bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple myeloma immunoglobulin lambda translocations portend poor prognosis
Authors: Barwick Benjamin G. , Neri Paola , Bahlis Nizar J. , Nooka Ajay K. , Dhodapkar Madhav V. , Jaye David L. , Hofmeister Craig C. , Kaufman Jonathan L. , Gupta Vikas A. , Auclair Daniel , Keats Jonathan J. , Lonial Sagar , Vertino Paula M. , Boise Lawrence H. 
Published: April 2019

AbstractMultiple myeloma is a malignancy of antibody-secreting plasma cells. Most patients benefit from current therapies, however, 20% of patients relapse or die within two years and are deemed high risk. Here we analyze structural variants from 795 newly-diagnosed patients as part of the CoMMpass study. We report translocations involving the immunoglobulin lambda (IgL) locus are present in 10% of patients, and indicative of poor prognosis. This is particularly true for IgL-MYC translocations, which coincide with focal amplifications of enhancers at both loci. Importantly, 78% of IgL-MYC translocations co-occur with hyperdiploid disease, a marker of standard risk, suggesting that IgL-MYC-translocated myeloma is being misclassified. Patients with IgL-translocations fail to benefit from IMiDs, which target IKZF1, a transcription factor that binds the IgL enhancer at some of the highest levels in the myeloma epigenome. These data implicate IgL translocation as a driver of poor prognosis which may be due to IMiD resistance.
Nuclear membrane protein Lem2 regulates nuclear size through membrane flow
Authors: Kume Kazunori , Cantwell Helena , Burrell Alana , Nurse Paul 
Published: April 2019

AbstractThe size of the membrane-bound nucleus scales with cell size in a wide range of cell types but the mechanisms determining overall nuclear size remain largely unknown. Here we investigate the role of fission yeast inner nuclear membrane proteins in determining nuclear size, and propose that the Lap2-Emerin-Man1 domain protein Lem2 acts as a barrier to membrane flow between the nucleus and other parts of the cellular membrane system. Lem2 deletion increases membrane flow into and out of the nuclear envelope in response to changes in membrane synthesis and nucleocytoplasmic transport, altering nuclear size. The endoplasmic reticulum protein Lnp1 acts as a secondary barrier to membrane flow, functionally compensating for lack of Lem2. We propose that this is part of the mechanism that maintains nuclear size proportional to cellular membrane content and thus to cell size. Similar regulatory principles may apply to other organelles in the eukaryotic subcellular membrane network.
Sr[Li2Al2O2N2]:Eu2+—A high performance red phosphor to brighten the future
Authors: Hoerder Gregor J. , Seibald Markus , Baumann Dominik , Schröder Thorsten , Peschke Simon , Schmid Philipp C. , Tyborski Tobias , Pust Philipp , Stoll Ion , Bergler Michael , Patzig Christian , Reißaus Stephan , Krause Michael , Berthold Lutz , Höche Thomas , Johrendt Dirk , Huppertz Hubert 
Published: April 2019

AbstractInnovative materials for phosphor converted white light-emitting diodes are in high demand owing to the huge potential of the light-emitting diode technology to reduce energy consumption worldwide. As the primary blue diode is already highly optimized, the conversion phosphors are of crucial importance for any further improvements. We report on the discovery of the high performance red phosphor Sr[Li2Al2O2N2]:Eu2+meeting all requirements for a phosphor’s optical properties. It combines the optimal spectral position for a red phosphor, as defined in the 2016 Research & Development-plan of the United States government, with an exceptionally small spectral full width at half maximum and excellent thermal stability. A white mid-power phosphor-converted light-emitting diode prototype utilising Sr[Li2Al2O2N2]:Eu2+shows an increase of 16% in luminous efficacy compared to currently available commercial high colour-rendering phosphor-converted light-emitting diodes, while retaining excellent high colour rendition. This phosphor enables a big leap in energy efficiency of white emitting phosphor-converted light-emitting-diodes.
TORC1 modulation in adipose tissue is required for organismal adaptation to hypoxia in Drosophila
Authors: Lee Byoungchun , Barretto Elizabeth C. , Grewal Savraj S. 
Published: April 2019

AbstractAnimals often develop in environments where conditions such as food, oxygen and temperature fluctuate. The ability to adapt their metabolism to these fluctuations is important for normal development and viability. In most animals, low oxygen (hypoxia) is deleterious. However some animals can alter their physiology to tolerate hypoxia. Here we show that TORC1 modulation in adipose tissue is required for organismal adaptation to hypoxia in Drosophila. We find that hypoxia rapidly suppresses TORC1 signaling in Drosophila larvae via TSC-mediated inhibition of Rheb. We show that this hypoxia-mediated inhibition of TORC1 specifically in the larval fat body is essential for viability. Moreover, we find that these effects of TORC1 inhibition on hypoxia tolerance are mediated through remodeling of fat body lipid storage. These studies identify the larval adipose tissue as a key hypoxia-sensing tissue that coordinates whole-body development and survival to changes in environmental oxygen by modulating TORC1 and lipid metabolism.
A chemical toolbox for the study of bromodomains and epigenetic signaling
Authors: Wu Qin , Heidenreich David , Zhou Stanley , Ackloo Suzanne , Krämer Andreas , Nakka Kiran , Lima-Fernandes Evelyne , Deblois Genevieve , Duan Shili , Vellanki Ravi N. , Li Fengling , Vedadi Masoud , Dilworth Jeffrey , Lupien Mathieu , Brennan Paul E. , Arrowsmith Cheryl H. , Müller Susanne , Fedorov Oleg , Filippakopoulos Panagis , Knapp Stefan 
Published: April 2019

AbstractBromodomains (BRDs) are conserved protein interaction modules which recognize (read) acetyl-lysine modifications, however their role(s) in regulating cellular states and their potential as targets for the development of targeted treatment strategies is poorly understood. Here we present a set of 25 chemical probes, selective small molecule inhibitors, covering 29 human bromodomain targets. We comprehensively evaluate the selectivity of this probe-set using BROMOscanand demonstrate the utility of the set identifying roles of BRDs in cellular processes and potential translational applications. For instance, we discovered crosstalk between histone acetylation and the glycolytic pathway resulting in a vulnerability of breast cancer cell lines under conditions of glucose deprivation or GLUT1 inhibition to inhibition of BRPF2/3 BRDs. This chemical probe-set will serve as a resource for future applications in the discovery of new physiological roles of bromodomain proteins in normal and disease states, and as a toolset for bromodomain target validation.
Humanising the mouse genome piece by piece
Authors: Zhu Fei , Nair Remya R. , Fisher Elizabeth M. C. , Cunningham Thomas J. 
Published: April 2019

AbstractTo better understand human health and disease, researchers create a wide variety of mouse models that carry human DNA. With recent advances in genome engineering, the targeted replacement of mouse genomic regions with orthologous human sequences has become increasingly viable, ranging from finely tuned humanisation of individual nucleotides and amino acids to the incorporation of many megabases of human DNA. Here, we examine emerging technologies for targeted genomic humanisation, we review the spectrum of existing genomically humanised mouse models and the insights such models have provided, and consider the lessons learned for designing such models in the future.
Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease
Authors: Kikuchi Koichi , Saigusa Daisuke , Kanemitsu Yoshitomi , Matsumoto Yotaro , Thanai Paxton , Suzuki Naoto , Mise Koki , Yamaguchi Hiroaki , Nakamura Tomohiro , Asaji Kei , Mukawa Chikahisa , Tsukamoto Hiroki , Sato Toshihiro , Oikawa Yoshitsugu , Iwasaki Tomoyuki , Oe Yuji , Tsukimi Tomoya , Fukuda Noriko N. , HO Hsin-Jung , Nanto-Hara Fumika , Ogura Jiro , Saito Ritsumi , Nagao Shizuko , Ohsaki Yusuke , Shimada Satoshi , Suzuki Takehiro , Toyohara Takafumi , Mishima Eikan , Shima Hisato , Akiyama Yasutoshi , Akiyama Yukako , Ichijo Mariko , Matsuhashi Tetsuro , Matsuo Akihiro , Ogata Yoshiaki , Yang Ching-Chin , Suzuki Chitose , Breeggemann Matthew C. , Heymann Jurgen , Shimizu Miho , Ogawa Susumu , Takahashi Nobuyuki , Suzuki Takashi , Owada Yuji , Kure Shigeo , Mano Nariyasu , Soga Tomoyoshi , Wada Takashi , Kopp Jeffrey B. , Fukuda Shinji , Hozawa Atsushi , Yamamoto Masayuki , Ito Sadayoshi , Wada Jun , Tomioka Yoshihisa , Abe Takaaki 
Published: April 2019

AbstractDiabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.
The dynamic and structural properties of axonemal tubulins support the high length stability of cilia
Authors: Orbach Ron , Howard Jonathon 
Published: April 2019

AbstractCilia and flagella play essential roles in cell motility, sensing and development. These organelles have tightly controlled lengths, and the axoneme, which forms the core structure, has exceptionally high stability. This is despite being composed of microtubules that are often characterized as highly dynamic. To understand how ciliary tubulin contribute to stability, we develop a procedure to differentially extract tubulins from different components of axonemes purified from Chlamydomonas reinhardtii, and characterize their properties. We find that the microtubules support length stability by two distinct mechanisms: low dynamicity, and unusual stability of the protofilaments. The high stability of the protofilaments manifests itself in the formation of curved tip structures, up to a few microns long. These structures likely reflect intrinsic curvature of GTP or GDP·Pi tubulin and provide structural insights into the GTP-cap. Together, our study provides insights into growth, stability and the role of post-translational modifications of axonemal microtubules.
Low yield and abiotic origin of N2O formed by the complete nitrifier Nitrospira inopinata
Authors: Kits K. Dimitri , Jung Man-Young , Vierheilig Julia , Pjevac Petra , Sedlacek Christopher J. , Liu Shurong , Herbold Craig , Stein Lisa Y. , Richter Andreas , Wissel Holger , Brüggemann Nicolas , Wagner Michael , Daims Holger 
Published: April 2019

AbstractNitrous oxide (N2O) and nitric oxide (NO) are atmospheric trace gases that contribute to climate change and affect stratospheric and ground-level ozone concentrations. Ammonia oxidizing bacteria (AOB) and archaea (AOA) are key players in the nitrogen cycle and major producers of N2O and NO globally. However, nothing is known about N2O and NO production by the recently discovered and widely distributed complete ammonia oxidizers (comammox). Here, we show that the comammox bacterium Nitrospira inopinata is sensitive to inhibition by an NO scavenger, cannot denitrify to N2O, and emits N2O at levels that are comparable to AOA but much lower than AOB. Furthermore, we demonstrate that N2O formed by N. inopinata formed under varying oxygen regimes originates from abiotic conversion of hydroxylamine. Our findings indicate that comammox microbes may produce less N2O during nitrification than AOB.
Vps11 and Vps18 of Vps-C membrane traffic complexes are E3 ubiquitin ligases and fine-tune signalling
Authors: Segala Gregory , Bennesch Marcela A. , Ghahhari Nastaran Mohammadi , Pandey Deo Prakash , Echeverria Pablo C. , Karch François , Maeda Robert K. , Picard Didier 
Published: April 2019

AbstractIn response to extracellular signals, many signalling proteins associated with the plasma membrane are sorted into endosomes. This involves endosomal fusion, which depends on the complexes HOPS and CORVET. Whether and how their subunits themselves modulate signal transduction is unknown. We show that Vps11 and Vps18 (Vps11/18), two common subunits of the HOPS/CORVET complexes, are E3 ubiquitin ligases. Upon overexpression of Vps11/Vps18, we find perturbations of ubiquitination in signal transduction pathways. We specifically demonstrate that Vps11/18 regulate several signalling factors and pathways, including Wnt, estrogen receptor α (ERα), and NFκB. For ERα, we demonstrate that the Vps11/18-mediated ubiquitination of the scaffold protein PELP1 impairs the activation of ERα by c-Src. Thus, proteins involved in membrane traffic, in addition to performing their well-described role in endosomal fusion, fine-tune signalling in several different ways, including through ubiquitination.
RNA G-quadruplex is resolved by repetitive and ATP-dependent mechanism of DHX36
Authors: Tippana Ramreddy , Chen Michael C. , Demeshkina Natalia A. , Ferré-D’Amaré Adrian R. , Myong Sua 
Published: April 2019

AbstractDHX36 is a DEAH-box helicase that resolves parallel G-quadruplex structures formed in DNA and RNA. The recent co-crystal structure of DHX36 bound G4-DNA revealed an intimate contact, but did not address the role of ATP hydrolysis in G4 resolving activity. Here, we demonstrate that unlike on G4-DNA, DHX36 displays ATP-independent unfolding of G4-RNA followed by ATP-dependent refolding, generating a highly asymmetric pattern of activity. Interestingly, DHX36 refolds G4-RNA in several steps, reflecting the discrete steps in forming the G4 structure. We show that the ATP-dependent activity of DHX36 arises from the RNA tail rather than the G4. Mutations that perturb G4 contact result in quick dissociation of the protein from RNA upon ATP hydrolysis, while mutations that interfere with binding the RNA tail induce dysregulated activity. We propose that the ATP-dependent activity of DHX36 may be useful for dynamically resolving various G4-RNA structures in cells.
Liquid marble-derived solid-liquid hybrid superparticles for CO2 capture
Authors: Rong Xia , Ettelaie Rammile , Lishchuk Sergey V. , Cheng Huaigang , Zhao Ning , Xiao Fukui , Cheng Fangqin , Yang Hengquan 
Published: April 2019

AbstractThe design of effective CO2 capture materials is an ongoing challenge. Here we report a concept to overcome current limitations associated with both liquid and solid CO2 capture materials by exploiting a solid-liquid hybrid superparticle (SLHSP). The fabrication of SLHSP involves assembly of hydrophobic silica nanoparticles on the liquid marble surface, and co-assembly of hydrophilic silica nanoparticles and tetraethylenepentamine within the interior of the liquid marble. The strong interfacial adsorption force and the strong interactions between amine and silica are identified to be key elements for high robustness. The developed SLHSPs exhibit excellent CO2 sorption capacity, high sorption rate, long-term stability and reduced amine loss in industrially preferred fixed bed setups. The outstanding performances are attributed to the unique structure which hierarchically organizes the liquid and solid at microscales.
Unraveling the dislocation core structure at a van der Waals gap in bismuth telluride
Authors: Medlin D. L. , Yang N. , Spataru C. D. , Hale L. M. , Mishin Y. 
Published: April 2019

AbstractTetradymite-structured chalcogenides such as bismuth telluride (Bi2Te3) are of significant interest for thermoelectric energy conversion and as topological insulators. Dislocations play a critical role during synthesis and processing of such materials and can strongly affect their functional properties. The dislocations between quintuple layers present special interest since their core structure is controlled by the van der Waals interactions between the layers. In this work, using atomic-resolution electron microscopy, we resolve the basal dislocation core structure in Bi2Te3, quantifying the disregistry of the atomic planes across the core. We show that, despite the existence of a stable stacking fault in the basal plane gamma surface, the dislocation core spreading is mainly due to the weak bonding between the layers, which leads to a small energy penalty for layer sliding parallel to the van der Waals gap. Calculations within a semidiscrete variational Peierls-Nabarro model informed by first-principles calculations support our experimental findings.
A small molecule promotes cartilage extracellular matrix generation and inhibits osteoarthritis development
Authors: Shi Yuanyuan , Hu Xiaoqing , Cheng Jin , Zhang Xin , Zhao Fengyuan , Shi Weili , Ren Bo , Yu Huilei , Yang Peng , Li Zong , Liu Qiang , Liu Zhenlong , Duan Xiaoning , Fu Xin , Zhang Jiying , Wang Jianquan , Ao Yingfang 
Published: April 2019

AbstractDegradation of extracellular matrix (ECM) underlies loss of cartilage tissue in osteoarthritis, a common disease for which no effective disease-modifying therapy currently exists. Here we describe BNTA, a small molecule with ECM modulatory properties. BNTA promotes generation of ECM components in cultured chondrocytes isolated from individuals with osteoarthritis. In human osteoarthritic cartilage explants, BNTA treatment stimulates expression of ECM components while suppressing inflammatory mediators. Intra-articular injection of BNTA delays the disease progression in a trauma-induced rat model of osteoarthritis. Furthermore, we identify superoxide dismutase 3 (SOD3) as a mediator of BNTA activity. BNTA induces SOD3 expression and superoxide anion elimination in osteoarthritic chondrocyte culture, and ectopic SOD3 expression recapitulates the effect of BNTA on ECM biosynthesis. These observations identify SOD3 as a relevant drug target, and BNTA as a potential therapeutic agent in osteoarthritis.
Mettl3-mediated mRNA m6A methylation promotes dendritic cell activation
Authors: Wang Huamin , Hu Xiang , Huang Mingyan , Liu Juan , Gu Yan , Ma Lijia , Zhou Qi , Cao Xuetao 
Published: April 2019

AbstractN6-methyladenosine (m6A) modification plays important roles in various cellular responses by regulating mRNA biology. However, how m6A modification is involved in innate immunity via affecting the translation of immune transcripts remains to be further investigated. Here we report that RNA methyltransferase Mettl3-mediated mRNA m6A methylation promotes dendritic cell (DC) activation and function. Specific depletion of Mettl3 in DC resulted in impaired phenotypic and functional maturation of DC, with decreased expression of co-stimulatory molecules CD40, CD80 and cytokine IL-12, and reduced ability to stimulate T cell responses both in vitro and in vivo. Mechanistically, Mettl3-mediated m6A of CD40, CD80 and TLR4 signaling adaptor Tirap transcripts enhanced their translation in DC for stimulating T cell activation, and strengthening TLR4/NF-κB signaling-induced cytokine production. Our findings identify a new role for Mettl3-mediated m6A modification in increasing translation of certain immune transcripts for physiological promotion of DC activation and DC-based T cell response.
High-fidelity bosonic quantum state transfer using imperfect transducers and interference
Authors: Lau Hoi-Kwan , Clerk Aashish A. 
Published: April 2019

AbstractWe consider imperfect two-mode bosonic quantum transducers that cannot completely transfer an initial source-system quantum state due to insufficient coupling strength or other Hamiltonian non-idealities. We show that such transducers can generically be made perfect by using interference and phase-sensitive amplification. Our approach is based on the realization that a particular kind of imperfect transducer (one which implements a swapped quantum non-demolition (QND) gate) can be made into a perfect one-way transducer using feed-forward and/or injected squeezing. We show that a generic imperfect transducer can be reduced to this case by repeating the imperfect transduction operation twice, interspersed with amplification. Crucially, our scheme only requires the ability to implement squeezing operations and/or homodyne measurement on one of the two modes involved. It is thus ideally suited to schemes where there is an asymmetry in the ability to control the two coupled systems (e.g., microwave-to-optics quantum state transfer). We also discuss a correction protocol that requires no injected squeezing and/or feed-forward operation.
The multiplex network of human diseases
Authors: Halu Arda , De Domenico Manlio , Arenas Alex , Sharma Amitabh 
Published: April 2019

AbstractUntangling the complex interplay between phenotype and genotype is crucial to the effective characterization and subtyping of diseases. Here we build and analyze the multiplex network of 779 human diseases, which consists of a genotype-based layer and a phenotype-based layer. We show that diseases with common genetic constituents tend to share symptoms, and uncover how phenotype information helps boost genotype information. Moreover, we offer a flexible classification of diseases that considers their molecular underpinnings alongside their clinical manifestations. We detect cohesive groups of diseases that have high intra-group similarity at both the molecular and the phenotypic level. Inspecting these disease communities, we demonstrate the underlying pathways that connect diseases mechanistically. We observe monogenic disorders grouped together with complex diseases for which they increase the risk factor. We propose potentially new disease associations that arise as a unique feature of the information flow within and across the two layers.
Topographic controls of soil organic carbon on soil-mantled landscapes
Authors: Patton Nicholas R. , Lohse Kathleen A. , Seyfried Mark S. , Godsey Sarah E. , Parsons Susan B. 
Published: April 2019

AbstractLarge uncertainties in global carbon (C) budgets stem from soil carbon estimates and associated challenges in distributing soil organic carbon (SOC) at local to landscape scales owing to lack of information on soil thickness and controls on SOC storage. Here we show that 94% of the fine-scale variation in total profile SOC within a 1.8 km2semi-arid catchment in Idaho, U.S.A. can be explained as a function of aspect and hillslope curvature when the entire vertical dimension of SOC is measured and fine-resolution (3 m) digital elevation models are utilized. Catchment SOC stocks below 0.3 m depth based on our SOC-curvature model account for >50% of the total SOC indicating substantial underestimation of stocks if sampled at shallower depths. A rapid assessment method introduced here also allows for accurate catchment-wide total SOC inventory estimation with a minimum of one soil pit and topographic data if spatial distribution of total profile SOC is not required. Comparison of multiple datasets shows generality in linear SOC-curvature and -soil thickness relationships at multiple scales. We conclude that mechanisms driving variations in carbon storage in hillslope catchment soils vary spatially at relatively small scales and can be described in a deterministic fashion given adequate topographic data.