bluuebunny/crossref_metadata_2025_split huggingface dataset:
Considering socio-political framings when analyzing coastal climate change effects can prevent maldevelopment on small islands
Authors: David C. Gabriel , Hennig Arne , Ratter Beate M. W. , Roeber Volker , Zahid  , Schlurmann Torsten 
Published: October 2021

AbstractAdapting to climate change and sea level rise is challenging on small islands. False adaptation can lead to adverse impacts on natural and societal dynamics. Therefore, an interdisciplinary perspective on the interaction of natural dynamics, societal demands, and political decisions is crucial. In this sense, this study scrutinizes coastal processes and socio-political dimensions of erosion on the reef island Fuvahmulah, the Maldives. The national government and Fuvahmulah’s population have an opposed perception and attribution of the drivers and processes behind Fuvahmulah’s most pressing coastal issue – coastal erosion. To review these perceptions, natural dynamics are recreated with process-based methods and discussed regarding present and projected marine pressures. Population surveys and interviews with actors in coastal development complement the physical insights into erosion on Fuvahmulah and describe the socio-political dimension of climate change adaptation on small islands. This interdisciplinary approach demonstrates how small-islands’ adaptive capacities are typically impaired and disclose the potential of local knowledge to overcome maldevelopment.
RN7SK small nuclear RNA controls bidirectional transcription of highly expressed gene pairs in skin
Authors: Bandiera Roberto , Wagner Rebecca E. , Britto-Borges Thiago , Dieterich Christoph , Dietmann Sabine , Bornelöv Susanne , Frye Michaela 
Published: October 2021

AbstractPausing of RNA polymerase II (Pol II) close to promoters is a common regulatory step in RNA synthesis, and is coordinated by a ribonucleoprotein complex scaffolded by the noncoding RNA RN7SK. The function of RN7SK-regulated gene transcription in adult tissue homoeostasis is currently unknown. Here, we deplete RN7SK during mouse and human epidermal stem cell differentiation. Unexpectedly, loss of this small nuclear RNA specifically reduces transcription of numerous cell cycle regulators leading to cell cycle exit and differentiation. Mechanistically, we show that RN7SK is required for efficient transcription of highly expressed gene pairs with bidirectional promoters, which in the epidermis co-regulated cell cycle and chromosome organization. The reduction in transcription involves impaired splicing and RNA decay, but occurs in the absence of chromatin remodelling at promoters and putative enhancers. Thus, RN7SK is directly required for efficient Pol II transcription of highly transcribed bidirectional gene pairs, and thereby exerts tissue-specific functions, such as maintaining a cycling cell population in the epidermis.
Temporal evolution of master regulator Crp identifies pyrimidines as catabolite modulator factors
Authors: Lauritsen Ida , Frendorf Pernille Ott , Capucci Silvia , Heyde Sophia A. H. , Blomquist Sarah D. , Wendel Sofie , Fischer Emil C. , Sekowska Agnieszka , Danchin Antoine , Nørholm Morten H. H. 
Published: October 2021

AbstractThe evolution of microorganisms often involves changes of unclear relevance, such as transient phenotypes and sequential development of multiple adaptive mutations in hotspot genes. Previously, we showed that ageing colonies of an E. coli mutant unable to produce cAMP when grown on maltose, accumulated mutations in the crp gene (encoding a global transcription factor) and in genes involved in pyrimidine metabolism such as cmk; combined mutations in both crp and cmk enabled fermentation of maltose (which usually requires cAMP-mediated Crp activation for catabolic pathway expression). Here, we study the sequential generation of hotspot mutations in those genes, and uncover a regulatory role of pyrimidine nucleosides in carbon catabolism. Cytidine binds to the cytidine regulator CytR, modifies the expression of sigma factor 32 (RpoH), and thereby impacts global gene expression. In addition, cytidine binds and activates a Crp mutant directly, thus modulating catabolic pathway expression, and could be the catabolite modulating factor whose existence was suggested by Jacques Monod and colleagues in 1976. Therefore, transcription factor Crp appears to work in concert with CytR and RpoH, serving a dual role in sensing both carbon availability and metabolic flux towards DNA and RNA. Our findings show how certain alterations in metabolite concentrations (associated with colony ageing and/or due to mutations in metabolic or regulatory genes) can drive the evolution in non-growing cells.
Deglacial variability of South China hydroclimate heavily contributed by autumn rainfall
Authors: He Chengfei , Liu Zhengyu , Otto-Bliesner Bette L. , Brady Esther C. , Zhu Chenyu , Tomas Robert , Gu Sifan , Han Jing , Jin Yishuai 
Published: October 2021

AbstractThe deglacial hydroclimate in South China remains a long-standing topic of debate due to the lack of reliable moisture proxies and inconsistent model simulations. A recent hydroclimate proxy suggests that South China became wet in cold stadials during the last deglaciation, with the intensification proposed to be contributed mostly by the East Asian summer monsoon (EASM). Here, based on a deglacial simulation in a state-of-the-art climate model that well reproduces the evolution of EASM, winter monsoon (EAWM) and the associated water isotopes in East Asia, we propose that the intensified hydroclimate in South China is also contributed heavily by the rainfall in autumn, during the transition between EASM and EAWM. The excessive rainfall in autumn results from the convergence between anomalous northerly wind due to amplified land-sea thermal contrast and anomalous southerly wind associated with the anticyclone over Western North Pacific, both of which are, in turn, forced by the slowdown of the Atlantic thermohaline circulation. Regardless the rainfall change, however, the modeled δ18Op remains largely unchanged in autumn. Our results provide new insights to East Asia monsoon associated with climate change in the North Atlantic.
Structure and inhibition of Cryptococcus neoformans sterylglucosidase to develop antifungal agents
Authors: Pereira de Sa Nivea , Taouil Adam , Kim Jinwoo , Clement Timothy , Hoffmann Reece M. , Burke John E. , Rizzo Robert C. , Ojima Iwao , Del Poeta Maurizio , Airola Michael V. 
Published: October 2021

AbstractPathogenic fungi exhibit a heavy burden on medical care and new therapies are needed. Here, we develop the fungal specific enzyme sterylglucosidase 1 (Sgl1) as a therapeutic target. Sgl1 converts the immunomodulatory glycolipid ergosterol 3β-D-glucoside to ergosterol and glucose. Previously, we found that genetic deletion of Sgl1 in the pathogenic fungus Cryptococcus neoformans (Cn) results in ergosterol 3β-D-glucoside accumulation, renders Cn non-pathogenic, and immunizes mice against secondary infections by wild-type Cn, even in condition of CD4+ T cell deficiency. Here, we disclose two distinct chemical classes that inhibit Sgl1 function in vitro and in Cn cells. Pharmacological inhibition of Sgl1 phenocopies a growth defect of the Cn Δsgl1 mutant and prevents dissemination of wild-type Cn to the brain in a mouse model of infection. Crystal structures of Sgl1 alone and with inhibitors explain Sgl1’s substrate specificity and enable the rational design of antifungal agents targeting Sgl1.
Mapping epigenetic divergence in the massive radiation of Lake Malawi cichlid fishes
Authors: Vernaz Grégoire , Malinsky Milan , Svardal Hannes , Du Mingliu , Tyers Alexandra M. , Santos M. Emília , Durbin Richard , Genner Martin J. , Turner George F. , Miska Eric A. 
Published: October 2021

AbstractEpigenetic variation modulates gene expression and can be heritable. However, knowledge of the contribution of epigenetic divergence to adaptive diversification in nature remains limited. The massive evolutionary radiation of Lake Malawi cichlid fishes displaying extensive phenotypic diversity despite extremely low sequence divergence is an excellent system to study the epigenomic contribution to adaptation. Here, we present a comparative genome-wide methylome and transcriptome study, focussing on liver and muscle tissues in phenotypically divergent cichlid species. In both tissues we find substantial methylome divergence among species. Differentially methylated regions (DMR), enriched in evolutionary young transposons, are associated with transcription changes of ecologically-relevant genes related to energy expenditure and lipid metabolism, pointing to a link between dietary ecology and methylome divergence. Unexpectedly, half of all species-specific DMRs are shared across tissues and are enriched in developmental genes, likely reflecting distinct epigenetic developmental programmes. Our study reveals substantial methylome divergence in closely-related cichlid fishes and represents a resource to study the role of epigenetics in species diversification.
Self-assembled multifunctional neural probes for precise integration of optogenetics and electrophysiology
Authors: Zou Liang , Tian Huihui , Guan Shouliang , Ding Jianfei , Gao Lei , Wang Jinfen , Fang Ying 
Published: October 2021

AbstractOptogenetics combined with electrical recording has emerged as a powerful tool for investigating causal relationships between neural circuit activity and function. However, the size of optogenetically manipulated tissue is typically 1-2 orders of magnitude larger than that can be electrically recorded, rendering difficulty for assigning functional roles of recorded neurons. Here we report a viral vector-delivery optrode (VVD-optrode) system for precise integration of optogenetics and electrophysiology in the brain. Our system consists of flexible microelectrode filaments and fiber optics that are simultaneously self-assembled in a nanoliter-scale, viral vector-delivery polymer carrier. The highly localized delivery and neuronal expression of opsin genes at microelectrode-tissue interfaces ensure high spatial congruence between optogenetically manipulated and electrically recorded neuronal populations. We demonstrate that this multifunctional system is capable of optogenetic manipulation and electrical recording of spatially defined neuronal populations for three months, allowing precise and long-term studies of neural circuit functions.
DHHC9-mediated GLUT1 S-palmitoylation promotes glioblastoma glycolysis and tumorigenesis
Authors: Zhang Zhenxing , Li Xin , Yang Fan , Chen Chao , Liu Ping , Ren Yi , Sun Pengkai , Wang Zixiong , You Yongping , Zeng Yi-Xin , Li Xinjian 
Published: October 2021

AbstractGlucose transporter GLUT1 is a transmembrane protein responsible for the uptake of glucose into the cells of many tissues through facilitative diffusion. Plasma membrane (PM) localization is essential for glucose uptake by GLUT1. However, the mechanism underlying GLUT1 PM localization remains enigmatic. We find that GLUT1 is palmitoylated at Cys207, and S-palmitoylation is required for maintaining GLUT1 PM localization. Furthermore, we identify DHHC9 as the palmitoyl transferase responsible for this critical posttranslational modification. Knockout of DHHC9 or mutation of GLUT1 Cys207 to serine abrogates palmitoylation and PM distribution of GLUT1, and impairs glycolysis, cell proliferation, and glioblastoma (GBM) tumorigenesis. In addition, DHHC9 expression positively correlates with GLUT1 PM localization in GBM specimens and indicates a poor prognosis in GBM patients. These findings underscore that DHHC9-mediated GLUT1 S-palmitoylation is critical for glucose supply during GBM tumorigenesis.
Ni-catalyzed hydroalkylation of olefins with N-sulfonyl amines
Authors: Yan Xiao-Biao , Li Lun , Wu Wen-Qiang , Xu Lun , Li Ke , Liu Yu-Cheng , Shi Hang 
Published: October 2021

AbstractHydroalkylation, the direct addition of a C(sp3)–H bond across an olefin, is a desirable strategy to produce valuable, complex structural motifs in functional materials, pharmaceuticals, and natural products. Herein, we report a reliable method for accessing α-branched amines via nickel-catalyzed hydroalkylation reactions. Specifically, by using bis(cyclooctadiene)nickel (Ni(cod)2) together with a phosphine ligand, we achieved a formal C(sp3)–H bond insertion reaction between olefins and N-sulfonyl amines without the need for an external hydride source. The amine not only provides the alkyl motif but also delivers hydride to the olefin by means of a nickel-engaged β–hydride elimination/reductive elimination process. This method provides a platform for constructing chiral α-branched amines by using a P-chiral ligand, demonstrating its potential utility in organic synthesis. Notably, a sulfonamidyl boronate complex formed in situ under basic conditions promotes ring-opening of the azanickellacycle reaction intermediate, leading to a significant improvement of the catalytic efficiency.
A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex
Authors: Yao Zizhen , Liu Hanqing , Xie Fangming , Fischer Stephan , Adkins Ricky S. , Aldridge Andrew I. , Ament Seth A. , Bartlett Anna , Behrens M. Margarita , Van den Berge Koen , Bertagnolli Darren , de Bézieux Hector Roux , Biancalani Tommaso , Booeshaghi A. Sina , Bravo Héctor Corrada , Casper Tamara , Colantuoni Carlo , Crabtree Jonathan , Creasy Heather , Crichton Kirsten , Crow Megan , Dee Nick , Dougherty Elizabeth L. , Doyle Wayne I. , Dudoit Sandrine , Fang Rongxin , Felix Victor , Fong Olivia , Giglio Michelle , Goldy Jeff , Hawrylycz Mike , Herb Brian R. , Hertzano Ronna , Hou Xiaomeng , Hu Qiwen , Kancherla Jayaram , Kroll Matthew , Lathia Kanan , Li Yang Eric , Lucero Jacinta D. , Luo Chongyuan , Mahurkar Anup , McMillen Delissa , Nadaf Naeem M. , Nery Joseph R. , Nguyen Thuc Nghi , Niu Sheng-Yong , Ntranos Vasilis , Orvis Joshua , Osteen Julia K. , Pham Thanh , Pinto-Duarte Antonio , Poirion Olivier , Preissl Sebastian , Purdom Elizabeth , Rimorin Christine , Risso Davide , Rivkin Angeline C. , Smith Kimberly , Street Kelly , Sulc Josef , Svensson Valentine , Tieu Michael , Torkelson Amy , Tung Herman , Vaishnav Eeshit Dhaval , Vanderburg Charles R. , van Velthoven Cindy , Wang Xinxin , White Owen R. , Huang Z. Josh , Kharchenko Peter V. , Pachter Lior , Ngai John , Regev Aviv , Tasic Bosiljka , Welch Joshua D. , Gillis Jesse , Macosko Evan Z. , Ren Bing , Ecker Joseph R. , Zeng Hongkui , Mukamel Eran A. 
Published: October 2021

AbstractSingle-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain1–3. With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas—containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities—is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions4. We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis.
An atlas of gene regulatory elements in adult mouse cerebrum
Authors: Li Yang Eric , Preissl Sebastian , Hou Xiaomeng , Zhang Ziyang , Zhang Kai , Qiu Yunjiang , Poirion Olivier B. , Li Bin , Chiou Joshua , Liu Hanqing , Pinto-Duarte Antonio , Kubo Naoki , Yang Xiaoyu , Fang Rongxin , Wang Xinxin , Han Jee Yun , Lucero Jacinta , Yan Yiming , Miller Michael , Kuan Samantha , Gorkin David , Gaulton Kyle J. , Shen Yin , Nunn Michael , Mukamel Eran A. , Behrens M. Margarita , Ecker Joseph R. , Ren Bing 
Published: October 2021

AbstractThe mammalian cerebrum performs high-level sensory perception, motor control and cognitive functions through highly specialized cortical and subcortical structures1. Recent surveys of mouse and human brains with single-cell transcriptomics2–6and high-throughput imaging technologies7,8have uncovered hundreds of neural cell types distributed in different brain regions, but the transcriptional regulatory programs that are responsible for the unique identity and function of each cell type remain unknown. Here we probe the accessible chromatin in more than 800,000 individual nuclei from 45 regions that span the adult mouse isocortex, olfactory bulb, hippocampus and cerebral nuclei, and use the resulting data to map the state of 491,818 candidatecis-regulatory DNA elements in 160 distinct cell types. We find high specificity of spatial distribution for not only excitatory neurons, but also most classes of inhibitory neurons and a subset of glial cell types. We characterize the gene regulatory sequences associated with the regional specificity within these cell types. We further link a considerable fraction of thecis-regulatory elements to putative target genes expressed in diverse cerebral cell types and predict transcriptional regulators that are involved in a broad spectrum of molecular and cellular pathways in different neuronal and glial cell populations. Our results provide a foundation for comprehensive analysis of gene regulatory programs of the mammalian brain and assist in the interpretation of noncoding risk variants associated with various neurological diseases and traits in humans.
Morphological diversity of single neurons in molecularly defined cell types
Authors: Peng Hanchuan , Xie Peng , Liu Lijuan , Kuang Xiuli , Wang Yimin , Qu Lei , Gong Hui , Jiang Shengdian , Li Anan , Ruan Zongcai , Ding Liya , Yao Zizhen , Chen Chao , Chen Mengya , Daigle Tanya L. , Dalley Rachel , Ding Zhangcan , Duan Yanjun , Feiner Aaron , He Ping , Hill Chris , Hirokawa Karla E. , Hong Guodong , Huang Lei , Kebede Sara , Kuo Hsien-Chi , Larsen Rachael , Lesnar Phil , Li Longfei , Li Qi , Li Xiangning , Li Yaoyao , Li Yuanyuan , Liu An , Lu Donghuan , Mok Stephanie , Ng Lydia , Nguyen Thuc Nghi , Ouyang Qiang , Pan Jintao , Shen Elise , Song Yuanyuan , Sunkin Susan M. , Tasic Bosiljka , Veldman Matthew B. , Wakeman Wayne , Wan Wan , Wang Peng , Wang Quanxin , Wang Tao , Wang Yaping , Xiong Feng , Xiong Wei , Xu Wenjie , Ye Min , Yin Lulu , Yu Yang , Yuan Jia , Yuan Jing , Yun Zhixi , Zeng Shaoqun , Zhang Shichen , Zhao Sujun , Zhao Zijun , Zhou Zhi , Huang Z. Josh , Esposito Luke , Hawrylycz Michael J. , Sorensen Staci A. , Yang X. William , Zheng Yefeng , Gu Zhongze , Xie Wei , Koch Christof , Luo Qingming , Harris Julie A. , Wang Yun , Zeng Hongkui 
Published: October 2021

AbstractDendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits.
Isoform cell-type specificity in the mouse primary motor cortex
Authors: Booeshaghi A. Sina , Yao Zizhen , van Velthoven Cindy , Smith Kimberly , Tasic Bosiljka , Zeng Hongkui , Pachter Lior 
Published: October 2021

AbstractFull-length SMART-seq1 single-cell RNA sequencing can be used to measure gene expression at isoform resolution, making possible the identification of specific isoform markers for different cell types. Used in conjunction with spatial RNA capture and gene-tagging methods, this enables the inference of spatially resolved isoform expression for different cell types. Here, in a comprehensive analysis of 6,160 mouse primary motor cortex cells assayed with SMART-seq, 280,327 cells assayed with MERFISH2 and 94,162 cells assayed with 10x Genomics sequencing3, we find examples of isoform specificity in cell types—including isoform shifts between cell types that are masked in gene-level analysis—as well as examples of transcriptional regulation. Additionally, we show that isoform specificity helps to refine cell types, and that a multi-platform analysis of single-cell transcriptomic data leveraging multiple measurements provides a comprehensive atlas of transcription in the mouse primary motor cortex that improves on the possibilities offered by any single technology.
Thalamic circuits for independent control of prefrontal signal and noise
Authors: Mukherjee Arghya , Lam Norman H. , Wimmer Ralf D. , Halassa Michael M. 
Published: October 2021

AbstractInteractions between the mediodorsal thalamus and the prefrontal cortex are critical for cognition. Studies in humans indicate that these interactions may resolve uncertainty in decision-making1, but the precise mechanisms are unknown. Here we identify two distinct mediodorsal projections to the prefrontal cortex that have complementary mechanistic roles in decision-making under uncertainty. Specifically, we found that a dopamine receptor (D2)-expressing projection amplifies prefrontal signals when task inputs are sparse and a kainate receptor (GRIK4) expressing-projection suppresses prefrontal noise when task inputs are dense but conflicting. Collectively, our data suggest that there are distinct brain mechanisms for handling uncertainty due to low signals versus uncertainty due to high noise, and provide a mechanistic entry point for correcting decision-making abnormalities in disorders that have a prominent prefrontal component2–6.