bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isotopic tracing reveals single-cell assimilation of a macroalgal polysaccharide by a few marine Flavobacteria and Gammaproteobacteria
Authors: Thomas François , Le Duff Nolwen , Wu Ting-Di , Cébron Aurélie , Uroz Stéphane , Riera Pascal , Leroux Cédric , Tanguy Gwenn , Legeay Erwan , Guerquin-Kern Jean-Luc 
Published: May 2021

Abstract
Algal polysaccharides constitute a diverse and abundant reservoir of organic matter for marine heterotrophic bacteria, central to the oceanic carbon cycle. We investigated the uptake of alginate, a major brown macroalgal polysaccharide, by microbial communities from kelp-dominated coastal habitats. Congruent with cell growth and rapid substrate utilization, alginate amendments induced a decrease in bacterial diversity and a marked compositional shift towards copiotrophic bacteria. We traced 13C derived from alginate into specific bacterial incorporators and quantified the uptake activity at the single-cell level, using halogen in situ hybridization coupled to nanoscale secondary ion mass spectrometry (HISH-SIMS) and DNA stable isotope probing (DNA-SIP). Cell-specific alginate uptake was observed for Gammaproteobacteria and Flavobacteriales, with carbon assimilation rates ranging from 0.14 to 27.50 fg C µm−3 h−1. DNA-SIP revealed that only a few initially rare Flavobacteriaceae and Alteromonadales taxa incorporated 13C from alginate into their biomass, accounting for most of the carbon assimilation based on bulk isotopic measurements. Functional screening of metagenomic libraries gave insights into the genes of alginolytic Alteromonadales active in situ. These results highlight the high degree of niche specialization in heterotrophic communities and help constraining the quantitative role of polysaccharide-degrading bacteria in coastal ecosystems.
Ablation of dynamin-related protein 1 promotes diabetes-induced synaptic injury in the hippocampus
Authors: Park Gyeongah , Lee Jong Youl , Han Hye Min , An Hyeong Seok , Jin Zhen , Jeong Eun Ae , Kim Kyung Eun , Shin Hyun Joo , Lee Jaewoong , Kang Dawon , Kim Hyun Joon , Bae Yong Chul , Roh Gu Seob 
Published: May 2021

AbstractDynamin-related protein 1 (Drp1)-mediated mitochondrial dysfunction is associated with synaptic injury in the diabetic brain. However, the dysfunctional mitochondria by Drp1 deletion in the diabetic brain are poorly understood. Here, we investigated the effects of neuron-specific Drp1 deletion on synaptic damage and mitophagy in the hippocampus of a high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice. HFD/STZ-induced diabetic mice exhibited metabolic disturbances and synaptic damages. Floxed Drp1 mice were crossed with Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα)-Cre mice, to generate neuron-specific Drp1 knockout (Drp1cKO) mice, which showed marked mitochondrial swelling and dendritic spine loss in hippocampal neurons. In particular, diabetic Drp1cKO mice exhibited an increase in dendritic spine loss and higher levels of oxidative stress and neuroinflammation compared with diabetic wild-type (WT) mice. Diabetic WT mice generally displayed increased Drp1-induced small mitochondrial morphology in hippocampal neurons, but large mitochondria were prominently observed in diabetic Drp1cKO mice. The levels of microtubule-associated protein 1 light-chain 3 and lysosomal-associated membrane protein 1 proteins were significantly increased in the hippocampus of diabetic Drp1cKO mice compared with diabetic WT mice. The inhibition of Drp1 adversely promotes synaptic injury and neurodegeneration in the diabetic brain. The findings suggest that the exploratory mechanisms behind Drp1-mediated mitochondrial dysfunction could provide a possible therapeutic target for diabetic brain complications.
SOX2 promotes chemoresistance, cancer stem cells properties, and epithelial–mesenchymal transition by β-catenin and Beclin1/autophagy signaling in colorectal cancer
Authors: Zhu Yin , Huang Shimiao , Chen Shengyuan , Chen Jiaxuan , Wang Zhiqing , Wang Yadong , Zheng Haoxuan 
Published: May 2021

AbstractSex-determining region Y-box2 (SOX2), a master regulator of embryonic and induced pluripotent stem cells, drives cancer stem cells (CSCs) properties, fuels tumor initiation, and contributes to tumor aggressiveness. Our previous study has demonstrated the oncogenic role of SOX2 in colorectal cancer (CRC). In this study, we sought to elucidate the underlying mechanisms. Cell function experiments were performed to detect chemoresistance, proliferation, stemness, migration, and invasion in vitro. Chromatin immunoprecipitation, co-immunoprecipitation, luciferase reporter assay, and immunofluorescence were performed to explore the regulation of ABCC2, β-catenin, and Beclin1 by SOX2. The carcinogenic role of SOX2-β-catenin/Beclin1-ABCC2 axis in vivo was analyzed by CRC tissues and xenograft models. Here, we reported that SOX2 sustained chemoresistance by transcriptional activation of ABCC2 expression. Suppressing either β-catenin or autophagy signaling curbed SOX2-driven chemoresistance, stemness, and epithelial–mesenchymal transition (EMT). Mechanistically, SOX2 combined with β-catenin and increased its nuclear expression and transcriptional activity. Transcriptional activation of Beclin1 expression by SOX2 consequently activating autophagy and inducing malignant phenotype. Furthermore, overexpression of β-catenin or Beclin1 facilitated ABCC2 expression. The clinical analyses showed that high expression of ABCC2 and Beclin1 were positively correlated with SOX2 and were associated with poor prognosis in CRC patients. Finally, xenograft models revealed that inhibition of SOX2 expression and autophagy restrained tumor growth and chemoresistance in vivo. Conclusively, we demonstrated a novel mechanism by which the SOX2-β-catenin/Beclin1/autophagy signaling axis regulates chemoresistance, stemness, and EMT in CRC. Our findings provide novel insights into CRC carcinogenesis and may help develop potential therapeutic candidates for CRC.
Multiple roles of H2A.Z in regulating promoter chromatin architecture in human cells
Authors: Cole Lauren , Kurscheid Sebastian , Nekrasov Maxim , Domaschenz Renae , Vera Daniel L. , Dennis Jonathan H. , Tremethick David J. 
Published: May 2021

AbstractChromatin accessibility of a promoter is fundamental in regulating transcriptional activity. The histone variant H2A.Z has been shown to contribute to this regulation, but its role has remained poorly understood. Here, we prepare high-depth maps of the position and accessibility of H2A.Z-containing nucleosomes for all human Pol II promoters in epithelial, mesenchymal and isogenic cancer cell lines. We find that, in contrast to the prevailing model, many different types of active and inactive promoter structures are observed that differ in their nucleosome organization and sensitivity to MNase digestion. Key aspects of an active chromatin structure include positioned H2A.Z MNase resistant nucleosomes upstream or downstream of the TSS, and a MNase sensitive nucleosome at the TSS. Furthermore, the loss of H2A.Z leads to a dramatic increase in the accessibility of transcription factor binding sites. Collectively, these results suggest that H2A.Z has multiple and distinct roles in regulating gene expression dependent upon its location in a promoter.
The lncRNA Caren antagonizes heart failure by inactivating DNA damage response and activating mitochondrial biogenesis
Authors: Sato Michio , Kadomatsu Tsuyoshi , Miyata Keishi , Warren Junco S. , Tian Zhe , Zhu Shunshun , Horiguchi Haruki , Makaju Aman , Bakhtina Anna , Morinaga Jun , Sugizaki Taichi , Hirashima Kaname , Yoshinobu Kumiko , Imasaka Mai , Araki Masatake , Komohara Yoshihiro , Wakayama Tomohiko , Nakagawa Shinichi , Franklin Sarah , Node Koichi , Araki Kimi , Oike Yuichi 
Published: May 2021

AbstractIn the past decade, many long noncoding RNAs (lncRNAs) have been identified and their in vitro functions defined, although in some cases their functions in vivo remain less clear. Moreover, unlike nuclear lncRNAs, the roles of cytoplasmic lncRNAs are less defined. Here, using a gene trapping approach in mouse embryonic stem cells, we identify Caren (short for cardiomyocyte-enriched noncoding transcript), a cytoplasmic lncRNA abundantly expressed in cardiomyocytes. Caren maintains cardiac function under pathological stress by inactivating the ataxia telangiectasia mutated (ATM)-DNA damage response (DDR) pathway and activating mitochondrial bioenergetics. The presence of Caren transcripts does not alter expression of nearby (cis) genes but rather decreases translation of an mRNA transcribed from a distant gene encoding histidine triad nucleotide-binding protein 1 (Hint1), which activates the ATM-DDR pathway and reduces mitochondrial respiratory capacity in cardiomyocytes. Therefore, the cytoplasmic lncRNA Caren functions in cardioprotection by regulating translation of a distant gene and maintaining cardiomyocyte homeostasis.
Cohesin-protein Shugoshin-1 controls cardiac automaticity via HCN4 pacemaker channel
Authors: Liu Donghai , Song Andrew Taehun , Qi Xiaoyan , van Vliet Patrick Piet , Xiao Jiening , Xiong Feng , Andelfinger Gregor , Nattel Stanley 
Published: May 2021

AbstractEndogenous cardiac pacemaker function regulates the rate and rhythm of cardiac contraction. The mutation p.Lys23Glu in the cohesin protein Shugoshin-1 causes severe heart arrhythmias due to sinoatrial node dysfunction and a debilitating gastrointestinal motility disorder, collectively termed the Chronic Atrial and Intestinal Dysrhythmia Syndrome, linking Shugoshin-1 and pacemaker activity. Hyperpolarization-activated, cyclic nucleotide-gated cation channel 4 (HCN4) is the predominant pacemaker ion-channel in the adult heart and carries the majority of the “funny” current, which strongly contributes to diastolic depolarization in pacemaker cells. Here, we study the mechanism by which Shugoshin-1 affects cardiac pacing activity with two cell models: neonatal rat ventricular myocytes and Chronic Atrial and Intestinal Dysrhythmia Syndrome patient-specific human induced pluripotent stem cell derived cardiomyocytes. We find that Shugoshin-1 interacts directly with HCN4 to promote and stabilize cardiac pacing. This interaction enhances funny-current by optimizing HCN4 cell-surface expression and function. The clinical p.Lys23Glu mutation leads to an impairment in the interaction between Shugoshin-1 and HCN4, along with depressed funny-current and dysrhythmic activity in induced pluripotent stem cell derived cardiomyocytes derived from Chronic Atrial and Intestinal Dysrhythmia Syndrome patients. Our work reveals a critical non-canonical, cohesin-independent role for Shugoshin-1 in maintaining cardiac automaticity and identifies potential therapeutic avenues for cardiac pacemaking disorders, in particular Chronic Atrial and Intestinal Dysrhythmia Syndrome.
Calcium isotope evidence for early Archaean carbonates and subduction of oceanic crust
Authors: Antonelli Michael A. , Kendrick Jillian , Yakymchuk Chris , Guitreau Martin , Mittal Tushar , Moynier Frédéric 
Published: May 2021

AbstractContinents are unique to Earth and played a role in coevolution of the atmosphere, hydrosphere, and biosphere. Debate exists, however, regarding continent formation and the onset of subduction-driven plate tectonics. We present Ca isotope and trace-element data from modern and ancient (4.0 to 2.8 Ga) granitoids and phase equilibrium models indicating that Ca isotope fractionations are dominantly controlled by geothermal gradients. The results require gradients of 500–750 °C/GPa, as found in modern (hot) subduction-zones and consistent with the operation of subduction throughout the Archaean. Two granitoids from the Nuvvuagittuq Supracrustal Belt, Canada, however, cannot be explained through magmatic processes. Their isotopic signatures were likely inherited from carbonate sediments. These samples (> 3.8 Ga) predate the oldest known carbonates preserved in the rock record and confirm that carbonate precipitation in Eoarchaean oceans provided an important sink for atmospheric CO2. Our results suggest that subduction-driven plate tectonic processes started prior to ~3.8 Ga.
Mastocytosis-derived extracellular vesicles deliver miR-23a and miR-30a into pre-osteoblasts and prevent osteoblastogenesis and bone formation
Authors: Kim Do-Kyun , Bandara Geethani , Cho Young-Eun , Komarow Hirsh D. , Donahue Danielle R. , Karim Baktiar , Baek Moon-Chang , Kim Ho Min , Metcalfe Dean D. , Olivera Ana 
Published: May 2021

AbstractOsteoporosis and other manifestations of bone disease are frequent in patients with systemic mastocytosis (SM) in association with the presence of mast cell infiltrates in bone marrow, although the mechanisms behind bone disease remain poorly understood. We find that extracellular vesicles (EVs) released by neoplastic mast cells and present in the serum of patients with SM (SM-EVs) block osteoblast differentiation and mineralization in culture, and when injected into mice diminish the expression of osteoblast markers, and trabecular bone volume and microarchitecture. We demonstrate that miRNA-30a and miRNA-23a, increased in SM-EVs and neoplastic mast cell-derived EVs, attenuate osteoblast maturation by suppressing expression of RUNX2 and SMAD1/5, essential drivers of osteogenesis. Thus, SM-EVs carry and deliver miRNAs that epigenetically interfere with bone formation and can contribute to bone mass reduction in SM. These findings also suggest possibilities for novel approaches to the management of bone disease in mast cell proliferative disorders.
Quantification of FRET-induced angular displacement by monitoring sensitized acceptor anisotropy using a dim fluorescent donor
Authors: Laskaratou Danai , Fernández Guillermo Solís , Coucke Quinten , Fron Eduard , Rocha Susana , Hofkens Johan , Hendrix Jelle , Mizuno Hideaki 
Published: May 2021

AbstractFörster resonance energy transfer (FRET) between fluorescent proteins has become a common platform for designing genetically encoded biosensors. For live cell imaging, the acceptor-to-donor intensity ratio is most commonly used to readout FRET efficiency, which largely depends on the proximity between donor and acceptor. Here, we introduce an anisotropy-based mode of FRET detection (FADED: FRET-induced Angular Displacement Evaluation via Dim donor), which probes for relative orientation rather than proximity alteration. A key element in this technique is suppression of donor bleed-through, which allows measuring purer sensitized acceptor anisotropy. This is achieved by developing Geuda Sapphire, a low-quantum-yield FRET-competent fluorescent protein donor. As a proof of principle, Ca2+ sensors were designed using calmodulin as a sensing domain, showing sigmoidal dose response to Ca2+. By monitoring the anisotropy, a Ca2+ rise in living HeLa cells is observed upon histamine challenging. We conclude that FADED provides a method for quantifying the angular displacement via FRET.
CD200–CD200R immune checkpoint engagement regulates ILC2 effector function and ameliorates lung inflammation in asthma
Authors: Shafiei-Jahani Pedram , Helou Doumet Georges , Hurrell Benjamin P. , Howard Emily , Quach Christine , Painter Jacob D. , Galle-Treger Lauriane , Li Meng , Loh Yong-Hwee Eddie , Akbari Omid 
Published: May 2021

AbstractThe prevalence of asthma and airway hyperreactivity (AHR) is increasing at an alarming rate. Group 2 innate lymphoid cells (ILC2s) are copious producers of type 2 cytokines, which leads to AHR and lung inflammation. Here, we show that mouse ILC2s express CD200 receptor (CD200R) and this expression is inducible. CD200R engagement inhibits activation, proliferation and type 2 cytokine production, indicating an immunoregulatory function for the CD200–CD200R axis on ILC2s. Furthermore, CD200R engagement inhibits both canonical and non-canonical NF-κB signaling pathways in activated ILC2s. Additionally, we demonstrate both preventative and therapeutic approaches utilizing CD200R engagement on ILC2s, which lead to improved airway resistance, dynamic compliance and eosinophilia. These results show CD200R is expressed on human ILC2s, and its engagement ameliorates AHR in humanized mouse models, emphasizing the translational applications for treatment of ILC2-related diseases such as allergic asthma.
A dual-target molecular mechanism of pyrethrum repellency against mosquitoes
Authors: Liu Feng , Wang Qiang , Xu Peng , Andreazza Felipe , Valbon Wilson R. , Bandason Elizabeth , Chen Mengli , Yan Ru , Feng Bo , Smith Leticia B. , Scott Jeffrey G. , Takamatsu Genki , Ihara Makoto , Matsuda Kazuhiko , Klimavicz James , Coats Joel , Oliveira Eugenio E. , Du Yuzhe , Dong Ke 
Published: May 2021

AbstractPyrethrum extracts from flower heads of Chrysanthemum spp. have been used worldwide in insecticides and repellents. While the molecular mechanisms of its insecticidal action are known, the molecular basis of pyrethrum repellency remains a mystery. In this study, we find that the principal components of pyrethrum, pyrethrins, and a minor component, (E)-β-farnesene (EBF), each activate a specific type of olfactory receptor neurons in Aedes aegypti mosquitoes. We identify Ae. aegypti odorant receptor 31 (AaOr31) as a cognate Or for EBF and find that Or31-mediated repellency is significantly synergized by pyrethrin-induced activation of voltage-gated sodium channels. Thus, pyrethrum exerts spatial repellency through a novel, dual-target mechanism. Elucidation of this two-target mechanism may have potential implications in the design and development of a new generation of synthetic repellents against major mosquito vectors of infectious diseases.
PONDx: real-life utilization and decision impact of the 21-gene assay on clinical practice in Italy
Authors: Cognetti Francesco , Masetti Riccardo , Fabi Alessandra , Bianchi Giulia , Santini Donatella , Rognone Alessia , Catania Giovanna , Angelucci Domenico , Naso Giuseppe , Giuliano Mario , Vassalli Lucia , Vici Patrizia , Scognamiglio Giovanni , Generali Daniele , Zambelli Alberto , Colleoni Marco , Tinterri Corrado , Scanzi Francesco , Vigna Leonardo , Scavina Paola , Gamucci Teresa , Marrazzo Emilia , Scinto Angelo Fedele , Berardi Rossana , Fabbri Maria Agnese , Pinotti Graziella , Franco Daniela , Terribile Daniela Andreina , Tonini Giuseppe , Cianniello Daniela , Barni Sandro 
Published: May 2021

AbstractClinicopathological prognostic features have limited value to identify with precision newly diagnosed patients with hormone receptor (HR)-positive, HER2-negative breast cancer (BC), who would benefit from chemotherapy (CT) in addition to adjuvant hormonal therapy (HT). The 21-gene Oncotype DX Breast Recurrence Score® (RS) assay has been demonstrated to predict CT benefit, hence supporting personalized decisions on adjuvant CT. The multicenter, prospective, observational study PONDx investigated the real-life use of RS® results in Italy and its impact on treatment decisions. Physicians’ treatment recommendations (HT ± CT) were documented before and after availability of RS results, and changes in recommendations were determined. In the HR+ HER2− early BC population studied (N = 1738), physicians recommended CT + HT in 49% of patients pre-RS. RS-guided treatment decisions resulted in 36% reduction of CT recommendations. PONDx confirms that RS results provide clinically relevant information for CT recommendation in early-stage BC, resulting in a reduction of more than a third of CT use.
Modeling poliovirus replication dynamics from live time-lapse single-cell imaging data
Authors: Teufel Ashley I. , Liu Wu , Draghi Jeremy A. , Cameron Craig E. , Wilke Claus O. 
Published: May 2021

AbstractViruses experience selective pressure on the timing and order of events during infection to maximize the number of viable offspring they produce. Additionally, they may experience variability in cellular environments encountered, as individual eukaryotic cells can display variation in gene expression among cells. This leads to a dynamic phenotypic landscape that viruses must face to replicate. To examine replication dynamics displayed by viruses faced with this variable landscape, we have developed a method for fitting a stochastic mechanistic model of viral infection to time-lapse imaging data from high-throughput single-cell poliovirus infection experiments. The model’s mechanistic parameters provide estimates of several aspects associated with the virus’s intracellular dynamics. We examine distributions of parameter estimates and assess their variability to gain insight into the root causes of variability in viral growth dynamics. We also fit our model to experiments performed under various drug treatments and examine which parameters differ under these conditions. We find that parameters associated with translation and early stage viral replication processes are essential for the model to capture experimentally observed dynamics. In aggregate, our results suggest that differences in viral growth data generated under different treatments can largely be captured by steps that occur early in the replication process.
Elliptically polarized high-harmonic radiation for production of isolated attosecond pulses
Authors: Bengs Ulrich , Zhavoronkov Nickolai 
Published: May 2021

AbstractCircularly polarized attosecond pulses are powerful tool to study chiral light-matter interaction via chiral electron dynamics. However, access to isolated circularly polarized attosecond pulses enabling straightforward interpretation of measurements, still remains a challenge. In this work, we experimentally demonstrate the generation of highly elliptically polarized high-harmonics in a two-color, bi-circular, collinear laser field. The intensity and shape of the combined few-cycle driving radiation is optimized to produce a broadband continuum with enhanced spectral chirality in the range of 15-55 eV supporting the generation of isolated attosecond pulses with duration down to 150 as. We apply spectrally resolved polarimetry to determine the full Stokes vector of different spectral components of the continuum, yielding a homogenous helicity distribution with ellipticity in the range of 0.8-0.95 and a negligible unpolarized content.