bluuebunny/crossref_metadata_2025 huggingface dataset:
“I'm on My Way to a Heav'nly Lan’”:Porgy and Bessas American Religious Export to the USSR
Authors: LESON LENA
Published: May 2021

Scholars have explored the use of Breen-Davis'sPorgy and Bessand its stellar ensemble cast to counter Soviet criticism of US race relations during the Cold War—but an equally prominent theme in contemporary coverage of the production is spirituality. Onstage as well as off, the Soviet tour ofPorgy and Bessreflected both American and Soviet ideas about religion's role in international diplomacy in the mid-1950s. This article explores religiosity in the Breen-Davis production as well as the reception of the 1955–56 Soviet tour both in the United States, where the production represented a hopeful vision of the nation's racial tolerance and religious pluralism, and in the USSR, where the tour's twin messages of American spiritual superiority and racial equality were challenged by Soviet authorities. Drawing on materials from the Robert Breen Archives housed in the Jerome Lawrence and Robert Lee Theatre Research Institute at Ohio State University, this article considers Breen-Davis'sPorgy and Bessas a religious export to the USSR, enriching our understanding of US cultural diplomacy and Cold War–era musical exchange with broader implications for American–Soviet history, religious studies, and opera analysis.
The ASCAP-BMI Feud, Status Panic, and the Struggle for Cold War Consensus
Authors: BRACKETT JOHN
Published: May 2021

By the 1950s, ASCAP and its associated songwriters and composers seemed out of touch with contemporary musical tastes and industry trends. With the introduction of competition in the form of BMI in 1939, many members of ASCAP were experiencing a sense of status anxiety, an anxiety exacerbated by the many cultural, social, political, and economic changes that swept across postwar US society. Rather than adapt to the changing musical landscape of the 1950s, some members argued that ASCAP's fading cultural prestige and diminished influence within the music industry were the result of a conspiracy perpetrated by the broadcast networks and BMI. This article examines how, in an attempt to reassert the status and prestige they had enjoyed before the war, ASCAP and its supporters exploited contemporary Cold War anxieties as part of their ongoing feud with BMI. In congressional hearings from 1956 and 1958, individuals and organizations sympathetic to ASCAP portrayed BMI as part of a coordinated conspiracy that not only threatened free market practices through the establishment of an alleged “electronic curtain,” but also sought to foist an inferior product on audiences who were being manipulated by “hidden persuaders.” I suggest that the rhetoric that dominated both of these hearings reflects ideological debates that were being fought at the height of the Cold War, debates involving the culture of consensus and the image of the “American Way.”
Future Sea Level Change Under Coupled Model Intercomparison Project Phase 5 and Phase 6 Scenarios From the Greenland and Antarctic Ice Sheets
Authors: Payne Antony J. , Nowicki Sophie , Abe‐Ouchi Ayako , Agosta Cécile , Alexander Patrick , Albrecht Torsten , Asay‐Davis Xylar , Aschwanden Andy , Barthel Alice , Bracegirdle Thomas J. , Calov Reinhard , Chambers Christopher , Choi Youngmin , Cullather Richard , Cuzzone Joshua , Dumas Christophe , Edwards Tamsin L. , Felikson Denis , Fettweis Xavier , Galton‐Fenzi Benjamin K. , Goelzer Heiko , Gladstone Rupert , Golledge Nicholas R. , Gregory Jonathan M. , Greve Ralf , Hattermann Tore , Hoffman Matthew J. , Humbert Angelika , Huybrechts Philippe , Jourdain Nicolas C. , Kleiner Thomas , Munneke Peter Kuipers , Larour Eric , Le clec'h Sebastien , Lee Victoria , Leguy Gunter , Lipscomb William H. , Little Christopher M. , Lowry Daniel P. , Morlighem Mathieu , Nias Isabel , Pattyn Frank , Pelle Tyler , Price Stephen F. , Quiquet Aurélien , Reese Ronja , Rückamp Martin , Schlegel Nicole‐Jeanne , Seroussi Hélène , Shepherd Andrew , Simon Erika , Slater Donald , Smith Robin S. , Straneo Fiammetta , Sun Sainan , Tarasov Lev , Trusel Luke D. , Van Breedam Jonas , van de Wal Roderik , van den Broeke Michiel , Winkelmann Ricarda , Zhao Chen , Zhang Tong , Zwinger Thomas
Published: May 2021

Projections of the sea level contribution from the Greenland and Antarctic ice sheets (GrIS and AIS) rely on atmospheric and oceanic drivers obtained from climate models. The Earth System Models participating in the Coupled Model Intercomparison Project phase 6 (CMIP6) generally project greater future warming compared with the previous Coupled Model Intercomparison Project phase 5 (CMIP5) effort. Here we use four CMIP6 models and a selection of CMIP5 models to force multiple ice sheet models as part of the Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6). We find that the projected sea level contribution at 2100 from the ice sheet model ensemble under the CMIP6 scenarios falls within the CMIP5 range for the Antarctic ice sheet but is significantly increased for Greenland. Warmer atmosphere in CMIP6 models results in higher Greenland mass loss due to surface melt. For Antarctica, CMIP6 forcing is similar to CMIP5 and mass gain from increased snowfall counteracts increased loss due to ocean warming.
Role of Groundwater in Sustaining Northern Himalayan Rivers
Authors: Yao Yingying , Zheng Chunmiao , Andrews Charles B. , Scanlon Bridget R. , Kuang Xingxing , Zeng Zhenzhong , Jeong Su‐Jong , Lancia Michele , Wu Yiping , Li Guoshuai
Published: May 2021

The Himalayas are critical for supplying water for ∼2 billion people who live downstream, and available water is highly sensitive to climate change. The role of the groundwater system in sustaining the northern Himalayan rivers remains unknown, and this compromises Asia's future water sustainability. Here, we quantify the spatiotemporal contribution of groundwater to river flows in the Yarlung Zangbo Basin (upper reaches of Brahmaputra). Our results show that the groundwater recharge represents ∼23% of mean annual precipitation, translating into ∼30 km3/yr of baseflow, which contributes ∼55% of the total river discharge in the upstream reaches to ∼27% in the downstream reaches. The percentage of groundwater contribution is inversely related to topographic steepness and total precipitation, with the steepest topography and highest precipitation in the eastern Himalayas. This study fills a knowledge gap on groundwater in the Himalayas and is a foundation for projecting water changes under climatic warming.
Dissolved Organic Matter in the Upwelling System off Peru: Imprints of Bacterial Activity and Water Mass Characteristics
Authors: Maßmig Marie , Engel Anja
Published: May 2021

Microbial degradation of dissolved organic matter (DOM) contributes to the formation and preservation of oxygen minimum zones (OMZs) in the ocean, but information on the spatial distribution and molecular composition of DOM in OMZ regions is scarce. We quantified molecular components of DOM that is, dissolved amino acids (DAA) and dissolved combined carbohydrates (DCCHO), in the upwelling region off Peru. We found the highest concentrations of DCCHO in fully oxygenated surface waters steeply declining at shallow depth. The highest DAA concentrations were observed close to the surface also, but attenuation of DAA concentration over depth was less pronounced. Compositional changes of DCCHO were strongest within more oxygenated waters. Compositional changes of DAA were also evident under suboxic conditions (<5 µmol O2 kg−1) and indicated bacterial peptide degradation. Moreover, specific free amino acids (alanine and threonine) were enhanced within suboxic waters, pointing to a potential production of dissolved organic nitrogen under suboxic conditions. Our results therewith suggest that deoxygenation supports a spatial decoupling of DCCHO and DAA production and degradation dynamics and give new insights to carbon and nitrogen cycling in the OMZ off Peru.
Logjams and Channel Morphology Influence Sediment Storage, Transformation of Organic Matter, and Carbon Storage Within Mountain Stream Corridors
Authors: Sutfin Nicholas A. , Wohl Ellen , Fegel Timothy , Day Natalie , Lynch Laurel
Published: May 2021

The flow of organic matter (OM) along rivers and retention within floodplains contributes significantly to terrestrial carbon storage and ecosystem function. The storage and cycling of OM largely depend upon hydrogeomorphic characteristics of streams and valleys, including channel geometry and the connectivity of water across and within the floodplain. To examine the role of river morphology on carbon dynamics in mountain streams, we (a) quantify organic carbon (OC) storage in fine sediment, litter, and wood along 24 forested gravel‐bed stream reaches in the Rocky Mountains of CO, USA, (b) examine morphological factors that regulate sediment and OC storage (e.g., channel width, slope, logjams), and (c) utilize fluorescence spectroscopy to examine how the composition of fluorescent dissolved OM in surface water and floodplain fine sediment are influenced by channel morphology. Multivariate regression of the study reaches, which have varying degrees of confinement, slope, and elevation, indicates that OC storage per area is higher in less confined valleys, in lower gradient stream reaches, and at higher elevations. Within unconfined valleys, limited storage of fine sediment and greater microbial transformation of OM in multithread channel reaches decreases OC storage per area (252 ± 39 Mg C ha−1) relative to single‐thread channel reaches (346 ± 177 Mg C ha−1). Positive feedbacks between channel morphology and persistent channel‐spanning logjams that divert flow into multiple channels may limit the aggradation of floodplain fine sediment. Although multithread stream reaches are less effective OC reservoirs, they are hotspots for OM decomposition and provide critical resources to downstream food webs.
Chicxulub Impact Changed Tropical Rain Forest Biodiversity Forever
Authors: Basilio Humberto
Published: May 2021

Sixty-six million years ago, an asteroid reset most of life on Earth. But without this catastrophic event, the composition of neotropical rain forests wouldn’t be the same.
Simulated Southern Ocean Upwelling at the Last Glacial Maximum and Early Deglaciation: The Role of Eddy‐Induced Overturning Circulation
Authors: Chen Changlin , Wang Guihua
Published: May 2021

We explore the changes in Southern Ocean upwelling patterns during the last glacial maximum (LGM) and early deglaciation using a fully coupled climate model with ocean eddies parameterized via the Gent‐McWilliams scheme. Relative to the preindustrial climate, the model simulates an equatorward shift of the upwelling of the residual circulation in the Southern Ocean during the LGM, which is consistent with paleo‐evidence of export production. This change in upwelling primarily arose from an altered eddy‐induced meridional overturning circulation (MOC) that resulted from the expanded sea ice and enhanced buoyancy loss around Antarctica during the LGM, which modulated the slope of buoyancy surface in the Southern Ocean. We have also found that there was a poleward shift of the upwelling of the residual circulation in the Southern Ocean during the early deglaciation, which was different than the change in the wind‐driven upwelling and primarily driven by variations in the eddy‐induced MOC.
Rapid Injections of MeV Electrons and Extremely Fast Step‐Like Outer Radiation Belt Enhancements
Authors: Kim H.‐J. , Lee D.‐Y. , Wolf R. , Bortnik J. , Kim K.‐C. , Lyons L. , Choe W. , Noh S.‐J. , Choi K.‐E. , Yue C. , Li J.
Published: May 2021

Rapid injection of MeV electrons associated with strong substorm dipolarization has been suggested as a potential explanation for some radiation belt enhancement events. However, it has been difficult to quantify the contribution of MeV electron injections to radiation belt enhancements. This paper presents two isolated MeV electron injection events for which we quite precisely quantify how the entire outer‐belt immediately changed with the injections. Tracking detailed outer‐belt evolution observed by Van Allen Probes, for both events, we identify large step‐like relativistic electron enhancements (roughly 1 order of magnitude increase for ∼2 MeV electron fluxes) for L ≳ 3.8 and L ≳ 4.6, respectively, that occurred on ∼30‐min time scales nearly instantaneously with the injections. The enhancements occurred almost simultaneously for 10s keV to multi‐MeV electrons, with the lowest L of enhancement region located farther out for higher energy. The outer‐belt stayed at these new levels for ≳several hours without substantial subsequent enhancements.
On the Relevance of Geodetic Deformation Rates to Earthquake Potential
Authors: Wang Kelin , Zhu Yijie , Nissen Edwin , Shen Zheng‐Kang
Published: May 2021

Despite the importance of viscoelasticity in the evolution of crustal stress/strain being widely recognized, the interpretation of interseismic geodetic measurements for assessing earthquake potential is still based overwhelmingly on elastic models. The reasons for this disparity include conflating deformation rates with deformation itself and the lack of a succinct representation of the seismic readiness of a locked fault in a viscoelastic Earth. Using a classical viscoelastic model for strike‐slip faults, we reiterate the commonly overlooked message that, if the recurrence interval is long, most of the strain energy for the next earthquake accrues early in the cycle, and low strain rates later in the cycle by no means indicate diminished rupture potential. Fault stress stays near failure for much of the late interseismic period which may explain why slow slip‐rate faults have more variable recurrence intervals than fast slip‐rate faults. We propose to use displacement deficit instead of slip deficit to represent seismic readiness.
Comprehensive Insights Into O3 Changes During the COVID‐19 From O3 Formation Regime and Atmospheric Oxidation Capacity
Authors: Zhu Shengqiang , Poetzscher James , Shen Juanyong , Wang Siyu , Wang Peng , Zhang Hongliang
Published: May 2021

Economic activities and the associated emissions have significantly declined during the 2019 novel coronavirus (COVID‐19) pandemic, which has created a natural experiment to assess the impact of the emitted precursor control policy on ozone (O3) pollution. In this study, we utilized comprehensive satellite, ground‐level observations, and source‐oriented chemical transport modeling to investigate the O3 variations during the COVID‐19 pandemic in China. Here, we found that the significant elevated O3 in the North China Plain (40%) and Yangtze River Delta (35%) were mainly attributed to the enhanced atmospheric oxidation capacity (AOC) in these regions, associated with the meteorology and emission reduction during lockdown. Besides, O3 formation regimes shifted from VOC‐limited regimes to NOx‐limited and transition regimes with the decline of NOx during lockdown. We suggest that future O3 control policies should comprehensively consider the effects of AOC on the O3 elevation and coordinated regulations of the O3 precursor emissions.
Postwildfire Soil‐Hydraulic Recovery and the Persistence of Debris Flow Hazards
Authors: Thomas Matthew A. , Rengers Francis K. , Kean Jason W. , McGuire Luke A. , Staley Dennis M. , Barnhart Katherine R. , Ebel Brian A.
Published: May 2021

Deadly and destructive debris flows often follow wildfire, but understanding of changes in the hazard potential with time since fire is poor. We develop a simulation‐based framework to quantify changes in the hydrologic triggering conditions for debris flows as postwildfire infiltration properties evolve through time. Our approach produces time‐varying rainfall intensity‐duration thresholds for runoff‐ and infiltration‐generated debris flows with physics‐based hydrologic simulations that are parameterized with widely available hydroclimatic, vegetation reflectance, and soil texture data. When we apply our thresholding protocol to a test case in the San Gabriel Mountains (California, USA), the results are consistent with existing regional empirical thresholds and rainstorms that caused runoff‐ and infiltration‐generated debris flows soon after and three years following a wildfire, respectively. We find that the hydrologic triggering mechanisms for the two observed debris flow types are coupled with the effects of fire on the soil saturated hydraulic conductivity. Specifically, the rainfall intensity needed to generate debris flows via runoff increases with time following wildfire while the rainfall duration needed to produce debris flows via subsurface pore‐water pressures decreases. We also find that variations in soil moisture, rainfall climatology, median grain size, and root reinforcement could impact the median annual probability of postwildfire debris flows. We conclude that a simulation‐based method for calculating rainfall thresholds is a tractable approach to improve situational awareness of debris flow hazard in the years following wildfire. Further development of our framework will be important to quantify postwildfire hazard levels in variable climates, vegetation types, and fire regimes.
Targeting of adipose tissue macrophages by bee venom phospholipase A2 attenuates high-fat diet-induced obesity
Authors: Jeong Hyunju , Lee Chanju , Cheng Chenyu , Chou Hung Chun , Yang HyeJin , Bae Hyunsu
Published: May 2021

Background/objectives

Adipose tissue macrophages (ATMs) exist in either the M1 or M2 form. The anti-inflammatory M2 ATMs accumulate in lean individuals, whereas the pro-inflammatory M1 ATMs accumulate in obese individuals. Bee venom phospholipase A2 (bvPLA2), a major component in honeybee (Apis mellifera) venom, exerts potent anti-inflammatory effects via interactions with regulatory T cells (Treg) and macrophages. This study investigated the effects of bvPLA2 on a high-fat diet (HFD)-induced obesity in mice.

Subjects/methods

For in vivo experiments, male C57BL/6, CD206-deficient, and Treg-depleted mice models were fed either a normal diet 41.86 kJ (ND, 10 kcal% fat) or high-fat diet 251.16 kJ (HFD, 60 kcal% fat). Each group was i.p. injected with PBS or bvPLA2 (0.5 mg/kg) every 3 days for 11 weeks. Body weight and food intake were measured weekly. Histological changes in the white adipose tissue (WAT), liver, and kidney as well as the immune phenotypes of the WAT were examined. Immune cells, cytokines, and lipid profiles were also evaluated. The direct effects of bvPLA2 on 3T3-L1 pre-adipocytes and bone marrow-derived macrophages were measured in vitro.

Results

bvPLA2 markedly decreased bodyweight in HFD-fed mice. bvPLA2 treatment also decreased lipid accumulation in the liver and reduced kidney inflammation in the mice. It was confirmed that bvPLA2 exerted immunomodulatory effects through the CD206 receptor. In addition, bvPLA2 decreased M1 ATM and alleviated the M1/M2 imbalance in vivo. However, bvPLA2 did not directly inhibit adipogenesis in the 3T3-L1 adipose cells in vitro.

Conclusions

bvPLA2 is a potential therapeutic strategy for the management of obesity by regulating adipose tissue macrophage homeostasis.
WAPL induces cervical intraepithelial neoplasia modulated with estrogen signaling without HPV E6/E7
Authors: Kumagai Katsuyoshi , Takanashi Masakatsu , Ohno Shin-ichiro , Harada Yuichirou , Fujita Koji , Oikawa Keiki , Sudo Katsuko , Ikeda Shun-ichi , Nishi Hirotaka , Oikawa Kosuke , Kuroda Masahiko
Published: May 2021

Since cervical cancer still afflicts women around the world, it is necessary to understand the underlying mechanism of cervical cancer development. Infection with HPV is essential for the development of cervical intraepithelial neoplasia (CIN). In addition, estrogen receptor signaling is implicated in the development of cervical cancer. Previously, we have isolated human wings apart-like (WAPL), which is expected to cause chromosomal instability in the process of HPV-infected precancerous lesions to cervical cancer. However, the role of WAPL in the development of CIN is still unknown. In this study, in order to elucidate the role of WAPL in the early lesion, we established WAPL overexpressing mice (WAPL Tg mice) and HPV E6/E7 knock-in (KI) mice. WAPL Tg mice developed CIN lesion without HPV E6/E7. Interestingly, in WAPL Tg mice estrogen receptor 1 (ESR1) showed reduction as compared with the wild type, but cell growth factors MYC and Cyclin D1 controlled by ESR1 expressed at high levels. These results suggested that WAPL facilitates sensitivity of ESR1 mediated by some kind of molecule, and as a result, affects the expression of MYC and Cyclin D1 in cervical cancer cells. To detect such molecules, we performed microarray analysis of the uterine cervix in WAPL Tg mice, and focused MACROD1, a co-activator of ESR1. MACROD1 expression was increased in WAPL Tg mice compared with the wild type. In addition, knockdown of WAPL induced the downregulation of MACROD1, MYC, and Cyclin D1 but not ESR1 expression. Furthermore, ESR1 sensitivity assay showed lower activity in WAPL or MACROD1 downregulated cells than control cells. These data suggested that WAPL increases ESR1 sensitivity by activating MACROD1, and induces the expression of MYC and Cyclin D1. Therefore, we concluded that WAPL not only induces chromosomal instability in cervical cancer tumorigenesis, but also plays a key role in activating estrogen receptor signaling in early tumorigenesis.
N6-methyladenosine demethylase FTO impairs hepatic ischemia–reperfusion injury via inhibiting Drp1-mediated mitochondrial fragmentation
Authors: Du Ying Dong , Guo Wen Yuan , Han Cong Hui , Wang Ying , Chen Xiao Song , Li Da Wei , Liu Jin Long , Zhang Ming , Zhu Nan , Wang Xin
Published: May 2021

Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role and the underlying regulatory mechanism in the liver remain largely unexplored. In the present study, we showed that fat mass and obesity-associated protein (FTO, an m6A demethylase) was involved in mitochondrial function during hepatic ischemia–reperfusion injury (HIRI). We found that the expression of m6A demethylase FTO was decreased during HIRI. In contrast, the level of m6A methylated RNA was enhanced. Adeno-associated virus-mediated liver-specific overexpression of FTO (AAV8-TBG-FTO) ameliorated the HIRI, repressed the elevated level of m6A methylated RNA, and alleviated liver oxidative stress and mitochondrial fragmentation in vivo and in vitro. Moreover, dynamin-related protein 1 (Drp1) was a downstream target of FTO in the progression of HIRI. FTO contributed to the hepatic protective effect via demethylating the mRNA of Drp1 and impairing the Drp1-mediated mitochondrial fragmentation. Collectively, our findings demonstrated the functional importance of FTO-dependent hepatic m6A methylation during HIRI and provided valuable insights into the therapeutic mechanisms of FTO.
Circular RNA hsa_circ_0006401 promotes proliferation and metastasis in colorectal carcinoma
Authors: Zhang Chenjing , Zhou Xiaolu , Geng Xiaoge , Zhang Yu , Wang Jingya , Wang Yanan , Jing Jiyong , Zhou Xuelong , Pan Wensheng
Published: May 2021

Dysregulation of circular RNA (circRNA) expression is involved in the progression of cancer. Here, we aimed to study the potential function of hsa_circ_0006401 in colorectal cancer (CRC). CircRNA hsa_circ_0006401 expression levels in CRC and adjacent nontumor tissues were analyzed by real-time quantitative PCR (qRT-PCR) and circRNA in situ hybridization (RNA-ISH). Then, CRC cell proliferation was assessed by cell counting. Wound-healing and transwell assays were utilized to detect the effect of hsa_circ_0006401 on CRC migration. A circRNA-ORF construct was created, and a specific antibody against the splice junction of hsa_circ_0006401 was prepared. Finally, the proteins directly binding to hsa_circ_0006401 peptides were identified by immunoprecipitation combined with mass spectrometry. In our study, we found hsa_circ_0006401 was closely related to CRC metastasis and exhibited upregulated expression in metastatic CRC tissue samples. Proliferation and migration were inhibited in vitro when hsa_circ_0006401 expression was silenced. Downregulation of hsa_circ_0006401 expression decreased CRC proliferation and liver metastasis in vivo. A 198-aa peptide was encoded by sequences of the splice junction absent from col6a3. Hsa_circ_0006401 promoted CRC proliferation and migration by encoding the hsa_circ_0006401 peptide. Hsa_circ_0006401 peptides decreased the mRNA and protein level of the host gene col6a3 by promoting col6a3 mRNA stabilation. In conclusion, our study revealed that circRNAs generated from col6a3 that contain an open-reading frame (ORF) encode a novel 198-aa functional peptide and hsa_circ_0006401 peptides promote stability of the host gene col6a3 mRNA to promote CRC proliferation and metastasis.
Interrogation of gender disparity uncovers androgen receptor as the transcriptional activator for oncogenic miR-125b in gastric cancer
Authors: Liu Ben , Zhou Meng , Li Xiangchun , Zhang Xining , Wang Qinghua , Liu Luyang , Yang Meng , Yang Da , Guo Yan , Zhang Qiang , Zheng Hong , Wang Qiong , Li Lian , Chu Xinlei , Wang Wei , Li Haixin , Song Fengju , Pan Yuan , Zhang Wei , Chen Kexin
Published: May 2021

There is a male preponderance in gastric cancer (GC), which suggests a role of androgen and androgen receptor (AR). However, the mechanism of AR signaling in GC especially in female patients remains obscure. We sought to identify the AR signaling pathway that might be related to prognosis and examine the potential clinical utility of the AR antagonist for treatment. Deep learning and gene set enrichment analysis was used to identify potential critical factors associated with gender bias in GC (n = 1390). Gene expression profile analysis was performed to screen differentially expressed genes associated with AR expression in the Tianjin discovery set (n = 90) and TCGA validation set (n = 341). Predictors of survival were identified via lasso regression analyses and validated in the expanded Tianjin cohort (n = 373). In vitro and in vivo experiments were established to determine the drug effect. The GC gender bias was attributable to sex chromosome abnormalities and AR signaling dysregulation. The candidates for AR-related gene sets were screened, and AR combined with miR-125b was associated with poor prognosis, particularly among female patients. AR was confirmed to directly regulatemiR-125bexpression. AR-miR-125b signaling pathway inhibited apoptosis and promoted proliferation. AR antagonist, bicalutamide, exerted anti-tumor activities and induced apoptosis both in vitro and in vivo, using GC cell lines and female patient-derived xenograft (PDX) model. We have shed light on gender differences by revealing a hormone-regulated oncogenic signaling pathway in GC. Our preclinical studies suggest that AR is a potential therapeutic target for this deadly cancer type, especially in female patients.
GIPC2 is an endocrine-specific tumor suppressor gene for both sporadic and hereditary tumors of RET- and SDHB-, but not VHL-associated clusters of pheochromocytoma/paraganglioma
Authors: Dong Yeqing , Huang Yongsheng , Fan Chengyan , Wang Liang , Zhang Ran , Li Wenhua , Guo Zhengguang , Wang Dong , Zheng Zhi
Published: May 2021

Pheochromocytoma/paraganglioma (PPGL) is an endocrine tumor of the chromaffin cells in the adrenal medulla or the paraganglia. Currently, about 70% of PPGLs can be explained by germline or somatic mutations in several broadly expressed susceptibility genes including RET, VHL, and SDHB, while for the remaining, mainly sporadic cases, the pathogenesis is still unclear. Even for known susceptible genes, how mutations in these mostly ubiquitous genes result in tissue-specific pathogenesis remains unanswered, and why RET-mutated tumors almost always occur in the adrenal while SDHB-mutated tumors mostly occur extra-adrenal remains a mystery. By analyzing 22 sporadic PPGLs using SNP 6.0 genotyping arrays combined with expression profiling of 4 normal and 4 tumor tissues, we identified GIPC2, a gene located at 1p31.1 with preferential expression in adrenal and inducible by adrenal glucocorticoid, as a novel putative tumor suppressor gene for PPGLs. Copy number deletion and GIPC2 promoter hypermethylation but not GIPC2 mutation, accompanied with reduced GIPC2 expression, were observed in 39 of 55 PPGLs in our cohort. Examination of a published expression database consisting of 188 PPGLs found little GIPC2 expression in Cluster 1A (SDHx-associated) and Cluster 2A (NF1/RET-associated) tumors, but less pronounced reduction of GIPC2 expression in Cluster 1B (VHL-associated) and Cluster 2B/2C tumors. GIPC2 induced p27, suppressed MAPK/ERK and HIF-1ɑ pathways as well as cancer cell proliferation. Overexpressing GIPC2 in PC12 cells inhibited tumor growth in nude mice. We found GIPC2 interacted with the nucleoprotein NONO and both proteins regulated p27 transcription through the same GGCC box on p27 promoter. Significantly, low expression of both GIPC2 and p27 was associated with shorter disease-free survival time of PPGLs patients in the TCGA database. We found that PPGL-causing mutations in RET and in SDHB could lead to primary rat adrenal chromaffin cell proliferation, ERK activation, and p27 downregulation, all requiring downregulating GIPC2. Notably, the RET-mutant effect required the presence of dexamethasone while the SDHB-mutant effect required its absence, providing a plausible explanation for the tumor location preference. In contrast, the PPGL-predisposing VHL mutations had no effect on proliferation and GIPC2 expression but caused p53 downregulation and reduced apoptosis in chromaffin cells compared with wild-type VHL. Thus, our study raises the importance of cortical hormone in PPGL development, and GIPC2 as a novel tumor suppressor provides a unified molecular mechanism for the tumorigenesis of both sporadic and hereditary tumors of Clusters 1A and 2A concerning SDHB and RET, but not tumors of Cluster 1B concerning VHL and other clusters.
Attenuation of inhibitory PAS domain protein-induced cell death by synthetic peptides derived from Mcl-1 transmenbrane domain
Authors: Kasai Shuya , Yasumoto Ken-ichi , Sogawa Kazuhiro
Published: May 2021

Expression of Inhibitory PAS domain protein (IPAS) induces apoptosis by inhibiting the anti-apoptotic activity of mitochondrial pro-survival proteins including Bcl-xL and Mcl-1 through direct binding. Analysis to examine the IPAS-binding region in Bcl-xL demonstrated that the C-terminal transmembrane (TM) domain is indispensable for the specific binding. A chimeric protein composed of the TM domain of Mcl-1 fused to the C-terminus of Citrine also exhibited a binding affinity to IPAS, and markedly attenuated apoptosis caused by the overexpression of Cerulean-IPAS in SH-SY5Y cells. HIV-1 TAT cell-penetrating peptide-conjugated synthetic peptides that cover whole or parts of the Mcl-1 TM domain showed anti-apoptotic activity in the CoCl2-induced cell death in PC12 cells. Administration of these highly effective anti-apoptotic peptides to mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that produces a reliable mouse model of Parkinson’s disease (PD) decreased neuronal cell loss in the substantia nigra pars compacta. Therefore, the peptides may be considered promising therapeutic agents for neurodegenerative disorders such as PD and stroke.
Microbiota-mediated protection against antibiotic-resistant pathogens
Authors: Panwar Rekha B. , Sequeira Richard P. , Clarke Thomas B.
Published: May 2021

Colonization by the microbiota provides one of our most effective barriers against infection by pathogenic microbes. The microbiota protects against infection by priming immune defenses, by metabolic exclusion of pathogens from their preferred niches, and through direct antimicrobial antagonism. Disruption of the microbiota, especially by antibiotics, is a major risk factor for bacterial pathogen colonization. Restoration of the microbiota through microbiota transplantation has been shown to be an effective way to reduce pathogen burden in the intestine but comes with a number of drawbacks, including the possibility of transferring other pathogens into the host, lack of standardization, and potential disruption to host metabolism. More refined methods to exploit the power of the microbiota would allow us to utilize its protective power without the drawbacks of fecal microbiota transplantation. To achieve this requires detailed understanding of which members of the microbiota protect against specific pathogens and the mechanistic basis for their effects. In this review, we will discuss the clinical and experimental evidence that has begun to reveal which members of the microbiota protect against some of the most troublesome antibiotic-resistant pathogens: Klebsiella pneumoniae, vancomycin-resistant enterococci, and Clostridioides difficile.
Explosive fragmentation of Prince Rupert’s drops leads to well-defined fragment sizes
Authors: Kooij Stefan , van Dalen Gerard , Molinari Jean-François , Bonn Daniel
Published: May 2021

Anyone who has ever broken a dish or a glass knows that the resulting fragments range from roughly the size of the object all the way down to indiscernibly small pieces: typical fragment size distributions of broken brittle materials follow a power law, and therefore lack a characteristic length scale. The origin of this power-law behavior is still unclear, especially why it is such an universal feature. Here we study the explosive fragmentation of glass Prince Rupert’s drops, and uncover a fundamentally different breakup mechanism. The Prince Rupert’s drops explode due to their large internal stresses resulting in an exponential fragment size distribution with a well-defined fragment size. We demonstrate that generically two distinct breakup processes exist, random and hierarchical, that allows us to fully explain why fragment size distributions are power-law in most cases but exponential in others. We show experimentally that one can even break the same material in different ways to obtain either random or hierarchical breakup, giving exponential and power-law distributed fragment sizes respectively. That a random breakup process leads to well-defined fragment sizes is surprising and is potentially useful to control fragmentation of brittle solids.
Size, microhabitat, and loss of larval feeding drive cranial diversification in frogs
Authors: Bardua Carla , Fabre Anne-Claire , Clavel Julien , Bon Margot , Das Kalpana , Stanley Edward L. , Blackburn David C. , Goswami Anjali
Published: May 2021

Habitat is one of the most important factors shaping organismal morphology, but it may vary across life history stages. Ontogenetic shifts in ecology may introduce antagonistic selection that constrains adult phenotype, particularly with ecologically distinct developmental phases such as the free-living, feeding larval stage of many frogs (Lissamphibia: Anura). We test the relative influences of developmental and ecological factors on the diversification of adult skull morphology with a detailed analysis of 15 individual cranial regions across 173 anuran species, representing every extant family. Skull size, adult microhabitat, larval feeding, and ossification timing are all significant factors shaping aspects of cranial evolution in frogs, with late-ossifying elements showing the greatest disparity and fastest evolutionary rates. Size and microhabitat show the strongest effects on cranial shape, and we identify a “large size-wide skull” pattern of anuran, and possibly amphibian, evolutionary allometry. Fossorial and aquatic microhabitats occupy distinct regions of morphospace and display fast evolution and high disparity. Taxa with and without feeding larvae do not notably differ in cranial morphology. However, loss of an actively feeding larval stage is associated with higher evolutionary rates and disparity, suggesting that functional pressures experienced earlier in ontogeny significantly impact adult morphological evolution.
Chiral singlet superconductivity in the weakly correlated metal LaPt3P
Authors: Biswas P. K. , Ghosh S. K. , Zhao J. Z. , Mayoh D. A. , Zhigadlo N. D. , Xu Xiaofeng , Baines C. , Hillier A. D. , Balakrishnan G. , Lees M. R.
Published: May 2021

Chiral superconductors are novel topological materials with finite angular momentum Cooper pairs circulating around a unique chiral axis, thereby spontaneously breaking time-reversal symmetry. They are rather scarce and usually feature triplet pairing: a canonical example is the chiral p-wave state realized in the A-phase of superfluid He3. Chiral triplet superconductors are, however, topologically fragile with the corresponding gapless boundary modes only weakly protected against symmetry-preserving perturbations in contrast to their singlet counterparts. Using muon spin relaxation measurements, here we report that the weakly correlated pnictide compound LaPt3P has the two key features of a chiral superconductor: spontaneous magnetic fields inside the superconducting state indicating broken time-reversal symmetry and low temperature linear behaviour in the superfluid density indicating line nodes in the order parameter. Using symmetry analysis, first principles band structure calculation and mean-field theory, we unambiguously establish that the superconducting ground state of LaPt3P is a chiral d-wave singlet.
Proportion and risk factors for death by euthanasia in dogs in the UK
Authors: Pegram Camilla , Gray Carol , Packer Rowena M. A. , Richards Ysabelle , Church David B. , Brodbelt Dave C. , O’Neill Dan G.
Published: May 2021

The loss of a pet can be particularly distressing for owners, whether the method of death is euthanasia or is unassisted. Using primary-care clinical data, this study aimed to report the demographic and clinical factors associated with euthanasia, relative to unassisted death, in dogs. Method of death (euthanasia or unassisted) and clinical cause of death were extracted from a random sample of 29,865 dogs within the VetCompass Programme from a sampling frame of 905,544 dogs under UK veterinary care in 2016. Multivariable logistic regression modelling was used to evaluate associations between risk factors and method of death. Of the confirmed deaths, 26,676 (89.3%) were euthanased and 2,487 (8.3%) died unassisted. After accounting for confounding factors, 6 grouped-level disorders had higher odds in euthanased dogs (than dogs that died unassisted), using neoplasia as the baseline. The disorders with greatest odds included: poor quality of life (OR 16.28), undesirable behaviour (OR 11.36) and spinal cord disorder (OR 6.00). Breed, larger bodyweight and increasing age were additional risk factors for euthanasia. The results highlight that a large majority of owners will face euthanasia decisions and these findings can support veterinarians and owners to better prepare for such an eventuality.
Secure multiparty quantum key agreement against collusive attacks
Authors: Abulkasim Hussein , Mashatan Atefeh , Ghose Shohini
Published: May 2021

Quantum key agreement enables remote participants to fairly establish a secure shared key based on their private inputs. In the circular-type multiparty quantum key agreement mode, two or more malicious participants can collude together to steal private inputs of honest participants or to generate the final key alone. In this work, we focus on a powerful collusive attack strategy in which two or more malicious participants in particular positions, can learn sensitive information or generate the final key alone without revealing their malicious behaviour. Many of the current circular-type multiparty quantum key agreement protocols are not secure against this collusive attack strategy. As an example, we analyze the security of a recently proposed multiparty key agreement protocol to show the vulnerability of existing circular-type multiparty quantum key agreement protocols against this collusive attack. Moreover, we design a general secure multiparty key agreement model that would remove this vulnerability from such circular-type key agreement protocols and describe the necessary steps to implement this model. The proposed model is general and does not depend on the specific physical implementation of the quantum key agreement.
Serial profiling of cell-free DNA and nucleosome histone modifications in cell cultures
Authors: Ungerer Vida , Bronkhorst Abel J. , Van den Ackerveken Priscilla , Herzog Marielle , Holdenrieder Stefan
Published: May 2021

Recent advances in basic research have unveiled several strategies for improving the sensitivity and specificity of cell-free DNA (cfDNA) based assays, which is a prerequisite for broadening its clinical use. Included among these strategies is leveraging knowledge of both the biogenesis and physico-chemical properties of cfDNA towards the identification of better disease-defining features and optimization of methods. While good progress has been made on this front, much of cfDNA biology remains uncharted. Here, we correlated serial measurements of cfDNA size, concentration and nucleosome histone modifications with various cellular parameters, including cell growth rate, viability, apoptosis, necrosis, and cell cycle phase in three different cell lines. Collectively, the picture emerged that temporal changes in cfDNA levels are rather irregular and not the result of constitutive release from live cells. Instead, changes in cfDNA levels correlated with intermittent cell death events, wherein apoptosis contributed more to cfDNA release in non-cancer cells and necrosis more in cancer cells. Interestingly, the presence of a ~ 3 kbp cfDNA population, which is often deemed to originate from accidental cell lysis or active release, was found to originate from necrosis. High-resolution analysis of this cfDNA population revealed an underlying DNA laddering pattern consisting of several oligo-nucleosomes, identical to those generated by apoptosis. This suggests that necrosis may contribute significantly to the pool of mono-nucleosomal cfDNA fragments that are generally interrogated for cancer mutational profiling. Furthermore, since active steps are often taken to exclude longer oligo-nucleosomes from clinical biospecimens and subsequent assays this raises the question of whether important pathological information is lost.
Stochastic modelling of cellulose hydrolysis with Gauss and Weibull distributed transition probabilities
Authors: Duru Joseph Mcgreg , Pârvulescu Oana Cristina , Dobre Tănase , Răducanu Cristian Eugen
Published: May 2021

Two Markov-type stochastic models were developed to describe the kinetics of acid hydrolysis of cellulose. One of them involved a Gauss (normal) distribution of probabilities of chemical bond breaking, the other a Weibull distribution. It was considered that the random breaking of cellulose was based on the cleavage of a parent macromolecule into two descendants. Model equations and kinetics of acid hydrolysis of cellulose consisting of 10 and 100 units of cellobiose were presented. The effects of acid concentration and temperature on the kinetics of hydrolysis process were taken into account. The results obtained applying both stochastic models were in a reasonable agreement with those obtained using a deterministic kinetic model. These stochastic models can accurately describe the kinetics of acid hydrolysis and cover the drawbacks of some deterministic kinetic models, e.g., large number of model equations and parameters, modification of parameter values by changing the process conditions.
Diamine vapor treatment of viscoelastic graphene oxide liquid crystal for gas barrier coating
Authors: Choi Seung Eun , Kim Sung-Soo , Choi Eunji , Kim Ji Hoon , Choi Yunkyu , Kang Junhyeok , Kwon Ohchan , Kim Dae Woo
Published: May 2021

A layered graphene oxide/ethylenediamine (GO/EDA) composite film was developed by exposing aqueous GO liquid crystal (GOLC) coating to EDA vapor and its effects on the gas barrier performance of GO film were systematically investigated. When a GO/EDA coating with a thickness of approximately 1 μm was applied to a neat polyethylene terephthalate (PET) film, the resultant film was highly impermeable to gas molecules, particularly reducing the gas permeance up to 99.6% for He and 98.5% for H2 in comparison to the neat PET film. The gas barrier properties can be attributed to the long diffusion length through stacked GO nanosheets. The EDA can crosslink oxygen-containing groups of GO, enhancing the mechanical properties of the GO/EDA coating with hardness and elastic modulus values up to 1.14 and 28.7 GPa, respectively. By the synergistic effect of the viscoelastic properties of GOLC and the volatility of EDA, this coating method can be applied to complex geometries and EDA intercalation can be spontaneously achieved through the scaffold of the GOLC.
Microdroplet-based system for culturing of environmental microorganisms using FNAP-sort
Authors: Saito Kanako , Ota Yuri , Tourlousse Dieter M. , Matsukura Satoko , Fujitani Hirotsugu , Morita Masamune , Tsuneda Satoshi , Noda Naohiro
Published: May 2021

Droplet microfluidics has emerged as a powerful technology for improving the culturing efficiency of environmental microorganisms. However, its widespread adoption has been limited due to considerable technical challenges, especially related to identification and manipulation of individual growth-positive droplets. Here, we combined microfluidic droplet technology with on-chip “fluorescent nucleic acid probe in droplets for bacterial sorting” (FNAP-sort) for recovery of growth-positive droplets and droplet microdispensing to establish an end-to-end workflow for isolation and culturing of environmental microbes. As a proof-of-concept, we demonstrate the ability of our technique to yield high-purity cultures of rare microorganisms from a representative complex environmental microbiome. As our system employs off-the-shelf commercially available equipment, we believe that it can be readily adopted by others and may thus find widespread use toward culturing the high proportion of as-of-yet uncultured microorganisms in different biomes.
Application of cryopreservation to tooth germ transplantation for root development and tooth eruption
Authors: Li Xinghan , Nakamura Megumi , Tian Weidong , Sasano Yasuyuki
Published: May 2021

We cryopreserved mouse tooth germs with widely open cervical margins of the enamel organ to overcome difficulties in cryoprotectant permeation and tested their efficacy by transplanting them into recipient mice. The upper right first molar germs of 8-day-old donor mice were extracted and categorized into the following four groups according to cryopreservation time: no cryopreservation, 1 week, 1 month, and 3 months. The donor tooth germs were transplanted into the upper right first molar germ sockets of the 8-day-old recipient mice. The upper left first molars of the recipient mice were used as controls. The outcome of the transplantation was assessed at 1, 2, and 3 weeks after transplantation. Stereomicroscopic evaluation revealed that most of the transplanted teeth erupted by 3 weeks after transplantation. Micro-computed tomography analysis revealed root elongation in the transplanted groups as well as in the controls. There was no significant difference between the cryopreserved and non-cryopreserved transplanted teeth, but the roots of the cryopreserved teeth were significantly shorter than those of the control teeth. Histological examination revealed root and periodontal ligament formations in all the transplanted groups. These results suggest that the transplantation of cryopreserved tooth germs facilitates subsequent root elongation and tooth eruption.
Publisher Correction: Human blood plasma factors affect the adhesion kinetics of Staphylococcus aureus to central venous catheters
Authors: Gunaratnam Gubesh , Spengler Christian , Trautmann Simone , Jung Philipp , Mischo Johannes , Wieland Ben , Metz Carlos , Becker Sören L. , Hannig Matthias , Jacobs Karin , Bischoff Markus
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.