bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empirical investigation of mutation rate for herbicide resistance
Authors: Casale Federico A. , Giacomini Darci A. , Tranel Patrick J. 
Published: May 2019

AbstractIn a predictable natural selection process, herbicides select for adaptive alleles that allow weed populations to survive. These resistance alleles may be available immediately from the standing genetic variation within the population or may arise from immigration via pollen or seeds from other populations. Moreover, because all populations are constantly generating new mutant genotypes by de novo mutations, resistant mutants may arise spontaneously in any herbicide-sensitive weed population. Recognizing that the relative contribution of each of these three sources of resistance alleles influences what strategies should be applied to counteract herbicide-resistance evolution, we aimed to add experimental information to the resistance evolutionary framework. Specifically, the objectives of this experiment were to determine the de novo mutation rate conferring herbicide resistance in a natural plant population and to test the hypothesis that the mutation rate increases when plants are stressed by sublethal herbicide exposure. We used grain amaranth (Amaranthus hypochondriacus L.) and resistance to acetolactate synthase (ALS)-inhibiting herbicides as a model system to discover spontaneous herbicide-resistant mutants. After screening 70.8 million plants, however, we detected no spontaneous resistant genotypes, indicating the probability of finding a spontaneous ALS-resistant mutant in a given sensitive population is lower than 1.4 × 10−8. This empirically determined upper limit is lower than expected from theoretical calculations based on previous studies. We found no evidence that herbicide stress increased the mutation rate, but were not able to robustly test this hypothesis. The results found in this study indicate that de novo mutations conferring herbicide resistance might occur at lower frequencies than previously expected.
The Importance of Sampling Variability in Assessments of ENSO‐PM2.5 Relationships: A Case Study for the South Central United States
Authors: Previdi Michael , Fiore Arlene M. 
Published: May 2019

AbstractWe assess seasonal mean relationships between the El Niño–Southern Oscillation (ENSO) and surface fine particulate matter (PM2.5) over the United States using observations from 1999 to 2015. Through a case study of the springtime PM2.5 response to ENSO in the South Central United States, we demonstrate that sampling variability is large on the 17‐year time scale of the observations, leading to large uncertainty in the estimated relationships. The PM2.5 response in the South Central United States is dominated by decreases in soil dust concentrations during El Niño, which we link to changes in cloud cover and near‐surface wind speed. The observed dust response during 1999–2015 is about 25% stronger than the long‐term mean ENSO‐forced signal estimated from climate model control simulations. Given a different 17‐year period, this discrepancy could be even larger. Our findings underscore the importance of accounting for sampling uncertainty in studies of ENSO's air quality impacts.
Exploring the Sources of Unexpected High Methane Concentrations and Fluxes From Alpine Headwater Streams
Authors: Flury S. , Ulseth A. J. 
Published: May 2019

AbstractThe dynamics of methane generation and evasion from well‐oxygenated, oligotrophic streams have been traditionally neglected. We estimated evasion of methane and assessed its sources and production pathways using a stable isotope approach in 16 oxygen‐rich and C‐poor (dissolved organic carbon: 55.32 ± 57.56 μmol/L) Alpine headwater streams. Methane was often supersaturated relative to the atmosphere (0.093 ± 0.179 μmol/L). Fluxes (0.87 ± 1.34 mmol·m−2·day−1) were unexpectedly high and comparable to those from high‐latitude lakes and reservoirs. Our findings suggest that methane in the streambed was largely produced from carbon dioxide reduction, whereas acetoclastic pathways and major deliveries from adjacent soils, assessed from a mass balance, may have contributed to stream water methane. This study sheds new light on high‐alpine streams as a hitherto unaccounted source of methane to the atmosphere.
Thicker Clouds and Accelerated Arctic Sea Ice Decline: The Atmosphere‐Sea Ice Interactions in Spring
Authors: Huang Yiyi , Dong Xiquan , Bailey David A. , Holland Marika M. , Xi Baike , DuVivier Alice K. , Kay Jennifer E. , Landrum Laura L. , Deng Yi 
Published: May 2019

AbstractObservations show that increased Arctic cloud cover in the spring is linked with sea ice decline. As the atmosphere and sea ice can influence each other, which one plays the leading role in spring remains unclear. Here we demonstrate, through observational data diagnosis and numerical modeling, that there is active coupling between the atmosphere and sea ice in early spring. Sea ice melting and thus the presence of more open water lead to stronger evaporation and promote cloud formation that increases downward longwave flux, leading to even more ice melt. Spring clouds are a driving force in the disappearance of sea ice and displacing the mechanism of atmosphere‐sea ice coupling from April to June. These results suggest the need to accurately model interactions of Arctic clouds and radiation in Earth System Models in order to improve projections of the future of the Arctic.
Heavy Ice Precipitation Band in an Oceanic Extratropical Cyclone Observed by GPM/DPR: 1. A Case Study
Authors: Akiyama Shizuka , Shige Shoichi , Yamamoto Munehisa K. , Iguchi Toshio 
Published: May 2019

AbstractHeavy ice precipitation (HIP) flags in the products of dual‐frequency precipitation radar (DPR) on board the Global Precipitation Measurement (GPM) core satellite indicate the existence of large ice particles. In this study, we analyzed the distribution of a HIP band detected along the warm front of an oceanic extratropical cyclone. The HIP band was more than 125 km long and probably exceeded the 245‐km range of the Ku‐band precipitation radar. We found two zones with distinct microphysical processes in the HIP band. Ice particles near the echo top height showed little change in their median size with height, where frontogenetical updraft was maximum. This suggests that particles are generated and grown in this zone by the updrafts. In the zone below, the particle sizes increased as the height decreased, implying particles aggregate as they fall.
Responses of Different Types of Pulsating Aurora in Cosmic Noise Absorption
Authors: Yang Bing , Spanswick Emma , Liang Jun , Grono Eric , Donovan Eric 
Published: May 2019

AbstractA recent study (Grono & Donovan, 2018, https://doi.org/10.5194/angeo‐36‐891‐2018) reported two distinct categories of pulsating aurora: patchy pulsating aurora (PPA) and amorphous pulsating aurora (APA). In this study we compare the auroral intensity of five PPA events and seven APA events monitored by the Time History of Events and Macroscale Interactions during Substorms (THEMIS) All‐Sky Imagers with co‐located cosmic noise absorption (CNA) from the Geospace Observatory wide‐beam riometers. Our results show significant correlations between CNA and the auroral intensity of the APA events but no correlation between CNA and the auroral intensity of the PPA events. Analysis of conjunctions with the electron flux data obtained from the FAST satellite, we found that electrons responsible for APA may extend to higher energy range than those for PPA.
Low Subsurface Water Storage Capacity Relative to Annual Rainfall Decouples Mediterranean Plant Productivity and Water Use From Rainfall Variability
Authors: Hahm W. J. , Dralle D. N. , Rempe D. M. , Bryk A. B. , Thompson S. E. , Dawson T. E. , Dietrich W. E. 
Published: May 2019

AbstractPlant water stress in response to rainfall variability is mediated by subsurface water storage, yet the controls on stored plant‐available water remain poorly understood. Here we develop a probabilistic water balance model for Mediterranean climates that relates the amount of water stored over the wet season to annual rainfall statistics and subsurface storage capacity in soil and weathered bedrock. This model predicts that low storage capacity—relative to winter rainfall—results in similar year‐to‐year summer water availability, as both relatively wet and dry winters replenish storage. Observed water balances in seven catchments in the Northern California Coast Ranges exhibited this dynamic. We hypothesized that plants would be decoupled from precipitation variability at these storage‐capacity‐limited sites and observed that summer productivity and water use (inferred from the enhanced vegetation index) were independent of winter rainfall totals. These areas emerged largely unscathed from recent extreme drought, despite widespread plant mortality elsewhere.
Redox Chemistry and Molybdenum Burial in a Mesoproterozoic Lake
Authors: Rico K. I. , Sheldon N. D. , Gallagher T. M. , Chappaz A. 
Published: May 2019

AbstractWhile marine sediments have been used to constrain a history of redox chemistry throughout the Precambrian, far fewer data have been generated from lakes. With major biological innovations thought to have occurred in Proterozoic lakes, understanding their chemistry is critical for understanding the evolution of eukaryotic life. We use sediment geochemistry to characterize the redox conditions of the Nonesuch Formation (~1.1 Ga) and a modern analogue for the Proterozoic: the Middle Island Sinkhole in Lake Huron (USA). Iron speciation, Mo contents, and Mo‐U covariation demonstrate oxic and anoxic—not euxinic—environments, with no clear indicators of enhanced biological productivity in the Nonesuch Formation. Moderate Mo enrichments observed in the Nonesuch Formation are not attributed to euxinia, but instead to an authigenic particulate shuttle. We suggest that the Fe and Mo sediment geochemistry of these lacustrine systems reflect only local water column and sediment burial conditions and not atmospheric oxygenation.
Gegen Qinlian decoction enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by remodelling the gut microbiota and the tumour microenvironment
Authors: Lv Ji , Jia Yitao , Li Jing , Kuai Wentao , Li Yang , Guo Fang , Xu Xinjian , Zhao Zhaolong , Lv Jian , Li Zhongxin 
Published: May 2019

AbstractTherapeutic antibodies targeting PD-1 have made major breakthroughs in cancer treatment. However, the majority of colorectal cancer (CRC) cases are microsatellite stable (MSS) and do not respond to anti-PD-1-based immunotherapy. Combination therapy will be an ideal strategy to overcome this limitation. Gegen Qinlian decoction (GQD), a classical traditional Chinese medicine (TCM) formula, has been clinically proven to be effective in the treatment of ulcerative colitis (UC) and type 2 diabetes mellitus. Here, a systemic pharmacological study revealed that GQD acts through multiple targets and pathways in the human body. Combination therapy with GQD and anti-mouse PD-1 potently inhibited the growth of CT26 tumours in a xenograft model. Gut microbiota analysis revealed that combination therapy with GQD and anti-mouse PD-1 significantly enriched for s__Bacteroides_acidifaciens and s__uncultured_organism_g__norank_f__Bacteroidales_S24-7_group. Based on metabolomic analyses, profoundly altered metabolites were identified in the combination therapy group. Two metabolic signalling pathways, namely, glycerophospholipid metabolism and sphingolipid metabolism, were explored. In particular, we found that combination therapy with GQD and anti-mouse PD-1 significantly increased the proportion of CD8+ T cells in peripheral blood and tumour tissues. Direct treatment with GQD and anti-mouse PD-1 increased the expression of IFN-γ, which is a critical factor in antitumour immunotherapy. In addition, combination therapy with GQD and anti-mouse PD-1 downregulated PD-1 and increased IL-2 levels, suggesting that the combination therapy could effectively restore T-cell functions by suppressing inhibitory checkpoints. The application of the Chinese medicinal formula GQD with PD-1 blockade-based immunotherapy can be a novel therapeutic strategy for CRC patients with MSS tumours.
Delineating the role of eIF2α in retinal degeneration
Authors: Starr Christopher R. , Gorbatyuk Marina S. 
Published: May 2019

AbstractActivation of the unfolded protein response has been detected in various animal models of retinal degeneration. The PERK branch converges on eIF2α to regulate protein synthesis. We previously reported that diseased retinas produce less protein as they degenerate. We also proposed that the majority of this reduction in protein synthesis may not be due to control of eIF2α. Nevertheless, multiple research groups have reported that modulating eIF2α levels may be a viable strategy in the treatment of neurodegenerative diseases. Here, using two genetic approaches, a systemic Gadd34 knockout and a photoreceptor conditional Perk knockout, to alter p-eIF2α levels in rd16 mice, we demonstrate not only that degenerating retinas may not use this mechanism to signal for a decline in protein synthesis rates but also that modulation of p-eIF2α levels is insufficient to delay retinal degeneration.
HMGB1 contributes to SASH1 methylation to attenuate astrocyte adhesion
Authors: Wu Ronghua , Yan Yingying , Ma Chao , Chen Han , Dong Zhangji , Wang Yongjun , Liu Yan , Liu Mei , Yang Liu 
Published: May 2019

AbstractSAM and SH3 domain-containing 1 (SASH1), a scaffold protein, is regarded as a tumor suppressor. Recent studies have verified the decreased expression of SASH1 in many tumors. Our previous clinical investigation found that SASH1 was widely expressed in normal brain tissues but reduced or absent in glioma tissues. However, the functions of SASH1 in normal astrocytes and the reasons for the reductions in SASH1 levels in glioma tissues are unclear. In this study, we found that in astrocytes, SASH1 functions in cell adhesion. We observed that knockdown of SASH1 expression in cultured astrocytes significantly decreased cell adhesion and increased invasion. Conversely, overexpression of SASH1 in C6 cells markedly promoted cell adhesion and decreased cell invasion. In addition, we found that the expression level of one member of the integrin family, integrin β8, was significantly reduced in SASH1-downregulated astrocytes and elevated in SASH1-upregulated C6 cells. Furthermore, the results of methylation and ChIP assays showed that the methylation level of the SASH1 gene was markedly higher in C6 cells than in astrocytes and that HMGB1 could bind to the CpG islands of the SASH1 gene. HMGB1 overexpression in astrocytes significantly increased the methylation level of the SASH1 gene. This study reveals, for the first time, that HMGB1 contributes to the methylation of the SASH1 gene, and our findings suggest that methylation downregulates the expression of the SASH1 gene and later reduces integrin β8 expression, thereby reducing cell adhesion and promoting cell migration.
ZNF479 downregulates metallothionein-1 expression by regulating ASH2L and DNMT1 in hepatocellular carcinoma
Authors: Wu Yi-Ju , Ko Bor-Sheng , Liang Shu-Man , Lu Yi-Jhu , Jan Yee-Jee , Jiang Shih-Sheng , Shyue Song-Kun , Chen Linyi , Liou Jun-Yang 
Published: May 2019

AbstractDecreased expression of metallothionein-1 (MT-1) is associated with a poor prognosis in hepatocellular carcinoma (HCC). Here, we found that MT-1 expression was suppressed by 14-3-3ε, and MT-1 overexpression abolished 14-3-3ε-induced cell proliferation and tumor growth. We identified that 14-3-3ε induced expression of ZNF479, a novel potential transcriptional regulator by gene expression profiling and ZNF479 contributed to 14-3-3ε-suppressed MT-1 expression. ZNF479 induced the expression of DNMT1, UHRF1, and mixed-lineage leukemia (MLL) complex proteins (ASH2L and Menin), and increased tri-methylated histone H3 (H3K4me3) levels, but suppressed H3K4 (H3K4me2) di-methylation. ZNF479-suppressed MT-1 expression was restored by silencing of ASH2L and DNMT1. Furthermore, ZNF479 expression was higher in HCC tissues than that in the non-cancerous tissues. Expression analyses revealed a positive correlation between the expression of ZNF479 and DNMT1, UHRF1, ASH2L, and Menin, and an inverse correlation with that of ZNF479, ASH2L, Menin, and MT-1 isoforms. Moreover, correlations between the expression of ZNF479 and its downstream factors were more pronounced in HCC patients with hepatitis B. Here, we found that ZNF479 regulates MT-1 expression by modulating ASH2L in HCC. Approaches that target ZNF479/MLL complex/MT-1 or related epigenetic regulatory factors are potential therapeutic strategies for HCC.
Sprouty1 is a weight-loss target gene in human adipose stem/progenitor cells that is mandatory for the initiation of adipogenesis
Authors: Mandl Markus , Wagner Sonja A. , Hatzmann Florian M. , Mitterberger-Vogt Maria C. , Zwierzina Marit E. , Mattesich Monika , Zwerschke Werner 
Published: May 2019

AbstractThe differentiation of adipose stem/progenitor cells (ASCs) into adipocytes contributes to adipose tissue expansion in obesity. This process is regulated by numerous signalling pathways including MAPK signalling. In the present study, we show that weight loss (WL) interventions induce upregulation of Sprouty1 (SPRY1), a negative regulator of MAPK signalling, in human ASCs and elucidate the role of the Sprouty1/MAPK interaction for adipogenic differentiation. We found that the Sprouty1 protein levels are low in proliferating ASCs, increasing in density arrested ASCs at the onset of adipogenic differentiation and decreasing in the course of adipogenesis. Knock-down (KD) of Sprouty1 by RNA interference led to elevated MAPK activity and reduced expression of the early adipogenic transcription factor CCAAT/enhancer-binding protein β (C/EBP β), concomitant with an abrogation of adipogenesis. Intriguingly, co-treatment of Sprouty1 KD ASCs with differentiation medium and the pharmacological MEK inhibitor U0126 blunted ERK phosphorylation; however, failed to rescue adipogenic differentiation. Thus, the effects of the Sprouty1 KD are not reversed by inhibiting MAPK signalling although the inhibition of MAPK signalling by U0126 did not prevent adipogenic differentiation in wild type ASCs. In conclusion, we show that Sprouty1 is induced after WL in ASCs of formerly obese people acting as a negative regulator of MAPK signalling, which is necessary to properly trigger adipogenesis at early stages by a C/EBP β dependent mechanism.
Interspecies conservation of organisation and function between nonhomologous regional centromeres
Authors: Tong Pin , Pidoux Alison L. , Toda Nicholas R. T. , Ard Ryan , Berger Harald , Shukla Manu , Torres-Garcia Jesus , Müller Carolin A. , Nieduszynski Conrad A. , Allshire Robin C. 
Published: May 2019

AbstractDespite the conserved essential function of centromeres, centromeric DNA itself is not conserved. The histone-H3 variant, CENP-A, is the epigenetic mark that specifies centromere identity. Paradoxically, CENP-A normally assembles on particular sequences at specific genomic locations. To gain insight into the specification of complex centromeres, here we take an evolutionary approach, fully assembling genomes and centromeres of related fission yeasts. Centromere domain organization, but not sequence, is conserved between Schizosaccharomyces pombe, S. octosporus and S. cryophilus with a central CENP-ACnp1 domain flanked by heterochromatic outer-repeat regions. Conserved syntenic clusters of tRNA genes and 5S rRNA genes occur across the centromeres of S. octosporus and S. cryophilus, suggesting conserved function. Interestingly, nonhomologous centromere central-core sequences from S. octosporus and S. cryophilus are recognized in S. pombe, resulting in cross-species establishment of CENP-ACnp1 chromatin and functional kinetochores. Therefore, despite the lack of sequence conservation, Schizosaccharomyces centromere DNA possesses intrinsic conserved properties that promote assembly of CENP-A chromatin.
The economics of malaria control in an age of declining aid
Authors: Maskin Eric , Monga Célestin , Thuilliez Josselin , Berthélemy Jean-Claude 
Published: May 2019

AbstractThis article examines financing in the fight against malaria. After briefly describing malaria control plans in Africa since 2000, it offers a stylized model of the economics of malaria and shows how health aid can help escape the malaria trap.
African elephant poaching rates correlate with local poverty, national corruption and global ivory price
Authors: Hauenstein Severin , Kshatriya Mrigesh , Blanc Julian , Dormann Carsten F. , Beale Colin M. 
Published: May 2019

AbstractPoaching is contributing to rapid declines in elephant populations across Africa. Following high-profile changes in the political environment, the overall number of illegally killed elephants in Africa seems to be falling, but to evaluate potential conservation interventions we must understand the processes driving poaching rates at local and global scales. Here we show that annual poaching rates in 53 sites strongly correlate with proxies of ivory demand in the main Chinese markets, whereas between-country and between-site variation is strongly associated with indicators of corruption and poverty. Our analysis reveals a recent decline in annual poaching mortality rate from an estimated peak of over 10% in 2011 to <4% in 2017. Based on these findings, we suggest that continued investment in law enforcement could further reduce poaching, but is unlikely to succeed without action that simultaneously reduces ivory demand and tackles corruption and poverty.
The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models
Authors: Martínez-Vélez Naiara , Garcia-Moure Marc , Marigil Miguel , González-Huarriz Marisol , Puigdelloses Montse , Gallego Pérez-Larraya Jaime , Zalacaín Marta , Marrodán Lucía , Varela-Guruceaga Maider , Laspidea Virginia , Aristu Jose Javier , Ramos Luis Isaac , Tejada-Solís Sonia , Díez-Valle Ricardo , Jones Chris , Mackay Alan , Martínez-Climent Jose A. , García-Barchino Maria Jose , Raabe Eric , Monje Michelle , Becher Oren J. , Junier Marie Pierre , El-Habr Elias A. , Chneiweiss Herve , Aldave Guillermo , Jiang Hong , Fueyo Juan , Patiño-García Ana , Gomez-Manzano Candelaria , Alonso Marta M. 
Published: May 2019

AbstractPediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032).