bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial genome and its regulator TFAM modulates head and neck tumourigenesis through intracellular metabolic reprogramming and activation of oncogenic effectors
Authors: Hsieh Yi-Ta , Tu Hsi-Feng , Yang Muh-Hwa , Chen Yi-Fen , Lan Xiang-Yun , Huang Chien-Ling , Chen Hsin-Ming , Li Wan-Chun 
Published: October 2021

AbstractMitochondrial transcriptional factor A (TFAM) acts as a key regulatory to control mitochondrial DNA (mtDNA); the impact of TFAM and mtDNA in modulating carcinogenesis is controversial. Current study aims to define TFAM mediated regulations in head and neck cancer (HNC). Multifaceted analyses in HNC cells genetically manipulated for TFAM were performed. Clinical associations of TFAM and mtDNA encoded Electron Transport Chain (ETC) genes in regulating HNC tumourigenesis were also examined in HNC specimens. At cellular level, TFAM silencing led to an enhanced cell growth, motility and chemoresistance whereas enforced TFAM expression significantly reversed these phenotypic changes. These TFAM mediated cellular changes resulted from (1) metabolic reprogramming by directing metabolism towards aerobic glycolysis, based on the detection of less respiratory capacity in accompany with greater lactate production; and/or (2) enhanced ERK1/2-Akt-mTORC-S6 signalling activity in response to TFAM induced mtDNA perturbance. Clinical impacts of TFAM and mtDNA were further defined in carcinogen-induced mouse tongue cancer and clinical human HNC tissues; as the results showed that TFAM and mtDNA expression were significantly dropped in tumour compared with their normal counterparts and negatively correlated with disease progression. Collectively, our data uncovered a tumour-suppressing role of TFAM and mtDNA in determining HNC oncogenicity and potentially paved the way for development of TFAM/mtDNA based scheme for HNC diagnosis.
Blood pressure, frailty status, and all-cause mortality in elderly hypertensives; The Nambu Cohort Study
Authors: Inoue Taku , Matsuoka Mitsuteru , Shinjo Tetsuji , Tamashiro Masahiro , Oba Kageyuki , Kakazu Masanori , Moromizato Takuhiro , Arasaki Osamu , Arima Hisatomi 
Published: October 2021

AbstractAntihypertensive therapy is pivotal for reducing cardiovascular events. The 2019 Guidelines for the Management of Hypertension set a target blood pressure (BP) of <140/90 mmHg for persons older than 75 years of age. Optimal BP levels for older persons with frailty, however, are controversial because evidence for the relationship between BP level and prognosis by frailty status is limited. Here, we evaluated the relationship between systolic BP and frailty status with all-cause mortality in ambulatory older hypertensive patients using data from the Nambu Cohort study. A total of 535 patients (age 78 [70–84] years, 51% men, 37% with frailty) were prospectively followed for a mean duration of 41 (34–43) months. During the follow-up period, 49 patients died. Mortality rates stratified by systolic BP and frailty status were lowest in patients with systolic BP < 140 mmHg and non-frailty, followed by those with systolic BP ≥ 140 mmHg and non-frailty. Patients with frailty had the highest mortality regardless of the BP level. The adjusted hazard ratios (95% confidence intervals) of each category for all-cause mortality were as follows: ≥140 mmHg/Non-frailty 3.19 (1.12–11.40), <140 mmHg/Frailty 4.72 (1.67–16.90), and ≥140 mmHg/Frailty 3.56 (1.16–13.40) compared with <140 mmHg/Non-frailty as a reference. These results indicated that frail patients have a poor prognosis regardless of their BP levels. Non-frail patients, however, with systolic BP levels <140 mmHg had a better prognosis. Frailty may be a marker to differentiate patients who are likely to gain benefit from antihypertensive medication among older hypertensives.
Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions
Authors: Liu Shu , Hossinger André , Heumüller Stefanie-Elisabeth , Hornberger Annika , Buravlova Oleksandra , Konstantoulea Katerina , Müller Stephan A. , Paulsen Lydia , Rousseau Frederic , Schymkowitz Joost , Lichtenthaler Stefan F. , Neumann Manuela , Denner Philip , Vorberg Ina M. 
Published: October 2021

AbstractProtein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells, thereby templating their own aberrant conformation onto soluble homotypic proteins. Proteopathic seeds can be released into the extracellular space, secreted in association with extracellular vesicles (EV) or exchanged by direct cell-to-cell contact. The extent to which each of these pathways contribute to the prion-like spreading of protein misfolding is unclear. Exchange of cellular cargo by both direct cell contact or via EV depends on receptor-ligand interactions. We hypothesized that enabling these interactions through viral ligands enhances intercellular proteopathic seed transmission. Using different cellular models propagating prions or pathogenic Tau aggregates, we demonstrate that vesicular stomatitis virus glycoprotein and SARS-CoV-2 spike S increase aggregate induction by cell contact or ligand-decorated EV. Thus, receptor-ligand interactions are important determinants of intercellular aggregate dissemination. Our data raise the possibility that viral infections contribute to proteopathic seed spreading by facilitating intercellular cargo transfer.
Scattering interference signature of a pair density wave state in the cuprate pseudogap phase
Authors: Wang Shuqiu , Choubey Peayush , Chong Yi Xue , Chen Weijiong , Ren Wangping , Eisaki H. , Uchida S. , Hirschfeld Peter J. , Davis J. C. Séamus 
Published: October 2021

AbstractAn unidentified quantum fluid designated the pseudogap (PG) phase is produced by electron-density depletion in the CuO2 antiferromagnetic insulator. Current theories suggest that the PG phase may be a pair density wave (PDW) state characterized by a spatially modulating density of electron pairs. Such a state should exhibit a periodically modulating energy gap $${\Delta }_{{{{{{\rm{P}}}}}}}({{{{{\boldsymbol{r}}}}}})$$

Δ

P

(

r

)

in real-space, and a characteristic quasiparticle scattering interference (QPI) signature $${\Lambda }_{{{{{{\rm{P}}}}}}}({{{{{\boldsymbol{q}}}}}})$$

Λ

P

(

q

)

in wavevector space. By studying strongly underdoped Bi2Sr2CaDyCu2O8 at hole-density ~0.08 in the superconductive phase, we detect the 8a0-periodic $${\Delta }_{{{{{{\rm{P}}}}}}}({{{{{\boldsymbol{r}}}}}})$$

Δ

P

(

r

)

modulations signifying a PDW coexisting with superconductivity. Then, by visualizing the temperature dependence of this electronic structure from the superconducting into the pseudogap phase, we find the evolution of the scattering interference signature $$\Lambda ({{{{{\boldsymbol{q}}}}}})$$
Λ

(

q

)

that is predicted specifically for the temperature dependence of an 8a0-periodic PDW. These observations are consistent with theory for the transition from a PDW state coexisting with d-wave superconductivity to a pure PDW state in the Bi2Sr2CaDyCu2O8 pseudogap phase.
A mutational hotspot that determines highly repeatable evolution can be built and broken by silent genetic changes
Authors: Horton James S. , Flanagan Louise M. , Jackson Robert W. , Priest Nicholas K. , Taylor Tiffany B. 
Published: October 2021

AbstractMutational hotspots can determine evolutionary outcomes and make evolution repeatable. Hotspots are products of multiple evolutionary forces including mutation rate heterogeneity, but this variable is often hard to identify. In this work, we reveal that a near-deterministic genetic hotspot can be built and broken by a handful of silent mutations. We observe this when studying homologous immotile variants of the bacteria Pseudomonas fluorescens, AR2 and Pf0-2x. AR2 resurrects motility through highly repeatable de novo mutation of the same nucleotide in >95% lines in minimal media (ntrB A289C). Pf0-2x, however, evolves via a number of mutations meaning the two strains diverge significantly during adaptation. We determine that this evolutionary disparity is owed to just 6 synonymous variations within the ntrB locus, which we demonstrate by swapping the sites and observing that we are able to both break (>95% to 0%) and build (0% to 80%) a deterministic mutational hotspot. Our work reveals a key role for silent genetic variation in determining adaptive outcomes.
A metabolome atlas of the aging mouse brain
Authors: Ding Jun , Ji Jian , Rabow Zachary , Shen Tong , Folz Jacob , Brydges Christopher R. , Fan Sili , Lu Xinchen , Mehta Sajjan , Showalter Megan R. , Zhang Ying , Araiza Renee , Bower Lynette R. , Lloyd K. C. Kent , Fiehn Oliver 
Published: October 2021

AbstractThe mammalian brain relies on neurochemistry to fulfill its functions. Yet, the complexity of the brain metabolome and its changes during diseases or aging remain poorly understood. Here, we generate a metabolome atlas of the aging wildtype mouse brain from 10 anatomical regions spanning from adolescence to old age. We combine data from three assays and structurally annotate 1,547 metabolites. Almost all metabolites significantly differ between brain regions or age groups, but not by sex. A shift in sphingolipid patterns during aging related to myelin remodeling is accompanied by large changes in other metabolic pathways. Functionally related brain regions (brain stem, cerebrum and cerebellum) are also metabolically similar. In cerebrum, metabolic correlations markedly weaken between adolescence and adulthood, whereas at old age, cross-region correlation patterns reflect decreased brain segregation. We show that metabolic changes can be mapped to existing gene and protein brain atlases. The brain metabolome atlas is publicly available (https://mouse.atlas.metabolomics.us/) and serves as a foundation dataset for future metabolomic studies.
Coordination tailoring of Cu single sites on C3N4 realizes selective CO2 hydrogenation at low temperature
Authors: Yang Tang , Mao Xinnan , Zhang Ying , Wu Xiaoping , Wang Lu , Chu Mingyu , Pao Chih-Wen , Yang Shize , Xu Yong , Huang Xiaoqing 
Published: October 2021

AbstractCO2 hydrogenation has attracted great attention, yet the quest for highly-efficient catalysts is driven by the current disadvantages of poor activity, low selectivity, and ambiguous structure-performance relationship. We demonstrate here that C3N4-supported Cu single atom catalysts with tailored coordination structures, namely, Cu–N4 and Cu–N3, can serve as highly selective and active catalysts for CO2 hydrogenation at low temperature. The modulation of the coordination structure of Cu single atom is readily realized by simply altering the treatment parameters. Further investigations reveal that Cu–N4 favors CO2 hydrogenation to form CH3OH via the formate pathway, while Cu–N3 tends to catalyze CO2 hydrogenation to produce CO via the reverse water-gas-shift (RWGS) pathway. Significantly, the CH3OH productivity and selectivity reach 4.2 mmol g–1 h–1 and 95.5%, respectively, for Cu–N4 single atom catalyst. We anticipate this work will promote the fundamental researches on the structure-performance relationship of catalysts.
Photoactivatable ribonucleosides mark base-specific RNA-binding sites
Authors: Bae Jong Woo , Kim Sangtae , Kim V. Narry , Kim Jong-Seo 
Published: October 2021

AbstractRNA-protein interaction can be captured by crosslinking and enrichment followed by tandem mass spectrometry, but it remains challenging to pinpoint RNA-binding sites (RBSs) or provide direct evidence for RNA-binding. To overcome these limitations, we here developed pRBS-ID, by incorporating the benefits of UVA-based photoactivatable ribonucleoside (PAR; 4-thiouridine and 6-thioguanosine) crosslinking and chemical RNA cleavage. pRBS-ID robustly detects peptides crosslinked to PAR adducts, offering direct RNA-binding evidence and identifying RBSs at single amino acid-resolution with base-specificity (U or G). Using pRBS-ID, we could profile uridine-contacting RBSs globally and discover guanosine-contacting RBSs, which allowed us to characterize the base-specific interactions. We also applied the search pipeline to analyze the datasets from UVC-based RBS-ID experiments, altogether offering a comprehensive list of human RBSs with high coverage (3,077 RBSs in 532 proteins in total). pRBS-ID is a widely applicable platform to investigate the molecular basis of posttranscriptional regulation.
PHF3 regulates neuronal gene expression through the Pol II CTD reader domain SPOC
Authors: Appel Lisa-Marie , Franke Vedran , Bruno Melania , Grishkovskaya Irina , Kasiliauskaite Aiste , Kaufmann Tanja , Schoeberl Ursula E. , Puchinger Martin G. , Kostrhon Sebastian , Ebenwaldner Carmen , Sebesta Marek , Beltzung Etienne , Mechtler Karl , Lin Gen , Vlasova Anna , Leeb Martin , Pavri Rushad , Stark Alexander , Akalin Altuna , Stefl Richard , Bernecky Carrie , Djinovic-Carugo Kristina , Slade Dea 
Published: October 2021

AbstractThe C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Pol II) is a regulatory hub for transcription and RNA processing. Here, we identify PHD-finger protein 3 (PHF3) as a regulator of transcription and mRNA stability that docks onto Pol II CTD through its SPOC domain. We characterize SPOC as a CTD reader domain that preferentially binds two phosphorylated Serine-2 marks in adjacent CTD repeats. PHF3 drives liquid-liquid phase separation of phosphorylated Pol II, colocalizes with Pol II clusters and tracks with Pol II across the length of genes. PHF3 knock-out or SPOC deletion in human cells results in increased Pol II stalling, reduced elongation rate and an increase in mRNA stability, with marked derepression of neuronal genes. Key neuronal genes are aberrantly expressed in Phf3 knock-out mouse embryonic stem cells, resulting in impaired neuronal differentiation. Our data suggest that PHF3 acts as a prominent effector of neuronal gene regulation by bridging transcription with mRNA decay.
Altered growth conditions more than reforestation counteracted forest biomass carbon emissions 1990–2020
Authors: Le Noë Julia , Erb Karl-Heinz , Matej Sarah , Magerl Andreas , Bhan Manan , Gingrich Simone 
Published: October 2021

AbstractUnderstanding the carbon (C) balance in global forest is key for climate-change mitigation. However, land use and environmental drivers affecting global forest C fluxes remain poorly quantified. Here we show, following a counterfactual modelling approach based on global Forest Resource Assessments, that in 1990–2020 deforestation is the main driver of forest C emissions, partly counteracted by increased forest growth rates under altered conditions: In the hypothetical absence of changes in forest (i) area, (ii) harvest or (iii) burnt area, global forest biomass would reverse from an actual cumulative net C source of c. 0.74 GtC to a net C sink of 26.9, 4.9 and 0.63 GtC, respectively. In contrast, (iv) without growth rate changes, cumulative emissions would be 7.4 GtC, i.e., 10 times higher. Because this sink function may be discontinued in the future due to climate-change, ending deforestation and lowering wood harvest emerge here as key climate-change mitigation strategies.
A new opportunity for the emerging tellurium semiconductor: making resistive switching devices
Authors: Yang Yifei , Xu Mingkun , Jia Shujing , Wang Bolun , Xu Lujie , Wang Xinxin , Liu Huan , Liu Yuanshuang , Guo Yuzheng , Wang Lidan , Duan Shukai , Liu Kai , Zhu Min , Pei Jing , Duan Wenrui , Liu Dameng , Li Huanglong 
Published: October 2021

AbstractThe development of the resistive switching cross-point array as the next-generation platform for high-density storage, in-memory computing and neuromorphic computing heavily relies on the improvement of the two component devices, volatile selector and nonvolatile memory, which have distinct operating current requirements. The perennial current-volatility dilemma that has been widely faced in various device implementations remains a major bottleneck. Here, we show that the device based on electrochemically active, low-thermal conductivity and low-melting temperature semiconducting tellurium filament can solve this dilemma, being able to function as either selector or memory in respective desired current ranges. Furthermore, we demonstrate one-selector-one-resistor behavior in a tandem of two identical Te-based devices, indicating the potential of Te-based device as a universal array building block. These nonconventional phenomena can be understood from a combination of unique electrical-thermal properties in Te. Preliminary device optimization efforts also indicate large and unique design space for Te-based resistive switching devices.
Exome sequencing and analysis of 454,787 UK Biobank participants
Authors: Backman Joshua D. , Li Alexander H. , Marcketta Anthony , Sun Dylan , Mbatchou Joelle , Kessler Michael D. , Benner Christian , Liu Daren , Locke Adam E. , Balasubramanian Suganthi , Yadav Ashish , Banerjee Nilanjana , Gillies Christopher E. , Damask Amy , Liu Simon , Bai Xiaodong , Hawes Alicia , Maxwell Evan , Gurski Lauren , Watanabe Kyoko , Kosmicki Jack A. , Rajagopal Veera , Mighty Jason ,   Regeneron Genetics Center,   DiscovEHR, Jones Marcus , Mitnaul Lyndon , Stahl Eli , Coppola Giovanni , Jorgenson Eric , Habegger Lukas , Salerno William J. , Shuldiner Alan R. , Lotta Luca A. , Overton John D. , Cantor Michael N. , Reid Jeffrey G. , Yancopoulos George , Kang Hyun M. , Marchini Jonathan , Baras Aris , Abecasis Gonçalo R. , Ferreira Manuel A. R. 
Published: October 2021

AbstractA major goal in human genetics is to use natural variation to understand the phenotypic consequences of altering each protein-coding gene in the genome. Here we used exome sequencing1 to explore protein-altering variants and their consequences in 454,787 participants in the UK Biobank study2. We identified 12 million coding variants, including around 1 million loss-of-function and around 1.8 million deleterious missense variants. When these were tested for association with 3,994 health-related traits, we found 564 genes with trait associations at P ≤ 2.18 × 10−11. Rare variant associations were enriched in loci from genome-wide association studies (GWAS), but most (91%) were independent of common variant signals. We discovered several risk-increasing associations with traits related to liver disease, eye disease and cancer, among others, as well as risk-lowering associations for hypertension (SLC9A3R2), diabetes (MAP3K15, FAM234A) and asthma (SLC27A3). Six genes were associated with brain imaging phenotypes, including two involved in neural development (GBE1, PLD1). Of the signals available and powered for replication in an independent cohort, 81% were confirmed; furthermore, association signals were generally consistent across individuals of European, Asian and African ancestry. We illustrate the ability of exome sequencing to identify gene–trait associations, elucidate gene function and pinpoint effector genes that underlie GWAS signals at scale.
Chromosome-scale assembly and high-density genetic map of the yellow drum, Nibea albiflora
Authors: Xu Dongdong , Zhang Wanchang , Chen Ruiyi , Song Hongbin , Tian Lu , Tan Peng , Wang Ligai , Zhu Qihui , Wu Bin , Lou Bao , Min Jiumeng , Zhou Juhong 
Published: October 2021

AbstractThe yellow drum (Nibea albiflora) is an economically important sciaenid fish in East Asian countries. In this study, we sequenced and assembled a near-complete gynogenetic yellow drum genome. We generated 45.63 Gb of Illumina short-reads and 80.27 Gb of PacBio long-reads and assembled them into a 628.01-Mb genome with a contig N50 of 4.42 Mb. Twenty-four chromosomes with a scaffold N50 of 26.73 Mb were obtained using the Hi-C analysis. We predicted a set of 27,069 protein-coding genes, of which 1,581 and 2,583 were expanded and contracted gene families, respectively. The most expanded genes were categorised into the protein binding, zinc-ion binding and ATP binding functional pathways. We built a high-density genetic linkage map that spanned 4,300.2 cM with 24 linkage groups and a resolution of 0.69 cM. The high-quality reference genome and annotated profiles that we produced will not only increase our understanding of the genetic architecture of economic traits in the yellow drum, but also help us explore the evolution and unique biological characteristics of sciaenid fishes.
The changing face of floodplains in the Mississippi River Basin detected by a 60-year land use change dataset
Authors: Rajib Adnan , Zheng Qianjin , Golden Heather E. , Wu Qiusheng , Lane Charles R. , Christensen Jay R. , Morrison Ryan R. , Annis Antonio , Nardi Fernando 
Published: October 2021

AbstractFloodplains provide essential ecosystem functions, yet >80% of European and North American floodplains are substantially modified. Despite floodplain changes over the past century, comprehensive, long-term land use change data within large river basin floodplains are limited. Long-term land use data can be used to quantify floodplain functions and provide spatially explicit information for management, restoration, and flood-risk mitigation. We present a comprehensive dataset quantifying floodplain land use change along the 3.3 million km2 Mississippi River Basin (MRB) covering 60 years (1941–2000) at 250-m resolution. We developed four unique products as part of this work, a(n): (i) Google Earth Engine interactive map visualization interface, (ii) Python code that runs in any internet browser, (iii) online tutorial with visualizations facilitating classroom code application, and (iv) instructional video demonstrating code application and database reproduction. Our data show that MRB’s natural floodplain ecosystems have been substantially altered to agricultural and developed land uses. These products will support MRB resilience and sustainability goals by advancing data-driven decision making on floodplain restoration, buyout, and conservation scenarios.
A magnetic copper organic framework material as an efficient and recyclable catalyst for the synthesis of 1,2,3-triazole derivatives
Authors: Arefi Elham , Khojastehnezhad Amir , Shiri Ali 
Published: October 2021

AbstractIn this study, a core–shell magnetic metal organic framework (MOF) catalyst was introduced based on Fe3O4 magnetic nanoparticles (MNPs) and copper organic frameworks. In this catalyst, Fe3O4 MNPs have been coated with MOFs in which copper was the inorganic nodes and 1,3,5-benzenetricarboxylic acid was the organic linkers. Then, the core–shell structures and catalytic efficiency have been confirmed properly and completely with various analyses such as FT-IR, TEM, SEM, TEM mapping, SEM mapping, EDX, PXRD, TGA, ICP and VSM. The Cu moieties in MOF and shell structures can catalyze the synthesis of 1,2,3-triazole derivatives with good to excellent yields in the presence of water as a green solvent. Moreover, this catalyst showed the high reusability due to the super paramagnetic properties.