bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-4-dependent Jagged1 expression/processing is associated with survival of chronic lymphocytic leukemia cells but not with Notch activation
Authors: De Falco Filomena , Del Papa Beatrice , Baldoni Stefano , Sabatini Rita , Falzetti Franca , Di Ianni Mauro , Martelli Maria Paola , Mezzasoma Federica , Pelullo Maria , Marconi Pierfrancesco , Sportoletti Paolo , Screpanti Isabella , Rosati Emanuela 
Published: November 2018

AbstractAs previously reported, chronic lymphocytic leukemia (CLL) cells show constitutive Notch1/2 activation and express the Notchligand Jagged1. Despite increasing knowledge of the impact of Notch alterations on CLL biology and pathogenesis, the role of Jagged1 expressed in CLL cells remains undefined. In other cell types, it has been shown that after Notch engagement, Jagged1 not only activates Notch in signal-receiving cell, but also undergoes proteolytic activation in signal-sending cell, triggering a signaling with biological effects. We investigated whether Jagged1 expressed in CLL cells undergoes proteolytic processing and/or is able to induce Notch activation through autocrine/paracrine loops, focusing on the effect that CLL prosurvival factor IL-4 could exert on the Notch-Jagged1 system in these cells. We found that Jagged1 was constitutively processed in CLL cells and generated an intracellular fragment that translocated into the nucleus, and an extracellular fragment released into the culture supernatant. IL-4 enhanced expression of Jagged1 and its intracellular fragments, as well as Notch1/2 activation. The IL-4-induced increase in Notch1/2 activation was independent of the concomitant upregulated Jagged1 levels. Indeed, blocking Notch-Jagged1 interactions among CLL cells with Jagged1 neutralizing antibodies did not affect the expression of the Notch target Hes1. Notably, anti-Jagged1 antibodies partially prevented the IL-4-induced increase in Jagged1 processing and cell viability, suggesting that Jagged1 processing is one of the events contributing to IL-4-induced CLL cell survival. Consistent with this, Jagged1 silencing by small interfering RNA partially counteracted the capacity of IL-4 to promote CLL cell survival. Investigating the pathways whereby IL-4 promoted Notch1/2 activation in CLL cells independent of Jagged1, we found that PI3Kδ/AKT and PKCδ were involved in upregulating Notch1 and Notch2 proteins, respectively. Overall, this study provides new insights into the Notch-ligand system in CLL cells and suggests that targeting this system may be exploited as a novel/additional therapy approach for CLL.
Three-dimensional in vitro modeling of malignant bone disease recapitulates experimentally accessible mechanisms of osteoinhibition
Authors: McNeill Eoin P. , Reese Robert W. , Tondon Abishek , Clough Bret H. , Pan Simin , Froese Jeremiah , Palmer Daniel , Krause Ulf , Loeb David M. , Kaunas Roland , Gregory Carl A. 
Published: November 2018

AbstractMalignant bone disease (MBD) occurs when tumors establish in bone, causing catastrophic tissue damage as a result of accelerated bone destruction and inhibition of repair. The resultant so-called osteolytic lesions (OL) take the form of tumor-filled cavities in bone that cause pain, fractures, and associated morbidity. Furthermore, the OL microenvironment can support survival of tumor cells and resistance to chemotherapy. Therefore, a deeper understanding of OL formation and MBD progression is imperative for the development of future therapeutic strategies. Herein, we describe a novel in vitro platform to study bone–tumor interactions based on three-dimensional co-culture of osteogenically enhanced human mesenchymal stem cells (OEhMSCs) in a rotating wall vessel bioreactor (RWV) while attached to micro-carrier beads coated with extracellular matrix (ECM) composed of factors found in anabolic bone tissue. Osteoinhibition was recapitulated in this model by co-culturing the OEhMSCs with a bone–tumor cell line (MOSJ-Dkk1) that secretes the canonical Wnt (cWnt) inhibitor Dkk-1, a tumor-borne osteoinhibitory factor widely associated with several forms of MBD, or intact tumor fragments from Dkk-1 positive patient-derived xenografts (PDX). Using the model, we observed that depending on the conditions of growth, tumor cells can biochemically inhibit osteogenesis by disrupting cWnt activity in OEhMSCs, while simultaneously co-engrafting with OEhMSCs, displacing them from the niche, perturbing their activity, and promoting cell death. In the absence of detectable co-engraftment with OEhMSCs, Dkk-1 positive PDX fragments had the capacity to enhance OEhMSC proliferation while inhibiting their osteogenic differentiation. The model described has the capacity to provide new and quantifiable insights into the multiple pathological mechanisms of MBD that are not readily measured using monolayer culture or animal models.
Sex separation induces differences in the olfactory sensory receptor repertoires of male and female mice
Authors: van der Linden Carl , Jakob Susanne , Gupta Pooja , Dulac Catherine , Santoro Stephen W. 
Published: November 2018

AbstractWithin the mammalian olfactory sensory epithelium, experience-dependent changes in the rate of neuronal turnover can alter the relative abundance of neurons expressing specific chemoreceptors. Here we investigate how the mouse olfactory sensory receptor repertoire changes as a function of exposure to odors emitted from members of the opposite sex, which are highly complex and sexually dimorphic. Upon housing mice either sex-separated or sex-combined until six months of age, we find that sex-separated mice exhibit significantly more numerous differentially expressed genes within their olfactory epithelia. A subset of these chemoreceptors exhibit altered expression frequencies following both sex-separation and olfactory deprivation. We show that several of these receptors detect either male- or female-specific odors. We conclude that the distinct odor experiences of sex-separated male and female mice induce sex-specific differences in the abundance of neurons that detect sexually dimorphic odors.
Immediate neurophysiological effects of transcranial electrical stimulation
Authors: Liu Anli , Vöröslakos Mihály , Kronberg Greg , Henin Simon , Krause Matthew R. , Huang Yu , Opitz Alexander , Mehta Ashesh , Pack Christopher C. , Krekelberg Bart , Berényi Antal , Parra Lucas C. , Melloni Lucia , Devinsky Orrin , Buzsáki György 
Published: November 2018

AbstractNoninvasive brain stimulation techniques are used in experimental and clinical fields for their potential effects on brain network dynamics and behavior. Transcranial electrical stimulation (TES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), has gained popularity because of its convenience and potential as a chronic therapy. However, a mechanistic understanding of TES has lagged behind its widespread adoption. Here, we review data and modelling on the immediate neurophysiological effects of TES in vitro as well as in vivo in both humans and other animals. While it remains unclear how typical TES protocols affect neural activity, we propose that validated models of current flow should inform study design and artifacts should be carefully excluded during signal recording and analysis. Potential indirect effects of TES (e.g., peripheral stimulation) should be investigated in more detail and further explored in experimental designs. We also consider how novel technologies may stimulate the next generation of TES experiments and devices, thus enhancing validity, specificity, and reproducibility.
Magnetic reconnection driven by electron dynamics
Authors: Kuramitsu Y. , Moritaka T. , Sakawa Y. , Morita T. , Sano T. , Koenig M. , Gregory C. D. , Woolsey N. , Tomita K. , Takabe H. , Liu Y. L. , Chen S. H. , Matsukiyo S. , Hoshino M. 
Published: November 2018

AbstractMagnetic reconnections play essential roles in space, astrophysical, and laboratory plasmas, where the anti-parallel magnetic field components re-connect and the magnetic energy is converted to the plasma energy as Alfvénic out flows. Although the electron dynamics is considered to be essential, it is highly challenging to observe electron scale reconnections. Here we show the experimental results on an electron scale reconnection driven by the electron dynamics in laser-produced plasmas. We apply a weak-external magnetic field in the direction perpendicular to the plasma propagation, where the magnetic field is directly coupled with only the electrons but not for the ions. Since the kinetic pressure of plasma is much larger than the magnetic pressure, the magnetic field is distorted and locally anti-parallel. We observe plasma collimations, cusp and plasmoid like features with optical diagnostics. The plasmoid propagates at the electron Alfvén velocity, indicating a reconnection driven by the electron dynamics.
Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6+ cancer cell and macrophage polarization
Authors: Choi Seo-Hyun , Kim A-Ram , Nam Jae-Kyung , Kim Jin-Mo , Kim Jee-Youn , Seo Haeng Ran , Lee Hae-June , Cho Jaeho , Lee Yoon-Jin 
Published: November 2018

AbstractIt remains controversial whether targeting tumour vasculature can improve radiotherapeutic efficacy. We report that radiation-induced endothelial-to-mesenchymal transition (EndMT) leads to tumour vasculature with abnormal SMA+NG2+ pericyte recruitment during tumour regrowth after radiotherapy. Trp53 (but not Tgfbr2) deletion in endothelial cells (ECs) inhibited radiation-induced EndMT, reducing tumour regrowth and metastases with a high CD44v6+ cancer-stem-cell (CSC) content after radiotherapy. Osteopontin, an EndMT-related angiocrine factor suppressed by EC-Trp53 deletion, stimulated proliferation in dormant CD44v6+ cells in severely hypoxic regions after radiation. Radiation-induced EndMT significantly regulated tumour-associated macrophage (TAM) polarization. CXCR4 upregulation in radioresistant tumour ECs was highly associated with SDF-1+ TAM recruitment and M2 polarization of TAMs, which was suppressed by Trp53 deletion. These EndMT-related phenomena were also observed in irradiated human lung cancer tissues. Our findings suggest that targeting tumour EndMT might enhance radiotherapy efficacy by inhibiting the re-activation of dormant hypoxic CSCs and promoting anti-tumour immune responses.
Robo signalling controls pancreatic progenitor identity by regulating Tead transcription factors
Authors: Escot Sophie , Willnow David , Naumann Heike , Di Francescantonio Silvia , Spagnoli Francesca M. 
Published: November 2018

AbstractA complex interplay of intrinsic factors and extrinsic signalling pathways controls both cell lineage commitment and maintenance of cell identity. Loss of defined cellular states is the cause of many different cancers, including pancreatic cancer. Recent findings suggest a clinical role for the conserved SLIT/ROBO signalling pathway in pancreatic cancer. However, whilst this pathway has been extensively studied in many processes, a role for Slit and Robo genes in pancreas cell identity and plasticity has not been established yet. Here, we identify Slit/Robo signalling as a key regulator of pancreatic progenitor identity. We find that Robo1 and Robo2 are required for preserving pancreatic cell identity shortly after fate induction and, subsequently, for expansion of the pancreatic progenitor pool in the mouse. Furthermore, we show that Robo receptors control the expression of Tead transcription factors as well as its downstream transcriptional activity. Our work identifies an interplay between Slit/Robo pathway and Tead intrinsic regulators, functioning as gatekeeper of pancreatic cell identity.
Fast kinetics of multivalent intercalation chemistry enabled by solvated magnesium-ions into self-established metallic layered materials
Authors: Li Zhenyou , Mu Xiaoke , Zhao-Karger Zhirong , Diemant Thomas , Behm R. Jürgen , Kübel Christian , Fichtner Maximilian 
Published: November 2018

AbstractRechargeable magnesium batteries are one of the most promising candidates for next-generation battery technologies. Despite recent significant progress in the development of efficient electrolytes, an on-going challenge for realization of rechargeable magnesium batteries remains to overcome the sluggish kinetics caused by the strong interaction between double charged magnesium-ions and the intercalation host. Herein, we report that a magnesium battery chemistry with fast intercalation kinetics in the layered molybdenum disulfide structures can be enabled by using solvated magnesium-ions ([Mg(DME)x]2+). Our study demonstrates that the high charge density of magnesium-ion may be mitigated through dimethoxyethane solvation, which avoids the sluggish desolvation process at the cathode-electrolyte interfaces and reduces the trapping force of the cathode lattice to the cations, facilitating magnesium-ion diffusion. The concept of using solvation effect could be a general and effective route to tackle the sluggish intercalation kinetics of magnesium-ions, which can potentially be extended to other host structures.
Contactless steam generation and superheating under one sun illumination
Authors: Cooper Thomas A. , Zandavi Seyed H. , Ni George W. , Tsurimaki Yoichiro , Huang Yi , Boriskina Svetlana V. , Chen Gang 
Published: November 2018

AbstractSteam generation using solar energy provides the basis for many sustainable desalination, sanitization, and process heating technologies. Recently, interest has arisen for low-cost floating structures that absorb solar radiation and transfer energy to water via thermal conduction, driving evaporation. However, contact between water and the structure leads to fouling and pins the vapour temperature near the boiling point. Here we demonstrate solar-driven evaporation using a structure not in contact with water. The structure absorbs solar radiation and re-radiates infrared photons, which are directly absorbed by the water within a sub-100 μm penetration depth. Due to the physical separation from the water, fouling is entirely avoided. Due to the thermal separation, the structure is no longer pinned at the boiling point, and is used to superheat the generated steam. We generate steam with temperatures up to 133 °C, demonstrating superheated steam in a non-pressurized system under one sun illumination.
ROBO2 is a stroma suppressor gene in the pancreas and acts via TGF-β signalling
Authors: Pinho Andreia V. , Van Bulck Mathias , Chantrill Lorraine , Arshi Mehreen , Sklyarova Tatyana , Herrmann David , Vennin Claire , Gallego-Ortega David , Mawson Amanda , Giry-Laterriere Marc , Magenau Astrid , Leuckx Gunther , Baeyens Luc , Gill Anthony J. , Phillips Phoebe , Timpson Paul , Biankin Andrew V. , Wu Jianmin , Rooman Ilse 
Published: November 2018

AbstractWhereas genomic aberrations in the SLIT-ROBO pathway are frequent in pancreatic ductal adenocarcinoma (PDAC), their function in the pancreas is unclear. Here we report that in pancreatitis and PDAC mouse models, epithelial Robo2 expression is lost while Robo1 expression becomes most prominent in the stroma. Cell cultures of mice with loss of epithelial Robo2 (Pdx1Cre;Robo2F/F) show increased activation of Robo1+ myofibroblasts and induction of TGF-β and Wnt pathways. During pancreatitis, Pdx1Cre;Robo2F/F mice present enhanced myofibroblast activation, collagen crosslinking, T-cell infiltration and tumorigenic immune markers. The TGF-β inhibitor galunisertib suppresses these effects. In PDAC patients, ROBO2 expression is overall low while ROBO1 is variably expressed in epithelium and high in stroma. ROBO2low;ROBO1high patients present the poorest survival. In conclusion, Robo2 acts non-autonomously as a stroma suppressor gene by restraining myofibroblast activation and T-cell infiltration. ROBO1/2 expression in PDAC patients may guide therapy with TGF-β inhibitors or other stroma /immune modulating agents.
Tumour-elicited neutrophils engage mitochondrial metabolism to circumvent nutrient limitations and maintain immune suppression
Authors: Rice Christopher M. , Davies Luke C. , Subleski Jeff J. , Maio Nunziata , Gonzalez-Cotto Marieli , Andrews Caroline , Patel Nimit L. , Palmieri Erika M. , Weiss Jonathan M. , Lee Jung-Min , Annunziata Christina M. , Rouault Tracey A. , Durum Scott K. , McVicar Daniel W. 
Published: November 2018

AbstractNeutrophils are a vital component of immune protection, yet in cancer they may promote tumour progression, partly by generating reactive oxygen species (ROS) that disrupts lymphocyte functions. Metabolically, neutrophils are often discounted as purely glycolytic. Here we show that immature, c-Kit+ neutrophils subsets can engage in oxidative mitochondrial metabolism. With limited glucose supply, oxidative neutrophils use mitochondrial fatty acid oxidation to support NADPH oxidase-dependent ROS production. In 4T1 tumour-bearing mice, mitochondrial fitness is enhanced in splenic neutrophils and is driven by c-Kit signalling. Concordantly, tumour-elicited oxidative neutrophils are able to maintain ROS production and T cell suppression when glucose utilisation is restricted. Consistent with these findings, peripheral blood neutrophils from patients with cancer also display increased immaturity, mitochondrial content and oxidative phosphorylation. Together, our data suggest that the glucose-restricted tumour microenvironment induces metabolically adapted, oxidative neutrophils to maintain local immune suppression.
Opposite macroevolutionary responses to environmental changes in grasses and insects during the Neogene grassland expansion
Authors: Kergoat Gael J. , Condamine Fabien L. , Toussaint Emmanuel F. A. , Capdevielle-Dulac Claire , Clamens Anne-Laure , Barbut Jérôme , Goldstein Paul Z. , Le Ru Bruno 
Published: November 2018

AbstractThe rise of Neogene C4 grasslands is one of the most drastic changes recently experienced by the biosphere. A central - and widely debated - hypothesis posits that Neogene grasslands acted as a major adaptive zone for herbivore lineages. We test this hypothesis with a novel model system, the Sesamiina stemborer moths and their associated host-grasses. Using a comparative phylogenetic framework integrating paleoenvironmental proxies we recover a negative correlation between the evolutionary trajectories of insects and plants. Our results show that paleoenvironmental changes generated opposing macroevolutionary dynamics in this insect-plant system and call into question the role of grasslands as a universal adaptive cradle. This study illustrates the importance of implementing environmental proxies in diversification analyses to disentangle the relative impacts of biotic and abiotic drivers of macroevolutionary dynamics.
Raman fingerprint of two terahertz spin wave branches in a two-dimensional honeycomb Ising ferromagnet
Authors: Jin Wencan , Kim Hyun Ho , Ye Zhipeng , Li Siwen , Rezaie Pouyan , Diaz Fabian , Siddiq Saad , Wauer Eric , Yang Bowen , Li Chenghe , Tian Shangjie , Sun Kai , Lei Hechang , Tsen Adam W. , Zhao Liuyan , He Rui 
Published: November 2018

AbstractTwo-dimensional (2D) magnetism has been long sought-after and only very recently realized in atomic crystals of magnetic van der Waals materials. So far, a comprehensive understanding of the magnetic excitations in such 2D magnets remains missing. Here we report polarized micro-Raman spectroscopy studies on a 2D honeycomb ferromagnet CrI3. We show the definitive evidence of two sets of zero-momentum spin waves at frequencies of 2.28 terahertz (THz) and 3.75 THz, respectively, that are three orders of magnitude higher than those of conventional ferromagnets. By tracking the thickness dependence of both spin waves, we reveal that both are surface spin waves with lifetimes an order of magnitude longer than their temporal periods. Our results of two branches of high-frequency, long-lived surface spin waves in 2D CrI3 demonstrate intriguing spin dynamics and intricate interplay with fluctuations in the 2D limit, thus opening up opportunities for ultrafast spintronics incorporating 2D magnets.
Plasma redox imbalance caused by albumin oxidation promotes lung-predominant NETosis and pulmonary cancer metastasis
Authors: Inoue Minoru , Nakashima Ryota , Enomoto Masahiro , Koike Yuhki , Zhao Xiao , Yip Kenneth , Huang Shao Hui , Waldron John N. , Ikura Mitsuhiko , Liu Fei-Fei , Bratman Scott V. 
Published: November 2018

AbstractNeutrophil extracellular traps (NETs) promote cancer metastasis in preclinical models following massive exogenous inflammatory stimuli. It remains unknown whether cancer hosts under physiologic conditions experience NETosis and consequent metastasis. Here we show that plasma redox imbalance caused by albumin oxidation promotes inflammation-independent NETosis. Albumin is the major source of free thiol that maintains redox balance. Oxidation of albumin-derived free thiol is sufficient to trigger NETosis via accumulation of reactive oxygen species within neutrophils. The resultant NETs are found predominantly within lungs where they contribute to the colonization of circulating tumor cells leading to pulmonary metastases. These effects are abrogated by pharmacologic inhibition of NET formation. Moreover, albumin oxidation is associated with pulmonary metastasis in a cohort of head and neck cancer patients. These results implicate plasma redox balance as an endogenous and physiologic regulator of NETosis and pulmonary cancer metastasis, providing new therapeutic and diagnostic opportunities for combatting cancer progression.
Z-ring membrane anchors associate with cell wall synthases to initiate bacterial cell division
Authors: Pazos Manuel , Peters Katharina , Casanova Mercedes , Palacios Pilar , VanNieuwenhze Michael , Breukink Eefjan , Vicente Miguel , Vollmer Waldemar 
Published: November 2018

AbstractDuring the transition from elongation to septation, Escherichia coli establishes a ring-like peptidoglycan growth zone at the future division site. This preseptal peptidoglycan synthesis does not require the cell division-specific peptidoglycan transpeptidase PBP3 or most of the other cell division proteins, but it does require FtsZ, its membrane-anchor ZipA and at least one of the bi-functional transglycosylase-transpeptidases, PBP1A or PBP1B. Here we show that PBP1A and PBP1B interact with ZipA and localise to preseptal sites in cells with inhibited PBP3. ZipA stimulates the glycosyltransferase activity of PBP1A. The membrane-anchored cell division protein FtsN localises at preseptal sites and stimulates both activities of PBP1B. Genes zipA and ftsN can be individually deleted in ftsA* mutant cells, but the simultaneous depletion of both proteins is lethal and cells do not establish preseptal sites. Our data support a model according to which ZipA and FtsN-FtsA have semi-redundant roles in connecting the cytosolic FtsZ ring with the membrane-anchored peptidoglycan synthases during the preseptal phase of envelope growth.