bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrated meta-analysis of peripheral blood metabolites and biological functions in major depressive disorder
Authors: Pu Juncai , Liu Yiyun , Zhang Hanping , Tian Lu , Gui Siwen , Yu Yue , Chen Xiang , Chen Yue , Yang Lining , Ran Yanqin , Zhong Xiaogang , Xu Shaohua , Song Xuemian , Liu Lanxiang , Zheng Peng , Wang Haiyang , Xie Peng 
Published: January 2020

AbstractMajor depressive disorder (MDD) is a serious mental illness, characterized by high morbidity, which has increased in recent decades. However, the molecular mechanisms underlying MDD remain unclear. Previous studies have identified altered metabolic profiles in peripheral tissues associated with MDD. Using curated metabolic characterization data from a large sample of MDD patients, we meta-analyzed the results of metabolites in peripheral blood. Pathway and network analyses were then performed to elucidate the biological themes within these altered metabolites. We identified 23 differentially expressed metabolites between MDD patients and controls from 46 studies. MDD patients were characterized by higher levels of asymmetric dimethylarginine, tyramine, 2-hydroxybutyric acid, phosphatidylcholine (32:1), and taurochenodesoxycholic acid and lower levels of l-acetylcarnitine, creatinine, l-asparagine, l-glutamine, linoleic acid, pyruvic acid, palmitoleic acid, l-serine, oleic acid, myo-inositol, dodecanoic acid, l-methionine, hypoxanthine, palmitic acid, l-tryptophan, kynurenic acid, taurine, and 25-hydroxyvitamin D compared with controls. l-tryptophan and kynurenic acid were consistently downregulated in MDD patients, regardless of antidepressant exposure. Depression rating scores were negatively associated with decreased levels of l-tryptophan. Pathway and network analyses revealed altered amino acid metabolism and lipid metabolism, especially for the tryptophan–kynurenine pathway and fatty acid metabolism, in the peripheral system of MDD patients. Taken together, our integrated results revealed that metabolic changes in the peripheral blood were associated with MDD, particularly decreased l-tryptophan and kynurenic acid levels, and alterations in the tryptophan–kynurenine and fatty acid metabolism pathways. Our findings may facilitate biomarker development and the elucidation of the molecular mechanisms that underly MDD.
The importance of a developmental perspective in Psychiatry: what do recent genetic-epidemiological findings show?
Authors: Thapar Anita , Riglin Lucy 
Published: January 2020

AbstractThere is growing appreciation that a developmental perspective is helpful in Psychiatry. However, clinical practice and research, especially in an era of very large sample sizes, often ignore the developmental context. In this perspective piece, we discuss why a developmental view is important in Psychiatry and how recent genetic-epidemiological findings further highlight this. DSM-5 childhood neurodevelopmental disorders such as ADHD, typically onset in early childhood but can persist into adult life; the same ADHD genetic loading appears to contribute across the life course. However, recent longitudinal studies have observed that ADHD symptoms may emerge later during adolescence and adult life in some individuals although the etiology of this late-onset group is unclear. The epidemiology and genetics of depression do not appear to be the same in childhood, adolescence, and adult life. Recent genetic findings further highlight this. Autistic type problems and irritability also appear to show developmental variation in their genetic etiology. These findings raise the question of whether social communication and irritability have the same meaning at different ages. Schizophrenia typically onsets after adolescence. However, it is commonly preceded by childhood antecedents that do not resemble schizophrenia itself but do appear to index schizophrenia genetic liability. We conclude that there is a need for clinicians and scientists to adopt a developmental perspective in clinical practice and research by considering age-at-onset and changes over time as well as different developmental periods when interpreting clinical symptoms.
Nur77-activated lncRNA WFDC21P attenuates hepatocarcinogenesis via modulating glycolysis
Authors: Guan Yun-feng , Huang Qiao-ling , Ai Yuan-li , Chen Qi-tao , Zhao Wen-xiu , Wang Xiao-min , Wu Qiao , Chen Hang-zi 
Published: January 2020

AbstractHepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Orphan nuclear receptor Nur77, which is low expressed in HCC, functions as a tumor suppressor to suppress HCC. However, the detailed mechanism is still not well understood. Here, we demonstrate that Nur77 could inhibit HCC development via transcriptional activation of the lncRNA WAP four-disulfide core domain 21 pseudogene (WFDC21P). Nur77 binds to its response elements on the WFDC21P promoter to directly induce WFDC21P transcription, which inhibits HCC cell proliferation, tumor growth, and tumor metastasis both in vitro and in vivo. In clinical HCC samples, WFDC21P expression positively correlated with that of Nur77, and the loss of WFDC21P is associated with worse prognosis. Mechanistically, WFDC21P could inhibit glycolysis by simultaneously interacting with PFKP and PKM2, two key enzymes in glycolysis. These interactions not only abrogate the tetramer formation of PFKP to impede its catalytic activity but also prevent the nuclear translocation of PKM2 to suppress its function as a transcriptional coactivator. Cytosporone-B (Csn-B), an agonist for Nur77, could stimulate WFDC21P expression and suppress HCC in a WFDC21P-dependent manner. Therefore, our study reveals a new HCC suppressor and connects the glycolytic remodeling of HCC with the Nur77-WFDC21P-PFKP/PKM2 axis.
Transmissible gastroenteritis virus targets Paneth cells to inhibit the self-renewal and differentiation of Lgr5 intestinal stem cells via Notch signaling
Authors: Wu Aimin , Yu Bing , Zhang Keying , Xu Zhiwen , Wu De , He Jun , Luo Junqiu , Luo Yuheng , Yu Jie , Zheng Ping , Che Lianqiang , Mao Xiangbing , Huang Zhiqing , Wang Lan , Zhao Jun , Chen Daiwen 
Published: January 2020

AbstractInfection with transmissible gastroenteritis virus (TGEV) has been associated with villous atrophy within 48 h, which seriously disrupts intestinal homeostasis. However, the underlying mechanisms remain elusive. In this study, we found that TGEV infection severely disrupted intestinal homeostasis via inhibition of self-renewal and differentiation in Lgr5 intestinal stem cells (ISCs). Profoundly, TGEV-encoded NSP10/NSP16 protein complex-mediated the inactivation of Notch signaling provided a mechanistic explanation for this phenomenon. Initial invasions by TGEV-targeted Paneth cells through aminopeptidase N (APN) receptor, then inducing mitochondrial damage and ROS generation in them, ultimately causing Paneth cell decrease and loss of Notch factors (DII4 and Hes5), which are essential for Lgr5 ISCs self-renewal and differentiation. Interestingly, loss of Notch signaling induced goblet cells differentiation at the cost of absorptive enterocytes and promoted mucins secretion, which accelerated TGEV replication. Therefore, the more differentiation of goblet cells, the greater TGEV infection in jejunum. These results provide a detailed mechanistic pathway by which villous atrophy sharply occurs in TGEV-infected jejunum within 48 h. Thus, the pathogenesis of TGEV can be described as a “bottom up scenario”, which is contrary to the traditional “top down” hypothesis. Together, our findings provide a potential link between diarrheal virus infection and crypt cells response that regulates Paneth cells function and Lgr5 ISCs fate and could be exploited for therapeutic application.
Genome-scale CRISPR screening for potential targets of ginsenoside compound K
Authors: Yang Yuanyuan , Liu Xiaojian , Li Shuang , Chen Yanhao , Zhao Yongxu , Wei Yuda , Qiu Yan , Liu Yan , Zhou Zhihua , Han Jun , Wu Guohao , Ding Qiurong 
Published: January 2020

AbstractGinsenosides exhibit a large variety of biological activities in maintaining physical health; however, the molecule underpinnings underlining these biological activities remain to be defined. Here, we took a cellular condition that compound K (CK) induces autophagic cell death in HeLa cells, and setup a high-throughput genetic screening using CRISPR technology. We have identified a number of CK-resistant and CK-sensitive genes, and further validated PMAIP1 as a CK-resistant gene and WASH1 as a CK-sensitive gene. Compound K treatment reduces the expression of WASH1, which further accelerates the autophagic cell death, highlighting WASH1 as an interesting downstream mediator of CK effects. Overall, our study offers an easy-to-adopt platform to study the functional mediators of ginsenosides, and provides a candidate list of genes that are potential targets of CK.
Emergence of chirality and structural complexity in single crystals at the molecular and morphological levels
Authors: di Gregorio Maria Chiara , Shimon Linda J. W. , Brumfeld Vlad , Houben Lothar , Lahav Michal , van der Boom Milko E. 
Published: January 2020

AbstractNaturally occurring single crystals having a multidomain morphology are a counterintuitive phenonomon: the macroscopic appearance is expected to follow the symmetry of the unit cell. Growing such crystals in the lab is a great challenge, especially from organic molecules. We achieve here uniform metallo-organic crystals that exhibit single crystallinity with apparently distinct domains and chirality. The chirality is present at both the molecular and macroscopic levels, although only achiral elements are used. “Yo-yo”-like structures having opposite helical handedness evolve from initially formed seemingly achiral cylinders. This non-polyhedral morphology coexists with a continuous coordination network forming homochiral channels. This work sheds light on the enigmatic aspects of fascinating crystallization processes occurring in biological mineralization. Our findings open up opportunities to generate new porous and hierarchical chiral materials.
JMJD3 and UTX determine fidelity and lineage specification of human neural progenitor cells
Authors: Shan Yongli , Zhang Yanqi , Zhao Yuan , Wang Tianyu , Zhang Jingyuan , Yao Jiao , Ma Ning , Liang Zechuan , Huang Wenhao , Huang Ke , Zhang Tian , Su Zhenghui , Chen Qianyu , Zhu Yanling , Wu Chuman , Zhou Tiancheng , Sun Wei , Wei Yanxing , Zhang Cong , Li Chenxu , Su Shuquan , Liao Baojian , Zhong Mei , Zhong Xiaofen , Nie Jinfu , Pei Duanqing , Pan Guangjin 
Published: January 2020

AbstractNeurogenesis, a highly orchestrated process, entails the transition from a pluripotent to neural state and involves neural progenitor cells (NPCs) and neuronal/glial subtypes. However, the precise epigenetic mechanisms underlying fate decision remain poorly understood. Here, we delete KDM6s (JMJD3 and/or UTX), the H3K27me3 demethylases, in human embryonic stem cells (hESCs) and show that their deletion does not impede NPC generation from hESCs. However, KDM6-deficient NPCs exhibit poor proliferation and a failure to differentiate into neurons and glia. Mechanistically, both JMJD3 and UTX are found to be enriched in gene loci essential for neural development in hNPCs, and KDM6 impairment leads to H3K27me3 accumulation and blockade of DNA accessibility at these genes. Interestingly, forced expression of neuron-specific chromatin remodelling BAF (nBAF) rescues the neuron/glia defect in KDM6-deficient NPCs despite H3K27me3 accumulation. Our findings uncover the differential requirement of KDM6s in specifying NPCs and neurons/glia and highlight the contribution of individual epigenetic regulators in fate decisions in a human development model.
Distinctive phenotypes and functions of innate lymphoid cells in human decidua during early pregnancy
Authors: Huhn Oisín , Ivarsson Martin A. , Gardner Lucy , Hollinshead Mike , Stinchcombe Jane C , Chen Puran , Shreeve Norman , Chazara Olympe , Farrell Lydia E. , Theorell Jakob , Ghadially Hormas , Parham Peter , Griffiths Gillian , Horowitz Amir , Moffett Ashley , Sharkey Andrew M. , Colucci Francesco 
Published: January 2020

AbstractDuring early pregnancy, decidual innate lymphoid cells (dILCs) interact with surrounding maternal cells and invading fetal extravillous trophoblasts (EVT). Here, using mass cytometry, we characterise five main dILC subsets: decidual NK cells (dNK)1–3, ILC3s and proliferating NK cells. Following stimulation, dNK2 and dNK3 produce more chemokines than dNK1 including XCL1 which can act on both maternal dendritic cells and fetal EVT. In contrast, dNK1 express receptors including Killer-cell Immunoglobulin-like Receptors (KIR), indicating they respond to HLA class I ligands on EVT. Decidual NK have distinctive organisation and content of granules compared with peripheral blood NK cells. Acquisition of KIR correlates with higher granzyme B levels and increased chemokine production in response to KIR activation, suggesting a link between increased granule content and dNK1 responsiveness. Our analysis shows that dILCs are unique and provide specialised functions dedicated to achieving placental development and successful reproduction.
Eighty-eight variants highlight the role of T cell regulation and airway remodeling in asthma pathogenesis
Authors: Olafsdottir Thorunn A. , Theodors Fannar , Bjarnadottir Kristbjorg , Bjornsdottir Unnur Steina , Agustsdottir Arna B. , Stefansson Olafur A. , Ivarsdottir Erna V. , Sigurdsson Jon K. , Benonisdottir Stefania , Eyjolfsson Gudmundur I. , Gislason David , Gislason Thorarinn , Guðmundsdóttir Steinunn , Gylfason Arnaldur , Halldorsson Bjarni V. , Halldorsson Gisli H. , Juliusdottir Thorhildur , Kristinsdottir Anna M. , Ludviksdottir Dora , Ludviksson Bjorn R. , Masson Gisli , Norland Kristjan , Onundarson Pall T. , Olafsson Isleifur , Sigurdardottir Olof , Stefansdottir Lilja , Sveinbjornsson Gardar , Tragante Vinicius , Gudbjartsson Daniel F. , Thorleifsson Gudmar , Sulem Patrick , Thorsteinsdottir Unnur , Norddahl Gudmundur L. , Jonsdottir Ingileif , Stefansson Kari 
Published: January 2020

AbstractAsthma is one of the most common chronic diseases affecting both children and adults. We report a genome-wide association meta-analysis of 69,189 cases and 702,199 controls from Iceland and UK biobank. We find 88 asthma risk variants at 56 loci, 19 previously unreported, and evaluate their effect on other asthma and allergic phenotypes. Of special interest are two low frequency variants associated with protection against asthma; a missense variant inTNFRSF8and 3‘ UTR variant inTGFBR1. Functional studies show that theTNFRSF8variant reduces TNFRSF8 expression both on cell surface and in soluble form, acting as loss of function. eQTL analysis suggests that theTGFBR1variant acts through gain of function and together with an intronic variant in a downstream gene,SMAD3, points to defective TGFβR1 signaling as one of the biological perturbations increasing asthma risk. Our results increase the number of asthma variants and implicate genes with known role in T cell regulation, inflammation and airway remodeling in asthma pathogenesis.
Design of a unidirectional water valve in Tillandsia
Authors: Raux Pascal S. , Gravelle Simon , Dumais Jacques 
Published: January 2020

AbstractThe bromeliad Tillandsia landbeckii thrives in the Atacama desert of Chile using the fog captured by specialized leaf trichomes to satisfy its water needs. However, it is still unclear how the trichome of T. landbeckii and other Tillandsia species is able to absorb fine water droplets during intermittent fog events while also preventing evaporation when the plant is exposed to the desert’s hyperarid conditions. Here, we explain how a 5800-fold asymmetry in water conductance arises from a clever juxtaposition of a thick hygroscopic wall and a semipermeable membrane. While absorption is achieved by osmosis of liquid water, evaporation under dry external conditions shifts the liquid-gas interface forcing water to diffuse through the thick trichome wall in the vapor phase. We confirm this mechanism by fabricating artificial composite membranes mimicking the trichome structure. The reliance on intrinsic material properties instead of moving parts makes the trichome a promising basis for the development of microfluidics valves.
Mutational signatures in tumours induced by high and low energy radiation in Trp53 deficient mice
Authors: Rose Li Yun , Halliwill Kyle D. , Adams Cassandra J. , Iyer Vivek , Riva Laura , Mamunur Rashid , Jen Kuang-Yu , del Rosario Reyno , Fredlund Erik , Hirst Gillian , Alexandrov Ludmil B. , Adams David , Balmain Allan 
Published: January 2020

AbstractIonising radiation (IR) is a recognised carcinogen responsible for cancer development in patients previously treated using radiotherapy, and in individuals exposed as a result of accidents at nuclear energy plants. However, the mutational signatures induced by distinct types and doses of radiation are unknown. Here, we analyse the genetic architecture of mammary tumours, lymphomas and sarcomas induced by high (56Fe-ions) or low (gamma) energy radiation in mice carrying Trp53 loss of function alleles. In mammary tumours, high-energy radiation is associated with induction of focal structural variants, leading to genomic instability and Met amplification. Gamma-radiation is linked to large-scale structural variants and a point mutation signature associated with oxidative stress. The genomic architecture of carcinomas, sarcomas and lymphomas arising in the same animals are significantly different. Our study illustrates the complex interactions between radiation quality, germline Trp53 deficiency and tissue/cell of origin in shaping the genomic landscape of IR-induced tumours.
Nickel-catalyzed allylic carbonylative coupling of alkyl zinc reagents with tert-butyl isocyanide
Authors: Weng Yangyang , Zhang Chenhuan , Tang Zaiquan , Shrestha Mohini , Huang Wenyi , Qu Jingping , Chen Yifeng 
Published: January 2020

AbstractTransition metal-catalyzed carbonylation with carbon nucleophiles is one of the most prominent methods to construct ketones, which are highly versatile motifs prevalent in a variety of organic compounds. In comparison to the well-established palladium catalytic system, the nickel-catalyzed carbonylative coupling is much underdeveloped due to the strong binding affinity of CO to nickel. By leveraging easily accessible tert-butyl isocyanide as the CO surrogate, we present a nickel-catalyzed allylic carbonylative coupling with alkyl zinc reagent, allowing for the practical and straightforward preparation of synthetically important β,γ-unsaturated ketones in a linear-selective fashion with excellent trans-selectivity under mild conditions. Moreover, the undesired polycarbonylation process which is often encountered in palladium chemistry could be completely suppressed. This nickel-based method features excellent functional group tolerance, even including the active aryl iodide functionality to allow the orthogonal derivatization of β,γ-unsaturated ketones. Preliminary mechanistic studies suggest that the reaction proceeds via a π-allylnickel intermediate.
Extending the coherence of a quantum dot hybrid qubit
Authors: Thorgrimsson Brandur , Kim Dohun , Yang Yuan-Chi , Smith L. W. , Simmons C. B. , Ward Daniel R. , Foote Ryan H. , Corrigan J. , Savage D. E. , Lagally M. G. , Friesen Mark , Coppersmith S. N. , Eriksson M. A. 
Published: January 2020

AbstractIdentifying and ameliorating dominant sources of decoherence are important steps in understanding and improving quantum systems. Here, we show that the free induction decay time ($$T_2^*$$T2*) and the Rabi decay rate (ΓRabi) of the quantum dot hybrid qubit can be increased by more than an order of magnitude by appropriate tuning of the qubit parameters and operating points. By operating in the spin-like regime of this qubit, and choosing parameters that increase the qubit’s resilience to charge noise (which we show is presently the limiting noise source for this qubit), we achieve a Ramsey decay time $$T_2^*$$T2* of 177 ns and a Rabi decay time 1/ΓRabi exceeding 1 μs. We find that the slowest ΓRabi is limited by fluctuations in the Rabi frequency induced by charge noise and not by fluctuations in the qubit energy itself.
An Optimised Protocol Harnessing Laser Capture Microdissection for Transcriptomic Analysis on Matched Primary and Metastatic Colorectal Tumours
Authors: Ong Chin-Ann J. , Tan Qiu Xuan , Lim Hui Jun , Shannon Nicholas B. , Lim Weng Khong , Hendrikson Josephine , Ng Wai Har , Tan Joey W. S. , Koh Kelvin K. N. , Wasudevan Seettha D. , Ng Cedric C. Y. , Rajasegaran Vikneswari , Lim Tony Kiat Hon , Ong Choon Kiat , Kon Oi Lian , Teh Bin Tean , Tan Grace H. C. , Chia Claramae Shulyn , Soo Khee Chee , Teo Melissa C. C. 
Published: January 2020

AbstractGeneration of large amounts of genomic data is now feasible and cost-effective with improvements in next generation sequencing (NGS) technology. Ribonucleic acid sequencing (RNA-Seq) is becoming the preferred method for comprehensively characterising global transcriptome activity. Unique to cytoreductive surgery (CRS), multiple spatially discrete tumour specimens could be systematically harvested for genomic analysis. To facilitate such downstream analyses, laser capture microdissection (LCM) could be utilized to obtain pure cell populations. The aim of this protocol study was to develop a methodology to obtain high-quality expression data from matched primary tumours and metastases by utilizing LCM to isolate pure cellular populations. We demonstrate an optimized LCM protocol which reproducibly delivered intact RNA used for RNA sequencing and quantitative polymerase chain reaction (qPCR). After pathologic annotation of normal epithelial, tumour and stromal components, LCM coupled with cDNA library generation provided for successful RNA sequencing. To illustrate our framework’s potential to identify targets that would otherwise be missed with conventional bulk tumour sequencing, we performed qPCR and immunohistochemical technical validation to show that the genes identified were truly expressed only in certain sub-components. This study suggests that the combination of matched tissue specimens with tissue microdissection and NGS provides a viable platform to unmask hidden biomarkers and provides insight into tumour biology at a higher resolution.
Synchronization of the Normal Human Peripheral Immune System: A Comprehensive Circadian Systems Immunology Analysis
Authors: Beam Craig A. , Wasserfall Clive , Woodwyk Alyssa , Akers McKenzie , Rauch Heather , Blok Thomas , Mason Patrice , Vos Duncan , Perry Daniel , Brusko Todd , Peakman Mark , Atkinson Mark 
Published: January 2020

AbstractIn this study, we sought to fill an important gap in fundamental immunology research by conducting a comprehensive systems immunology analysis of daily variation in the normal human peripheral immune system. Although variation due to circadian rhythmicity was not a significant source of variation in daily B-cell levels or any CD4+ functional subset, it accounted for more than 25% of CD4+ regulatory T-cell variation and over 50% of CD8+ central memory variation. Circadian rhythmicity demonstrated phase alignment within functional phenotypes. In addition, we observed that previously-described mechanistic relationships can also appear in the peripheral system as phase shifting in rhythmic patterns. We identified a set of immune factors which are ubiquitously correlated with other factors and further analysis also identified a tightly-correlated “core” set whose relational structure persisted after analytically removing circadian-related variation. This core set consisted of CD8+ and its subpopulations and the NK population. In sum, the peripheral immune system can be conceptualized as a dynamic, interconnected wave-field repeating its pattern on a daily basis. Our data provide a comprehensive inventory of synchronization and correlation within this wave-field and we encourage use of our data to discover unknown mechanistic relationships which can then be tested in the laboratory.