bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ribosomal protein RPL26 is the principal target of UFMylation
Authors: Walczak Christopher P. , Leto Dara E. , Zhang Lichao , Riepe Celeste , Muller Ryan Y. , DaRosa Paul A. , Ingolia Nicholas T. , Elias Joshua E. , Kopito Ron R. 
Published: January 2019

Significance
Ubiquitin fold modifier 1 (UFM1) is a ubiquitin-like posttranslational modifier that is essential for tissue development in metazoans. Genetic ablation of UFM1 or the genes that encode the enzymes that conjugate UFM1 to protein targets causes endoplasmic reticulum (ER) stress, suggesting a role for this modification in ER protein homeostasis. Here, we show that RPL26, a largely uncharacterized ribosomal protein, is the primary cellular target of UFMylation. Ribosomal RPL26 is subject to a dynamic cycle of UFMylation and de-UFMylation, catalyzed by enzymes that are tethered to the cytoplasmic surface of the ER. UFMylated RPL26 and the UFMylation machinery are in close proximity to the SEC61 translocon, suggesting a role for UFMylation in protein biogenesis at the ER.
COmplexome Profiling ALignment (COPAL) reveals remodeling of mitochondrial protein complexes in Barth syndrome
Authors: Van Strien Joeri , Guerrero-Castillo Sergio , Chatzispyrou Iliana A , Houtkooper Riekelt H , Brandt Ulrich , Huynen Martijn A 
Published: January 2019

Abstract

Motivation
Complexome profiling combines native gel electrophoresis with mass spectrometry to obtain the inventory, composition and abundance of multiprotein assemblies in an organelle. Applying complexome profiling to determine the effect of a mutation on protein complexes requires separating technical and biological variations from the variations caused by that mutation.

Results
We have developed the COmplexome Profiling ALignment (COPAL) tool that aligns multiple complexome profiles with each other. It includes the abundance profiles of all proteins on two gels, using a multi-dimensional implementation of the dynamic time warping algorithm to align the gels. Subsequent progressive alignment allows us to align multiple profiles with each other. We tested COPAL on complexome profiles from control mitochondria and from Barth syndrome (BTHS) mitochondria, which have a mutation in tafazzin gene that is involved in remodeling the inner mitochondrial membrane phospholipid cardiolipin. By comparing the variation between BTHS mitochondria and controls with the variation among either, we assessed the effects of BTHS on the abundance profiles of individual proteins. Combining those profiles with gene set enrichment analysis allows detecting significantly affected protein complexes. Most of the significantly affected protein complexes are located in the inner mitochondrial membrane (mitochondrial contact site and cristae organizing system, prohibitins), or are attached to it (the large ribosomal subunit).

Availability and implementation
COPAL is written in python and is available from http://github.com/cmbi/copal.

Supplementary information
Supplementary data are available at Bioinformatics online.
Institutional volume affects long-term survival following lung transplantation in the USA
Authors: Kilic Arman , Gleason Thomas G , Kagawa Hiroshi , Kilic Ahmet , Sultan Ibrahim 
Published: January 2019

AbstractOBJECTIVESThe aim of this study was to evaluate the impact of institutional volume on long-term outcomes following lung transplantation (LTx) in the USA.METHODSAdults undergoing LTx were identified in the United Network for Organ Sharing registry. Patients were divided into equal size tertiles according to the institutional volume. All-cause mortality following LTx was evaluated using the risk-adjusted multivariable Cox regression and the Kaplan–Meier analyses, and compared between these volume cohorts at 3 points: 90 days, 1 year (excluding 90-day deaths) and 10 years (excluding 1-year deaths). Lowess smoothing plots and receiver-operating characteristic analyses were performed to identify optimal volume thresholds associated with long-term survival.RESULTSA total of 13 370 adult LTx recipients were identified. The mean annual centre volume was 33.6 ± 20.1. After risk adjustment, low-volume centres were found to be at increased risk for 90-day mortality, [hazard ratio (HR) 1.56, P < 0.001], 1-year mortality excluding 90-day deaths (HR 1.46, P < 0.001) and 10-year mortality excluding 1-year deaths (HR 1.22, P < 0.001). These findings persisted when the centre volume was modelled as a continuous variable. The Kaplan–Meier analysis also demonstrated significant reductions in survival at each of these time points for low-volume centres (each P < 0.001). The 10-year survival conditional on 1-year survival was 37.4% in high-volume centres vs 28.0% in low-volume centres (P < 0.001). The optimal annual volume threshold for long-term survival was 26 LTx/year.CONCLUSIONSThe institutional volume impacts long-term survival following LTx, even after excluding deaths within the first post-transplant year. Identifying the processes of care that lead to longer survival in high-volume centres is prudent.
Star Wars or Strategic Defense Initiative: What's in a Name?
Authors: Stimmer Anette 
Published: January 2019

Abstract
Popular culture can influence debates over security policy. This article studies the use of Star Wars in the debate over Reagan's Strategic Defense Initiative (SDI). The term Star Wars was widely used to refer to SDI during debates in the 1980s. Scholars have pointed to both disabling and enabling effects of popular culture on political debates. This article refines these effects and introduces a third effect that comes from the widespread use of popular culture: a neutralizing effect that turns popular culture references into descriptive shorthands. Studying these dynamics contributes to our understanding of why popular culture is or is not used as a framing device and how it is used and perceived by decision-makers. I rely on content analysis of newspaper articles, congressional records, and political speeches and incorporate findings from elite interviews and the norm literature to conduct my analysis. I find that critics capitalized on linkages between the movie franchise and the policy to frame Reagan's missile defense system as Star Wars and to criticize his policy proposal. This science-fictionalization soon constituted the sociopolitical context surrounding Reagan's missile defense initiative. Most decision-makers perceived the Star Wars label to have a disabling effect as it cast doubt on the viability and desirability of SDI. Opponents initially tried to mobilize this effect, whereas most proponents argued against the label or refrained from using it. Few tapped into the enabling potential of Star Wars to communicate the potential benefits of SDI. The introduction of the professional term SDI helped proponents mitigate science-fictionalization in expert settings, while among the public the widespread use of the Star Wars label neutralized its meaning and turned it into a descriptive shorthand.
Progenitor constraints on the Type Ia supernova SN 2014J from Hubble Space Telescope H β and [O  iii] observations
Authors: Graur Or , Woods Tyrone E 
Published: January 2019

ABSTRACT
Type Ia supernovae are understood to arise from the thermonuclear explosion of a carbon–oxygen white dwarf, yet the evolutionary mechanisms leading to such events remain unknown. Many proposed channels, including the classical single-degenerate scenario, invoke a hot, luminous evolutionary phase for the progenitor, in which it is a prodigious source of photoionizing emission. Here, we examine the environment of SN 2014J for evidence of a photoionized nebula in pre- and post-explosion [O  iii] λ5007 Å and H β images taken with the Hubble Space Telescope. From the absence of any extended emission, we exclude a stable nuclear-burning white dwarf at the location of SN 2014J in the last ∼100 000 years, assuming a typical warm interstellar medium (ISM) particle density of 1 cm−3. These limits greatly exceed existing X-ray constraints at temperatures typical of known supersoft sources. Significant extreme-UV/soft X-ray emission prior to explosion remains plausible for lower ISM densities (e.g. $n_{\rm ISM}\sim 0.1\,\rm {cm}^{-3}$). In this case, however, any putative nebula would be even more extended, allowing deeper follow-up observations to resolve this ambiguity in the near future.
Introducing RpsA Point Mutation Δ438A or D123A into the Chromosome of M. tuberculosis Confirms its Role in Causing Resistance to Pyrazinamide
Authors: Shi Wanliang , Cui Peng , Niu Hongxia , Zhang Shuo , Tønjum Tone , Zhu Bingdong , Zhang Ying 
Published: January 2019

ABSTRACTPyrazinamide (PZA) is a unique frontiline drug for shortening tuberculosis treatment, but its mechanisms of action are elusive. We previously identified RpsA as a target of PZA and found an alanine deletion at position 438 (Δ438A) in RpsA associated with PZA resistance, but its role in PZA resistance is controversial. Here, we introduced RpsA mutation Δ438A or D123A into M. tuberculosis chromosome and demonstrated that the introduced RspA mutations are indeed responsible for PZA resistance.
Evolutionarily-conserved chromatin crosstalk generates a DOT1L-dose dependency in thymic lymphoma caused by loss of HDAC1
Authors: Vlaming Hanneke , McLean Chelsea M. , Korthout Tessy , Alemdehy Mir Farshid , Hendriks Sjoerd , Lancini Cesare , Palit Sander , Klarenbeek Sjoerd , Kwesi-Maliepaard Eliza Mari , Molenaar Thom M. , Hoekman Liesbeth , Schmidlin Thierry T. , Altelaar A.F. Maarten , van Welsem Tibor , Dannenberg Jan-Hermen , Jacobs Heinz , Leeuwen Fred van 
Published: January 2019

AbstractDOT1L methylates histone H3K79 and is aberrantly regulated in MLL-rearranged leukemia. Inhibitors have been developed to target DOT1L activity in leukemia but the cellular mechanisms that regulate DOT1L are still poorly understood. Here we identify the budding yeast histone deacetylase Rpd3 as a negative regulator of Dot1. At its target genes, the transcriptional repressor Rpd3 restricts H3K79 methylation, explaining the absence of H3K79me3 at a subset of genes in the yeast genome. Similar to the crosstalk in yeast, inactivation of the murine Rpd3 homolog HDAC1 in thymocytes led to an increase in H3K79 methylation. Thymic lymphomas that arise upon genetic deletion of Hdac1 retained the increased H3K79 methylation and were sensitive to reduced DOT1L dosage. Furthermore, cell lines derived from Hdac1Δ/Δ thymic lymphomas were sensitive to DOT1L inhibitor, which induced apoptosis. In summary, we identified an evolutionarily-conserved crosstalk between HDAC1 and DOT1L with impact in murine thymic lymphoma development.
Microhomology-mediated end joining drives complex rearrangements and over-expression of MYC and PVT1 in multiple myeloma
Authors: Mikulasova Aneta , Ashby Cody , Tytarenko Ruslana G. , Qu Pingping , Rosenthal Adam , Dent Judith A. , Ryan Katie R. , Bauer Michael A. , Wardell Christopher P. , Hoering Antje , Mavrommatis Konstantinos , Trotter Matthew , Deshpande Shayu , Yaccoby Shmuel , Tian Erming , Keats Jonathan , Auclair Daniel , Jackson Graham H. , Davies Faith E. , Thakurta Anjan , Morgan Gareth J. , Walker Brian A. 
Published: January 2019

AbstractMYC is a widely acting transcription factor and its deregulation is a crucial event in many human cancers. MYC is important biologically and clinically in multiple myeloma, but the mechanisms underlying its dysregulation are poorly understood. We show that MYC rearrangements are present in 36.0% of newly diagnosed myeloma patients, as detected in the largest set of next generation sequencing data to date (n=1267). Rearrangements were complex and associated with increased expression of MYC and PVT1, but not other genes at 8q24. The highest effect on gene expression was detected in cases where the MYC locus is juxtaposed next to super-enhancers associated with genes such as IGH, IGK, IGL, TXNDC5/BMP6, FAM46C and FOXO3. We identified three hotspots of recombination at 8q24, one of which is enriched for IGH-MYC translocations. Breakpoint analysis indicates primary myeloma rearrangements involving the IGH locus occur through non-homologous end joining, whereas secondary MYC rearrangements occur through microhomology-mediated end joining. This mechanism is different to lymphomas, where non-homologous end joining generates MYC rearrangements. Rearrangements resulted in over-expression of key genes and ChIP-seq identified that HK2, a member of the glucose metabolism pathway, is directly over-expressed through binding of MYC at its promoter.
Microglia motility depends on neuronal activity and promotes structural plasticity in the hippocampus
Authors: Nebeling Felix C. , Poll Stefanie , Schmid Lena C. , Mittag Manuel , Steffen Julia , Keppler Kevin , Fuhrmann Martin 
Published: January 2019

AbstractMicroglia, the resident immune cells of the brain, play a complex role in health and disease. They actively survey the brain parenchyma by physically interacting with other cells and structurally shaping the brain. Yet, the mechanisms underlying microglia motility and their significance for synapse stability, especially during adulthood, remain widely unresolved. Here we investigated the impact of neuronal activity on microglia motility and its implication for synapse formation and survival. We used repetitive two-photon in vivo imaging in the hippocampus of awake mice to simultaneously study microglia motility and their interaction with synapses. We found that microglia process motility depended on neuronal activity. Simultaneously, more dendritic spines emerged in awake compared to anesthetized mice. Interestingly, microglia contact rates with individual dendritic spines were associated with their stability. These results suggest that microglia are not only sensing neuronal activity, but participate in synaptic rewiring of the hippocampus during adulthood, which has profound relevance for learning and memory processes.
Copy number aberrations drive kinase re-wiring leading to genetic vulnerabilities in cancer
Authors: Memon Danish , Gill Michael B. , Papachristou Eva , Ochoa David , D’Santos Clive , Miller Martin L. , Beltrao Pedro 
Published: January 2019

AbstractSomatic DNA copy number variations (CNVs) are prevalent in cancer and can drive cancer progression albeit with often uncharacterized roles in altering cell signaling states. Here, we integrated genomic and proteomic data for 5598 tumor samples to identify CNVs leading to aberrant signal transduction. The resulting associations recapitulated known kinase-substrate relationships and further network analysis prioritized likely driver genes. A total of 44 robust pan-cancer gene-phosphosite associations were replicated in cell line samples. Of these, ARHGEF17, a predicted regulator of hippo-signaling, was further studied through (phospho)proteomics analysis where ARHGEF17 knockdown cells showed dys-regulation of hippo- and p38 signaling as well as immune related pathways. Using, RNAi, CRISPR and drug screening data we find evidence of kinase addiction in cancer cell lines identifying inhibitors for targeting of ‘kinase-dependent’ cell lines. We propose copy number status of genes as useful predictors of differential impact of kinase inhibition, a strategy that may be of use in the future for anticancer therapies.
The population dynamics of a canonical cognitive circuit
Authors: Chaudhuri Rishidev , Gerçek Berk , Pandey Biraj , Peyrache Adrien , Fiete Ila 
Published: January 2019

AbstractThe brain constructs distributed representations of key low-dimensional variables. These variables may be external stimuli or internal constructs of quantities relevant for survival, such as a sense of one’s location in the world. We consider that the high-dimensional population-level activity vectors are the fundamental representational currency of a neural circuit, and these vectors trace out a low-dimensional manifold whose dimension and topology matches those of the represented variable. This manifold perspective — applied to the mammalian head direction circuit across rich waking behaviors and sleep — enables powerful inferences about circuit representation and mechanism, including: Direct visualization and blind discovery that the network represents a one-dimensional circular variable across waking and REM sleep; fully unsupervised decoding of the coded variable; stability and attractor dynamics in the representation; the discovery of new dynamical trajectories during sleep; the limiting role of external rather than internal noise in the fidelity of memory states; and the conclusion that the circuit is set up to integrate velocity inputs according to classical continuous attractor models.
Deletion of a conserved Gata2 enhancer impairs haemogenic endothelium programming and adult haematopoiesis
Authors: Dobrzycki Tomasz , Mahony Christopher B. , Krecsmarik Monika , Koyunlar Cansu , Rispoli Rossella , Peulen-Zink Joke , Gussinklo Kirsten , Fedlaoui Bakhta , de Pater Emma , Patient Roger , Monteiro Rui 
Published: January 2019

AbstractHaematopoietic stem and progenitor cells (HSPCs) maintain the vertebrate blood system throughout life and their emergence from haemogenic endothelium (HE) is regulated by transcription factors such as Gata2. Here we deleted a conserved enhancer (i4 enhancer) driving pan-endothelial expression ofgata2aand showed that Gata2a is required for HE programming by regulating expression ofrunx1and of the second zebrafish Gata2 orthologue,gata2b. By 5 days, homozygousgata2aΔi4/Δi4larvae showed normal numbers of HSPCs, a recovery mediated by Notch signalling drivinggata2bandrunx1expression in HE. However,gata2aΔi4/Δi4adults showed oedema, susceptibility to infections and marrow hypo-cellularity, consistent with bone marrow failure found in GATA2 deficiency syndromes. Thus,gata2aexpression driven by the i4 enhancer is required for HE programming in embryos and maintenance of steady-state haematopoietic stem cell output in the adult. These enhancer mutants are a new paradigm to explore the pathophysiology of GATA2-related deficienciesin vivo.
IMCC: Quantitative Analysis of the Inter-module Connectivity for Bio-network
Authors: Wang Pengqian , Liu Jun , Yu Yanan , Zhang Yingying , Li Bing , Li Dongfeng , Xu Wenjuan , Liu Qiong , Wang Zhong 
Published: January 2019

AbstractInter-module connectivity, which tend to connect different communities and maintain network architectural integrity, is contributing to functional coordination and information flow between modules in perturbations. Detecting the strength of inter-module connection is essential to characterize the reactive bio-systematical variation. A quantitative evaluation method for inter-module connections is needed. Here, based on the high-throughput microarray data from mouse, an evaluation approach (named as IMCC) for inter-module connectivity was developed. The IMCC model, which is an integration of direct and indirect inter-module connections, successfully excluded inter-module connections without statistical significance or below the cutoff value, and provided a more comprehensive landscape of inter-module relationships. We showed that the IMCC method reflected a more precise functional coordination between modules according to KEGG database, were validated by topological parameter. Application of IMCC in genome-scale stroke networks deciphered characteristic pathological “core-periphery” structure of modular map and functional coordination module pair.Author summeryInter-module connectivity, which tend to connect different communities and maintain network architectural integrity, is contributing to functional coordination and information flow between modules in perturbations. Moreover, modular rearrangements provide more efficient ways for phenotype alteration, inter-module connections have been considered to be ‘‘evolutionary interaction switches”. Such modular map rewiring can be used as a network biomarker to characterize the dynamics of drug responses. Detecting the strength of inter-module connection is essential to characterize the reactive bio-systematical variation response to disease or drug. We aim to construct a quantitative evaluation method for inter-module connections. Thus, this study has implications in systematical exploration detailed variation of inter-module pharmacological action mode of drugs.
Drinking earth for wine. Estimation of soil erosion in the Prosecco DOCG area (NE Italy), toward a soil footprint of bottled sparkling wine production
Authors: Pappalardo SE , Gislimberti L , Ferrarese F , Garlato A , Vinci IC , De Marchi M , Mozzi P 
Published: January 2019

AbstractProsecco, one of the most widespread sparkling wine in the world, is produced in Northeast Italy by a rate of 400 M bottles per year, with the fastest growing demand in the global market at present. A production of 90 M bottles year−1 is currently running in the historical Prosecco sector (215 km2), defined as the Controlled and Guaranteed Designation of Origin (DOCG) area, in a steep hilly landscape of Veneto Region (Conegliano-Valdobbiadene) registered in 2017 for the UNESCO World Heritage tentative list. To sustain wine production agricultural intensification boosted to re-setting of hillslopes and land use changes toward new vineyard plantations. The aim of this study is to assess soil erosion rate, calculating a sort of “soil footprint” for wine production by i) estimation of the total soil erosion, ii) identification of the most critical areas, iii) simulation of different nature-based mitigation scenarios. RUSLE model was adopted to estimate soil erosion in Mg ha−1 year−1, using high resolution topographic data (LiDAR), 10 years rainfall data analysis, detailed land use and local soil characteristics.We found that the total soil erosion estimation for the Prosecco DOCG area is 546,263 Mg year−1, with an erosion rate of 25.4 t ha year−1, which is 11 times higher than the Italian average. Prosecco vineyards contributes to 400,000 Mg year−1, by a mean rate of 59.8 Mg ha−1 year−1, and encompass 74% of all the erosion in the whole DOCG area. Soil erosion modelled is mainly concentrated in cultivated hillslopes, highlighting critical areas with more than 40 Mg ha−1 year−1), mainly clustered on steep slopes.The modelled soil loss of a single bottle of Prosecco is, therefore, about 4.4 kg year−1. In contrast, alternative scenarios of different nature-based mitigation measures (hedgerows, buffer strips, and grass cover) showed that total erosion in the Prosecco DOCG area would be reduced to 275,140 Mg year−1, saving about the 50% of soil. In vineyards a general decrease of almost 3 times (from 400,000 to 135,161 Mg year−1) is also demonstrated, reducing on average the erosion rate from 59.8 to 19.2 Mg ha−1 year−1. This study highlights, thus, that an integrated soil erosion monitor system is needed in the DOCG area as well as the implementation of nature-based mitigation measures as sustainable agricultural layout for modern agroecosystems.