bluuebunny/crossref_metadata_2025_split huggingface dataset:
CXCR7 regulates epileptic seizures by controlling the synaptic activity of hippocampal granule cells
Authors: Xu Tao , Yu Xinyuan , Deng Jing , Ou Shu , Liu Xi , Wang Teng , Liu Ying , Yang Juan , Tan Changhong , Yuan Jinxian , Chen Yangmei 
Published: October 2019

AbstractC–X–C motif chemokine receptor 7 (CXCR7), which mediates the immune response in the brain, was recently reported to regulate neurological functions. However, the role of CXCR7 in epilepsy remains unclear. Here, we found that CXCR7 was upregulated in the hippocampal dentate gyrus (DG) of mice subjected to kainic acid (KA)-induced epilepsy and in the brain tissues of patients with temporal lobe epilepsy. Silencing CXCR7 in the hippocampal DG region exerted an antiepileptic effect on the KA-induced mouse model of epilepsy, whereas CXCR7 overexpression produced a seizure-aggravating effect. Mechanistically, CXCR7 selectively regulated N-methyl-d-aspartate receptor (NMDAR)-mediated synaptic neurotransmission in hippocampal dentate granule cells by modulating the cell membrane expression of the NMDAR subunit2A, which requires the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Thus, CXCR7 may regulate epileptic seizures and represents a novel target for antiepileptic treatments.
Symmetry group factorization reveals the structure-function relation in the neural connectome of Caenorhabditis elegans
Authors: Morone Flaviano , Makse Hernán A. 
Published: October 2019

AbstractThe neural connectome of the nematode Caenorhabditis elegans has been completely mapped, yet in spite of being one of the smallest connectomes (302 neurons), the design principles that explain how the connectome structure determines its function remain unknown. Here, we find symmetries in the locomotion neural circuit of C. elegans, each characterized by its own symmetry group which can be factorized into the direct product of normal subgroups. The action of these normal subgroups partitions the connectome into sectors of neurons that match broad functional categories. Furthermore, symmetry principles predict the existence of novel finer structures inside these normal subgroups forming feedforward and recurrent networks made of blocks of imprimitivity. These blocks constitute structures made of circulant matrices nested in a hierarchy of block-circulant matrices, whose functionality is understood in terms of neural processing filters responsible for fast processing of information.
Dynamic modulation of modal coupling in microelectromechanical gyroscopic ring resonators
Authors: Zhou Xin , Zhao Chun , Xiao Dingbang , Sun Jiangkun , Sobreviela Guillermo , Gerrard Dustin D. , Chen Yunhan , Flader Ian , Kenny Thomas W. , Wu Xuezhong , Seshia Ashwin A. 
Published: October 2019

AbstractUnderstanding and controlling modal coupling in micro/nanomechanical devices is integral to the design of high-accuracy timing references and inertial sensors. However, insight into specific physical mechanisms underlying modal coupling, and the ability to tune such interactions is limited. Here, we demonstrate that tuneable mode coupling can be achieved in capacitive microelectromechanical devices with dynamic electrostatic fields enabling strong coupling between otherwise uncoupled modes. A vacuum-sealed microelectromechanical silicon ring resonator is employed in this work, with relevance to the gyroscopic lateral modes of vibration. It is shown that a parametric pumping scheme can be implemented through capacitive electrodes surrounding the device that allows for the mode coupling strength to be dynamically tuned, as well as allowing greater flexibility in the control of the coupling stiffness. Electrostatic pump based sideband coupling is demonstrated, and compared to conventional strain-mediated sideband operations. Electrostatic coupling is shown to be very efficient, enabling strong, tunable dynamical coupling.
Split selectable markers
Authors: Jillette Nathaniel , Du Menghan , Zhu Jacqueline Jufen , Cardoz Peter , Cheng Albert Wu 
Published: October 2019

AbstractSelectable markers are widely used in transgenesis and genome editing for selecting engineered cells with a desired genotype but the variety of markers is limited. Here we present split selectable markers that each allow for selection of multiple “unlinked” transgenes in the context of lentivirus-mediated transgenesis as well as CRISPR-Cas-mediated knock-ins. Split marker gene segments fused to protein splicing elements called “inteins” can be separately co-segregated with different transgenic vectors, and rejoin via protein trans-splicing to reconstitute a full-length marker protein in host cells receiving all intended vectors. Using a lentiviral system, we create and validate 2-split Hygromycin, Puromycin, Neomycin and Blasticidin resistance genes as well as mScarlet fluorescent proteins. By combining split points, we create 3- and 6-split Hygromycin resistance genes, demonstrating that higher-degree split markers can be generated by a “chaining” design. We adapt the split marker system for selecting biallelically engineered cells after CRISPR gene editing. Future engineering of split markers may allow selection of a higher number of genetic modifications in target cells.
Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism
Authors: Huang Fengjie , Zheng Xiaojiao , Ma Xiaohui , Jiang Runqiu , Zhou Wangyi , Zhou Shuiping , Zhang Yunjing , Lei Sha , Wang Shouli , Kuang Junliang , Han Xiaolong , Wei Meilin , You Yijun , Li Mengci , Li Yitao , Liang Dandan , Liu Jiajian , Chen Tianlu , Yan Chao , Wei Runmin , Rajani Cynthia , Shen Chengxing , Xie Guoxiang , Bian Zhaoxiang , Li Houkai , Zhao Aihua , Jia Wei 
Published: October 2019

AbstractPu-erh tea displays cholesterol-lowering properties, but the underlying mechanism has not been elucidated. Theabrownin is one of the most active and abundant pigments in Pu-erh tea. Here, we show that theabrownin alters the gut microbiota in mice and humans, predominantly suppressing microbes associated with bile-salt hydrolase (BSH) activity. Theabrownin increases the levels of ileal conjugated bile acids (BAs) which, in turn, inhibit the intestinal FXR-FGF15 signaling pathway, resulting in increased hepatic production and fecal excretion of BAs, reduced hepatic cholesterol, and decreased lipogenesis. The inhibition of intestinal FXR-FGF15 signaling is accompanied by increased gene expression of enzymes in the alternative BA synthetic pathway, production of hepatic chenodeoxycholic acid, activation of hepatic FXR, and hepatic lipolysis. Our results shed light into the mechanisms behind the cholesterol- and lipid-lowering effects of Pu-erh tea, and suggest that decreased intestinal BSH microbes and/or decreased FXR-FGF15 signaling may be potential anti-hypercholesterolemia and anti-hyperlipidemia therapies.
Split intein-mediated selection of cells containing two plasmids using a single antibiotic
Authors: Palanisamy Navaneethan , Degen Anna , Morath Anna , Ballestin Ballestin Jara , Juraske Claudia , Öztürk Mehmet Ali , Sprenger Georg A. , Youn Jung-Won , Schamel Wolfgang W. , Di Ventura Barbara 
Published: October 2019

AbstractTo build or dissect complex pathways in bacteria and mammalian cells, it is often necessary to recur to at least two plasmids, for instance harboring orthogonal inducible promoters. Here we present SiMPl, a method based on rationally designed split enzymes and intein-mediated protein trans-splicing, allowing the selection of cells carrying two plasmids with a single antibiotic. We show that, compared to the traditional method based on two antibiotics, SiMPl increases the production of the antimicrobial non-ribosomal peptide indigoidine and the non-proteinogenic aromatic amino acid para-amino-L-phenylalanine from bacteria. Using a human T cell line, we employ SiMPl to obtain a highly pure population of cells double positive for the two chains of the T cell receptor, TCRα and TCRβ, using a single antibiotic. SiMPl has profound implications for metabolic engineering and for constructing complex synthetic circuits in bacteria and mammalian cells.
Procr-expressing progenitor cells are responsible for murine ovulatory rupture repair of ovarian surface epithelium
Authors: Wang Jingqiang , Wang Daisong , Chu Kun , Li Wen , Zeng Yi Arial 
Published: October 2019

AbstractOvarian surface epithelium (OSE) undergoes recurring ovulatory rupture and repair. The OSE replenishing mechanism post ovulation remains unclear. Here we report that the expression of Protein C Receptor (Procr) marks a progenitor population in adult mice that is responsible for OSE repair post ovulation. Procr+  cells are the major cell source for OSE repair. The mechanism facilitating the rapid re-epithelialization is through the immediate expansion of Procr+  cells upon OSE rupture. Targeted ablation of Procr+  cells impedes the repairing process. Moreover, Procr+  cells displayed robust colony-formation capacity in culture, which we harnessed and established a long-term culture and expansion system of OSE cells. Finally, we show that Procr+  cells and previously reported Lgr5+ cells have distinct lineage tracing behavior in OSE homeostasis. Our study suggests that Procr marks progenitor cells that are critical for OSE ovulatory rupture and homeostasis, providing insight into how adult stem cells respond upon injury.
Soil net nitrogen mineralisation across global grasslands
Authors: Risch A. C. , Zimmermann S. , Ochoa-Hueso R. , Schütz M. , Frey B. , Firn J. L. , Fay P. A. , Hagedorn F. , Borer E. T. , Seabloom E. W. , Harpole W. S. , Knops J. M. H. , McCulley R. L. , Broadbent A. A. D. , Stevens C. J. , Silveira M. L. , Adler P. B. , Báez S. , Biederman L. A. , Blair J. M. , Brown C. S. , Caldeira M. C. , Collins S. L. , Daleo P. , di Virgilio A. , Ebeling A. , Eisenhauer N. , Esch E. , Eskelinen A. , Hagenah N. , Hautier Y. , Kirkman K. P. , MacDougall A. S. , Moore J. L. , Power S. A. , Prober S. M. , Roscher C. , Sankaran M. , Siebert J. , Speziale K. L. , Tognetti P. M. , Virtanen R. , Yahdjian L. , Moser B. 
Published: October 2019

AbstractSoil nitrogen mineralisation (Nmin), the conversion of organic into inorganic N, is important for productivity and nutrient cycling. The balance between mineralisation and immobilisation (net Nmin) varies with soil properties and climate. However, because most global-scale assessments of net Nminare laboratory-based, its regulation under field-conditions and implications for real-world soil functioning remain uncertain. Here, we explore the drivers of realised (field) and potential (laboratory) soil net Nminacross 30 grasslands worldwide. We find that realised Nminis largely explained by temperature of the wettest quarter, microbial biomass, clay content and bulk density. Potential Nminonly weakly correlates with realised Nmin, but contributes to explain realised net Nminwhen combined with soil and climatic variables. We provide novel insights of global realised soil net Nminand show that potential soil net Nmindata available in the literature could be parameterised with soil and climate data to better predict realised Nmin.
Plasticity of the Mycobacterium tuberculosis respiratory chain and its impact on tuberculosis drug development
Authors: Beites Tiago , O’Brien Kathryn , Tiwari Divya , Engelhart Curtis A. , Walters Shaun , Andrews Jenna , Yang Hee-Jeong , Sutphen Michelle L. , Weiner Danielle M. , Dayao Emmanuel K. , Zimmerman Matthew , Prideaux Brendan , Desai Prashant V. , Masquelin Thierry , Via Laura E. , Dartois Véronique , Boshoff Helena I. , Barry Clifton E. , Ehrt Sabine , Schnappinger Dirk 
Published: October 2019

AbstractThe viability of Mycobacterium tuberculosis (Mtb) depends on energy generated by its respiratory chain. Cytochrome bc1-aa3 oxidase and type-2 NADH dehydrogenase (NDH-2) are respiratory chain components predicted to be essential, and are currently targeted for drug development. Here we demonstrate that an Mtb cytochrome bc1-aa3 oxidase deletion mutant is viable and only partially attenuated in mice. Moreover, treatment of Mtb-infected marmosets with a cytochrome bc1-aa3 oxidase inhibitor controls disease progression and reduces lesion-associated inflammation, but most lesions become cavitary. Deletion of both NDH-2 encoding genes (Δndh-2 mutant) reveals that the essentiality of NDH-2 as shown in standard growth media is due to the presence of fatty acids. The Δndh-2 mutant is only mildly attenuated in mice and not differently susceptible to clofazimine, a drug in clinical use proposed to engage NDH-2. These results demonstrate the intrinsic plasticity of Mtb’s respiratory chain, and highlight the challenges associated with targeting the pathogen’s respiratory enzymes for tuberculosis drug development.
Rewiring carbon metabolism in yeast for high level production of aromatic chemicals
Authors: Liu Quanli , Yu Tao , Li Xiaowei , Chen Yu , Campbell Kate , Nielsen Jens , Chen Yun 
Published: October 2019

AbstractThe production of bioactive plant compounds using microbial hosts is considered a safe, cost-competitive and scalable approach to their production. However, microbial production of some compounds like aromatic amino acid (AAA)-derived chemicals, remains an outstanding metabolic engineering challenge. Here we present the construction of aSaccharomyces cerevisiaeplatform strain able to produce high levels ofp-coumaric acid, an AAA-derived precursor for many commercially valuable chemicals. This is achieved through engineering the AAA biosynthesis pathway, introducing a phosphoketalose-based pathway to divert glycolytic flux towards erythrose 4-phosphate formation, and optimizing carbon distribution between glycolysis and the AAA biosynthesis pathway by replacing the promoters of several important genes at key nodes between these two pathways. This results in a maximump-coumaric acid titer of 12.5 g L−1and a maximum yield on glucose of 154.9 mg g−1.
Using slow frame rate imaging to extract fast receptive fields
Authors: Mano Omer , Creamer Matthew S. , Matulis Catherine A. , Salazar-Gatzimas Emilio , Chen Juyue , Zavatone-Veth Jacob A. , Clark Damon A. 
Published: October 2019

AbstractIn functional imaging, large numbers of neurons are measured during sensory stimulation or behavior. This data can be used to map receptive fields that describe neural associations with stimuli or with behavior. The temporal resolution of these receptive fields has traditionally been limited by image acquisition rates. However, even when acquisitions scan slowly across a population of neurons, individual neurons may be measured at precisely known times. Here, we apply a method that leverages the timing of neural measurements to find receptive fields with temporal resolutions higher than the image acquisition rate. We use this temporal super-resolution method to resolve fast voltage and glutamate responses in visual neurons in Drosophila and to extract calcium receptive fields from cortical neurons in mammals. We provide code to easily apply this method to existing datasets. This method requires no specialized hardware and can be used with any optical indicator of neural activity.
Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma
Authors: Gotoh Osamu , Sugiyama Yuko , Takazawa Yutaka , Kato Kazuyoshi , Tanaka Norio , Omatsu Kohei , Takeshima Nobuhiro , Nomura Hidetaka , Hasegawa Kosei , Fujiwara Keiichi , Taki Mana , Matsumura Noriomi , Noda Tetsuo , Mori Seiichi 
Published: October 2019

AbstractCarcinosarcoma (CS) of the uterus or ovary is a rare, aggressive and biphasic neoplasm composed of carcinoma and sarcoma elements. Previous genomic studies have identified the driver genes and genomic properties associated with CS. However, there is still no molecular subtyping scheme with clinical relevance for this disease. Here, we sequence 109 CS samples, focusing on 596 genes. We identify four molecular subtypes that resemble those observed in endometrial carcinoma:POLE-mutated, microsatellite instability, copy number high, and copy number low subtypes. These molecular subtypes are linked with DNA repair deficiencies, potential therapeutic strategies, and multiple clinicopathological features, including patient outcomes. Multi-regional comparative sequencing reveals genomic alteration-independent CS cell differentiation. Transcriptome and DNA methylome analyses confirm epithelial-mesenchymal transition as a mechanism of sarcoma differentiation. The current study thus provides therapeutic possibilities for CS as well as clues to understanding the molecular histogenic mechanism of its development.
Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets
Authors: Postema Merel C. , van Rooij Daan , Anagnostou Evdokia , Arango Celso , Auzias Guillaume , Behrmann Marlene , Filho Geraldo Busatto , Calderoni Sara , Calvo Rosa , Daly Eileen , Deruelle Christine , Di Martino Adriana , Dinstein Ilan , Duran Fabio Luis S. , Durston Sarah , Ecker Christine , Ehrlich Stefan , Fair Damien , Fedor Jennifer , Feng Xin , Fitzgerald Jackie , Floris Dorothea L. , Freitag Christine M. , Gallagher Louise , Glahn David C. , Gori Ilaria , Haar Shlomi , Hoekstra Liesbeth , Jahanshad Neda , Jalbrzikowski Maria , Janssen Joost , King Joseph A. , Kong Xiang Zhen , Lazaro Luisa , Lerch Jason P. , Luna Beatriz , Martinho Mauricio M. , McGrath Jane , Medland Sarah E. , Muratori Filippo , Murphy Clodagh M. , Murphy Declan G. M. , O’Hearn Kirsten , Oranje Bob , Parellada Mara , Puig Olga , Retico Alessandra , Rosa Pedro , Rubia Katya , Shook Devon , Taylor Margot J. , Tosetti Michela , Wallace Gregory L. , Zhou Fengfeng , Thompson Paul M. , Fisher Simon E. , Buitelaar Jan K. , Francks Clyde 
Published: October 2019

AbstractAltered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen’sd = −0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.
Practical and stereoselective electrocatalytic 1,2-diamination of alkenes
Authors: Cai Chen-Yan , Shu Xiao-Min , Xu Hai-Chao 
Published: October 2019

AbstractThe 1,2-diamine motif is widely present in natural products, pharmaceutical compounds, and catalysts used in asymmetric synthesis. The simultaneous introduction of two amino groups across an alkene feedstock is an appealing yet challenging approach for the synthesis of 1,2-diamines, primarily due to the inhibitory effect of the diamine products to transition metal catalysts and the difficulty in controlling reaction diastereoselectivity and regioselectivity. Herein we report a scalable electrocatalytic 1,2-diamination reaction that can be used to convert stable, easily available aryl alkenes and sulfamides to 1,2-diamines with excellent diastereoselectivity. Monosubstituted sulfamides react in a regioselective manner to afford 1,2-diamines bearing different substituents on the two amino groups. The combination of an organic redox catalyst and electricity not only obviates the use of any transition metal catalyst and oxidizing reagent, but also ensures broad reaction compatibility with a variety of electronically and sterically diverse substrates.
A multi-omics digital research object for the genetics of sleep regulation
Authors: Jan Maxime , Gobet Nastassia , Diessler Shanaz , Franken Paul , Xenarios Ioannis 
Published: October 2019

AbstractWith the aim to uncover the molecular pathways underlying the regulation of sleep, we recently assembled an extensive and comprehensive systems genetics dataset interrogating a genetic reference population of mice at the levels of the genome, the brain and liver transcriptomes, the plasma metabolome, and the sleep-wake phenome. To facilitate a meaningful and efficient re-use of this public resource by others we designed, describe in detail, and made available a Digital Research Object (DRO), embedding data, documentation, and analytics. We present and discuss both the advantages and limitations of our multi-modal resource and analytic pipeline. The reproducibility of the results was tested by a bioinformatician not implicated in the original project and the robustness of results was assessed by re-annotating genetic and transcriptome data from the mm9 to the mm10 mouse genome assembly.
A multi-modal data resource for investigating topographic heterogeneity in patient-derived xenograft tumors
Authors: Rajaram Satwik , Roth Maike A. , Malato Julia , VandenBerg Scott , Hann Byron , Atreya Chloe E. , Altschuler Steven J. , Wu Lani F. 
Published: October 2019

AbstractPatient-derived xenografts (PDXs) are an essential pre-clinical resource for investigating tumor biology. However, cellular heterogeneity within and across PDX tumors can strongly impact the interpretation of PDX studies. Here, we generated a multi-modal, large-scale dataset to investigate PDX heterogeneity in metastatic colorectal cancer (CRC) across tumor models, spatial scales and genomic, transcriptomic, proteomic and imaging assay modalities. To showcase this dataset, we present analysis to assess sources of PDX variation, including anatomical orientation within the implanted tumor, mouse contribution, and differences between replicate PDX tumors. A unique aspect of our dataset is deep characterization of intra-tumor heterogeneity via immunofluorescence imaging, which enables investigation of variation across multiple spatial scales, from subcellular to whole tumor levels. Our study provides a benchmark data resource to investigate PDX models of metastatic CRC and serves as a template for future, quantitative investigations of spatial heterogeneity within and across PDX tumor models.
A spatio-temporal continuous soil moisture dataset over the Tibet Plateau from 2002 to 2015
Authors: Cui Yaokui , Zeng Chao , Zhou Jie , Xie Hongjie , Wan Wei , Hu Ling , Xiong Wentao , Chen Xi , Fan Wenjie , Hong Yang 
Published: October 2019

AbstractSurface soil moisture is a key variable in the exchange of water and energy between the land surface and the atmosphere, and critical to meteorology, hydrology, and ecology. The Tibetan Plateau (TP), known as “The third pole of the world” and “Asia’s water towers”, exerts huge influences on and sensitive to global climates. In this situation, longer time series of soil moisture can provide sufficient information to understand the role of the TP. This paper presents the first comprehensive dataset (2002–2015) of spatio-temporal continuous soil moisture at 0.25° resolution, based on satellite-based optical (i.e. MODIS) and microwave (ECV) products using a machine learning method named general regression neural network (GRNN). The dataset itself reveals significant information on the soil moisture and its changes over the TP, and can aid to understand the potential driven mechanisms for climate change over the TP.