bluuebunny/crossref_metadata_2025_split huggingface dataset:
Erythroid differentiation regulator-1 induced by microbiota in early life drives intestinal stem cell proliferation and regeneration
Authors: Abo Hirohito , Chassaing Benoit , Harusato Akihito , Quiros Miguel , Brazil Jennifer C. , Ngo Vu L. , Viennois Emilie , Merlin Didier , Gewirtz Andrew T. , Nusrat Asma , Denning Timothy L. 
Published: January 2020

AbstractGut microbiota and their metabolites are instrumental in regulating intestinal homeostasis. However, early-life microbiota associated influences on intestinal development remain incompletely understood. Here we demonstrate that co-housing of germ-free (GF) mice with specific-pathogen free (SPF) mice at weaning (exGF) results in altered intestinal gene expression. Our results reveal that one highly differentially expressed gene, erythroid differentiation regulator-1 (Erdr1), is induced during development in SPF but not GF or exGF mice and localizes to Lgr5+ stem cells and transit amplifying (TA) cells. Erdr1 functions to induce Wnt signaling in epithelial cells, increase Lgr5+ stem cell expansion, and promote intestinal organoid growth. Additionally, Erdr1 accelerates scratch-wound closure in vitro, increases Lgr5+ intestinal stem cell regeneration following radiation-induced injury in vivo, and enhances recovery from dextran sodium sulfate (DSS)-induced colonic damage. Collectively, our findings indicate that early-life microbiota controls Erdr1-mediated intestinal epithelial proliferation and regeneration in response to mucosal damage.
Genetic screening identifies a SUMO protease dynamically maintaining centromeric chromatin
Authors: Mitra Sreyoshi , Bodor Dani L. , David Ana F. , Abdul-Zani Izma , Mata João F. , Neumann Beate , Reither Sabine , Tischer Christian , Jansen Lars E. T. 
Published: January 2020

AbstractCentromeres are defined by a self-propagating chromatin structure based on stable inheritance of CENP-A containing nucleosomes. Here, we present a genetic screen coupled to pulse-chase labeling that allow us to identify proteins selectively involved in deposition of nascent CENP-A or in long-term transmission of chromatin-bound CENP-A. These include factors with known roles in DNA replication, repair, chromatin modification, and transcription, revealing a broad set of chromatin regulators that impact on CENP-A dynamics. We further identify the SUMO-protease SENP6 as a key factor, not only controlling CENP-A stability but virtually the entire centromere and kinetochore. Loss of SENP6 results in hyper-SUMOylation of CENP-C and CENP-I but not CENP-A itself. SENP6 activity is required throughout the cell cycle, suggesting that a dynamic SUMO cycle underlies a continuous surveillance of the centromere complex that in turn ensures stable transmission of CENP-A chromatin.
YAP/TAZ direct commitment and maturation of lymph node fibroblastic reticular cells
Authors: Choi Sung Yong , Bae Hosung , Jeong Sun-Hye , Park Intae , Cho Hyunsoo , Hong Seon Pyo , Lee Da-Hye , Lee Choong-kun , Park Jin-Sung , Suh Sang Heon , Choi Jeongwoon , Yang Myung Jin , Jang Jeon Yeob , Onder Lucas , Moon Jeong Hwan , Jeong Han-Sin , Adams Ralf H. , Kim Jin-Man , Ludewig Burkhard , Song Joo-Hye , Lim Dae-Sik , Koh Gou Young 
Published: January 2020

AbstractFibroblastic reticular cells (FRCs) are immunologically specialized myofibroblasts of lymphoid organ, and FRC maturation is essential for structural and functional properties of lymph nodes (LNs). Here we show that YAP and TAZ (YAP/TAZ), the final effectors of Hippo signaling, regulate FRC commitment and maturation. Selective depletion of YAP/TAZ in FRCs impairs FRC growth and differentiation and compromises the structural organization of LNs, whereas hyperactivation of YAP/TAZ enhances myofibroblastic characteristics of FRCs and aggravates LN fibrosis. Mechanistically, the interaction between YAP/TAZ and p52 promotes chemokine expression that is required for commitment of FRC lineage prior to lymphotoxin-β receptor (LTβR) engagement, whereas LTβR activation suppresses YAP/TAZ activity for FRC maturation. Our findings thus present YAP/TAZ as critical regulators of commitment and maturation of FRCs, and hold promise for better understanding of FRC-mediated pathophysiologic processes.
The RNA-binding protein AKAP8 suppresses tumor metastasis by antagonizing EMT-associated alternative splicing
Authors: Hu Xiaohui , Harvey Samuel E. , Zheng Rong , Lyu Jingyi , Grzeskowiak Caitlin L. , Powell Emily , Piwnica-Worms Helen , Scott Kenneth L. , Cheng Chonghui 
Published: January 2020

AbstractAlternative splicing has been shown to causally contribute to the epithelial–mesenchymal transition (EMT) and tumor metastasis. However, the scope of splicing factors that govern alternative splicing in these processes remains largely unexplored. Here we report the identification of A-Kinase Anchor Protein (AKAP8) as a splicing regulatory factor that impedes EMT and breast cancer metastasis. AKAP8 not only is capable of inhibiting splicing activity of the EMT-promoting splicing regulator hnRNPM through protein–protein interaction, it also directly binds to RNA and alters splicing outcomes. Genome-wide analysis shows that AKAP8 promotes an epithelial cell state splicing program. Experimental manipulation of an AKAP8 splicing target CLSTN1 revealed that splice isoform switching of CLSTN1 is crucial for EMT. Moreover, AKAP8 expression and the alternative splicing of CLSTN1 predict breast cancer patient survival. Together, our work demonstrates the essentiality of RNA metabolism that impinges on metastatic breast cancer.
Isolation of Angola-like Marburg virus from Egyptian rousette bats from West Africa
Authors: Amman Brian R. , Bird Brian H. , Bakarr Ibrahim A. , Bangura James , Schuh Amy J. , Johnny Jonathan , Sealy Tara K. , Conteh Immah , Koroma Alusine H. , Foday Ibrahim , Amara Emmanuel , Bangura Abdulai A. , Gbakima Aiah A. , Tremeau-Bravard Alexandre , Belaganahalli Manjunatha , Dhanota Jasjeet , Chow Andrew , Ontiveros Victoria , Gibson Alexandra , Turay Joseph , Patel Ketan , Graziano James , Bangura Camilla , Kamanda Emmanuel S. , Osborne Augustus , Saidu Emmanuel , Musa Jonathan , Bangura Doris , Williams Samuel Maxwell Tom , Wadsworth Richard , Turay Mohamed , Edwin Lavalie , Mereweather-Thompson Vanessa , Kargbo Dickson , Bairoh Fatmata V. , Kanu Marilyn , Robert Willie , Lungai Victor , Guetiya Wadoum Raoul Emeric , Coomber Moinya , Kanu Osman , Jambai Amara , Kamara Sorie M. , Taboy Celine H. , Singh Tushar , Mazet Jonna A. K. , Nichol Stuart T. , Goldstein Tracey , Towner Jonathan S. , Lebbie Aiah 
Published: January 2020

AbstractMarburg virus (MARV) causes sporadic outbreaks of severe Marburg virus disease (MVD). Most MVD outbreaks originated in East Africa and field studies in East Africa, South Africa, Zambia, and Gabon identified the Egyptian rousette bat (ERB; Rousettus aegyptiacus) as a natural reservoir. However, the largest recorded MVD outbreak with the highest case–fatality ratio happened in 2005 in Angola, where direct spillover from bats was not shown. Here, collaborative studies by the Centers for Disease Control and Prevention, Njala University, University of California, Davis USAID-PREDICT, and the University of Makeni identify MARV circulating in ERBs in Sierra Leone. PCR, antibody and virus isolation data from 1755 bats of 42 species shows active MARV infection in approximately 2.5% of ERBs. Phylogenetic analysis identifies MARVs that are similar to the Angola strain. These results provide evidence of MARV circulation in West Africa and demonstrate the value of pathogen surveillance to identify previously undetected threats.
Redox-coupled proton pumping drives carbon concentration in the photosynthetic complex I
Authors: Schuller Jan M. , Saura Patricia , Thiemann Jacqueline , Schuller Sandra K. , Gamiz-Hernandez Ana P. , Kurisu Genji , Nowaczyk Marc M. , Kaila Ville R. I. 
Published: January 2020

AbstractPhotosynthetic organisms capture light energy to drive their energy metabolism, and employ the chemical reducing power to convert carbon dioxide (CO2) into organic molecules. Photorespiration, however, significantly reduces the photosynthetic yields. To survive under low CO2 concentrations, cyanobacteria evolved unique carbon-concentration mechanisms that enhance the efficiency of photosynthetic CO2 fixation, for which the molecular principles have remained unknown. We show here how modular adaptations enabled the cyanobacterial photosynthetic complex I to concentrate CO2 using a redox-driven proton-pumping machinery. Our cryo-electron microscopy structure at 3.2 Å resolution shows a catalytic carbonic anhydrase module that harbours a Zn2+ active site, with connectivity to proton-pumping subunits that are activated by electron transfer from photosystem I. Our findings illustrate molecular principles in the photosynthetic complex I machinery that enabled cyanobacteria to survive in drastically changing CO2 conditions.
YAP-dependent necrosis occurs in early stages of Alzheimer’s disease and regulates mouse model pathology
Authors: Tanaka Hikari , Homma Hidenori , Fujita Kyota , Kondo Kanoh , Yamada Shingo , Jin Xiaocen , Waragai Masaaki , Ohtomo Gaku , Iwata Atsushi , Tagawa Kazuhiko , Atsuta Naoki , Katsuno Masahisa , Tomita Naoki , Furukawa Katsutoshi , Saito Yuko , Saito Takashi , Ichise Ayaka , Shibata Shinsuke , Arai Hiroyuki , Saido Takaomi , Sudol Marius , Muramatsu Shin-ichi , Okano Hideyuki , Mufson Elliott J. , Sobue Gen , Murayama Shigeo , Okazawa Hitoshi 
Published: January 2020

AbstractThe timing and characteristics of neuronal death in Alzheimer’s disease (AD) remain largely unknown. Here we examine AD mouse models with an original marker, myristoylated alanine-rich C-kinase substrate phosphorylated at serine 46 (pSer46-MARCKS), and reveal an increase of neuronal necrosis during pre-symptomatic phase and a subsequent decrease during symptomatic phase. Postmortem brains of mild cognitive impairment (MCI) rather than symptomatic AD patients reveal a remarkable increase of necrosis. In vivo imaging reveals instability of endoplasmic reticulum (ER) in mouse AD models and genome-edited human AD iPS cell-derived neurons. The level of nuclear Yes-associated protein (YAP) is remarkably decreased in such neurons under AD pathology due to the sequestration into cytoplasmic amyloid beta (Aβ) aggregates, supporting the feature of YAP-dependent necrosis. Suppression of early-stage neuronal death by AAV-YAPdeltaC reduces the later-stage extracellular Aβ burden and cognitive impairment, suggesting that preclinical/prodromal YAP-dependent neuronal necrosis represents a target for AD therapeutics.
Programmable meroterpene synthesis
Authors: Shen Xingyu , Ting Chi P. , Xu Gong , Maimone Thomas J. 
Published: January 2020

AbstractThe bicyclo[3.3.1]nonane architecture is a privileged structural motif found in over 1000 natural products with relevance to neurodegenerative disease, bacterial and parasitic infection, and cancer among others. Despite disparate biosynthetic machinery, alkaloid, terpene, and polyketide-producing organisms have all evolved pathways to incorporate this carbocyclic ring system. Natural products of mixed polyketide/terpenoid origins (meroterpenes) are a particularly rich and important source of biologically active bicyclo[3.3.1]nonane-containing molecules. Herein we detail a fully synthetic strategy toward this broad family of targets based on an abiotic annulation/rearrangement strategy resulting in a 10-step total synthesis of garsubellin A, an enhancer of choline acetyltransferase and member of the large family of polycyclic polyprenylated acylphloroglucinols. This work solidifies a strategy for making multiple, diverse meroterpene chemotypes in a programmable assembly process involving a minimal number of chemical transformations.
Spatial attention enhances network, cellular and subthreshold responses in mouse visual cortex
Authors: Speed Anderson , Del Rosario Joseph , Mikail Navid , Haider Bilal 
Published: January 2020

AbstractInternal brain states strongly modulate sensory processing during behaviour. Studies of visual processing in primates show that attention to space selectively improves behavioural and neural responses to stimuli at the attended locations. Here we develop a visual spatial task for mice that elicits behavioural improvements consistent with the effects of spatial attention, and simultaneously measure network, cellular, and subthreshold activity in primary visual cortex. During trial-by-trial behavioural improvements, local field potential (LFP) responses to stimuli detected inside the receptive field (RF) strengthen. Moreover, detection inside the RF selectively enhances excitatory and inhibitory neuron responses to task-irrelevant stimuli and suppresses noise correlations and low frequency LFP fluctuations. Whole-cell patch-clamp recordings reveal that detection inside the RF increases synaptic activity that depolarizes membrane potential responses at the behaviorally relevant location. Our study establishes that mice display fundamental signatures of visual spatial attention spanning behavioral, network, cellular, and synaptic levels, providing new insight into rapid cognitive enhancement of sensory signals in visual cortex.
Vacuum Rabi splitting of a dark plasmonic cavity mode revealed by fast electrons
Authors: Bitton Ora , Gupta Satyendra Nath , Houben Lothar , Kvapil Michal , Křápek Vlastimil , Šikola Tomáš , Haran Gilad 
Published: January 2020

AbstractRecent years have seen a growing interest in strong coupling between plasmons and excitons, as a way to generate new quantum optical testbeds and influence chemical dynamics and reactivity. Strong coupling to bright plasmonic modes has been achieved even with single quantum emitters. Dark plasmonic modes fare better in some applications due to longer lifetimes, but are difficult to probe as they are subradiant. Here, we apply electron energy loss (EEL) spectroscopy to demonstrate that a dark mode of an individual plasmonic bowtie can interact with a small number of quantum emitters, as evidenced by Rabi-split spectra. Coupling strengths of up to 85 meV place the bowtie-emitter devices at the onset of the strong coupling regime. Remarkably, the coupling occurs at the periphery of the bowtie gaps, even while the electron beam probes their center. Our findings pave the way for using EEL spectroscopy to study exciton-plasmon interactions involving non-emissive photonic modes.
Identifying Eigen-like hydrated protons at negatively charged interfaces
Authors: Tyrode Eric , Sengupta Sanghamitra , Sthoer Adrien 
Published: January 2020

AbstractDespite the importance of the hydrogen ion in a wide range of biological, chemical, and physical processes, its molecular structure in solution remains lively debated. Progress has been primarily hampered by the extreme diffuse nature of the vibrational signatures of hydrated protons in bulk solution. Using the inherently surface-specific vibrational sum frequency spectroscopy technique, we show that at selected negatively charged interfaces, a resolved spectral feature directly linked to the H3O+ core in an Eigen-like species can be readily identified in a biologically compatible pH range. Centered at ~2540 cm−1, the band is seen to shift to ~1875 cm−1 when forming D3O+ upon isotopic substitution. The results offer the possibility of tracking and understanding from a molecular perspective the behavior of hydrated protons at charged interfaces.
A helitron-induced RabGDIα variant causes quantitative recessive resistance to maize rough dwarf disease
Authors: Liu Qingcai , Deng Suining , Liu Baoshen , Tao Yongfu , Ai Haiyue , Liu Jianju , Zhang Yongzhong , Zhao Yan , Xu Mingliang 
Published: January 2020

AbstractMaize rough dwarf disease (MRDD), caused by various species of the genus Fijivirus, threatens maize production worldwide. We previously identified a quantitative locus qMrdd1 conferring recessive resistance to one causal species, rice black-streaked dwarf virus (RBSDV). Here, we show that Rab GDP dissociation inhibitor alpha (RabGDIα) is the host susceptibility factor for RBSDV. The viral P7-1 protein binds tightly to the exon-10 and C-terminal regions of RabGDIα to recruit it for viral infection. Insertion of a helitron transposon into RabGDIα intron 10 creates alternative splicing to replace the wild-type exon 10 with a helitron-derived exon 10. The resultant splicing variant RabGDIα-hel has difficulty being recruited by P7-1, thus leading to quantitative recessive resistance to MRDD. All naturally occurring resistance alleles may have arisen from a recent single helitron insertion event. These resistance alleles are valuable to improve maize resistance to MRDD and potentially to engineer RBSDV resistance in other crops.
Targeting glutamine metabolism slows soft tissue sarcoma growth
Authors: Lee Pearl , Malik Dania , Perkons Nicholas , Huangyang Peiwei , Khare Sanika , Rhoades Seth , Gong Yao-Yu , Burrows Michelle , Finan Jennifer M. , Nissim Itzhak , Gade Terence P. F. , Weljie Aalim M. , Simon M. Celeste 
Published: January 2020

AbstractTumour cells frequently utilize glutamine to meet bioenergetic and biosynthetic demands of rapid cell growth. However, glutamine dependence can be highly variable between in vitro and in vivo settings, based on surrounding microenvironments and complex adaptive responses to glutamine deprivation. Soft tissue sarcomas (STSs) are mesenchymal tumours where cytotoxic chemotherapy remains the primary approach for metastatic or unresectable disease. Therefore, it is critical to identify alternate therapies to improve patient outcomes. Using autochthonous STS murine models and unbiased metabolomics, we demonstrate that glutamine metabolism supports sarcomagenesis. STS subtypes expressing elevated glutaminase (GLS) levels are highly sensitive to glutamine starvation. In contrast to previous studies, treatment of autochthonous tumour-bearing animals with Telaglenastat (CB-839), an orally bioavailable GLS inhibitor, successfully inhibits undifferentiated pleomorphic sarcoma (UPS) tumour growth. We reveal glutamine metabolism as critical for sarcomagenesis, with CB-839 exhibiting potent therapeutic potential.
Distinct temporal integration of noradrenaline signaling by astrocytic second messengers during vigilance
Authors: Oe Yuki , Wang Xiaowen , Patriarchi Tommaso , Konno Ayumu , Ozawa Katsuya , Yahagi Kazuko , Hirai Hirokazu , Tsuboi Takashi , Kitaguchi Tetsuya , Tian Lin , McHugh Thomas J. , Hirase Hajime 
Published: January 2020

AbstractAstrocytes may function as mediators of the impact of noradrenaline on neuronal function. Activation of glial α1-adrenergic receptors triggers rapid astrocytic Ca2+ elevation and facilitates synaptic plasticity, while activation of β-adrenergic receptors elevates cAMP levels and modulates memory consolidation. However, the dynamics of these processes in behaving mice remain unexplored, as do the interactions between the distinct second messenger pathways. Here we simultaneously monitored astrocytic Ca2+ and cAMP and demonstrate that astrocytic second messengers are regulated in a temporally distinct manner. In behaving mice, we found that while an abrupt facial air puff triggered transient increases in noradrenaline release and large cytosolic astrocytic Ca2+ elevations, cAMP changes were not detectable. By contrast, repeated aversive stimuli that lead to prolonged periods of vigilance were accompanied by robust noradrenergic axonal activity and gradual sustained cAMP increases. Our findings suggest distinct astrocytic signaling pathways can integrate noradrenergic activity during vigilance states to mediate distinct functions supporting memory.
An optochemical tool for light-induced dissociation of adherens junctions to control mechanical coupling between cells
Authors: Ollech Dirk , Pflästerer Tim , Shellard Adam , Zambarda Chiara , Spatz Joachim Pius , Marcq Philippe , Mayor Roberto , Wombacher Richard , Cavalcanti-Adam Elisabetta Ada 
Published: January 2020

AbstractThe cadherin-catenin complex at adherens junctions (AJs) is essential for the formation of cell-cell adhesion and epithelium integrity; however, studying the dynamic regulation of AJs at high spatio-temporal resolution remains challenging. Here we present an optochemical tool which allows reconstitution of AJs by chemical dimerization of the force bearing structures and their precise light-induced dissociation. For the dimerization, we reconstitute acto-myosin connection of a tailless E-cadherin by two ways: direct recruitment of α-catenin, and linking its cytosolic tail to the transmembrane domain. Our approach enables a specific ON-OFF switch for mechanical coupling between cells that can be controlled spatially on subcellular or tissue scale via photocleavage. The combination with cell migration analysis and traction force microscopy shows a wide-range of applicability and confirms the mechanical contribution of the reconstituted AJs. Remarkably, in vivo our tool is able to control structural and functional integrity of the epidermal layer in developing Xenopus embryos.
Evolutionary diversity in tropical tree communities peaks at intermediate precipitation
Authors: Neves Danilo M. , Dexter Kyle G. , Baker Timothy R. , Coelho de Souza Fernanda , Oliveira-Filho Ary T. , Queiroz Luciano P. , Lima Haroldo C. , Simon Marcelo F. , Lewis Gwilym P. , Segovia Ricardo A. , Arroyo Luzmila , Reynel Carlos , Marcelo-Peña José L. , Huamantupa-Chuquimaco Isau , Villarroel Daniel , Parada G. Alexander , Daza Aniceto , Linares-Palomino Reynaldo , Ferreira Leandro V. , Salomão Rafael P. , Siqueira Geovane S. , Nascimento Marcelo T. , Fraga Claudio N. , Pennington R. Toby 
Published: January 2020

AbstractGlobal patterns of species and evolutionary diversity in plants are primarily determined by a temperature gradient, but precipitation gradients may be more important within the tropics, where plant species richness is positively associated with the amount of rainfall. The impact of precipitation on the distribution of evolutionary diversity, however, is largely unexplored. Here we detail how evolutionary diversity varies along precipitation gradients by bringing together a comprehensive database on the composition of angiosperm tree communities across lowland tropical South America (2,025 inventories from wet to arid biomes), and a new, large-scale phylogenetic hypothesis for the genera that occur in these ecosystems. We find a marked reduction in the evolutionary diversity of communities at low precipitation. However, unlike species richness, evolutionary diversity does not continually increase with rainfall. Rather, our results show that the greatest evolutionary diversity is found in intermediate precipitation regimes, and that there is a decline in evolutionary diversity above 1,490 mm of mean annual rainfall. If conservation is to prioritise evolutionary diversity, areas of intermediate precipitation that are found in the South American ‘arc of deforestation’, but which have been neglected in the design of protected area networks in the tropics, merit increased conservation attention.