bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel approach reveals genomic landscapes of single-strand DNA breaks with nucleotide resolution in human cells
Authors: Cao Huifen , Salazar-García Lorena , Gao Fan , Wahlestedt Thor , Wu Chun-Lin , Han Xueer , Cai Ye , Xu Dongyang , Wang Fang , Tang Lu , Ricciardi Natalie , Cai DingDing , Wang Huifang , Chin Mario P. S. , Timmons James A. , Wahlestedt Claes , Kapranov Philipp 
Published: December 2019

AbstractSingle-strand breaks (SSBs) represent the major form of DNA damage, yet techniques to map these lesions genome-wide with nucleotide-level precision are limited. Here, we present a method, termed SSiNGLe, and demonstrate its utility to explore the distribution and dynamic changes in genome-wide SSBs in response to different biological and environmental stimuli. We validate SSiNGLe using two very distinct sequencing techniques and apply it to derive global profiles of SSBs in different biological states. Strikingly, we show that patterns of SSBs in the genome are non-random, specific to different biological states, enriched in regulatory elements, exons, introns, specific types of repeats and exhibit differential preference for the template strand between exons and introns. Furthermore, we show that breaks likely contribute to naturally occurring sequence variants. Finally, we demonstrate strong links between SSB patterns and age. Overall, SSiNGLe provides access to unexplored realms of cellular biology, not obtainable with current approaches.
PBRM1 acts as a p53 lysine-acetylation reader to suppress renal tumor growth
Authors: Cai Weijia , Su Liya , Liao Lili , Liu Zongzhi Z. , Langbein Lauren , Dulaimi Essel , Testa Joseph R. , Uzzo Robert G. , Zhong Zhijiu , Jiang Wei , Yan Qin , Zhang Qing , Yang Haifeng 
Published: December 2019

Abstractp53 acetylation is indispensable for its transcriptional activity and tumor suppressive function. However, the identity of reader protein(s) for p53 acetylation remains elusive. PBRM1, the second most highly mutated tumor suppressor gene in kidney cancer, encodes PBRM1. Here, we identify PBRM1 as a reader for p53 acetylation on lysine 382 (K382Ac) through its bromodomain 4 (BD4). Notably, mutations on key residues of BD4 disrupt recognition of p53 K382Ac. The mutation in BD4 also reduces p53 binding to promoters of target genes such as CDKN1A (p21). Consequently, the PBRM1 BD4 mutant fails to fully support p53 transcriptional activity and is defective as a tumor suppressor. We also find that expressions of PBRM1 and p21 correlate with each other in human kidney cancer samples. Our findings uncover a tumor suppressive mechanism of PBRM1 in kidney cancer and provide a mechanistic insight into the crosstalk between p53 and SWI/SNF complexes.
A first-principle mechanism for particulate aggregation and self-assembly in stratified fluids
Authors: Camassa Roberto , Harris Daniel M. , Hunt Robert , Kilic Zeliha , McLaughlin Richard M. 
Published: December 2019

AbstractAn extremely broad and important class of phenomena in nature involves the settling and aggregation of matter under gravitation in fluid systems. Here, we observe and model mathematically an unexpected fundamental mechanism by which particles suspended within stratification may self-assemble and form large aggregates without adhesion. This phenomenon arises through a complex interplay involving solute diffusion, impermeable boundaries, and aggregate geometry, which produces toroidal flows. We show that these flows yield attractive horizontal forces between particles at the same heights. We observe that many particles demonstrate a collective motion revealing a system which appears to solve jigsaw-like puzzles on its way to organizing into a large-scale disc-like shape, with the effective force increasing as the collective disc radius grows. Control experiments isolate the individual dynamics, which are quantitatively predicted by simulations. Numerical force calculations with two spheres are used to build many-body simulations which capture observed features of self-assembly.
The METLIN small molecule dataset for machine learning-based retention time prediction
Authors: Domingo-Almenara Xavier , Guijas Carlos , Billings Elizabeth , Montenegro-Burke J. Rafael , Uritboonthai Winnie , Aisporna Aries E. , Chen Emily , Benton H. Paul , Siuzdak Gary 
Published: December 2019

AbstractMachine learning has been extensively applied in small molecule analysis to predict a wide range of molecular properties and processes including mass spectrometry fragmentation or chromatographic retention time. However, current approaches for retention time prediction lack sufficient accuracy due to limited available experimental data. Here we introduce the METLIN small molecule retention time (SMRT) dataset, an experimentally acquired reverse-phase chromatography retention time dataset covering up to 80,038 small molecules. To demonstrate the utility of this dataset, we deployed a deep learning model for retention time prediction applied to small molecule annotation. Results showed that in 70$$\%$$%of the cases, the correct molecular identity was ranked among the top 3 candidates based on their predicted retention time. We anticipate that this dataset will enable the community to apply machine learning or first principles strategies to generate better models for retention time prediction.
Platinum–copper single atom alloy catalysts with high performance towards glycerol hydrogenolysis
Authors: Zhang Xi , Cui Guoqing , Feng Haisong , Chen Lifang , Wang Hui , Wang Bin , Zhang Xin , Zheng Lirong , Hong Song , Wei Min 
Published: December 2019

AbstractSelective hydrogenolysis of biomass-derived glycerol to propanediol is an important reaction to produce high value-added chemicals but remains a big challenge. Herein we report a PtCu single atom alloy (SAA) catalyst with single Pt atom dispersed on Cu nanoclusters, which exhibits dramatically boosted catalytic performance (yield: 98.8%) towards glycerol hydrogenolysis to 1,2-propanediol. Remarkably, the turnover frequency reaches up to 2.6 × 103 molglycerol·molPtCu–SAA−1·h−1, which is to our knowledge the largest value among reported heterogeneous metal catalysts. Both in situ experimental studies and theoretical calculations verify interface sites of PtCu–SAA serve as intrinsic active sites, in which the single Pt atom facilitates the breakage of central C–H bond whilst the terminal C–O bond undergoes dissociation adsorption on adjacent Cu atom. This interfacial synergistic catalysis based on PtCu–SAA changes the reaction pathway with a decreased activation energy, which can be extended to other noble metal alloy systems.
Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities
Authors: Migliavacca Eugenia , Tay Stacey K. H. , Patel Harnish P. , Sonntag Tanja , Civiletto Gabriele , McFarlane Craig , Forrester Terence , Barton Sheila J. , Leow Melvin K. , Antoun Elie , Charpagne Aline , Seng Chong Yap , Descombes Patrick , Feng Lei , Francis-Emmanuel Patrice , Garratt Emma S. , Giner Maria Pilar , Green Curtis O. , Karaz Sonia , Kothandaraman Narasimhan , Marquis Julien , Metairon Sylviane , Moco Sofia , Nelson Gail , Ngo Sherry , Pleasants Tony , Raymond Frederic , Sayer Avan A. , Ming Sim Chu , Slater-Jefferies Jo , Syddall Holly E. , Fang Tan Pei , Titcombe Philip , Vaz Candida , Westbury Leo D. , Wong Gerard , Yonghui Wu , Cooper Cyrus , Sheppard Allan , Godfrey Keith M. , Lillycrop Karen A. , Karnani Neerja , Feige Jerome N. 
Published: December 2019

AbstractThe causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD+ levels through perturbed NAD+ biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.
Multistaged discharge constructing heterostructure with enhanced solid-solution behavior for long-life lithium-oxygen batteries
Authors: Xu Shu-Mao , Liang Xiao , Wu Xue-Yan , Zhao Shen-Long , Chen Jun , Wang Kai-Xue , Chen Jie-Sheng 
Published: December 2019

AbstractInferior charge transport in insulating and bulk discharge products is one of the main factors resulting in poor cycling stability of lithium–oxygen batteries with high overpotential and large capacity decay. Here we report a two-step oxygen reduction approach by pre-depositing a potassium carbonate layer on the cathode surface in a potassium–oxygen battery to direct the growth of defective film-like discharge products in the successive cycling of lithium–oxygen batteries. The formation of defective film with improved charge transport and large contact area with a catalyst plays a critical role in the facile decomposition of discharge products and the sustained stability of the battery. Multistaged discharge constructing lithium peroxide-based heterostructure with band discontinuities and a relatively low lithium diffusion barrier may be responsible for the growth of defective film-like discharge products. This strategy offers a promising route for future development of cathode catalysts that can be used to extend the cycling life of lithium–oxygen batteries.
Relaxed purifying selection in autopolyploids drives transposable element over-accumulation which provides variants for local adaptation
Authors: Baduel Pierre , Quadrana Leandro , Hunter Ben , Bomblies Kirsten , Colot Vincent 
Published: December 2019

AbstractPolyploidization is frequently associated with increased transposable element (TE) content. However, what drives TE dynamics following whole genome duplication (WGD) and the evolutionary implications remain unclear. Here, we leverage whole-genome resequencing data available for ~300 individuals of Arabidopsis arenosa, a well characterized natural diploid-autotetraploid plant species, to address these questions. Based on 43,176 TE insertions we detect in these genomes, we demonstrate that relaxed purifying selection rather than transposition bursts is the main driver of TE over-accumulation after WGD. Furthermore, the increased pool of TE insertions in tetraploids is especially enriched within or near environmentally responsive genes. Notably, we show that the major flowering-time repressor gene FLC is disrupted by a TE insertion specifically in the rapid-cycling tetraploid lineage that colonized mainland railways. Together, our findings indicate that tetrasomy leads to an enhanced accumulation of genic TE insertions, some of which likely contribute to local adaptation.
Controllability governs the balance between Pavlovian and instrumental action selection
Authors: Dorfman Hayley M. , Gershman Samuel J. 
Published: December 2019

AbstractA Pavlovian bias to approach reward-predictive cues and avoid punishment-predictive cues can conflict with instrumentally-optimal actions. Here, we propose that the brain arbitrates between Pavlovian and instrumental control by inferring which is a better predictor of reward. The instrumental predictor is more flexible; it can learn values that depend on both stimuli and actions, whereas the Pavlovian predictor learns values that depend only on stimuli. The arbitration theory predicts that the Pavlovian predictor will be favored when rewards are relatively uncontrollable, because the additional flexibility of the instrumental predictor is not useful. Consistent with this hypothesis, we find that the Pavlovian approach bias is stronger under low control compared to high control contexts.
Hydroxide promotes carbon dioxide electroreduction to ethanol on copper via tuning of adsorbed hydrogen
Authors: Luo Mingchuan , Wang Ziyun , Li Yuguang C. , Li Jun , Li Fengwang , Lum Yanwei , Nam Dae-Hyun , Chen Bin , Wicks Joshua , Xu Aoni , Zhuang Taotao , Leow Wan Ru , Wang Xue , Dinh Cao-Thang , Wang Ying , Wang Yuhang , Sinton David , Sargent Edward H. 
Published: December 2019

AbstractProducing liquid fuels such as ethanol from CO2, H2O, and renewable electricity offers a route to store sustainable energy. The search for efficient electrocatalysts for the CO2 reduction reaction relies on tuning the adsorption strength of carbonaceous intermediates. Here, we report a complementary approach in which we utilize hydroxide and oxide doping of a catalyst surface to tune the adsorbed hydrogen on Cu. Density functional theory studies indicate that this doping accelerates water dissociation and changes the hydrogen adsorption energy on Cu. We synthesize and investigate a suite of metal-hydroxide-interface-doped-Cu catalysts, and find that the most efficient, Ce(OH)x-doped-Cu, exhibits an ethanol Faradaic efficiency of 43% and a partial current density of 128 mA cm−2. Mechanistic studies, wherein we combine investigation of hydrogen evolution performance with the results of operando Raman spectroscopy, show that adsorbed hydrogen hydrogenates surface *HCCOH, a key intermediate whose fate determines branching to ethanol versus ethylene.
Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke
Authors: Abraham Gad , Malik Rainer , Yonova-Doing Ekaterina , Salim Agus , Wang Tingting , Danesh John , Butterworth Adam S. , Howson Joanna M. M. , Inouye Michael , Dichgans Martin 
Published: December 2019

AbstractRecent genome-wide association studies in stroke have enabled the generation of genomic risk scores (GRS) but their predictive power has been modest compared to established stroke risk factors. Here, using a meta-scoring approach, we develop a metaGRS for ischaemic stroke (IS) and analyse this score in the UK Biobank (n = 395,393; 3075 IS events by age 75). The metaGRS hazard ratio for IS (1.26, 95% CI 1.22–1.31 per metaGRS standard deviation) doubles that of a previous GRS, identifying a subset of individuals at monogenic levels of risk: the top 0.25% of metaGRS have three-fold risk of IS. The metaGRS is similarly or more predictive compared to several risk factors, such as family history, blood pressure, body mass index, and smoking. We estimate the reductions needed in modifiable risk factors for individuals with different levels of genomic risk and suggest that, for individuals with high metaGRS, achieving risk factor levels recommended by current guidelines may be insufficient to mitigate risk.
Polyanions provide selective control of APC/C interactions with the activator subunit
Authors: Mizrak Arda , Morgan David O. 
Published: December 2019

AbstractTransient interactions between the anaphase-promoting complex/cyclosome (APC/C) and its activator subunit Cdc20 or Cdh1 generate oscillations in ubiquitylation activity necessary to maintain the order of cell cycle events. Activator binds the APC/C with high affinity and exhibits negligible dissociation kinetics in vitro, and it is not clear how the rapid turnover of APC/C-activator complexes is achieved in vivo. Here, we describe a mechanism that controls APC/C-activator interactions based on the availability of substrates. We find that APC/C-activator dissociation is stimulated by abundant cellular polyanions such as nucleic acids and polyphosphate. Polyanions also interfere with substrate ubiquitylation. However, engagement with high-affinity substrate blocks the inhibitory effects of polyanions on activator binding and APC/C activity. We propose that this mechanism amplifies the effects of substrate affinity on APC/C function, stimulating processive ubiquitylation of high-affinity substrates and suppressing ubiquitylation of low-affinity substrates.
Neonatal annulus fibrosus regeneration occurs via recruitment and proliferation of Scleraxis-lineage cells
Authors: Torre Olivia M. , Mroz Victoria , Benitez Anthony R. Martinez , Huang Alice H. , Iatridis James C. 
Published: December 2019

AbstractIntervertebral disc (IVD) injuries are a cause of degenerative changes in adults which can lead to back pain, a leading cause of disability. We developed a model of neonatal IVD regeneration with full functional restoration and investigate the cellular dynamics underlying this unique healing response. We employed genetic lineage tracing in mice using Scleraxis (Scx) and Sonic hedgehog (Shh) to fate-map annulus fibrosus (AF) and nucleus pulposus (NP) cells, respectively. Results indicate functional AF regeneration after severe herniation injury occurs in neonates and not adults. AF regeneration is mediated by Scx-lineage cells that lose ScxGFP expression and adopt a stem/progenitor phenotype (Sca-1, days 3–14), proliferate, and then redifferentiate towards type I collagen producing, ScxGFP+ annulocytes at day 56. Non Scx-lineage cells were also transiently observed during neonatal repair, including Shh-lineage cells, macrophages, and myofibroblasts; however, these populations were no longer detected by day 56 when annulocytes redifferentiate. Overall, repair did not occur in adults. These results identify an exciting cellular mechanism of neonatal AF regeneration that is predominantly driven by Scx-lineage annulocytes.
Development of neural perceptual vowel spaces during the first year of life
Authors: McCarthy Kathleen M. , Skoruppa Katrin , Iverson Paul 
Published: December 2019

AbstractThis study measured infants’ neural responses for spectral changes between all pairs of a set of English vowels. In contrast to previous methods that only allow for the assessment of a few phonetic contrasts, we present a new method that allows us to assess changes in spectral sensitivity across the entire vowel space and create two-dimensional perceptual maps of the infants’ vowel development. Infants aged four to eleven months were played long series of concatenated vowels, and the neural response to each vowel change was assessed using the Acoustic Change Complex (ACC) from EEG recordings. The results demonstrated that the youngest infants’ responses more closely reflected the acoustic differences between the vowel pairs and reflected higher weight to first-formant variation. Older infants had less acoustically driven responses that seemed a result of selective increases in sensitivity for phonetically similar vowels. The results suggest that phonetic development may involve a perceptual warping for confusable vowels rather than uniform learning, as well as an overall increasing sensitivity to higher-frequency acoustic information.
Raman Spectra Shift of Few-Layer IV-VI 2D Materials
Authors: Park Minwoo , Choi Jin Sik , Yang Li , Lee Hoonkyung 
Published: December 2019

AbstractRaman spectroscopy is the most commonly used method to investigate structures of materials. Recently, few-layered IV-VI 2D materials (SnS, SnSe, GeS, and GeSe) have been found and ignited significant interest in electronic and optical applications. However, unlike few-layer graphene, in which its interlayer structures such as the number of its layers are confirmed through measurement of the Raman scattering, few-layer IV-VI 2D materials have not yet been developed to the point of understanding their interlayer structure. Here we performed first-principles calculations on Raman spectroscopy for few-layer IV-VI 2D materials. In addition to achieving consistent results with measurements of bulk structures, we revealed significant red and blue shifts of characteristic Raman modes up to 100 cm−1 associated with the layer number. These shifts of lattice vibrational modes originate from the change of the bond lengths between the metal atoms and chalcogen atoms through the change of the interlayer interactions. Particularly, our study shows weak covalent bonding between interlayers, making the evolution of Raman signals according to the thickness different from other vdW materials. Our results suggest a new way for obtaining information of layer structure of few-layer IV-VI 2D materials through Raman spectroscopy.
Characterization of cancer omics and drug perturbations in panels of lung cancer cells
Authors: Suzuki Ayako , Onodera Keiichi , Matsui Ken , Seki Masahide , Esumi Hiroyasu , Soga Tomoyoshi , Sugano Sumio , Kohno Takashi , Suzuki Yutaka , Tsuchihara Katsuya 
Published: December 2019

AbstractTo better understand the disruptions of transcriptional regulations and gene expression in lung cancers, we constructed a multi-omics catalogue of the responses of lung cancer cells to a series of chemical compounds. We generated and analyzed 3,240 RNA-seq and 3,393 ATAC-seq libraries obtained from 23 cell lines treated with 95 well-annotated compounds. To demonstrate the power of the created multi-omics resource, we attempted to identify drugs that could induce the designated changes alone or in combination. The basal multi-omics information was first integrated into co-expression modules. Among these modules, we identified a stress response module that may be a promising drug intervention target, as new combinations of compounds that could be used to regulate this module and the consequent phenotypic appearance of cancer cells have been identified. We believe that the multi-omics profiles generated in this study and the strategy used to stratify them will lead to more rational and efficient development of anticancer drugs.
Zika virus infection causes temporary paralysis in adult mice with motor neuron synaptic retraction and evidence for proximal peripheral neuropathy
Authors: Morrey John D. , Oliveira Alexandre L. R. , Wang Hong , Zukor Katherine , de Castro Mateus Vidigal , Siddharthan Venkatraman 
Published: December 2019

AbstractClinical evidence is mounting that Zika virus can contribute to Guillain-Barré syndrome which causes temporary paralysis, yet the mechanism is unknown. We investigated the mechanism of temporary acute flaccid paralysis caused by Zika virus infection in aged interferon αβ-receptor knockout mice used for their susceptibility to infection. Twenty-five to thirty-five percent of mice infected subcutaneously with Zika virus developed motor deficits including acute flaccid paralysis that peaked 8-10 days after viral challenge. These mice recovered within a week. Despite Zika virus infection in the spinal cord, motor neurons were not destroyed. We examined ultrastructures of motor neurons and synapses by transmission electron microscopy. The percent coverage of motor neurons by boutons was reduced by 20%; more specifically, flattened-vesicle boutons were reduced by 46%, and were normalized in recovering mice. Using electromyographic procedures employed in people to help diagnose Guillain-Barré syndrome, we determined that nerve conduction velocities between the sciatic notch and the gastrocnemius muscle were unchanged in paralyzed mice. However, F-wave latencies were increased in paralyzed mice, which suggests that neuropathy may exist between the sciatic notch to the nerve rootlets. Reversible synaptic retraction may be a previously unrecognized cofactor along with peripheral neuropathy for the development of Guillain-Barré syndrome during Zika virus outbreaks.