bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small phytoplankton contribute greatly to CO2-fixation after the diatom bloom in the Southern Ocean
Authors: Irion Solène , Christaki Urania , Berthelot Hugo , L’Helguen Stéphane , Jardillier Ludwig 
Published: March 2021

Abstract
Phytoplankton is composed of a broad-sized spectrum of phylogenetically diverse microorganisms. Assessing CO2-fixation intra- and inter-group variability is crucial in understanding how the carbon pump functions, as each group of phytoplankton may be characterized by diverse efficiencies in carbon fixation and export to the deep ocean. We measured the CO2-fixation of different groups of phytoplankton at the single-cell level around the naturally iron-fertilized Kerguelen plateau (Southern Ocean), known for intense diatoms blooms suspected to enhance CO2 sequestration. After the bloom, small cells (&lt;20 µm) composed of phylogenetically distant taxa (prymnesiophytes, prasinophytes, and small diatoms) were growing faster (0.37 ± 0.13 and 0.22 ± 0.09 division d−1 on- and off-plateau, respectively) than larger diatoms (0.11 ± 0.14 and 0.09 ± 0.11 division d−1 on- and off-plateau, respectively), which showed heterogeneous growth and a large proportion of inactive cells (19 ± 13%). As a result, small phytoplankton contributed to a large proportion of the CO2 fixation (41–70%). The analysis of pigment vertical distribution indicated that grazing may be an important pathway of small phytoplankton export. Overall, this study highlights the need to further explore the role of small cells in CO2-fixation and export in the Southern Ocean.
Human-associated microbiota suppress invading bacteria even under disruption by antibiotics
Authors: Letten Andrew D , Baumgartner Michael , Pfrunder-Cardozo Katia R , Levine Jonathan M , Hall Alex R 
Published: March 2021

Abstract
In light of their adverse impacts on resident microbial communities, it is widely predicted that broad-spectrum antibiotics can promote the spread of resistance by releasing resistant strains from competition with other strains and species. We investigated the competitive suppression of a resistant strain of Escherichia coli inoculated into human-associated communities in the presence and absence of the broad and narrow spectrum antibiotics rifampicin and polymyxin B, respectively. We found strong evidence of community-level suppression of the resistant strain in the absence of antibiotics and, despite large changes in community composition and abundance following rifampicin exposure, suppression of the invading resistant strain was maintained in both antibiotic treatments. Instead, the strength of competitive suppression was more strongly associated with the source community (stool sample from individual human donor). This suggests microbiome composition strongly influences the competitive suppression of antibiotic-resistant strains, but at least some antibiotic-associated disruption can be tolerated before competitive release is observed. A deeper understanding of this association will aid the development of ecologically-aware strategies for managing antibiotic resistance.
EphA2 super-enhancer promotes tumor progression by recruiting FOSL2 and TCF7L2 to activate the target gene EphA2
Authors: Cui Shuang , Wu Qiong , Liu Ming , Su Mu , Liu ShiYou , Shao Lan , Han Xiao , He Hongjuan 
Published: March 2021

AbstractSuper-enhancers or stretch enhancers (SEs) consist of large clusters of active transcription enhancers which promote the expression of critical genes that define cell identity during development and disease. However, the role of many super-enhancers in tumor cells remains unclear. This study aims to explore the function and mechanism of a new super-enhancer in various tumor cells. A new super-enhancer that exists in a variety of tumors named EphA2-Super-enhancer (EphA2-SE) was found using multiple databases and further identified. CRISPR/Cas9-mediated deletion of EphA2-SE results in the significant downregulation of its target gene EphA2. Mechanistically, we revealed that the core active region of EphA2-SE comprises E1 component enhancer, which recruits TCF7L2 and FOSL2 transcription factors to drive the expression of EphA2, induce cell proliferation and metastasis. Bioinformatics analysis of RNA-seq data and functional experiments in vitro illustrated that EphA2-SE deletion inhibited cell growth and metastasis by blocking PI3K/AKT and Wnt/β-catenin pathway in HeLa, HCT-116 and MCF-7 cells. Overexpression of EphA2 in EphA2-SE−/− clones rescued the effect of EphA2-SE deletion on proliferation and metastasis. Subsequent xenograft animal model revealed that EphA2-SE deletion suppressed tumor proliferation and survival in vivo. Taken together, these findings demonstrate that EphA2-SE plays an oncogenic role and promotes tumor progression in various tumors by recruiting FOSL2 and TCF7L2 to drive the expression of oncogene EphA2.
Overexpression of Annexin A2 promotes proliferation by forming a Glypican 1/c-Myc positive feedback loop: prognostic significance in human glioma
Authors: Li Xin , Nie Shengdan , Lv Ziyang , Ma Lingran , Song Yuxi , Hu Zhongxu , Hu Xin , Liu Zhiqiang , Zhou Gaoya , Dai Zhijie , Song Tao , Liu Jiajia , Wang Shan 
Published: March 2021

AbstractIn order to set up a reliable prediction system for the tumor grade and prognosis in glioma patients, we clarify the complicated crosstalk of Annexin A2 (ANXA2) with Glypican 1 (GPC1) and demonstrate whether combined indexes of ANXA2 and GPC1 could improve the prognostic evaluation for glioma patients. We found that ANXA2-induced glioma cell proliferation in a c-Myc-dependent manner. ANXA2 increased the expression of GPC1 via c-Myc and the upregulated GPC1 further promoted the c-Myc level, forming a positive feedback loop, which eventually led to enhanced proliferation of glioma cells. Both mRNA and protein levels of ANXA2 were upregulated in glioma tissues and coincided with the overexpression of GPC1. Besides, we utilized tissue microarrays (TMAs) and immunohistochemistry to demonstrate that glioma patients with both high expression of ANXA2 and GPC1 tended to have higher rate of tumor recurrence and shorter overall survival (OS). In conclusion, the overexpression of ANXA2 promotes proliferation of glioma cells by forming a GPC1/c-Myc positive feedback loop, and ANXA2 together with its downstream target GPC1 could be a potential “combination biomarker” for predicting prognosis of glioma patients.
Transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neurons
Authors: Yang Lin , Su Zihao , Wang Ziwu , Li Zhenmeiyu , Shang Zicong , Du Heng , Liu Guoping , Qi Dashi , Yang Zhengang , Xu Zhejun , Zhang Zhuangzhi 
Published: March 2021

AbstractThe striatum is structurally highly diverse, and its organ functionality critically depends on normal embryonic development. Although several studies have been conducted on the gene functional changes that occur during striatal development, a system-wide analysis of the underlying molecular changes is lacking. Here, we present a comprehensive transcriptome profile that allows us to explore the trajectory of striatal development and identify the correlation between the striatal development and Huntington’s disease (HD). Furthermore, we applied an integrative transcriptomic profiling approach based on machine learning to systematically map a global landscape of 277 transcription factor (TF) networks. Most of these TF networks are linked to biological processes, and some unannotated genes provide information about the corresponding mechanisms. For example, we found that the Meis2 and Six3 were crucial for the survival of striatal neurons, which were verified using conditional knockout (CKO) mice. Finally, we used RNA-Seq to speculate their downstream targets.
Gut-Ex-Vivo system as a model to study gluten response in celiac disease
Authors: Gagliardi Mara , Clemente Nausicaa , Monzani Romina , Fusaro Luca , Ferrari Eleonora , Saverio Valentina , Grieco Giovanna , Pańczyszyn Elżbieta , Carton Flavia , Santoro Claudio , Del Mare-Roumani Sara , Amidror Sivan , Yissachar Nissan , Boccafoschi Francesca , Zucchelli Silvia , Corazzari Marco 
Published: March 2021

AbstractCeliac disease (CD) is a complex immune-mediated chronic disease characterized by a consistent inflammation of the gastrointestinal tract induced by gluten intake in genetically predisposed individuals. Although initiated by the interaction between digestion-derived gliadin, a gluten component, peptides, and the intestinal epithelium, the disorder is highly complex and involving other components of the intestine, such as the immune system. Therefore, conventional model systems, mainly based on two- or three-dimension cell cultures and co-cultures, cannot fully recapitulate such a complex disease. The development of mouse models has facilitated the study of different interacting cell types involved in the disorder, together with the impact of environmental factors. However, such in vivo models are often expensive and time consuming. Here we propose an organ ex vivo culture (gut-ex-vivo system) based on small intestines from gluten-sensitive mice cultivated in a dynamic condition, able to fully recapitulate the biochemical and morphological features of the mouse model exposed to gliadin (4 weeks), in 16 h. Indeed, upon gliadin exposure, we observed: i) a down-regulation of cystic fibrosis transmembrane regulator (CFTR) and an up-regulation of transglutaminase 2 (TG2) at both mRNA and protein levels; ii) increased intestinal permeability associated with deregulated tight junction protein expression; iii) induction and production of pro-inflammatory cytokines such as interleukin (IL)-15, IL-17 and interferon gamma (IFNγ); and iv) consistent alteration of intestinal epithelium/villi morphology. Altogether, these data indicate that the proposed model can be efficiently used to study the pathogenesis of CD, test new or repurposed molecules to accelerate the search for new treatments, and to study the impact of the microbiome and derived metabolites, in a time- and cost- effective manner.
Hyperbolic enhancement of photocurrent patterns in minimally twisted bilayer graphene
Authors: Sunku S. S. , Halbertal D. , Stauber T. , Chen S. , McLeod A. S. , Rikhter A. , Berkowitz M. E. , Lo C. F. B. , Gonzalez-Acevedo D. E. , Hone J. C. , Dean C. R. , Fogler M. M. , Basov D. N. 
Published: March 2021

AbstractQuasi-periodic moiré patterns and their effect on electronic properties of twisted bilayer graphene have been intensely studied. At small twist angle θ, due to atomic reconstruction, the moiré superlattice morphs into a network of narrow domain walls separating micron-scale AB and BA stacking regions. We use scanning probe photocurrent imaging to resolve nanoscale variations of the Seebeck coefficient occurring at these domain walls. The observed features become enhanced in a range of mid-infrared frequencies where the hexagonal boron nitride substrate is optically hyperbolic. Our results illustrate the capabilities of the nano-photocurrent technique for probing nanoscale electronic inhomogeneities in two-dimensional materials.
A computer-guided design tool to increase the efficiency of cellular conversions
Authors: Jung Sascha , Appleton Evan , Ali Muhammad , Church George M. , del Sol Antonio 
Published: March 2021

AbstractHuman cell conversion technology has become an important tool for devising new cell transplantation therapies, generating disease models and testing gene therapies. However, while transcription factor over-expression-based methods have shown great promise in generating cell types in vitro, they often endure low conversion efficiency. In this context, great effort has been devoted to increasing the efficiency of current protocols and the development of computational approaches can be of great help in this endeavor. Here we introduce a computer-guided design tool that combines a computational framework for prioritizing more efficient combinations of instructive factors (IFs) of cellular conversions, called IRENE, with a transposon-based genomic integration system for efficient delivery. Particularly, IRENE relies on a stochastic gene regulatory network model that systematically prioritizes more efficient IFs by maximizing the agreement of the transcriptional and epigenetic landscapes between the converted and target cells. Our predictions substantially increased the efficiency of two established iPSC-differentiation protocols (natural killer cells and melanocytes) and established the first protocol for iPSC-derived mammary epithelial cells with high efficiency.
Moiré excitons in MoSe2-WSe2 heterobilayers and heterotrilayers
Authors: Förg Michael , Baimuratov Anvar S. , Kruchinin Stanislav Yu. , Vovk Ilia A. , Scherzer Johannes , Förste Jonathan , Funk Victor , Watanabe Kenji , Taniguchi Takashi , Högele Alexander 
Published: March 2021

AbstractLayered two-dimensional materials exhibit rich transport and optical phenomena in twisted or lattice-incommensurate heterostructures with spatial variations of interlayer hybridization arising from moiré interference effects. Here, we report experimental and theoretical studies of excitons in twisted heterobilayers and heterotrilayers of transition metal dichalcogenides. Using MoSe2-WSe2 stacks as representative realizations of twisted van der Waals bilayer and trilayer heterostructures, we observe contrasting optical signatures and interpret them in the theoretical framework of interlayer moiré excitons in different spin and valley configurations. We conclude that the photoluminescence of MoSe2-WSe2 heterobilayer is consistent with joint contributions from radiatively decaying valley-direct interlayer excitons and phonon-assisted emission from momentum-indirect reservoirs that reside in spatially distinct regions of moiré supercells, whereas the heterotrilayer emission is entirely due to momentum-dark interlayer excitons of hybrid-layer valleys. Our results highlight the profound role of interlayer hybridization for transition metal dichalcogenide heterostacks and other realizations of multi-layered semiconductor van der Waals heterostructures.
Integration of Alzheimer’s disease genetics and myeloid genomics identifies disease risk regulatory elements and genes
Authors: Novikova Gloriia , Kapoor Manav , TCW Julia , Abud Edsel M. , Efthymiou Anastasia G. , Chen Steven X. , Cheng Haoxiang , Fullard John F. , Bendl Jaroslav , Liu Yiyuan , Roussos Panos , Björkegren Johan LM , Liu Yunlong , Poon Wayne W. , Hao Ke , Marcora Edoardo , Goate Alison M. 
Published: March 2021

AbstractGenome-wide association studies (GWAS) have identified more than 40 loci associated with Alzheimer’s disease (AD), but the causal variants, regulatory elements, genes and pathways remain largely unknown, impeding a mechanistic understanding of AD pathogenesis. Previously, we showed that AD risk alleles are enriched in myeloid-specific epigenomic annotations. Here, we show that they are specifically enriched in active enhancers of monocytes, macrophages and microglia. We integrated AD GWAS with myeloid epigenomic and transcriptomic datasets using analytical approaches to link myeloid enhancer activity to target gene expression regulation and AD risk modification. We identify AD risk enhancers and nominate candidate causal genes among their likely targets (includingAP4E1, AP4M1, APBB3, BIN1, MS4A4A, MS4A6A, PILRA, RABEP1, SPI1, TP53INP1, andZYX) in twenty loci. Fine-mapping of these enhancers nominates candidate functional variants that likely modify AD risk by regulating gene expression in myeloid cells. In the MS4A locus we identified a single candidate functional variant and validated it in human induced pluripotent stem cell (hiPSC)-derived microglia and brain. Taken together, this study integrates AD GWAS with multiple myeloid genomic datasets to investigate the mechanisms of AD risk alleles and nominates candidate functional variants, regulatory elements and genes that likely modulate disease susceptibility.
An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism
Authors: Nacke Marisa , Sandilands Emma , Nikolatou Konstantina , Román-Fernández Álvaro , Mason Susan , Patel Rachana , Lilla Sergio , Yelland Tamas , Galbraith Laura C. A. , Freckmann Eva C. , McGarry Lynn , Morton Jennifer P. , Shanks Emma , Leung Hing Y. , Markert Elke , Ismail Shehab , Zanivan Sara , Blyth Karen , Bryant David M. 
Published: March 2021

AbstractThe signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive cellular responses occur is unclear. Here, we report development of 3-Dimensional culture analyses to separately quantify growth and invasion. We identify that alternate variants of IQSEC1, an ARF GTPase Exchange Factor, act as switches to promote invasion over growth by controlling phosphoinositide metabolism. All IQSEC1 variants activate ARF5- and ARF6-dependent PIP5-kinase to promote PI(3,4,5)P3-AKT signalling and growth. In contrast, select pro-invasive IQSEC1 variants promote PI(3,4,5)P3 production to form invasion-driving protrusions. Inhibition of IQSEC1 attenuates invasion in vitro and metastasis in vivo. Induction of pro-invasive IQSEC1 variants and elevated IQSEC1 expression occurs in a number of tumour types and is associated with higher-grade metastatic cancer, activation of PI(3,4,5)P3 signalling, and predicts long-term poor outcome across multiple cancers. IQSEC1-regulated phosphoinositide metabolism therefore is a switch to induce invasion over growth in response to the same external signal. Targeting IQSEC1 as the central regulator of this switch may represent a therapeutic vulnerability to stop metastasis.
Schwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor-like protein 8
Authors: Weiss Tamara , Taschner-Mandl Sabine , Janker Lukas , Bileck Andrea , Rifatbegovic Fikret , Kromp Florian , Sorger Helena , Kauer Maximilian O. , Frech Christian , Windhager Reinhard , Gerner Christopher , Ambros Peter F. , Ambros Inge M. 
Published: March 2021

AbstractAdult Schwann cells (SCs) possess an inherent plastic potential. This plasticity allows SCs to acquire repair-specific functions essential for peripheral nerve regeneration. Here, we investigate whether stromal SCs in benign-behaving peripheral neuroblastic tumors adopt a similar cellular state. We profile ganglioneuromas and neuroblastomas, rich and poor in SC stroma, respectively, and peripheral nerves after injury, rich in repair SCs. Indeed, stromal SCs in ganglioneuromas and repair SCs share the expression of nerve repair-associated genes. Neuroblastoma cells, derived from aggressive tumors, respond to primary repair-related SCs and their secretome with increased neuronal differentiation and reduced proliferation. Within the pool of secreted stromal and repair SC factors, we identify EGFL8, a matricellular protein with so far undescribed function, to act as neuritogen and to rewire cellular signaling by activating kinases involved in neurogenesis. In summary, we report that human SCs undergo a similar adaptive response in two patho-physiologically distinct situations, peripheral nerve injury and tumor development.
Nano-imaging photoresponse in a moiré unit cell of minimally twisted bilayer graphene
Authors: Hesp Niels C. H. , Torre Iacopo , Barcons-Ruiz David , Herzig Sheinfux Hanan , Watanabe Kenji , Taniguchi Takashi , Krishna Kumar Roshan , Koppens Frank H. L. 
Published: March 2021

AbstractGraphene-based moiré superlattices have recently emerged as a unique class of tuneable solid-state systems that exhibit significant optoelectronic activity. Local probing at length scales of the superlattice should provide deeper insight into the microscopic mechanisms of photoresponse and the exact role of the moiré lattice. Here, we employ a nanoscale probe to study photoresponse within a single moiré unit cell of minimally twisted bilayer graphene. Our measurements reveal a spatially rich photoresponse, whose sign and magnitude are governed by the fine structure of the moiré lattice and its orientation with respect to measurement contacts. This results in a strong directional effect and a striking spatial dependence of the gate-voltage response within the moiré domains. The spatial profile and carrier-density dependence of the measured photocurrent point towards a photo-thermoelectric induced response that is further corroborated by good agreement with numerical simulations. Our work shows sub-diffraction photocurrent spectroscopy is an exceptional tool for uncovering the optoelectronic properties of moiré superlattices.
Dynamic relocalization of cytosolic type III secretion system components prevents premature protein secretion at low external pH
Authors: Wimmi Stephan , Balinovic Alexander , Jeckel Hannah , Selinger Lisa , Lampaki Dimitrios , Eisemann Emma , Meuskens Ina , Linke Dirk , Drescher Knut , Endesfelder Ulrike , Diepold Andreas 
Published: March 2021

AbstractMany bacterial pathogens use a type III secretion system (T3SS) to manipulate host cells. Protein secretion by the T3SS injectisome is activated upon contact to any host cell, and it has been unclear how premature secretion is prevented during infection. Here we report that in the gastrointestinal pathogens Yersinia enterocolitica and Shigella flexneri, cytosolic injectisome components are temporarily released from the proximal interface of the injectisome at low external pH, preventing protein secretion in acidic environments, such as the stomach. We show that in Yersinia enterocolitica, low external pH is detected in the periplasm and leads to a partial dissociation of the inner membrane injectisome component SctD, which in turn causes the dissociation of the cytosolic T3SS components. This effect is reversed upon restoration of neutral pH, allowing a fast activation of the T3SS at the native target regions within the host. These findings indicate that the cytosolic components form an adaptive regulatory interface, which regulates T3SS activity in response to environmental conditions.
Protein context shapes the specificity of SH3 domain-mediated interactions in vivo
Authors: Dionne Ugo , Bourgault Émilie , Dubé Alexandre K. , Bradley David , Chartier François J. M. , Dandage Rohan , Dibyachintan Soham , Després Philippe C. , Gish Gerald D. , Pham N. T. Hang , Létourneau Myriam , Lambert Jean-Philippe , Doucet Nicolas , Bisson Nicolas , Landry Christian R. 
Published: March 2021

AbstractProtein–protein interactions (PPIs) between modular binding domains and their target peptide motifs are thought to largely depend on the intrinsic binding specificities of the domains. The large family of SRC Homology 3 (SH3) domains contribute to cellular processes via their ability to support such PPIs. While the intrinsic binding specificities of SH3 domains have been studied in vitro, whether each domain is necessary and sufficient to define PPI specificity in vivo is largely unknown. Here, by combining deletion, mutation, swapping and shuffling of SH3 domains and measurements of their impact on protein interactions in yeast, we find that most SH3s do not dictate PPI specificity independently from their host protein in vivo. We show that the identity of the host protein and the position of the SH3 domains within their host are critical for PPI specificity, for cellular functions and for key biophysical processes such as phase separation. Our work demonstrates the importance of the interplay between a modular PPI domain such as SH3 and its host protein in establishing specificity to wire PPI networks. These findings will aid understanding how protein networks are rewired during evolution and in the context of mutation-driven diseases such as cancer.