bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metagenomes in the borderline ecosystems of the Antarctic cryptoendolithic communities
Authors: Coleine Claudia , Albanese Davide , Onofri Silvano , Tringe Susannah G. , Pennacchio Christa , Donati Claudio , Stajich Jason E. , Selbmann Laura 
Published: August 2019

AbstractAntarctic cryptoendolithic communities are microbial ecosystems dwelling inside rocks of ice-free areas in Continental Antarctica. In Antarctica, these ecosystems were first described from the McMurdo Dry Valleys, accounted as the best analogous of the Martian environment on Earth and thought to be devoid of life until the discovery of these cryptic life-forms. Our results present the first shotgun metagenomes of Antarctic cryptoendolithic lichen-dominated communities from 18 differently sun-exposed rock samples collected during the XXXI Italian Antarctic Expedition (2015-16), along an altitudinal transect from 834 up to 3100 m a.s.l. Here, we provide the raw data obtained with Illumina Novaseq sequencer, followed by initial functional and taxonomic analysis.Our results extend understanding of the microbial diversity and biological processes in the Antarctic desert and represent an invaluable resource for the scientific community as a base-line for further studies of this kind to examine the mechanisms and pathways necessary for life to adapt and evolve in the extremes.
Spatial and temporal control of CRISPR/Cas9-mediated gene editing delivered via a light-triggered liposome system
Authors: Aksoy Yagiz Alp , Chen Wenjie , Goldys Ewa M , Deng Wei 
Published: August 2019

ABSTRACTThe CRISPR-Cas9 and related systems offer a unique genome editing tool allowing facile and efficient introduction of heritable and locus-specific sequence modifications in the genome. Despite its molecular precision, temporal and spatial control of gene editing with CRISPR-Cas9 system is very limited. We developed a light-sensitive liposome delivery system that offers a high degree of spatial and temporal control of gene editing with CRISPR/Cas9 system. We demonstrated its high transfection efficiency, by assessing the targeted knockout of eGFP gene in human HEK293 cells (52.8% knockout). We further validated our results at a single-cell resolution using an in vivo eGFP reporter system in zebrafish (77% knockout). To the best of our knowledge we reported the first proof-of-concept of spatio-temporal control of CRISPR/Cas9 by using light-triggered liposomes in bothin vitroandin vivoenvironment.
Metadata-Guided Visual Representation Learning for Biomedical Images
Authors: Spiegel Stephan , Hossain Imtiaz , Ball Christopher , Zhang Xian 
Published: August 2019

AbstractMotivationThe clustering of biomedical images according to their phenotype is an important step in early drug discovery. Modern high-content-screening devices easily produce thousands of cell images, but the resulting data is usually unlabelled and it requires extra effort to construct a visual representation that supports the grouping according to the presented morphological characteristics.ResultsWe introduce a novel approach to visual representation learning that is guided by metadata. In high-context-screening, meta-data can typically be derived from the experimental layout, which links each cell image of a particular assay to the tested chemical compound and corresponding compound concentration. In general, there exists a one-to-many relationship between phenotype and compound, since various molecules and different dosage can lead to one and the same alterations in biological cells.Our empirical results show that metadata-guided visual representation learning is an effective approach for clustering biomedical images. We have evaluated our proposed approach on both benchmark and real-world biological data. Furthermore, we have juxtaposed implicit and explicit learning techniques, where both loss function and batch construction differ. Our experiments demonstrate that metadata-guided visual representation learning is able to identify commonalities and distinguish differences in visual appearance that lead to meaningful clusters, even without image-level annotations.NotePlease refer to the supplementary material for implementation details on metadata-guided visual representation learning strategies.
Cholesterol is a strong promotor of an α-Synuclein membrane binding mode that accelerates oligomerization
Authors: Jakubec Martin , Bariås Espen , Furse Samuel , Govasli Morten L. , George Vinnit , Turcu Diana , Iashchishyn Igor , Morozova-Roche Ludmilla , Halskau Øyvind 
Published: August 2019

AbstractDysregulation of the biosynthesis of cholesterol and other lipids has been implicated in neurological diseases, including Parkinson's disease, where the misfolding of membraneassociated α-Synuclein is a key molecular event. Recent research also suggests that α-Synuclein aggregation is influenced by the lipid environment. The exact molecular mechanisms responsible for cholesterol’s effect on α-Synuclein binding to lipids and how this binding may affect α-Synuclein oligomerization and fibrillation remain elusive, as does the relative importance of cholesterol versus other lipid factors. We probed the interactions and fibrillation behaviour of α-Synuclein using SMA nanodiscs, containing zwitterionic and anionic lipid model systems with and without cholesterol. SPR and ThT fluorescence assays were then employed to monitor α-Synuclein binding, as well as fibrillation in the absence and presence of membrane models.1H-15N correlated NMR was used to monitor the fold of α-Synuclein in response to nanodisc binding, and we determined individual residue apparent affinities for the nanodisc-contained bilayers. Cholesterol inhibited α-Synuclein interaction with lipid bilayers. We also find that cholesterol significantly promotes α-Synuclein fibrillation, with a more than 20-fold reduction of lag-times before fibrillation onset. When α-Synuclein-bilayer interactions were analysed for individual residues by solution-state NMR, we observed two different effects of cholesterol. In nanodiscs made of DOPC, cholesterol modulated the NAC part of α-Synuclein, leading to stronger interaction of this region with the lipid bilayer. In contrast, in the nanodiscs comprising DOPC, DOPE and DOPG, the NAC part was mostly unaffected by cholesterol, while the binding of the N-terminal and the C-terminal were both inhibited.
HspA1BIs a Prognostic Biomarker and Correlated With Immune Infiltrates in different subtypes of Breast Cancers
Authors: He Jian , Wang Hui 
Published: August 2019

ABSTRACTBackgroundHeat shock A1B, also known as HSP70kDa protein 1B, encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family.HspA1Bis a critical gene which related to many type of diseases by involving in the ubiquitin-proteasome pathway. However, the correlations ofHspA1Bto prognosis and tumor-infiltrating lymphocytes in different cancers remain unclear.MethodsHspA1Bexpression was evaluated on the Oncomine database and Tumor Immune Estimation Resource (TIMER) site. We analyzed the influence ofHspA1Bon clinical prognosis using Kaplan-Meier plotter, the PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). The correlations betweenHspA1Band cancer immune infiltrates was investigated via TIMER. In addition, correlations betweenHspA1Bexpression and gene marker sets of immune infiltrates were analyzed by TIMER and GEPIA.ResultsThree cohorts (GSE9195, GSE9893, GSE3494-GPL96)) of breast cancer patients showed that highHspA1Bexpression was associated with poorer overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). In addition, highHspA1Bexpression was significantly correlated with poor OS and progression-free survival (PFS) in bladder cancer, brain cancer and skin cancer. Moreover,HspA1Bsignificantly impacts the prognosis of diverse cancers via The Cancer Genome Atlas (TCGA).HspA1Bexpression was positively correlated with infiltrating levels of CD4+ T and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) indifferent subtypes of Breast cancer.HspA1Bexpression showed strong correlations with diverse immune marker sets in BRCA-Luminal.ConclusionsOur findings suggest thatHspA1Bis correlated with prognosis and immune infiltrating levels of, including those of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in multiple cancers, especially in colon and gastric cancer patients. In addition,HspA1Bexpression potentially contributes to regulation of tumor-associated macrophages (TAMs), DCs, T cell exhaustion and Tregs in colon and gastric cancer. These findings suggest thatHspA1Bcan be used as a prognostic biomarker for determining prognosis and immune infiltration in BRCA-Luminal subtype.
Cytochrome P450 26b1-mediated specification of vestibular striola and central zones is required for transient responses in linear acceleration
Authors: Ono Kazuya , Keller James , Ramírez Omar López , Garrido Antonia González , Zobeiri Omid , Chang Vanessa , Vijayakumar Sarath , Ayiotis Andrianna , Duester Gregg , Della Santina Charles C. , Jones Sherri M. , Cullen Kathleen , Eatock Ruth Anne , Wu Doris K. 
Published: August 2019

ABSTRACTEach vestibular sensory epithelia of the inner ear is divided into two zones, the striola and extrastriola in maculae of otolith organs and the central and peripheral zones in cristae of semicircular canals, that differ in morphology and physiology. We found that formation of striolar/central zones during embryogenesis requires Cytochrome P450 26b1 (Cyp26b1)-mediated degradation of retinoic acid (RA). In Cyp26b1 conditional knockout mice, the identities of the striolar/central zones were compromised, including abnormal innervating neurons and otoconia in otolith organs. Vestibular evoked potentials (VsEP) in response to jerk stimuli were largely absent. Vestibulo-ocular reflexes and standard motor performances such as forced swimming were unaffected, but mutants had head tremors and deficits in balance beam tests that were consistent with abnormal vestibular input. Thus, degradation of RA during embryogenesis is required for patterning highly specialized regions of the vestibular sensory epithelia that may provide acute feedback about head motion.
Spatiotemporal characterization of periocular mesenchyme heterogeneity during anterior segment development
Authors: Van Der Meulen Kristyn L. , Vöcking Oliver , Weaver Megan L. , Famulski Jakub K. 
Published: August 2019

ABSTRACTEstablishment of the ocular anterior segment (AS) is a critical event during development of the vertebrate visual system. Failure in this process leads to Anterior Segment Dysgenesis (ASD), which is characterized by congenital blindness and predisposition to glaucoma. The anterior segment is largely formed via a neural crest-derived population, the Periocular Mesenchyme (POM). In this study, we aimed to characterize POM behaviors and identities during zebrafish AS development. POM distributions and migratory dynamics were analyzed using transgenic zebrafish embryos (Tg[foxC1b:GFP], Tg[foxD3:GFP], Tg[pitx2:GFP], Tg[lmx1b.1:GFP], and Tg[sox10:GFP] throughout the course of early AS development (24-72hpf).In vivoimaging analysis revealed unique AS distribution and migratory behavior among the reporter lines, suggesting AS mesenchyme (ASM) is a heterogenous population. This was confirmed using doublein situhybridization. Furthermore, we generated ASM transcriptomic profiles from our reporter lines and using a four-way comparison analysis uncovered unique ASM subpopulation expression patterns. Taken together, our data reveal for the first time that AS-associated POM is not homogeneous but rather comprised of several unique subpopulations identifiable by their distributions, behaviors, and transcriptomic profiles.
Skill learning can be independent of speed and accuracy instructions
Authors: Vékony Teodóra , Marossy Hanna , Must Anita , Vécsei László , Janacsek Karolina , Nemeth Dezso 
Published: August 2019

AbstractA crucial question in skill learning research is how instruction affects the performance or the underlying representations. However, a little is known about its effect on one critical aspect of skill leaning, namely, picking-up statistical regularities. More specifically, how pre-learning speed vs. accuracy instructions affect the acquisition of non-adjacent second-order dependencies. Here, we trained two groups of participants on an implicit probabilistic sequence learning task: one group focusing on being fast and the other on being accurate. As expected, we detected strong instruction effect: accuracy instruction resulted in a nearly errorless performance, while speed instruction caused short reaction times. Despite the differences in the average reaction times and accuracy scores, we found a similar level of statistical learning in the training phase. After the training phase, we tested the two groups under the same instruction (focusing on both speed and accuracy), and they showed comparable performance, suggesting a similar level of underlying statistical representations. Our findings support that skill learning can result in robust representations, and they highlight that this form of knowledge may appear with almost errorless performance.
Biased connectivity of brain-wide inputs to ventral subiculum output neurons
Authors: Wee RWS , MacAskill AF 
Published: August 2019

AbstractThe ventral subiculum (vS) of the mouse hippocampus coordinates diverse behaviours through heterogeneous populations of projection neurons. These neurons transmit signals to multiple brain regions by integrating thousands of local and long-range synaptic inputs. However, whether each population is selectively innervated by different afferent input remains unknown. To address this question, we employed projection-specific rabies tracing to study the input-output relationship of vS output neurons. Analysis of brain-wide inputs reveals quantitative input differences that can be explained by the spatial location of postsynaptic neurons along the proximal-distal axis of vS and the identity of the downstream target. Further, the input from nucleus reuniens, an area thought to underlie vS and prefrontal cortex (PFC) reciprocal connectivity, is unexpectedly biased away from PFC-projecting vS neurons. Overall, we reveal prominent heterogeneity in brain-wide inputs to the vS parallel output circuitry, providing a basis for the selective control of individual projections during behaviour.
In-host population dynamics ofM. tuberculosisduring treatment failure
Authors: Vargas Roger , Freschi Luca , Marin Maximillian , Epperson L. Elaine , Smith Melissa , Oussenko Irina , Durbin David , Strong Michael , Salfinger Max , Farhat Maha Reda 
Published: August 2019

ABSTRACTBackgroundTuberculosis (TB) is a leading cause of death globally from an infectious agent. Understanding the population dynamics of TB’s causative agentMycobacterium tuberculosis(Mtb) in-host is vital for understanding the efficacy of antibiotic treatment. Here we use longitudinally collected clinical Mtb isolates that underwent Whole-Genome Sequencing (WGS) from the sputa of 307 subjects to investigate Mtb diversity during the course of active TB disease.Methods and findingsWe excluded cases suspected of reinfection or contamination to analyze data from 200 subjects, 167 of which met microbiological criteria for delayed culture conversion, treatment failure or relapse. Using technical and biological replicate samples, we defined an allele frequency threshold attributable to in-host evolution. Of the 167 subjects with unsuccessful treatment outcome, 27 (16%) developed new resistance mutations between sampling with 20/27 (74%) occurring in patients with pre-existing antibiotic resistance. Low abundance resistance variants at a purity of ≥19% in the first isolate predicts fixation of these variants in the subsequent sample with 27.0% sensitivity and 95.8% specificity. We identify significant in-host variation in seven genes associated with antibiotic resistance and twenty other genes, including metabolic genes and genes known to modulate host innate immunity by interacting with TLR2. We confirm Rv0095c, Rv1944c,PPE18, PPE54andPPE60to be under positive selection by assessing phylogenetic convergence across a global and genetically diverse independent sample of 20,352 isolates.ConclusionsOur large sample provides a comprehensive picture of the mutational dynamicsin-hostduring active TB disease. We demonstrate a framework to study temporal changes in Mtb population diversity using average depth WGS data. We show that minor variants can be used to inform antibiotic treatment regimens in patients with TB. Furthermore, we detect a signature of positive selection in-host, possibly stemming from innate immune pressure and informing our understanding of host-pathogen interactions.
Methyl-Metabolite Depletion Elicits Adaptive Responses to Support Heterochromatin Stability and Epigenetic Persistence
Authors: Haws Spencer A. , Yu Deyang , Ye Cunqi , Wille Coral K. , Nguyen Long C. , Krautkramer Kimberly A. , Tomasiewicz Jay L. , Yang Shany E. , Miller Blake R. , Liu Wallace H. , Igarashi Kazuhiko , Sridharan Rupa , Tu Benjamin P. , Cryns Vincent L. , Lamming Dudley W. , Denu John M. 
Published: August 2019

SummaryS-adenosylmethionine (SAM) is the methyl-donor substrate for DNA and histone methyltransferases that regulate cellular epigenetic states. This metabolism-epigenome link enables the sensitization of chromatin methylation to altered SAM abundance. However, a chromatin-wide understanding of the adaptive/responsive mechanisms that allow cells to actively protect epigenetic information during life-experienced fluctuations in SAM availability are unknown. We identified a robust response to SAM depletion that is highlighted by preferential cytoplasmic and nuclear de novo mono-methylation of H3 Lys 9 (H3K9) at the expense of global losses in histone di- and tri-methylation. Under SAM-depleted conditions, de novo H3K9 mono-methylation preserves heterochromatin stability and supports global epigenetic persistence upon metabolic recovery. This unique chromatin response was robust across the mouse lifespan and correlated with improved metabolic health, supporting a significant role for epigenetic adaptation to SAM depletion in vivo. Together, these studies provide the first evidence for active epigenetic adaptation and persistence to metabolic stress.
Cells collectively reshape habitability of temperature by helping each other replicate
Authors: Laman Trip Diederik S. , Youk Hyun 
Published: August 2019

SUMMARYHow the rising global temperatures affect organisms is a timely question. The conventional view is that high temperatures cause microbes to replicate slowly or die, both autonomously. Yet, microbes co-exist as a population, raising the underexplored question of whether they can cooperatively combat rising temperatures. Here we show that, at high temperatures, budding yeasts help each other and future generations of cells replicate by secreting and extracellularly accumulating glutathione - a ubiquitous heat-damage-reducing antioxidant. Yeasts thereby collectively delay and can halt population extinctions at high temperatures. As a surprising consequence, even for the same temperature, a yeast population can either exponentially grow, never grow, or grow after unpredictable durations (hours-to-days) of stasis, depending on its population density. Despite the conventional theory stating that heat-shocked cells autonomously die and cannot stop population extinctions, we found that non-growing yeast-populations at high temperatures - due to cells cooperatively accumulating extracellular glutathione - continuously decelerate and can eventually stop their approach to extinction, with higher population-densities stopping faster. We show that exporting glutathione, but not importing, is required for yeasts to survive high temperatures. Thus, cooperatively eliminating harmful extracellular agents – not glutathione’s actions inside individual cells – is both necessary and sufficient for surviving high temperatures. We developed a mathematical model - which is generally applicable to any cells that cooperatively replicate by secreting molecules - that recapitulates all these features. These results show how cells can cooperatively extend boundaries of life-permitting temperatures.
Enviromicsin breeding: applications and perspectives on envirotypic-assisted selection
Authors: Resende Rafael T. , Piepho Hans-Peter , Silva-Junior Orzenil B. , Silva Fabyano F. e , de Resende Marcos Deon V. , Grattapaglia Dario 
Published: August 2019

AbstractGenotype by Environment interaction (G × E) studies have focused mainly on estimating genetic parameters over a limited number of experimental trials. However, recent Geographic Information System (GIS) techniques have opened new frontiers for understanding and dealing with G × E. These advances allow increasing selection accuracy across all sites of interest, including those where experimental trials have not yet been deployed. Here, we introduce the term Enviromics under an envirotypic-assisted breeding framework and propose the GIS-GE method, i.e. a geospatial tool to maximize genetic gains by predicting the phenotypic performance of unobserved genotypes using “enviromic markers”. In summary, a particular site represents a set of envirotypes, each one representing a set of environmental factors that interact with the genetic background of genotypes, thus resulting in informative re-rankings to make decisions over different environments. Based on a simulated case study, we show that GIS-GE allows accurate (i) matching of genotypes to their most appropriate sites; (ii) definition of breeding areas that have high genetic correlation to ensure selection gains across environments; and (iii) indication of the best sites to carry out experiments for further analysis based on environments that maximize heritability. Envirotyping techniques provide a new class of markers for genetic studies, which are inexpensive, increasingly available and transferable across species. We envision a promising future for the integration of the Enviromics approach into breeding when coupled with next-generation genotyping/phenotyping and powerful statistical modeling of genetic diversity. Environmental scenarios can also be improved using information from strategic plans for biodiversity and genetic resources management, especially in the current perspective of dynamic climate change.Key messageWe propose the application ofEnviromicsto breeding practice, by which the similarity among sites assessed on an “omics” scale of environmental attributes drives the prediction of unobserved genotypes.
projectR: An R/Bioconductor package for transfer learning via PCA, NMF, correlation, and clustering
Authors: Sharma Gaurav , Colantuoni Carlo , Goff Loyal A , Fertig Elana J , Stein-O’Brien Genevieve 
Published: August 2019

AbstractMotivationDimension reduction techniques are widely used to interpret high-dimensional biological data. Features learned from these methods are used to discover both technical artifacts and novel biological phenomena. Such feature discovery is critically import to large single-cell datasets, where lack of a ground truth limits validation and interpretation. Transfer learning (TL) can be used to relate the features learned from one source dataset to a new target dataset to perform biologically-driven validation by evaluating their use in or association with additional sample annotations in that independent target dataset.ResultsWe developed an R/Bioconductor package, projectR, to perform TL for analyses of genomics data via TL of clustering, correlation, and factorization methods. We then demonstrate the utility TL for integrated data analysis with an example for spatial single-cell analysis.AvailabilityprojectR is available on Bioconductor and at https://github.com/genesofeve/projectR.Contactgsteinobrien@jhmi.edu; ejfertig@jhmi.edu