bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pan-cancer atlas of transcriptional dependence on DNA methylation and copy number aberrations
Authors: Fougner Christian , Höglander Elen K. , Lien Tonje G. , Sørlie Therese , Nord Silje , Lingjærde Ole Christian 
Published: May 2020

AbstractCancer transcriptomes are shaped by genetic and epigenetic features, such as DNA methylation and copy number aberrations. Knowledge of the relationships between gene expression and such features is fundamental to understanding the basis of tumor phenotypes. Here, we present a pan-cancer atlas of transcriptional dependence on DNA methylation and copy number aberrations (PANORAMA). Our analyses suggest that copy number alterations are a central driver of inter-tumor heterogeneity, while the majority of expression-methylation associations found in cancer are a reflection of cell-of-origin and normal cell admixture. The atlas is made available through an online tool athttps://pancancer.app.
Cognitive and Motor Correlates of Grey and White Matter Pathology in Parkinson’s Disease
Authors: Dadar Mahsa , Gee Myrlene , Shuaib Ashfaq , Duchesne Simon , Camicioli Richard 
Published: May 2020

AbstractIntroductionPrevious studies have found associations between grey matter atrophy and white matter hyperintensities (WMH) of vascular origin with cognitive and motor deficits in Parkinson’s disease (PD). Here we investigate these relationships in a sample of PD patients and age-matched healthy controls.MethodsData included 50 PD patients and 45 age-matched controls with T1-weighted and FLAIR scans at baseline, 18-months, and 36-months follow-up. Deformation-based morphometry was used to measure grey matter atrophy. SNIPE (Scoring by Nonlocal Image Patch Estimator) was used to measure Alzheimer’s disease-like textural patterns in the hippocampi. WMHs were segmented using T1-weighted and FLAIR images. The relationship between MRI features and clinical scores was assessed using mixed-effects models. The motor subscore of the Unified Parkinson’s Disease Rating Scale (UPDRSIII), number of steps in a walking trial, and Dementia Rating Scale (DRS) were used respectively as measures of motor function, gait, and cognition.ResultsSubstantia nigra atrophy was significantly associated with motor deficits, with a greater impact in PDs (p<0.05). Hippocampal SNIPE scores were associated with cognitve decline in both PD and controls (p<0.01). WMH burden was significantly associated with cognitive decline and increased motor deficits in the PD group, and gait deficits in both PD and controls (p<0.03).ConclusionWhile substantia nigra atrophy and WMH burden were significantly associated with additional motor deficits, WMH burden and hippocampal atrophy were associated with cognitive deficits in PD patients. These results suggest an additive contribution of both grey and white matter damage to the motor and cognitive deficits in PD.
Pathologic α-Synuclein Species Activate LRRK2 in Pro-Inflammatory Monocyte and Macrophage Responses
Authors: Xu Enquan , Boddu Ravindra , Abdelmotilib Hisham A. , Kelly Kaela , Sokratian Arpine , Harms Ashley S. , Schonhoff Aubrey M. , Bryant Nicole , Harmsen Irene E. , Schlossmacher Michael G. , Chandra Sidhanth , Krendelshchikova Valentina , Liu Zhiyong , West Andrew B. 
Published: May 2020

AbstractMissense mutations in theLRRK2gene that lead to LRRK2 kinase hyperactivity can cause Parkinson’s disease (PD). The link between LRRK2 and α-synuclein aggregation in PD remains enigmatic. Numerous reports suggest critical LRRK2 functions in microglial responses. Herein, we find that LRRK2-positive immune cells in the brain represent CD68-positive pro-inflammatory, monocyte-derived macrophages, distinct from microglia. Rod α-synuclein fibrils stimulate LRRK2 kinase activity in monocyte-derived macrophages, and LRRK2 mutations lead to enhanced recruitment of classical monocytes into the midbrain in response to α-synuclein. LRRK2 kinase inhibition blocks α-synuclein fibril induction of LRRK2 protein in both human and murine macrophages, with human cells demonstrating much higher LRRK2 levels and kinase activity than equivalent murine cells. Further, interferon-γ strongly induces LRRK2 kinase activity in primary human macrophages in comparison to weak effects observed in murine cells. These results highlight peripheral immune responses in LRRK2-linked paradigms that further connect two central proteins in PD.
Highly accurate long-read HiFi sequencing data for five complex genomes
Authors: Hon Ting , Mars Kristin , Young Greg , Tsai Yu-Chih , Karalius Joseph W. , Landolin Jane M. , Maurer Nicholas , Kudrna David , Hardigan Michael A. , Steiner Cynthia C. , Knapp Steven J. , Ware Doreen , Shapiro Beth , Peluso Paul , Rank David R. 
Published: May 2020

AbstractThe PacBio®HiFi sequencing method yields highly accurate long-read sequencing datasets with read lengths averaging 10-25 kb and accuracies greater than 99.5%. These accurate long reads can be used to improve results for complex applications such as single nucleotide and structural variant detection, genome assembly, assembly of difficult polyploid or highly repetitive genomes, and assembly of metagenomes. Currently, there is a need for sample data sets to both evaluate the benefits of these long accurate reads as well as for development of bioinformatic tools including genome assemblers, variant callers, and haplotyping algorithms. We present deep coverage HiFi datasets for five complex samples including the two inbred model genomesMus musculusandZea mays, as well as two complex genomes, octoploidFragaria×ananassaand the diploid anuranRana muscosa. Additionally, we release sequence data from a mock metagenome community. The datasets reported here can be used without restriction to develop new algorithms and explore complex genome structure and evolution. Data were generated on the PacBio Sequel II System.
Yeast Rgd3 is a phospho-regulated F-BAR-containing RhoGAP involved in the regulation of Rho3 distribution and cell morphology
Authors: Gingras Robert M. , Lwin Kyaw Myo , Miller Abigail M. , Bretscher Anthony 
Published: May 2020

AbstractPolarized growth requires the integration of polarity pathways with the delivery of exocytic vesicles for cell expansion and counterbalancing endocytic uptake. In budding yeast, the myosin-V Myo2 is aided by the kinesin-related protein Smy1 in carrying out the essential Sec4-dependent transport of secretory vesicles to sites of polarized growth. Over-expression suppressors of a conditionalmyo2 smy1mutant identified a novel F-BAR-containing RhoGAP, Rgd3, that has activity primarily on Rho3, but also Cdc42. Internally tagged Rho3 is restricted to the plasma membrane in a gradient corresponding to cell polarity that is altered upon Rgd3 over-expression. Rgd3 itself is localized to dynamic polarized vesicles that, while distinct from constitutive secretory vesicles, are dependent on actin and Myo2 function.In vitroRgd3 associates with liposomes in a PIP2-enhanced manner. Further, the Rgd3 C-terminal region contains several phosphorylatable residues within a reported SH3-binding motif. An unphosphorylated mimetic construct is active and highly polarized, while the phospho-mimetic form is not. Rgd3 is capable of activating Myo2, dependent on its phospho-state and Rgd3 overexpression rescues aberrant Rho3 localization and cell morphologies seen at the restrictive temperature in themyo2 smy1mutant. We propose a model where Rgd3 functions to modulate and maintain Rho3 polarity during growth.
Progress in quickly finding orthologs as reciprocal best hits
Authors: Hernández-Salmerón Julie E , Moreno-Hagelsieb Gabriel 
Published: May 2020

AbstractIntroductionFinding orthologs remains an important bottleneck in comparative genomics analyses. While the authors of software for the quick comparison of protein sequences evaluate the speed of their software and compare their results against the most usual software for the task, it is not common for them to evaluate their software for more particular uses, such as finding orthologs as reciprocal best hits (RBH). Here we compared RBH results, between prokaryotic genomes, obtained using software that runs faster than blastp. Namely, lastal, diamond, and MMseqs2.ResultsWe found that lastal required the least time to produce results. However, it yielded fewer results than any other program when comparing evolutionarily distant genomes. The program producing the most similar number of RBH as blastp was MMseqs2. This program also resulted in the lowest error estimates among the programs tested. The results with diamond were very close to those obtained with MMseqs2, with diamond running faster. Our results suggest that the best of the programs tested was diamond, ran with the “sensitive” option, which took 7% of the time as blastp to run, and produced results with lower error rates than blastp.AvailabilityA program to obtain reciprocal best hits using the software we tested is maintained athttps://github.com/Computational-conSequences/SequenceTools
Breeding success of Eleonora’s falcon (Falco eleonorae) in Cyprus revisited using survey techniques for cliff-nesting species
Authors: Hadjikyriakou Thomas G. , Kassinis Nikolaos , Skarlatos Dimitrios , Charilaou Pantelis , Kirschel Alexander N. G. 
Published: May 2020

ABSTRACTThe global breeding population of Eleonora’s falcon is distributed from the Canary Islands in the west, across the Mediterranean Sea, to Cyprus in the east. The remoteness of nesting colonies, which are predominantly located on sea cliffs and islets, renders breeding success estimation a challenging task, requiring a composite approach to assess each of the breeding stages. Early estimates of the breeding success of Eleonora’s falcon suggested that Akrotiri colony in Cyprus had the lowest breeding success among all the colonies throughout the species’ breeding range, at a level seemingly unsustainable, suggesting the colony might have been in danger of gradual extinction. Here we use a diversity of survey methods using boat, ground and aerial surveys, with the incorporation of photography and photogrammetry, to reassess the breeding success and the effect of nest characteristics on the Eleonora’s falcon breeding population in Cyprus. During a six-year study, we found that Cyprus hosts ~138 ± 8 breeding pairs and that breeding success equals 1.54 ± 0.85 fledglings per breeding pair, thus considerably higher than previous estimates. In addition, by analyzing temporal variation in breeding and nest characteristics, we found that early breeding and reuse of nests positively influence breeding success, but physical nest characteristics have a limited effect on colony productivity. The range of survey methods employed, as well as the array of photography techniques utilized, highly enhanced the efficiency and accuracy of this study, allowing us to overcome the challenge of inaccessibility of nesting cliffs.
Decomposition of transcriptional responses provides insights into differential antibiotic susceptibility
Authors: Sastry Anand , Dillon Nick , Poudel Saugat , Hefner Ying , Xu Sibei , Szubin Richard , Feist Adam , Nizet Victor , Palsson Bernhard 
Published: May 2020

AbstractResponses of bacteria to antibiotic treatments depend on their environments. Differences betweenin vitrotesting conditions and the physiological environments inside patients have resulted in poor antibiotic susceptibility predictions, contributing to treatment failures in the clinic. Here, we investigate how media composition affects antibiotic susceptibility in the laboratory strainE. coliK-12 MG1655, and contextualize these changes through machine learning of transcriptomics data. We show that complex transcriptional changes induced by different media or antibiotic treatment can be traced back to a few key regulators. Integration of results from machine learning with biochemical knowledge reveals fundamental shifts in respiration and iron availability that may explain media-dependent differential susceptibility to antibiotics. The data generation and analytical workflow used here can interrogate the regulatory state of a pathogen under any condition, and can be extended to additional strains and organisms for which data is available.
ALKBH7 mediates necrosis via rewiring of glyoxal metabolism
Authors: Kulkarni Chaitanya A. , Nadtochiy Sergiy M. , Kennedy Leslie , Zhang Jimmy , Chhim Sophea , Alwaseem Hanan , Murphy Elizabeth , Fu Dragony , Brookes Paul S. 
Published: May 2020

ABSTRACTAlkb homolog 7 (ALKBH7) is a mitochondrial α-ketoglutarate dioxygenase required for necrotic cell death in response to DNA alkylating agents, but its physiologic role within tissues remains unclear. Herein, we show that ALKBH7 plays a key role in the regulation of dialdehyde metabolism, which impacts cardiac survival in response to ischemia-reperfusion (IR) injury. Using a multi-omics approach, we do not find evidence that ALKBH7 functions as a prolyl-hydroxylase. However, we do find that mice lacking ALKBH7 exhibit a significant increase in glyoxalase I (GLO-1), a dialdehyde detoxifying enzyme. Consistent with increased dialdehyde production, metabolomics analysis reveals rewiring of metabolic pathways related to the toxic glycolytic by-product methylglyoxal (MGO), as well as accelerated glycolysis and elevated levels of MGO protein adducts, in mice lacking ALKBH7. Consistent with roles for both necrosis and glycative stress in cardiac IR injury, hearts from male but not femaleAlkbh7-/-mice are protected against IR, although somewhat unexpectedly this protection does not appear to involve modulation of the mitochondrial permeability transition pore. Highlighting the importance of MGO metabolism for the observed protection, removal of glucose as a metabolic substrate or pharmacologic inhibition of GLO-1 both abrogate cardioprotection in ALKBH7 deficient mice. Integrating these observations, we propose that ALKBH7 plays a role in the regulation of glyoxal metabolism, and that protection against necrosis and IR injury bought on by ALKBH7 deficiency originates from hormetic signaling in response to elevated MGO stress.
Dual-located WHIRLY1 affects salicylic acid homeostasisviacoordination of ICS1, PAL1 and BSMT1 duringArabidopsisplant aging
Authors: Lin Wenfang , Zhang Hong , Huang Dongmei , Schenke Dirk , Cai Daguang , Wu Binghua , Miao Ying 
Published: May 2020

AbstractSalicylic acid (SA) homeostasis determines also developmental senescence and is spatiotemporally controlled by various mechanisms, including biosynthesis, transport and conjugate formation. The alteration of WHIRLY1 (WHY1), a repressor of leaf natural senescence, with respect to allocation in the nucleus or chloroplast causes a perturbation in SA homeostasis, resulting in adverse plant senescence phenotypes. Loss ofWHY1resulted in a 5 days earlier SA peak compared to wild type plants which accumulated SA at 42 days after germination. SA accumulation coincided with an early leaf senescence phenotype, which could be prevented by ectopic expression of the nuclear WHY1 isoform (nWHY1). However, expressing the plastid WHY1 isoform (pWHY1) greatly enhanced cellular SA levels. A global transcriptional analysis in WHY1 loss-of-function background by expressing either pWHY1 or nWHY1 indicated that hormone metabolism related genes were most significantly altered. The pWHY1 isoform predominantly affected stress related gene expression, while the nWHY1 controlled rather developmental gene expression. Chromatin immunoprecipitation-qPCR (ChIP-qPCR) assays indicated that nWHY1 directly binds to the promoter region of isochorismate synthase (ICS1)to activateitsexpression at later stage, but indirectly activated S-adenosyl-L-methionine-dependent methyltransferase (BSMT1)gene expressionviaethylene response factor 109 (ERF109), while repressing phenylalanine ammonia lyase (PAL1)expressionviaR2R3-MYB member 15 (MYB15) at the early stage of development. Interestingly, rising SA levels exerted a feedback effect by inducing nWHY1 modification and pWHY1 accumulation. Thus, the alteration of WHY1 organelle isoforms and the feedback of SA intervened in a circularly integrated regulatory network during developmental or stress-induced senescence inArabidopsis.
A lectin that targets specific bacteria for killing on DNA-based extracellular traps
Authors: Farinholt Timothy , Dinh Christopher , Kuspa Adam 
Published: May 2020

AbstractAnimal defenses directed against bacteria include DNA-based extracellular traps (ETs) that are produced by innate immune cells. ET-bound bacteria are prevented from further tissue dissemination and are eventually killed by ET-bound antibacterial proteins. It is unclear how bacteria bind to ETs, though it has been proposed that the negatively-charged DNA scaffold of the ETs is involved. We have found that the bacterial-binding lectin CadA is a component of the ETs produced by the innate immune cells ofDictyostelium discoideumand is required for the binding and killing of twoEnterobacteriaceaeby ETs, but not other bacteria. Our results suggest that ETs selectively sequester bacteria and that lectins can facilitate bacterial killing by acting as ET-bacteria binding proteins.
Abasy Atlas v2.2: The most comprehensive and up-to-date inventory of meta-curated, historical, bacterial regulatory networks, their completeness and system-level characterization
Authors: Escorcia-Rodríguez Juan M. , Tauch Andreas , Freyre-González Julio A. 
Published: May 2020

AbstractSome organism-specific databases about regulation in bacteria have become larger, accelerated by high-throughput methodologies, while others are no longer updated or accessible. Each database homogenize its datasets, giving rise to heterogeneity across databases. Such heterogeneity mainly encompasses different names for a gene and different network representations, generating duplicated interactions that could bias network analyses. Abasy (Across-bacteriasystems) Atlas consolidates information from different sources into meta-curated regulatory networks in bacteria. The high-quality networks in Abasy Atlas enable cross-organisms analyses, such as benchmarking studies where gold standards are required. Nevertheless, network incompleteness still casts doubts on the conclusions of network analyses, and available sampling methods cannot reflect the curation process. To tackle this problem, the updated version of Abasy Atlas presented in this work provides historical snapshots of regulatory networks. Thus, network analyses can be performed at different completeness levels, making possible to identify potential bias and to predict future results. We leverage the recently found constraint in the complexity of regulatory networks to develop a novel model to quantify the total number of regulatory interactions as a function of the genome size. This completeness estimation is a valuable insight that may aid in the daunting task of network curation, prediction, and validation. The new version of Abasy Atlas provides 76 networks (204,282 regulatory interactions) covering 42 bacteria (64% Gram-positive and 36% Gram-negative) distributed in 9 species (Mycobacterium tuberculosis, Bacillus subtilis, Escherichia coli, Corynebacterium glutamicum, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes, Streptococcus pneumoniae, andStreptomyces coelicolor), containing 8,459 regulons and 4,335 modules.Database URLhttps://abasy.ccg.unam.mx/
Pro-inflammatory response of non-inflammatory Classical monocytes stimulated with LPSin vitro
Authors: Karsulovic Claudio , Tempio Fabian , Lopez Mercedes , Guerrero Julia , Goecke Annelise 
Published: May 2020

AbstractBACKGROUNDCD14 (Monocyte identifying Toll-Like Receptor) and CD16 (FcyRIII co-receptor, marker of inflammatory monocytes) were used to define 3 subpopulations of circulating monocytes with different attributes in terms of inflammatory and phagocytic capabilities. There are contradictory reports regarding response of circulating monocytes to pro-inflammatory or non-inflammatory stimuliin vitro. Here we aimed to analyze the phenotypic changes in circulating monocytes when stimulated with pro and non-inflammatory stimuli.METHODSWhole blood from 9 healthy donors was extracted and studied. Monocyte subpopulations were directly measured using flow cytometry with PBMC Ficoll extraction method. Pro-inflammatory interleukin IL-1β was measured by intracellular cytometry. Whole blood-extracted monocytes were stimulated using LPS and IL-4 as previously described. Changes against non-stimulated (N-S) populations were statistically analyzed.RESULTSCompared to N-S, LPS-stimulated monocytes display a singular milieu of markers, with higher levels of intracellular IL-1β in parallel raise of CD14+CD163-/CD14+CD163+ ratio. CD163 shows positive correlation with levels of IL-1β. In t-SNE (T-distributed Stochastic Neighbor Embedding) analysis, after LPS stimulation, subpopulation CD14+CD16-CD163-, containing mainly classical monocytes, show a higher number of IL-1β+ cells.CONCLUSIONClassical monocytes, the non-inflammatory subset, show higher levels of IL-1β in response to LPS narrowing down to a new subpopulation of monocytes CD14+CD16-CD163-, which correlates better with this interleukin response than widely used monocytes classification. Using CD163 in addition to CD16, we were able to show that classical monocytes display the most intense response to LPS. Additionally, CD163 appears to be a suitable addition to CD14-CD16 classification to improve its performance.
The structural basis for kinetochore stabilization by Cnn1/CENP-T
Authors: Hinshaw Stephen M. , Harrison Stephen C. 
Published: May 2020

ABSTRACTChromosome segregation depends on a regulated connection between spindle microtubules and centromeric DNA. The kinetochore, a massive modular protein assembly, mediates this connection and also serves as a signaling hub that integrates and responds to changing cues during the cell cycle. Kinetochore functions evolve as the cell cycle progresses, culminating in the assurance of a persistent chromosome-microtubule connection during anaphase, when sister chromatids must transit into daughter cells uninterrupted. We previously determined the structure of the Ctf19 complex, a group of kinetochore proteins at the centromeric base of the kinetochore. We now present a high-resolution structure of a Ctf19 complex sub-assembly involved in centromere-microtubule contact: the Ctf3 complex bound to the Cnn1-Wip1 heterodimer. The resulting composite model of the Ctf19 complex and live-cell imaging experiments provide a mechanism for Cnn1-Wip1 recruitment to the kinetochore. The mechanism suggests feedback regulation of Ctf19 complex assembly and unanticipated similarities in kinetochore organization between yeast and vertebrates.