bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seattle’s minimum wage ordinance did not affect supermarket food prices by food processing category
Authors: Spoden Amanda L , Buszkiewicz James H , Drewnowski Adam , Long Mark C , Otten Jennifer J 
Published: February 2018

AbstractObjectiveTo examine the impacts of Seattle’s minimum wage ordinance on food prices by food processing category.DesignSupermarket food prices were collected for 106 items using a University of Washington Center for Public Health Nutrition market basket at affected and unaffected supermarket chain stores at three times: March 2015 (1-month pre-policy enactment), May 2015 (1-month post-policy enactment) and May 2016 (1-year post-policy enactment). Food items were categorized into four food processing groups, from minimally to ultra-processed. Data were analysed across time using a multilevel, linear difference-in-differences model at the store and price level stratified by level of food processing.SettingSix large supermarket chain stores located in Seattle (‘intervention’) affected by the policy and six same-chain but unaffected stores in King County (‘control’), Washington, USA.SubjectsOne hundred and six food and beverage items.ResultsThe largest change in average price by food item was +$US 0·53 for ‘processed foods’ in King County between 1-month post-policy and 1-year post-policy enactment (P < 0·01). The smallest change was $US 0·00 for ‘unprocessed or minimally processed foods’ in Seattle between 1-month post-policy and 1-year post-policy enactment (P = 0·94). No significant changes in averaged chain prices were observed across food processing level strata in Seattle v. King County stores at 1-month or 1-year post-policy enactment.ConclusionsSupermarket food prices do not appear to be differentially impacted by Seattle’s minimum wage ordinance by level of the food’s processing. These results suggest that the early implementation of a city-level minimum wage policy does not alter supermarket food prices by level of food processing.
Real-time Bayesian non-parametric prediction of solvency risk
Authors: Hong Liang , Martin Ryan 
Published: February 2018

AbstractInsurance regulation often dictates that insurers monitor their solvency risk in real time and take appropriate actions whenever the risk exceeds their tolerance level. Bayesian methods are appealing for prediction problems thanks to their ability to naturally incorporate both sample variability and parameter uncertainty into a predictive distribution. However, handling data arriving in real time requires a flexible non-parametric model, and the Monte Carlo methods necessary to evaluate the predictive distribution in such cases are not recursive and can be too expensive to rerun each time new data arrives. In this paper, we apply a recently developed alternative perspective on Bayesian prediction based on copulas. This approach facilitates recursive Bayesian prediction without computing a posterior, allowing insurers to perform real-time updating of risk measures to assess solvency risk, and providing them with a tool for carrying out dynamic risk management strategies in today’s “big data” era.
ETV2 mediates endothelial transdifferentiation of glioblastoma
Authors: Zhao Chengjian , Gomez Gustavo A. , Zhao Yuwei , Yang Yu , Cao Dan , Lu Jing , Yang Hanshuo , Lin Shuo 
Published: February 2018

AbstractGlioblastoma multiforme (GBM) is characterized by extensive endothelial hyperplasia. Recent studies suggest that a subpopulation of endothelial cells originates via vasculogenesis by the transdifferentiation of GBM tumor cells into endothelial cells (endo-transdifferentiation). The molecular mechanism underlying this process remains poorly defined. Here, we show that the expression of ETS variant 2 (ETV2), a master regulator of endothelial cell development, is highly correlated with malignancy. Functional studies demonstrate that ETV2 is sufficient and necessary for the transdifferentiation of a subpopulation of CD133+/Nestin+ GBM/neural stem cells to an endothelial lineage. Combinational studies of ChIP-Seq with gain-of-function RNA-Seq data sets suggest that ETV2, in addition to activating vascular genes, represses proneural genes to direct endo-transdifferentiation. Since endo-transdifferentiation by ETV2 is VEGF-A independent, it likely accounts for the observed resistance of GBM tumor cells to anti-angiogenesis therapy. Further characterization of the regulatory networks mediated by ETV2 in endo-transdifferentiation of GBM tumor cells should lead to the identification of more effective therapeutic targets for GBM.
Regulation of senescence escape by the cdk4–EZH2–AP2M1 pathway in response to chemotherapy
Authors: Le Duff Mélanie , Gouju Julien , Jonchère Barbara , Guillon Jordan , Toutain Bertrand , Boissard Alice , Henry Cécile , Guette Catherine , Lelièvre Eric , Coqueret Olivier 
Published: February 2018

AbstractSenescence is a tumor suppressive mechanism that induces a permanent proliferative arrest in response to an oncogenic insult or to the genotoxic stress induced by chemotherapy. We have recently described that some cells can escape this arrest, either because senescence was incomplete or as a consequence of a phenotypic adaptation. Malignant cells which resisted senescence emerged as more transformed cells that resist anoikis and rely on survival pathways activated by Akt and Mcl-1. In this study, we further characterize senescence escape, investigating how emergent cells could reproliferate. During the initial step of chemotherapy-induced senescence (CIS), we found that cyclin D1 was upregulated and that cell emergence was prevented when its main partner cdk4 was inactivated. Results indicate that this kinase induced the upregulation of the EZH2 methylase, a component of the polycomb PRC2 complex. Downregulated during the early step of treatment, the methylase was reactivated in clones that escaped senescence. The inactivation of EZH2, either by siRNA or by specific inhibitors, led to a specific inhibition of cell emergence. We used quantitative proteomic analysis to identify new targets of the methylase involved in senescence escape. We identified proteins involved in receptor endocytosis and described new functions for the AP2M1 protein in the control of chemotherapy-mediated senescence. Our results indicate that AP2M1 is involved in the transmission of secreted signals produced by senescent cells, suggesting that this pathway might regulate specific receptors involved in the control of CIS escape. In light of these results, we therefore propose that the cdk4–EZH2–AP2M1 pathway plays an important role during chemotherapy resistance and senescence escape. Since targeted therapies are available against these proteins, we propose that they should be tested in the treatment of colorectal or breast cancers that become resistant to first-line genotoxic therapies.
Sphingolipid de novo biosynthesis is essential for intestine cell survival and barrier function
Authors: Li Zhiqiang , Kabir Inamul , Tietelman Gladys , Huan Chongmin , Fan Jianglin , Worgall Tilla , Jiang Xian-Cheng 
Published: February 2018

AbstractSerine palmitoyltransferase (SPT) is the rate-limiting enzyme for sphingolipid biosynthesis. SPT has two major subunits, SPTLC1 and SPTLC2. We previously found that liver Sptlc2 deficiency in early life impairs the development of adherens junctions. Here, we investigated the role of Sptlc2 deficiency in intestine. We treated Sptlc2-Flox/villin-Cre-ERT2 mice with tamoxifen (days 1, 2, and 3) to ablate Sptlc2 specifically in the intestine. At day 6 after tamoxifen treatment, Sptlc2-deficient mice had significantly decreased body weight with concurrent diarrhea and rectal bleeding. The number of goblet cells was reduced in both large and small intestine of Sptlc2-deficient mice compared with controls. Sptlc2 deficiency suppressed the level of mucin2 in the colon and increased circulating lipopolysaccharides, suggesting that SPT activity has a housekeeping function in the intestine. All Sptlc2-deficient mice died 7–10 days after tamoxifen treatment. Notably, supplementation with antibiotics and dexamethasone reduced lethality by 70%. We also found that colon specimens from patients with inflammatory bowel diseases had significantly reduced Sptlc2 expression, SPTLC2 staining, and goblet cell numbers. SPT activity is crucial for intestinal cell survival and barrier function.
Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling
Authors: Zhao Hong-Jin , Klausen Christian , Li Yan , Zhu Hua , Wang Yan-Ling , Leung Peter C. K. 
Published: February 2018

AbstractBMP2 expression is spatiotemporally correlated with embryo implantation and is crucial for endometrial decidualization and fertility in mice. BMP2 has been reported to increase the mesenchymal adhesion molecule N-cadherin and enhance cell invasion in cancer cells; moreover, studies suggest that N-cadherin promotes placental trophoblast invasion. However, whether BMP2 can promote trophoblast cell invasion during placentation remains unknown. The objective of our study was to investigate the effects of BMP2 on human trophoblast cell invasion and the involvement of N-cadherin and SMAD signaling. Primary and immortalized (HTR8/SVneo) cultures of human extravillous trophoblast (EVT) cells were used as study models. Treatment with recombinant human BMP2 increased HTR8/SVneo cell transwell Matrigel invasion as well as N-cadherin mRNA and protein levels, but had no significant effect on cell proliferation. Likewise, BMP2 treatment enhanced primary human EVT cell invasion and N-cadherin production. Basal and BMP2-induced invasion were attenuated by small interfering RNA-mediated downregulation of N-cadherin in both HTR8/SVneo and primary EVT cells. Intriguingly, BMP2 induced the phosphorylation/activation of both canonical SMAD1/5/8 and non-canonical SMAD2/3 signaling in HTR8/SVneo and primary EVT cells. Knockdown of SMAD2/3 or common SMAD4 totally abolished the effects of BMP2 on N-cadherin upregulation in HTR8/SVneo cells. Upregulation of SMAD2/3 phosphorylation and N-cadherin were totally abolished by type I receptor activin receptor-like kinases 2/3 (ALK2/3) inhibitor DMH1; moreover, knockdown of ALK2 or ALK3 inhibited N-cadherin upregulation. Interestingly, activation of SMAD2/3 and upregulation of N-cadherin were partially attenuated by ALK4/5/7 inhibitor SB431542 or knockdown of ALK4, but not ALK5. Our results show that BMP2 promotes trophoblast cell invasion by upregulating N-cadherin via non-canonical ALK2/3/4-SMAD2/3-SMAD4 signaling.
Multiple molecular mechanisms form a positive feedback loop driving amyloid β42 peptide-induced neurotoxicity via activation of the TRPM2 channel in hippocampal neurons
Authors: Li Xin , Jiang Lin-Hua 
Published: February 2018

AbstractEmerging evidence supports an important role for the ROS-sensitive TRPM2 channel in mediating age-related cognitive impairment in Alzheimer’s disease (AD), particularly neurotoxicity resulting from generation of excessive neurotoxic Aβ peptides. Here we examined the elusive mechanisms by which Aβ42 activates the TRPM2 channel to induce neurotoxicity in mouse hippocampal neurons. Aβ42-induced neurotoxicity was ablated by genetic knockout (TRPM2-KO) and attenuated by inhibition of the TRPM2 channel activity or activation through PARP-1. Aβ42-induced neurotoxicity was also inhibited by treatment with TPEN used as a Zn2+-specific chelator. Cell imaging revealed that Aβ42-induced lysosomal dysfunction, cytosolic Zn2+ increase, mitochondrial Zn2+ accumulation, loss of mitochondrial function, and mitochondrial generation of ROS. These effects were suppressed by TRPM2-KO, inhibition of TRPM2 or PARP-1, or treatment with TPEN. Bafilomycin-induced lysosomal dysfunction also resulted in TRPM2-dependent cytosolic Zn2+ increase, mitochondrial Zn2+ accumulation, and mitochondrial generation of ROS, supporting that lysosomal dysfunction and accompanying Zn2+ release trigger mitochondrial Zn2+ accumulation and generation of ROS. Aβ42-induced effects on lysosomal and mitochondrial functions besides neurotoxicity were also suppressed by inhibition of PKC and NOX. Furthermore, Aβ42-induced neurotoxicity was prevented by inhibition of MEK/ERK. Therefore, our study reveals multiple molecular mechanisms, including PKC/NOX-mediated generation of ROS, activation of MEK/ERK and PARP-1, lysosomal dysfunction and Zn2+ release, mitochondrial Zn2+ accumulation, loss of mitochondrial function, and mitochondrial generation of ROS, are critically engaged in forming a positive feedback loop that drives Aβ42-induced activation of the TRPM2 channel and neurotoxicity in hippocampal neurons. These findings shed novel and mechanistic insights into AD pathogenesis.
PLEKHN1 promotes apoptosis by enhancing Bax-Bak hetro-oligomerization through interaction with Bid in human colon cancer
Authors: Kuriyama Sei , Tsuji Tadahiro , Sakuma Tetsushi , Yamamoto Takashi , Tanaka Masamistu 
Published: February 2018

AbstractThe anti-apoptotic nature of cancer cells often impedes the effects of anti-cancer therapeutic agents. Multiple death signals influence mitochondria during apoptosis, and though many studies have attempted to elucidate these complicated pathways, Bax oligomerization, an important step in the process, remains controversial. Here we demonstrate that pleckstrin-homology N1 (PLEKHN1), also known as cardiolipin phosphatidic acid binding protein, plays pro-apoptotic roles during reactive oxygen species (ROS)–induced apoptosis. Human PLEKHN1 was expressed in several cancer cell lines of differing origin. Its expression was regulated by hypoxia, and it existed in the mitochondrial fraction. Genome editing of hPLEKHN1 in human colon cancer HT-29 cells revealed enhanced survival of knockout cells compared with that of parental cells in vitro and in vivo. Thapsigargin or hydrogen peroxide treatment activated multiple death signals including JNK, Bcl-2 family members, and caspases. PLEKHN1 was bound to Bid, a pro-apoptotic protein, and not to Bax, and PLEKHN1 could remove Bid from transient Bid–Bax complexes. Fluorescent time-lapse imaging revealed that PLEKHN1 aggregated with Bid during thapsigargin- or hydrogen peroxide-induced apoptosis prior to Bax aggregation. Inhibition of PLEKHN1 led to attenuation of Bax-Bak hetero-oligomerization and Bid translocation. The immunohistochemistry of cancer patient specimens showed that PLEKHN1 expression was absent from cancer region at the transition area of normal/cancer tissues. Collectively, the silencing of PLEKHN1 may be the key that cancer cells acquire the drug resistance.
Na+/Ca2+ exchanger 1 on nuclear envelope controls PTEN/Akt pathway via nucleoplasmic Ca2+ regulation during neuronal differentiation
Authors: Secondo Agnese , Esposito Alba , Petrozziello Tiziana , Boscia Francesca , Molinaro Pasquale , Tedeschi Valentina , Pannaccione Anna , Ciccone Roselia , Guida Natascia , Di Renzo Gianfranco , Annunziato Lucio 
Published: February 2018

AbstractNuclear envelope (NE) is a Ca2+-storing organelle controlling neuronal differentiation through nuclear Ca2+ concentrations ([Ca2+]n). However, how [Ca2+]n regulates this important function remains unknown. Here, we investigated the role of the nuclear form of the Na+/Ca2+ exchanger 1(nuNCX1) during the different stages of neuronal differentiation and the involvement of PTEN/PI3’K/Akt pathway. In neuronal cells, nuNCX1 was detected on the inner membrane of the NE where protein expression and activity of the exchanger increased during NGF-induced differentiation. nuNCX1 activation by Na+-free perfusion induced a time-dependent activation of nuclear-resident PI3K/Akt pathway in isolated nuclei. To discriminate the contribution of nuNCX1 from those of plasma membrane NCX, we generated a chimeric protein composed of the fluorophore EYFP, the exchanger inhibitory peptide, and the nuclear localization signal, named XIP-NLS. Fura-2 measurements on single nuclei and patch-clamp experiments in whole-cell configuration showed that XIP-NLS selectively inhibited nuNCX1. Once it reached the nuclear compartment, XIP-NLS increased the nucleoplasmic Ca2+ peak elicited by ATP and reduced Akt phosphorylation, GAP-43 and MAP-2 expression through nuclear-resident PTEN induction. Furthermore, in accordance with the prevention of the neuronal phenotype, XIP-NLS significantly reduced TTX-sensitive Na+ currents and membrane potential during neuronal differentiation. The selective inhibition of nuNCX1 by XIP-NLS increased the percentage of β III tubulin-positive immature neurons in mature cultures of MAP-2-positive cortical neurons, thus unraveling a new function for nuNCX1 in regulating neuronal differentiation through [Ca2+]n-dependent PTEN/PI3K/Akt pathway.
Fluorogenic RNA Mango aptamers for imaging small non-coding RNAs in mammalian cells
Authors: Autour Alexis , C. Y. Jeng Sunny , D. Cawte Adam , Abdolahzadeh Amir , Galli Angela , Panchapakesan Shanker S. S. , Rueda David , Ryckelynck Michael , Unrau Peter J. 
Published: February 2018

AbstractDespite having many key roles in cellular biology, directly imaging biologically important RNAs has been hindered by a lack of fluorescent tools equivalent to the fluorescent proteins available to study cellular proteins. Ideal RNA labelling systems must preserve biological function, have photophysical properties similar to existing fluorescent proteins, and be compatible with established live and fixed cell protein labelling strategies. Here, we report a microfluidics-based selection of three new high-affinity RNA Mango fluorogenic aptamers. Two of these are as bright or brighter than enhanced GFP when bound to TO1-Biotin. Furthermore, we show that the new Mangos can accurately image the subcellular localization of three small non-coding RNAs (5S, U6, and a box C/D scaRNA) in fixed and live mammalian cells. These new aptamers have many potential applications to study RNA function and dynamics both in vitro and in mammalian cells.
A CNOT gate between multiphoton qubits encoded in two cavities
Authors: Rosenblum S. , Gao Y. Y. , Reinhold P. , Wang C. , Axline C. J. , Frunzio L. , Girvin S. M. , Jiang Liang , Mirrahimi M. , Devoret M. H. , Schoelkopf R. J. 
Published: February 2018

AbstractEntangling gates between qubits are a crucial component for performing algorithms in quantum computers. However, any quantum algorithm must ultimately operate on error-protected logical qubits encoded in high-dimensional systems. Typically, logical qubits are encoded in multiple two-level systems, but entangling gates operating on such qubits are highly complex and have not yet been demonstrated. Here we realize a controlled NOT (CNOT) gate between two multiphoton qubits in two microwave cavities. In this approach, we encode a qubit in the high-dimensional space of a single cavity mode, rather than in multiple two-level systems. We couple two such encoded qubits together through a transmon, which is driven by an RF pump to apply the gate within 190 ns. This is two orders of magnitude shorter than the decoherence time of the transmon, enabling a high-fidelity gate operation. These results are an important step towards universal algorithms on error-corrected logical qubits.
Differential patterns of contextual organization of memory in first-episode psychosis
Authors: Murty Vishnu P. , McKinney Rachel A. , DuBrow Sarah , Jalbrzikowski Maria , Haas Gretchen L. , Luna Beatriz 
Published: February 2018

AbstractContextual information is used to support and organize episodic memory. Prior research has reliably shown memory deficits in psychosis; however, little research has characterized how this population uses contextual information during memory recall. We employed an approach founded in a computational framework of free recall to quantify how individuals with first episode of psychosis (FEP, N = 97) and controls (CON, N = 55) use temporal and semantic context to organize memory recall. Free recall was characterized using the Hopkins Verbal Learning Test-Revised (HVLT-R). We compared FEP and CON on three measures of free recall: proportion recalled, temporal clustering, and semantic clustering. Measures of temporal/semantic clustering quantified how individuals use contextual information to organize memory recall. We also assessed to what extent these measures relate to antipsychotic use and differentiated between different types of psychosis. We also explored the relationship between these measures and intelligence. In comparison to CON, FEP had reduced recall and less temporal clustering during free recall (p < 0.05, Bonferroni-corrected), and showed a trend towards greater semantic clustering (p = 0.10, Bonferroni-corrected). Within FEP, antipsychotic use and diagnoses did not differentiate between free recall accuracy or contextual organization of memory. IQ was related to free recall accuracy, but not the use of contextual information during recall in either group (p < 0.05, Bonferroni-corrected). These results show that in addition to deficits in memory recall, FEP differed in how they organize memories compared to CON.
Type 2 Innate Lymphocytes Actuate Immunity Against Tumours and Limit Cancer Metastasis
Authors: Saranchova Iryna , Han Jeffrey , Zaman Rysa , Arora Hitesh , Huang Hui , Fenninger Franz , Choi Kyung Bok , Munro Lonna , Pfeifer Cheryl G. , Welch Ian , Takei Fumio , Jefferies Wilfred A. 
Published: February 2018

AbstractType 2 innate lymphoid cells (ILC2) potentiate immune responses, however, their role in mediating adaptive immunity in cancer has not been assessed. Here, we report that mice genetically lacking ILC2s have significantly increased tumour growth rates and conspicuously higher frequency of circulating tumour cells (CTCs) and resulting metastasis to distal organs. Our data support the model that IL-33 dependent tumour-infiltrating ILC2s are mobilized from the lungs and other tissues through chemoattraction to enter tumours, and subsequently mediate tumour immune-surveillance by cooperating with dendritic cells to promote adaptive cytolytic T cell responses. We conclude that ILC2s play a fundamental, yet hitherto undescribed role in enhancing anti-cancer immunity and controlling tumour metastasis.
Reconstruction of the sialylation pathway in the ancestor of eukaryotes
Authors: Petit Daniel , Teppa Elin , Cenci Ugo , Ball Steven , Harduin-Lepers Anne 
Published: February 2018

AbstractThe biosynthesis of sialylated molecules of crucial relevance for eukaryotic cell life is achieved by sialyltransferases (ST) of the CAZy family GT29. These enzymes are widespread in the Deuterostoma lineages and more rarely described in Protostoma, Viridiplantae and various protist lineages raising the question of their presence in the Last eukaryotes Common Ancestor (LECA). If so, it is expected that the main enzymes associated with sialic acids metabolism are also present in protists. We conducted phylogenomic and protein sequence analyses to gain insights into the origin and ancient evolution of ST and sialic acid pathway in eukaryotes, Bacteria and Archaea. Our study uncovered the unreported occurrence of bacterial GT29 ST and evidenced the existence of 2 ST groups in the LECA, likely originating from the endosymbiotic event that generated mitochondria. Furthermore, distribution of the major actors of the sialic acid pathway in the different eukaryotic phyla indicated that these were already present in the LECA, which could also access to this essential monosaccharide either endogenously or via a sialin/sialidase uptake mechanism involving vesicles. This pathway was lost in several basal eukaryotic lineages including Archaeplastida despite the presence of two different ST groups likely assigned to other functions.