bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meltwater Penetration Through Temperate Ice Layers in the Percolation Zone at DYE‐2, Greenland Ice Sheet
Authors: Samimi Samira , Marshall Shawn J. , MacFerrin Michael 
Published: July 2020

AbstractMeltwater retention in the firn layer of the Greenland Ice Sheet has the potential to buffer sea level rise due to ice sheet melt. The capacity of the firn layer to store meltwater is unclear, however, because refrozen ice layers can act as impermeable barriers to meltwater percolation, promoting runoff rather than retention. We present time domain reflectometry and thermistor data, which demonstrate that meltwater successfully penetrates ice layers up to 12 cm thick in the near‐surface firn at DYE‐2, Greenland. Our observations indicate that ice layers within polar firn can be permeable when summer warming and latent heat release from meltwater refreezing raise firn temperatures to the melting point. The extent and depth of refreezing, as determined by the coupled thermodynamic and hydrological evolution in the firn, are more important than the presence of ice layers in governing meltwater infiltration and retention at our study site.
Experimental Investigations on the Effects of Dissolved Gases on the Freezing Dynamics of Ocean Worlds
Authors: Berton Mateo , Nathan Erica , Karani Hamid , Girona Társilo , Huber Christian , Williard Paul G. , Head James 
Published: July 2020

AbstractThe surfaces of icy moons are covered by fractures, other tectonic features, and active or ancient remains of cryovolcanism. These observations suggest active or recent tectonics, but there is still much unknown about the specific conditions surrounding the formation of these features. One important process leading to the fracture of the ice shell is the freezing and consequent pressurization of its ocean, because water expands upon freezing. However, the influence of dissolved non‐condensable gases (herein referred to as volatiles) on the aforementioned dynamics remains poorly constrained. In this study, we present a new experimental investigation to explore the effect of dissolved volatiles in the internal pressure evolution of 10 cm diameter water spheres subjected to freezing temperatures between ~−60°C and ~−20°C. Our experiments reveal that spheres with a reduced initial amount of volatiles dissolved undergo an abrupt transition with dramatic increase of (a) the time between consecutive ice shell fractures and (b) the pressure required to break the shell. We show from a simple numerical model that this transition occurs when exsolution (i.e., nucleation and growth of bubbles) occurs and the fluid inside the shell becomes significantly more compressible. Exsolution is, in turn, triggered by the gradual thickening of the ice shell, which increases the concentration of dissolved volatiles and eventually leads to saturation. These results suggest that the content of volatiles of icy satellites plays a significant role in their geologic history and potential for habitability.
Iron is not everything: unexpected complex metabolic responses between iron-cycling microorganisms
Authors: Cooper Rebecca E , Wegner Carl-Eric , Kügler Stefan , Poulin Remington X , Ueberschaar Nico , Wurlitzer Jens D , Stettin Daniel , Wichard Thomas , Pohnert Georg , Küsel Kirsten 
Published: July 2020

Abstract
Coexistence of microaerophilic Fe(II)-oxidizers and anaerobic Fe(III)-reducers in environments with fluctuating redox conditions is a prime example of mutualism, in which both partners benefit from the sustained Fe-pool. Consequently, the Fe-cycling machineries (i.e., metal-reducing or –oxidizing pathways) should be most affected during co-cultivation. However, contrasting growth requirements impeded systematic elucidation of their interactions. To disentangle underlying interaction mechanisms, we established a suboxic co-culture system of Sideroxydans sp. CL21 and Shewanella oneidensis. We showed that addition of the partner’s cell-free supernatant enhanced both growth and Fe(II)-oxidizing or Fe(III)-reducing activity of each partner. Metabolites of the exometabolome of Sideroxydans sp. CL21 are generally upregulated if stimulated with the partner´s spent medium, while S. oneidensis exhibits a mixed metabolic response in accordance with a balanced response to the partner. Surprisingly, RNA-seq analysis revealed genes involved in Fe-cycling were not differentially expressed during co-cultivation. Instead, the most differentially upregulated genes included those encoding for biopolymer production, lipoprotein transport, putrescine biosynthesis, and amino acid degradation suggesting a regulated inter-species biofilm formation. Furthermore, the upregulation of hydrogenases in Sideroxydans sp. CL21 points to competition for H2 as electron donor. Our findings reveal that a complex metabolic and transcriptomic response, but not accelerated formation of Fe-end products, drive interactions of Fe-cycling microorganisms.
Increasing operational and scientific efficiency in clinical trials
Authors: Kelly Deirdre , Spreafico Anna , Siu Lillian L. 
Published: July 2020

SummaryOperational and scientific inefficiencies in clinical trials represent roadblocks that need to be identified and circumvented to advance drug development in oncology. The collaboration of key stakeholders to advance this agenda is crucial to accelerate clinical research and ultimately benefit patient care through the optimal allocation of time and resources.
DDX5-targeting fully human monoclonal autoantibody inhibits proliferation and promotes differentiation of acute promyelocytic leukemia cells by increasing ROS production
Authors: Wu Jing , You Yan-Qiu , Ma Yan-Xiu , Kang Yan-Hua , Wu Tian , Wu Xiang-Ji , Hu Xiao-Xiao , Meng Qiao-Hong , Huang Yin , Zhang Na , Pan Xiao-Ben 
Published: July 2020

AbstractAcute promyelocytic leukemia (APL) therapy involves the compounds cytotoxic to both malignant tumor and normal cells. Relapsed APL is resistant to subsequent chemotherapy. Novel agents are in need to kill APL cells selectively with minimal toxicity. DDX5 has been recognized to be a novel target to suppress acute myeloid leukemia (AML). However, the role of DDX5 remains elusive in APL. Here a DDX5-targeting fully human monoclonal autoantibody named after 2F5 was prepared. It is demonstrated that 2F5 selectively inhibited APL cell proliferation without toxicity to normal neutrophil and tissues. Moreover, 2F5 was confirmed to induce G0/G1 phase arrest in APL cells, and promote APL cell differentiation combined with decreased DDX5 expression and increased reactive oxygen species (ROS) production. Knockdown of DDX5 by siRNA also inhibited proliferation, promoted cell differentiation and enhanced ROS production in APL cells. However, the ROS inhibitor reversed the effects of 2F5 on DDX5 and ROS in APL cells. Thus, we conclude that DDX5-targeting 2F5 inhibits APL cell proliferation, and promotes cell differentiation via induction of ROS. 2F5 showed the therapeutic value of fully human monoclonal autoantibody in APL, which provides a novel and valid approach for treatment of relapse/refractory APL.
Defining relative mutational difficulty to understand cancer formation
Authors: Shan Lin , Yu Jiao , He Zhengjin , Chen Shishuang , Liu Mingxian , Ding Hongyu , Xu Liang , Zhao Jie , Yang Ailing , Jiang Hai 
Published: July 2020

AbstractMost mutations in human cancer are low-frequency missense mutations, whose functional status remains hard to predict. Here, we show that depending on the type of nucleotide change and the surrounding sequences, the tendency to generate each type of nucleotide mutations varies greatly, even by several hundred folds. Therefore, a cancer-promoting mutation may appear only in a small number of cancer cases, if the underlying nucleotide change is too difficult to generate. We propose a method that integrates both the original mutation counts and their relative mutational difficulty. Using this method, we can accurately predict the functionality of hundreds of low-frequency missense mutations in p53, PTEN, and INK4A. Many loss-of-function p53 mutations with dominant negative effects were identified, and the functional importance of several regions in p53 structure were highlighted by this analysis. Our study not only established relative mutational difficulties for different types of mutations in human cancer, but also showed that by incorporating such a parameter, we can bring new angles to understanding cancer formation.
Wnt signaling and Loxl2 promote aggressive osteosarcoma
Authors: Matsuoka Kazuhiko , Bakiri Latifa , Wolff Lena I. , Linder Markus , Mikels-Vigdal Amanda , Patiño-García Ana , Lecanda Fernando , Hartmann Christine , Sibilia Maria , Wagner Erwin F. 
Published: July 2020

AbstractOsteosarcoma (OS) is the most frequent primary malignant bone tumor in urgent need of better therapies. Using genetically modified mouse models (GEMMs), we demonstrate that Wnt signaling promotes c-Fos-induced OS formation via the actions of the collagen-modifying enzyme Loxl2. c-Fos/AP-1 directly regulates the expression of the Wnt ligands Wnt7b and Wnt9a in OS cells through promoter binding, and Wnt7b and Wnt9a in turn promote Loxl2 expression in murine and human OS cells through the transcription factors Zeb1 and Zeb2. Concordantly, inhibition of Wnt ligand secretion by inactivating the Wnt-less (Wls) gene in osteoblasts in c-Fos GEMMs either early or in a therapeutic setting reduces Loxl2 expression and progression of OS. Wls-deficient osteosarcomas proliferate less, are less mineralized and are enriched in fibroblastic cells surrounded by collagen fibers. Importantly, Loxl2 inhibition using either the pan-Lox inhibitor BAPN or a specific inducible shRNA reduces OS cell proliferation in vitro and decreases tumor growth and lung colonization in murine and human orthotopic OS transplantation models. Finally, OS development is delayed in c-Fos GEMMs treated with BAPN or with specific Loxl2 blocking antibodies. Congruently, a strong correlation between c-FOS, LOXL2 and WNT7B/WNT9A expression is observed in human OS samples, and c-FOS/LOXL2 co-expression correlates with OS aggressiveness and decreased patient survival. Therefore, therapeutic targeting of Wnt and/or Loxl2 should be considered to potentiate the inadequate current treatments for pediatric, recurrent, and metastatic OS.
Proteome activity landscapes of tumor cell lines determine drug responses
Authors: Frejno Martin , Meng Chen , Ruprecht Benjamin , Oellerich Thomas , Scheich Sebastian , Kleigrewe Karin , Drecoll Enken , Samaras Patroklos , Hogrebe Alexander , Helm Dominic , Mergner Julia , Zecha Jana , Heinzlmeir Stephanie , Wilhelm Mathias , Dorn Julia , Kvasnicka Hans-Michael , Serve Hubert , Weichert Wilko , Kuster Bernhard 
Published: July 2020

AbstractIntegrated analysis of genomes, transcriptomes, proteomes and drug responses of cancer cell lines (CCLs) is an emerging approach to uncover molecular mechanisms of drug action. We extend this paradigm to measuring proteome activity landscapes by acquiring and integrating quantitative data for 10,000 proteins and 55,000 phosphorylation sites (p-sites) from 125 CCLs. These data are used to contextualize proteins and p-sites and predict drug sensitivity. For example, we find that Progesterone Receptor (PGR) phosphorylation is associated with sensitivity to drugs modulating estrogen signaling such as Raloxifene. We also demonstrate that Adenylate kinase isoenzyme 1 (AK1) inactivates antimetabolites like Cytarabine. Consequently, high AK1 levels correlate with poor survival of Cytarabine-treated acute myeloid leukemia patients, qualifying AK1 as a patient stratification marker and possibly as a drug target. We provide an interactive web application termed ATLANTiC (http://atlantic.proteomics.wzw.tum.de), which enables the community to explore the thousands of novel functional associations generated by this work.
An OTX2-PAX3 signaling axis regulates Group 3 medulloblastoma cell fate
Authors: Zagozewski Jamie , Shahriary Ghazaleh M. , Morrison Ludivine Coudière , Saulnier Olivier , Stromecki Margaret , Fresnoza Agnes , Palidwor Gareth , Porter Christopher J. , Forget Antoine , Ayrault Olivier , Hawkins Cynthia , Chan Jennifer A. , Vladoiu Maria C. , Sundaresan Lakshmikirupa , Arsenio Janilyn , Taylor Michael D. , Ramaswamy Vijay , Werbowetski-Ogilvie Tamra E. 
Published: July 2020

AbstractOTX2 is a potent oncogene that promotes tumor growth in Group 3 medulloblastoma. However, the mechanisms by which OTX2 represses neural differentiation are not well characterized. Here, we perform extensive multiomic analyses to identify an OTX2 regulatory network that controls Group 3 medulloblastoma cell fate. OTX2 silencing modulates the repressive chromatin landscape, decreases levels of PRC2 complex genes and increases the expression of neurodevelopmental transcription factors including PAX3 and PAX6. Expression of PAX3 and PAX6 is significantly lower in Group 3 medulloblastoma patients and is correlated with reduced survival, yet only PAX3 inhibits self-renewal in vitro and increases survival in vivo. Single cell RNA sequencing of Group 3 medulloblastoma tumorspheres demonstrates expression of an undifferentiated progenitor program observed in primary tumors and characterized by translation/elongation factor genes. Identification of mTORC1 signaling as a downstream effector of OTX2-PAX3 reveals roles for protein synthesis pathways in regulating Group 3 medulloblastoma pathogenesis.
Magnetic field boosted ferroptosis-like cell death and responsive MRI using hybrid vesicles for cancer immunotherapy
Authors: Yu Bo , Choi Bongseo , Li Weiguo , Kim Dong-Hyun 
Published: July 2020

AbstractWe report a strategy to boost Fenton reaction triggered by an exogenous circularly polarized magnetic field (MF) to enhance ferroptosis-like cell-death mediated immune response, as well as endow a responsive MRI capability by using a hybrid core-shell vesicles (HCSVs). HCSVs are prepared by loading ascorbic acid (AA) in the core and poly(lactic-co-glycolic acid) shell incorporating iron oxide nanocubes (IONCs). MF triggers the release of AA, resulting in the increase of ferrous ions through the redox reaction between AA and IONCs. A significant tumor suppression is achieved by Fenton reaction-mediated ferroptosis-like cell-death. The oxidative stress induced by the Fenton reaction leads to the exposure of calreticulin on tumor cells, which leads to dendritic cells maturation and the infiltration of cytotoxic T lymphocytes in tumor. Furthermore, the depletion of ferric ions during treatment enables monitoring of the Fe reaction in MRI-R2* signal change. This strategy provides a perspective on ferroptosis-based immunotherapy.
Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
Authors: Zaidi Syed H. , Harrison Tabitha A. , Phipps Amanda I. , Steinfelder Robert , Trinh Quang M. , Qu Conghui , Banbury Barbara L. , Georgeson Peter , Grasso Catherine S. , Giannakis Marios , Adams Jeremy B. , Alwers Elizabeth , Amitay Efrat L. , Barfield Richard T. , Berndt Sonja I. , Borozan Ivan , Brenner Hermann , Brezina Stefanie , Buchanan Daniel D. , Cao Yin , Chan Andrew T. , Chang-Claude Jenny , Connolly Charles M. , Drew David A. , Farris Alton Brad , Figueiredo Jane C. , French Amy J. , Fuchs Charles S. , Garraway Levi A. , Gruber Steve , Guinter Mark A. , Hamilton Stanley R. , Harlid Sophia , Heisler Lawrence E. , Hidaka Akihisa , Hopper John L. , Huang Wen-Yi , Huyghe Jeroen R. , Jenkins Mark A. , Krzyzanowski Paul M. , Lemire Mathieu , Lin Yi , Luo Xuemei , Mardis Elaine R. , McPherson John D. , Miller Jessica K. , Moreno Victor , Mu Xinmeng Jasmine , Nishihara Reiko , Papadopoulos Nickolas , Pasternack Danielle , Quist Michael J. , Rafikova Adilya , Reid Emma E. G. , Shinbrot Eve , Shirts Brian H. , Stein Lincoln D. , Teney Cherie D. , Timms Lee , Um Caroline Y. , Van Guelpen Bethany , Van Tassel Megan , Wang Xiaolong , Wheeler David A. , Yung Christina K. , Hsu Li , Ogino Shuji , Gsur Andrea , Newcomb Polly A. , Gallinger Steven , Hoffmeister Michael , Campbell Peter T. , Thibodeau Stephen N. , Sun Wei , Hudson Thomas J. , Peters Ulrike 
Published: July 2020

AbstractColorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR = 0.42, 95% CI: 0.21–0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR = 1.53, 95% CI: 1.21–1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features.
Enantiospecific electrochemical rearrangement for the synthesis of hindered triazolopyridinone derivatives
Authors: Ye Zenghui , Wu Yanqi , Chen Na , Zhang Hong , Zhu Kai , Ding Mingruo , Liu Min , Li Yong , Zhang Fengzhi 
Published: July 2020

AbstractTriazolopyridinone derivatives are of high value in both medicinal and material chemistry. However, the chiral or hindered triazolopyridinone derivatives remain an underexplored area of chemical space because they are difficult to prepare via conventional methods. Here we report an electrochemical rearrangement for the efficient synthesis of otherwise inaccessible triazolopyridinones with diverse alkyl carboxylic acids as starting materials. This enables the efficient preparation of more than 60 functionalized triazolopyridinones under mild conditions in a sustainable manner. This method is evaluated for the late stage modification of bioactive natural products, amino acids and pharmaceuticals, and it is further applied to the decagram scale preparation of enantiopure triazolopyridinones. The control experiments support a mechanism involving an oxidative cyclization and 1,2-carbon migration. This facile and scalable rearrangement demonstrates the power of electrochemical synthesis to access otherwise-inaccessible triazolopyridinones and may find wide application in organic, material and medicinal chemistry.
H3K9me3-mediated epigenetic regulation of senescence in mice predicts outcome of lymphoma patients
Authors: Schleich Kolja , Kase Julia , Dörr Jan R. , Trescher Saskia , Bhattacharya Animesh , Yu Yong , Wailes Elizabeth M. , Fan Dorothy N. Y. , Lohneis Philipp , Milanovic Maja , Lau Andrea , Lenze Dido , Hummel Michael , Chapuy Bjoern , Leser Ulf , Reimann Maurice , Lee Soyoung , Schmitt Clemens A. 
Published: July 2020

AbstractLesion-based targeting strategies underlie cancer precision medicine. However, biological principles – such as cellular senescence – remain difficult to implement in molecularly informed treatment decisions. Functional analyses in syngeneic mouse models and cross-species validation in patient datasets might uncover clinically relevant genetics of biological response programs. Here, we show that chemotherapy-exposed primary Eµ-myc transgenic lymphomas – with and without defined genetic lesions – recapitulate molecular signatures of patients with diffuse large B-cell lymphoma (DLBCL). Importantly, we interrogate the murine lymphoma capacity to senesce and its epigenetic control via the histone H3 lysine 9 (H3K9)-methyltransferase Suv(ar)39h1 and H3K9me3-active demethylases by loss- and gain-of-function genetics, and an unbiased clinical trial-like approach. A mouse-derived senescence-indicating gene signature, termed “SUVARness”, as well as high-level H3K9me3 lymphoma expression, predict favorable DLBCL patient outcome. Our data support the use of functional genetics in transgenic mouse models to incorporate basic biology knowledge into cancer precision medicine in the clinic.
A unified catalog of 204,938 reference genomes from the human gut microbiome
Authors: Almeida Alexandre , Nayfach Stephen , Boland Miguel , Strozzi Francesco , Beracochea Martin , Shi Zhou Jason , Pollard Katherine S. , Sakharova Ekaterina , Parks Donovan H. , Hugenholtz Philip , Segata Nicola , Kyrpides Nikos C. , Finn Robert D. 
Published: July 2020

AbstractComprehensive, high-quality reference genomes are required for functional characterization and taxonomic assignment of the human gut microbiota. We present the Unified Human Gastrointestinal Genome (UHGG) collection, comprising 204,938 nonredundant genomes from 4,644 gut prokaryotes. These genomes encode >170 million protein sequences, which we collated in the Unified Human Gastrointestinal Protein (UHGP) catalog. The UHGP more than doubles the number of gut proteins in comparison to those present in the Integrated Gene Catalog. More than 70% of the UHGG species lack cultured representatives, and 40% of the UHGP lack functional annotations. Intraspecies genomic variation analyses revealed a large reservoir of accessory genes and single-nucleotide variants, many of which are specific to individual human populations. The UHGG and UHGP collections will enable studies linking genotypes to phenotypes in the human gut microbiome.
CU-BEMS, smart building electricity consumption and indoor environmental sensor datasets
Authors: Pipattanasomporn Manisa , Chitalia Gopal , Songsiri Jitkomut , Aswakul Chaodit , Pora Wanchalerm , Suwankawin Surapong , Audomvongseree Kulyos , Hoonchareon Naebboon 
Published: July 2020

AbstractThis paper describes the release of the detailed building operation data, including electricity consumption and indoor environmental measurements, of the seven-story 11,700-m2 office building located in Bangkok, Thailand. The electricity consumption data (kW) are that of individual air conditioning units, lighting, and plug loads in each of the 33 zones of the building. The indoor environmental sensor data comprise temperature (°C), relative humidity (%), and ambient light (lux) measurements of the same zones. The entire datasets are available at one-minute intervals for the period of 18 months from July 1, 2018, to December 31, 2019. Such datasets can be used to support a wide range of applications, such as zone-level, floor-level, and building-level load forecasting, indoor thermal model development, validation of building simulation models, development of demand response algorithms by load type, anomaly detection methods, and reinforcement learning algorithms for control of multiple AC units.