bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seasonality and Source Apportionment of Nonmethane Volatile Organic Compounds at Boulder Reservoir, Colorado, Between 2017 and 2019
Authors: Pollack Ilana B. , Helmig Detlev , O'Dell Katelyn , Fischer Emily V. 
Published: April 2021

AbstractMultiyear observations of 13 nonmethane volatile organic compounds (NMVOCs) were collected at the Boulder Reservoir in the Colorado Northern Front Range Metropolitan Area (NFRMA). We separate abundances of NMVOCs in the 2017–2019 data into source contributions using two approaches that have been applied to prior NFRMA datasets. Positive matrix factorization analysis identifies five NMVOC factors in winter, spring, and fall that correspond to long‐lived and short‐lived NMVOCs from regional oil and natural gas (O&NG) production, traffic, local shorter‐lived alkenes, and regional anthropogenic background. In summer, there is an additional biogenic NMVOC factor dominated by isoprene. The PMF model indicates that 79 ± 1% of C2‐C5 alkanes in winter and 84 ± 20% in summer are attributed to O&NG activities. Ethyne is largely from traffic with contributions ranging from 45 ± 6% in winter to 87 ± 32% in summer. Ethene and propene are associated with a potentially separate source of shorter‐lived alkenes that we cannot identify. The largest contributing sectors to the observed hazardous air pollutants (HAPs) differ substantially by species and season. Benzene is attributed to O&NG production, traffic and other industrial activities. Toluene is predominantly attributed to regional anthropogenic activities in all seasons. Of the HAPs quantified in this dataset, hexane stands out as largely attributed to O&NG production. Consistent with prior analyses, this work shows that the NFRMA is more strongly influenced by O&NG sources than many other U.S. urban regions.
Controls on the Global Distribution of Martian Landslides
Authors: Roback Kevin P. , Ehlmann Bethany L. 
Published: April 2021

AbstractRecent acquisition of high‐resolution satellite imagery of the Martian surface has permitted landslides to be studied on a global scale on Mars for the first time. We apply the Scoops3D software package to compute slope stability for select regions of the Martian surface, combining calculations of slope stability with number of observed landslides (Crosta, Frattini, et al., 2018; Crosta, De Blasio, et al., 2018), as reported in a recently published inventory of Martian landslides, to understand controls on the global distribution of landslides on Mars. We find that the distribution of landslides does not simply follow the distribution of unstable slopes. In particular, there is an abundance of landslides around Tharsis, and especially in Valles Marineris and Noctis Labyrinthus, which is not explained by an abundance of unstable topography alone. We analyzed for but did not find a clear large‐scale lithologic or stratigraphic control on landslide occurrence from subsurface heterogeneities. Other possibilities to explain the increased occurrence of landslides in Tharsis include (1) thin weak unit(s) that is regionally widespread and at multiple stratigraphic levels, such as from interbedded ashes; (2) seismic activity related to the Tharsis's geological activity, and (3) possible groundwater near Valles Marineris into the Amazonian. Given the apparently young ages of many landslide deposits in Valles Marineris (Quantin et al., 2004), continued modern day analysis of lithologies in Valles Marineris and observations of Martian seismicity may act to strengthen or rebut the first two hypotheses.
Global phosphoproteomics reveals DYRK1A regulates CDK1 activity in glioblastoma cells
Authors: Recasens Ariadna , Humphrey Sean J. , Ellis Michael , Hoque Monira , Abbassi Ramzi H. , Chen Brianna , Longworth Mitchell , Needham Elise J. , James David E. , Johns Terrance G. , Day Bryan W. , Kassiou Michael , Yang Pengyi , Munoz Lenka 
Published: April 2021

AbstractBoth tumour suppressive and oncogenic functions have been reported for dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Herein, we performed a detailed investigation to delineate the role of DYRK1A in glioblastoma. Our phosphoproteomic and mechanistic studies show that DYRK1A induces degradation of cyclin B by phosphorylating CDC23, which is necessary for the function of the anaphase-promoting complex, a ubiquitin ligase that degrades mitotic proteins. DYRK1A inhibition leads to the accumulation of cyclin B and activation of CDK1. Importantly, we established that the phenotypic response of glioblastoma cells to DYRK1A inhibition depends on both retinoblastoma (RB) expression and the degree of residual DYRK1A activity. Moderate DYRK1A inhibition leads to moderate cyclin B accumulation, CDK1 activation and increased proliferation in RB-deficient cells. In RB-proficient cells, cyclin B/CDK1 activation in response to DYRK1A inhibition is neutralized by the RB pathway, resulting in an unchanged proliferation rate. In contrast, complete DYRK1A inhibition with high doses of inhibitors results in massive cyclin B accumulation, saturation of CDK1 activity and cell cycle arrest, regardless of RB status. These findings provide new insights into the complexity of context-dependent DYRK1A signalling in cancer cells.
Design of multi-scale protein complexes by hierarchical building block fusion
Authors: Hsia Yang , Mout Rubul , Sheffler William , Edman Natasha I. , Vulovic Ivan , Park Young-Jun , Redler Rachel L. , Bick Matthew J. , Bera Asim K. , Courbet Alexis , Kang Alex , Brunette T. J. , Nattermann Una , Tsai Evelyn , Saleem Ayesha , Chow Cameron M. , Ekiert Damian , Bhabha Gira , Veesler David , Baker David 
Published: April 2021

AbstractA systematic and robust approach to generating complex protein nanomaterials would have broad utility. We develop a hierarchical approach to designing multi-component protein assemblies from two classes of modular building blocks: designed helical repeat proteins (DHRs) and helical bundle oligomers (HBs). We first rigidly fuse DHRs to HBs to generate a large library of oligomeric building blocks. We then generate assemblies with cyclic, dihedral, and point group symmetries from these building blocks using architecture guided rigid helical fusion with new software named WORMS. X-ray crystallography and cryo-electron microscopy characterization show that the hierarchical design approach can accurately generate a wide range of assemblies, including a 43 nm diameter icosahedral nanocage. The computational methods and building block sets described here provide a very general route to de novo designed protein nanomaterials.
Defective viral genomes as therapeutic interfering particles against flavivirus infection in mammalian and mosquito hosts
Authors: Rezelj Veronica V. , Carrau Lucía , Merwaiss Fernando , Levi Laura I. , Erazo Diana , Tran Quang Dinh , Henrion-Lacritick Annabelle , Gausson Valérie , Suzuki Yasutsugu , Shengjuler Djoshkun , Meyer Bjoern , Vallet Thomas , Weger-Lucarelli James , Bernhauerová Veronika , Titievsky Avi , Sharov Vadim , Pietropaoli Stefano , Diaz-Salinas Marco A. , Legros Vincent , Pardigon Nathalie , Barba-Spaeth Giovanna , Brodsky Leonid , Saleh Maria-Carla , Vignuzzi Marco 
Published: April 2021

AbstractArthropod-borne viruses pose a major threat to global public health. Thus, innovative strategies for their control and prevention are urgently needed. Here, we exploit the natural capacity of viruses to generate defective viral genomes (DVGs) to their detriment. While DVGs have been described for most viruses, identifying which, if any, can be used as therapeutic agents remains a challenge. We present a combined experimental evolution and computational approach to triage DVG sequence space and pinpoint the fittest deletions, using Zika virus as an arbovirus model. This approach identifies fit DVGs that optimally interfere with wild-type virus infection. We show that the most fit DVGs conserve the open reading frame to maintain the translation of the remaining non-structural proteins, a characteristic that is fundamental across the flavivirus genus. Finally, we demonstrate that the high fitness DVG is antiviral in vivo both in the mammalian host and the mosquito vector, reducing transmission in the latter by up to 90%. Our approach establishes the method to interrogate the DVG fitness landscape, and enables the systematic identification of DVGs that show promise as human therapeutics and vector control strategies to mitigate arbovirus transmission and disease.
Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer
Authors: Nishina Takashi , Deguchi Yutaka , Ohshima Daisuke , Takeda Wakami , Ohtsuka Masato , Shichino Shigeyuki , Ueha Satoshi , Yamazaki Soh , Kawauchi Mika , Nakamura Eri , Nishiyama Chiharu , Kojima Yuko , Adachi-Akahane Satomi , Hasegawa Mizuho , Nakayama Mizuho , Oshima Masanobu , Yagita Hideo , Shibuya Kazutoshi , Mikami Tetuo , Inohara Naohiro , Matsushima Kouji , Tada Norihiro , Nakano Hiroyasu 
Published: April 2021

AbstractInterleukin (IL)-11 is a member of the IL-6 family of cytokines and is involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+cells in vivo, we generateIl11reporter mice. IL-11+cells appear in the colon in murine tumor and acute colitis models.Il11ra1orIl11deletion attenuates the development of colitis-associated colorectal cancer. IL-11+cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11+fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11+fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment.
Genetic perturbation of PU.1 binding and chromatin looping at neutrophil enhancers associates with autoimmune disease
Authors: Watt Stephen , Vasquez Louella , Walter Klaudia , Mann Alice L. , Kundu Kousik , Chen Lu , Sims Ying , Ecker Simone , Burden Frances , Farrow Samantha , Farr Ben , Iotchkova Valentina , Elding Heather , Mead Daniel , Tardaguila Manuel , Ponstingl Hannes , Richardson David , Datta Avik , Flicek Paul , Clarke Laura , Downes Kate , Pastinen Tomi , Fraser Peter , Frontini Mattia , Javierre Biola-Maria , Spivakov Mikhail , Soranzo Nicole 
Published: April 2021

AbstractNeutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with immune system traits and diseases. Here, we profile the binding of myeloid master regulator PU.1 in primary neutrophils across nearly a hundred volunteers. We show that variants associated with differential PU.1 binding underlie genetically-driven differences in cell count and susceptibility to autoimmune and inflammatory diseases. We integrate these results with other multi-individual genomic readouts, revealing coordinated effects of PU.1 binding variants on the local chromatin state, enhancer-promoter contacts and downstream gene expression, and providing a functional interpretation for 27 genes underlying immune traits. Collectively, these results demonstrate the functional role of PU.1 and its target enhancers in neutrophil transcriptional control and immune disease susceptibility.
Conserved long-range base pairings are associated with pre-mRNA processing of human genes
Authors: Kalmykova Svetlana , Kalinina Marina , Denisov Stepan , Mironov Alexey , Skvortsov Dmitry , Guigó Roderic , Pervouchine Dmitri 
Published: April 2021

AbstractThe ability of nucleic acids to form double-stranded structures is essential for all living systems on Earth. Current knowledge on functional RNA structures is focused on locally-occurring base pairs. However, crosslinking and proximity ligation experiments demonstrated that long-range RNA structures are highly abundant. Here, we present the most complete to-date catalog of conserved complementary regions (PCCRs) in human protein-coding genes. PCCRs tend to occur within introns, suppress intervening exons, and obstruct cryptic and inactive splice sites. Double-stranded structure of PCCRs is supported by decreased icSHAPE nucleotide accessibility, high abundance of RNA editing sites, and frequent occurrence of forked eCLIP peaks. Introns with PCCRs show a distinct splicing pattern in response to RNAPII slowdown suggesting that splicing is widely affected by co-transcriptional RNA folding. The enrichment of 3’-ends within PCCRs raises the intriguing hypothesis that coupling between RNA folding and splicing could mediate co-transcriptional suppression of premature pre-mRNA cleavage and polyadenylation.
Spin texture induced by non-magnetic doping and spin dynamics in 2D triangular lattice antiferromagnet h-Y(Mn,Al)O3
Authors: Park Pyeongjae , Park Kisoo , Oh Joosung , Lee Ki Hoon , Leiner Jonathan C. , Sim Hasung , Kim Taehun , Jeong Jaehong , Rule Kirrily C. , Kamazawa Kazuya , Iida Kazuki , Perring T. G. , Woo Hyungje , Cheong S.-W. , Zhitomirsky M. E. , Chernyshev A. L. , Park Je-Geun 
Published: April 2021

AbstractNovel effects induced by nonmagnetic impurities in frustrated magnets and quantum spin liquid represent a highly nontrivial and interesting problem. A theoretical proposal of extended modulated spin structures induced by doping of such magnets, distinct from the well-known skyrmions has attracted significant interest. Here, we demonstrate that nonmagnetic impurities can produce such extended spin structures in h-YMnO3, a triangular antiferromagnet with noncollinear magnetic order. Using inelastic neutron scattering (INS), we measured the full dynamical structure factor in Al-doped h-YMnO3 and confirmed the presence of magnon damping with a clear momentum dependence. Our theoretical calculations can reproduce the key features of the INS data, supporting the formation of the proposed spin textures. As such, our study provides the first experimental confirmation of the impurity-induced spin textures. It offers new insights and understanding of the impurity effects in a broad class of noncollinear magnetic systems.
Orally delivered MK-4482 inhibits SARS-CoV-2 replication in the Syrian hamster model
Authors: Rosenke Kyle , Hansen Frederick , Schwarz Benjamin , Feldmann Friederike , Haddock Elaine , Rosenke Rebecca , Barbian Kent , Meade-White Kimberly , Okumura Atsushi , Leventhal Shanna , Hawman David W. , Ricotta Emily , Bosio Catharine M. , Martens Craig , Saturday Greg , Feldmann Heinz , Jarvis Michael A. 
Published: April 2021

AbstractThe COVID-19 pandemic progresses unabated in many regions of the world. An effective antiviral against SARS-CoV-2 that could be administered orally for use following high-risk exposure would be of substantial benefit in controlling the COVID-19 pandemic. Herein, we show that MK-4482, an orally administered nucleoside analog, inhibits SARS-CoV-2 replication in the Syrian hamster model. The inhibitory effect of MK-4482 on SARS-CoV-2 replication is observed in animals when the drug is administered either beginning 12 h before or 12 h following infection in a high-risk exposure model. These data support the potential utility of MK-4482 to control SARS-CoV-2 infection in humans following high-risk exposure as well as for treatment of COVID-19 patients.
Classical MHC expression by DP thymocytes impairs the selection of non-classical MHC restricted innate-like T cells
Authors: Georgiev Hristo , Peng Changwei , Huggins Matthew A. , Jameson Stephen C. , Hogquist Kristin A. 
Published: April 2021

AbstractConventional T cells are selected by peptide-MHC expressed by cortical epithelial cells in the thymus, and not by cortical thymocytes themselves that do not express MHC I or MHC II. Instead, cortical thymocytes express non-peptide presenting MHC molecules like CD1d and MR1, and promote the selection of PLZF+iNKT and MAIT cells, respectively. Here, we report an inducible class-I transactivator mouse that enables the expression of peptide presenting MHC I molecules in different cell types. We show that MHC I expression in DP thymocytes leads to expansion of peptide specific PLZF+innate-like (PIL) T cells. Akin to iNKT cells, PIL T cells differentiate into three functional effector subsets in the thymus, and are dependent on SAP signaling. We demonstrate that PIL and NKT cells compete for a narrow niche, suggesting that the absence of peptide-MHC on DP thymocytes facilitates selection of non-peptide specific lymphocytes.
Ultraviolet irradiation-responsive dynamic ultralong organic phosphorescence in polymeric systems
Authors: Zhang Yongfeng , Gao Liang , Zheng Xian , Wang Zhonghao , Yang Chaolong , Tang Hailong , Qu Lunjun , Li Youbing , Zhao Yanli 
Published: April 2021

AbstractRoom temperature phosphorescence (RTP) has drawn extensive attention in recent years. Efficient stimulus-responsive phosphorescent organic materials are attractive, but are extremely rare because of unclear design principles and intrinsically spin-forbidden intersystem crossing. Herein, we present a feasible and facile strategy to achieve ultraviolet irradiation-responsive ultralong RTP (IRRTP) of some simple organic phosphors by doping into amorphous poly(vinyl alcohol) matrix. In addition to the observed green and yellow afterglow emission with distinct irradiation-enhanced phosphorescence, the phosphorescence lifetime can be tuned by varying the irradiation period of 254 nm light. Significantly, the dynamic phosphorescence lifetime could be increased 14.3 folds from 58.03 ms to 828.81 ms in one of the obtained hybrid films after irradiation for 45 min under ambient conditions. As such, the application in polychromatic screen printing and multilevel information encryption is demonstrated. The extraordinary IRRTP in the amorphous state endows these systems with a highly promising potential for smart flexible luminescent materials and sensors with dynamically controlled phosphorescence.
DNase II mediates a parthanatos-like developmental cell death pathway in Drosophila primordial germ cells
Authors: Tarayrah-Ibraheim Lama , Maurice Elital Chass , Hadary Guy , Ben-Hur Sharon , Kolpakova Alina , Braun Tslil , Peleg Yoav , Yacobi-Sharon Keren , Arama Eli 
Published: April 2021

AbstractDuring Drosophila embryonic development, cell death eliminates 30% of the primordial germ cells (PGCs). Inhibiting apoptosis does not prevent PGC death, suggesting a divergence from the conventional apoptotic program. Here, we demonstrate that PGCs normally activate an intrinsic alternative cell death (ACD) pathway mediated by DNase II release from lysosomes, leading to nuclear translocation and subsequent DNA double-strand breaks (DSBs). DSBs activate the DNA damage-sensing enzyme, Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) and the ATR/Chk1 branch of the DNA damage response. PARP-1 and DNase II engage in a positive feedback amplification loop mediated by the release of PAR polymers from the nucleus and the nuclear accumulation of DNase II in an AIF- and CypA-dependent manner, ultimately resulting in PGC death. Given the anatomical and molecular similarities with an ACD pathway called parthanatos, these findings reveal a parthanatos-like cell death pathway active during Drosophila development.
Hypothalamic Rax+ tanycytes contribute to tissue repair and tumorigenesis upon oncogene activation in mice
Authors: Mu Wenhui , Li Si , Xu Jingkai , Guo Xize , Wu Haoda , Chen Zhenhua , Qiao Lianyong , Helfer Gisela , Lu Falong , Liu Chong , Wu Qing-Feng 
Published: April 2021

AbstractHypothalamic tanycytes in median eminence (ME) are emerging as a crucial cell population that regulates endocrine output, energy balance and the diffusion of blood-born molecules. Tanycytes have recently been considered as potential somatic stem cells in the adult mammalian brain, but their regenerative and tumorigenic capacities are largely unknown. Here we found that Rax+ tanycytes in ME of mice are largely quiescent but quickly enter the cell cycle upon neural injury for self-renewal and regeneration. Mechanistically, Igf1r signaling in tanycytes is required for tissue repair under injury conditions. Furthermore, Braf oncogenic activation is sufficient to transform Rax+ tanycytes into actively dividing tumor cells that eventually develop into a papillary craniopharyngioma-like tumor. Together, these findings uncover the regenerative and tumorigenic potential of tanycytes. Our study offers insights into the properties of tanycytes, which may help to manipulate tanycyte biology for regulating hypothalamic function and investigate the pathogenesis of clinically relevant tumors.
Structural insight into the molecular mechanism of p53-mediated mitochondrial apoptosis
Authors: Wei Hudie , Qu Lingzhi , Dai Shuyan , Li Yun , Wang Haolan , Feng Yilu , Chen Xiaojuan , Jiang Longying , Guo Ming , Li Jun , Chen Zhuchu , Chen Lin , Zhang Ye , Chen Yongheng 
Published: April 2021

AbstractThe tumor suppressor p53 is mutated in approximately half of all human cancers. p53 can induce apoptosis through mitochondrial membrane permeabilization by interacting with and antagonizing the anti-apoptotic proteins BCL-xL and BCL-2. However, the mechanisms by which p53 induces mitochondrial apoptosis remain elusive. Here, we report a 2.5 Å crystal structure of human p53/BCL-xL complex. In this structure, two p53 molecules interact as a homodimer, and bind one BCL-xL molecule to form a ternary complex with a 2:1 stoichiometry. Mutations at the p53 dimer interface or p53/BCL-xL interface disrupt p53/BCL-xL interaction and p53-mediated apoptosis. Overall, our current findings of the bona fide structure of p53/BCL-xL complex reveal the molecular basis of the interaction between p53 and BCL-xL, and provide insight into p53-mediated mitochondrial apoptosis.
Dynamic contrast-enhanced breast MRI features correlate with invasive breast cancer angiogenesis
Authors: Xiao Jennifer , Rahbar Habib , Hippe Daniel S. , Rendi Mara H. , Parker Elizabeth U. , Shekar Neal , Hirano Michael , Cheung Kevin J. , Partridge Savannah C. 
Published: April 2021

AbstractAngiogenesis is a critical component of breast cancer development, and identification of imaging-based angiogenesis assays has prognostic and treatment implications. We evaluated the association of semi-quantitative kinetic and radiomic breast cancer features on dynamic contrast-enhanced (DCE)-MRI with microvessel density (MVD), a marker for angiogenesis. Invasive breast cancer kinetic features (initial peak percent enhancement [PE], signal enhancement ratio [SER], functional tumor volume [FTV], and washout fraction [WF]), radiomics features (108 total features reflecting tumor morphology, signal intensity, and texture), and MVD (by histologic CD31 immunostaining) were measured in 27 patients (1/2016–7/2017). Lesions with high MVD levels demonstrated higher peak SER than lesions with low MVD (mean: 1.94 vs. 1.61, area under the receiver operating characteristic curve [AUC] = 0.79, p = 0.009) and higher WF (mean: 50.6% vs. 22.5%, AUC = 0.87, p = 0.001). Several radiomics texture features were also promising for predicting increased MVD (maximum AUC = 0.84, p = 0.002). Our study suggests DCE-MRI can non-invasively assess breast cancer angiogenesis, which could stratify biology and optimize treatments.