imaging data, which will allow for creating accurate and efficient models. We demonstrate this by accurately predicting optical coherence tomography (OCT)-based retinal thickness measurements from simple infrared (IR) fundus images. Subsequently, learned representations outperformed advanced classifiers on a separate diabetic retinopathy classification task in a scenario of scarce training data. Our cross-modal, three-staged scheme effectively replaced 26,343 diabetic retinopathy annotations with 1,009 semantic segmentations on OCT and reached the same classification accuracy using only 25% of fundus images, without any drawbacks, since OCT is not required for predictions. We expect this concept will also apply to other multimodal clinical data-imaging, health records, and genomics data, and be applicable to corresponding sample-starved learning problems.
Similar distribution of T-cell subsets in Crohn’s disease and in diverticulitis provide evidence against a primary causal role for these cells in Crohn’s
Authors: Akarca Ayse U , Ellery Peter , Segal Anthony W , Marafioti Teresa 
Published: December 2019

AbstractBackground and AimsT lymphocytes are found in abnormally large numbers in the bowel in Crohn’s disease. This has led to the assumption by some that these cells play a causal role in the pathogenesis of what has been labelled an autoimmune disease. An alternative explanation for their presence is that, as part of the adaptive immune system, the accumulation of these cells is not a primary phenomenon, but is a secondary adaptive immune response to faecal material in the bowel wall. To distinguish between these two processes we compared the T-cell repertoire in the bowel in Crohn’s with that in diverticulitis, where the primary pathology is mechanical, with a subsequent immune response to the accumulated faecal material.MethodsSix cases of Crohn’s disease and six patients with diverticulitis were studied. Dewaxed sections of bowel were stained with Anti-CD4, Anti-CD8, Anti-FOXP3 and Anti-CD25 to identify cytotoxic T-cells, NK-Tcells; T-helper and T-reg T-cells.ResultsNo differences were found in the distribution of the different T-cell markers in either the mucosa or in areas of inflammation in the two conditions.ConclusionThe accumulation of T-lymphocytes in the bowel in Crohn’s disease is likely to be a sign of an adaptive immune response to faecal material within the bowel rather than an indication of a primary causal immune attack on the bowel that produces the disease.
Improving reliability in clinical neuroimaging: a study in transgender persons
Authors: Khorashad Behzad Sorouri , Khazai Behnaz , Talaei Ali , Acar Freya , Hudson Anna R. , Borji Nahid , Saberi Hedieh , Aminzadeh Behzad , Mueller Sven C. 
Published: December 2019

AbstractAlthough the neuroanatomy of transgender persons is slowly being charted, findings are presently discrepant. One important factor is the issue of power and low signal-to-noise (SNR) ratio in neuroimaging studies of rare study populations including endocrine or neurological patient groups. The present study assessed whether the reliability of findings across structural anatomical measures including thickness, volume, and surface area could be increased by using two back-to-back within session structural MRI scans in 40 transgender men (TM), 40 transgender women (TW), 30 cisgender men (CM), and 30 cisgender women (CW). Overall, findings in transgender persons were more consistent with at-birth assigned sex in brain volume and surface area while no group differences emerged for cortical thickness. Repeated measures analysis also indicated that having a second scan increased SNR in all ROIs, most notably bilateral frontal poles, accumbens nuclei and putamina. Furthermore, additional significant group differences emerged in cortical surface area when age and ICV were used as covariates. The results suggest that a simple time and cost effective measure to improve signal to noise ratio in rare clinical populations with low prevalence rates is a second anatomical scan when structural MRI is of interest.