bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder
Authors: Johnson Emma C. , Kapoor Manav , Hatoum Alexander S. , Zhou Hang , Polimanti Renato , Wendt Frank R. , Walters Raymond K. , Lai Dongbing , Kember Rachel L. , Hartz Sarah , Meyers Jacquelyn L. , Peterson Roseann E. , Ripke Stephan , Bigdeli Tim B. , Fanous Ayman H. , Pato Carlos N. , Pato Michele T. , Goate Alison M. , Kranzler Henry R. , O'Donovan Michael C. , Walters James T.R. , Gelernter Joel , Edenberg Howard J. , Agrawal Arpana 
Published: July 2021

AbstractBackgroundAlcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.MethodsWe used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.ResultsWe identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).ConclusionsOur findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
Scandinavian Approaches to Begging as a Policy Problem and the Double Insider/Outsider Status of Marginalized Intra-EU Migrants
Authors: BOREVI KARIN 
Published: July 2021

AbstractThe present article investigates how begging performed by citizens of new EU-member states in Eastern Europe was debated in parliaments in Denmark, Sweden and Norway during the period 2007–2017. The empirical analysis shows significant cross-country divergences: In Denmark, efforts targeted controlling migration, either directly or indirectly, via various deterrence strategies. In Sweden, the emphasis was rather on alleviating social needs while migrants reside in the country and trying to decrease their incentives to migrate in the first place by ameliorating conditions in sending countries. In Norway, one predominant framing revolved around the issue of human trafficking of beggars. Despite substantial differences, the analyses show a gradual shift in a similar direction in all three countries. While a social frame was initially more commonly understood as the appropriate way to approach begging, over time a criminal frame has gained ground in all three countries. The article argues that this development must be understood in light of marginalized intra-EU migrants’ legal status as both insiders and outsiders in the Scandinavian welfare states. Due to these individuals’ “in-between status”, neither conventional social policy nor immigration control measures are perceived as available, making policymakers more prone to turn to criminal policy tools.
Genetic diversity and GWAS of agronomic traits using an ICARDA lentil (Lens culinaris Medik.) Reference Plus collection
Authors: Rajendran Karthika , Coyne Clarice J. , Zheng Ping , Saha Gopesh , Main Dorrie , Amin Nurul , Ma Yu , Kisha Ted , Bett Kirstin E. , McGee Rebecca J. , Kumar Shiv 
Published: July 2021

AbstractGenotyping of lentil plant genetic resources holds the promise to increase the identification and utilization of useful genetic diversity for crop improvement. The International Center for Agriculture Research in the Dry Areas (ICARDA) lentil reference set plus collection of 176 accessions was genotyped using genotyping-by-sequencing (GBS) and 22,555 SNPs were identified. The population structure was investigated using Bayesian analysis (STRUCTURE, k = 3) and principal component analysis. The two methods are in concordance. Genome-wide association analysis (GWAS) using the filtered SNP set and ICARDA historical phenotypic data discovered putative markers for several agronomic traits including days to first flower, seeds per pod, seed weight and days to maturity. The genetic and genomic resources developed and utilized in this study are available to the research community interested in exploring the ICARDA reference set plus collection using GWAS.
Illuminating Active Subglacial Lake Processes With ICESat‐2 Laser Altimetry
Authors: Siegfried M. R. , Fricker H. A. 
Published: July 2021

AbstractAntarctica's basal water system contains more than 130 active lakes, and its evolution remains a major uncertainty in future ice sheet dynamics. Most of our current understanding has come from using satellite radar and laser altimetry acquired since 2003. NASA's ICESat‐2 laser altimetry mission, launched in September 2018, provides a new, small‐footprint altimetry data set with which to investigate Antarctic active subglacial lake processes. Here, we demonstrate the ability to continue monitoring active subglacial lakes at timescales shorter than the ICESat‐2's repeat cycle and generate self‐consistent time series of subglacial lake surface‐height anomalies from combined ICESat, CryoSat‐2, and ICESat‐2 altimetry. Focusing on three regions with the known significant lake activity, we show that ICESat‐2 laser altimetry can not only extend the record of subglacial lake activity but also provides better understanding of hydrological processes by capturing denser and more precise spatial detail.
Understanding the Mechanisms of Summer Extreme Precipitation Events in Xinjiang of Arid Northwest China
Authors: Ning Guicai , Luo Ming , Zhang Qiang , Wang Shigong , Liu Zhen , Yang Yuanjian , Wu Sijia , Zeng Zhaoliang 
Published: July 2021

AbstractAs one of the aridest regions in the mid‐latitudes, arid Northwest China (ANC) has scarce water resources year‐round, its annual total precipitation is mainly contributed by summer extreme precipitation events, which may also cause disastrous flash floods. However, the physical mechanism and climatic features of extreme precipitation events in ANC are not fully understood and warrant in‐depth investigations. Taking Xinjiang as an example, this study investigates the underlying mechanisms and long‐term trend of extreme precipitation events in ANC during 1961–2019 using observational and reanalysis data sets. Results suggest that summer extreme precipitation events in ANC are characterized by a zonal wave pattern with the deepening of the western Siberian trough, central Asian high, and Mongolian high. Under the effects of the zonal wave pattern, the westerly and the easterly airflows anomalously intensify and converge in ANC, transporting a large amount of water vapor from the Arctic Ocean, the Caspian Sea, the Aral Sea, the Arabian Sea, and eastern China to ANC. Meanwhile, a deep anomalous cyclone center induced by the deep wave pattern appears over ANC, thus providing favorable conditions for the occurrence of extreme precipitation events in ANC. Over the long‐term period, total summer precipitation and the frequency of extreme precipitation events in ANC show significant increasing trends, indicating that summer climate in ANC is becoming more humid, and extreme precipitation events are becoming more frequent. These findings provide scientific insights for understanding the formation mechanism of summer extreme precipitation events and mitigating the corresponding disasters in arid regions.
Effects of Ozone Isotopologue Formation on the Clumped‐Isotope Composition of Atmospheric O2
Authors: Yeung Laurence Y. , Murray Lee T. , Banerjee Asmita , Tie Xin , Yan Yuzhen , Atlas Elliot L. , Schauffler Sue M. , Boering Kristie A. 
Published: July 2021

AbstractTropospheric 18O18O is an emerging proxy for past tropospheric ozone and free‐tropospheric temperatures. The basis of these applications is the idea that isotope‐exchange reactions in the atmosphere drive 18O18O abundances toward isotopic equilibrium. However, previous work used an offline box‐model framework to explain the 18O18O budget, approximating the interplay of atmospheric chemistry and transport. This approach, while convenient, has poorly characterized uncertainties. To investigate these uncertainties, and to broaden the applicability of the 18O18O proxy, we developed a scheme to simulate atmospheric 18O18O abundances (quantified as ∆36 values) online within the GEOS‐Chem chemical transport model. These results are compared to both new and previously published atmospheric observations from the surface to 33 km. Simulations using a simplified O2 isotopic equilibration scheme within GEOS‐Chem show quantitative agreement with measurements only in the middle stratosphere; modeled ∆36 values are too high elsewhere. Investigations using a comprehensive model of the O‐O2‐O3 isotopic photochemical system and proof‐of‐principle experiments suggest that the simple equilibration scheme omits an important pressure dependence to ∆36 values: the anomalously efficient titration of 18O18O to form ozone. Incorporating these effects into the online ∆36 calculation scheme in GEOS‐Chem yields quantitative agreement for all available observations. While this previously unidentified bias affects the atmospheric budget of 18O18O in O2, the modeled change in the mean tropospheric ∆36 value since 1850 CE is only slightly altered; it is still quantitatively consistent with the ice‐core ∆36 record, implying that the tropospheric ozone burden increased less than 40% over the twentieth century.
Overcoming thermo-optical dynamics in broadband nanophotonic sensing
Authors: Wang Mingkang , Perez-Morelo Diego J. , Aksyuk Vladimir 
Published: July 2021

AbstractAdvances in integrated photonics open up exciting opportunities for batch-fabricated optical sensors using high-quality-factor nanophotonic cavities to achieve ultrahigh sensitivities and bandwidths. The sensitivity improves with increasing optical power; however, localized absorption and heating within a micrometer-scale mode volume prominently distorts the cavity resonances and strongly couples the sensor response to thermal dynamics, limiting the sensitivity and hindering the measurement of broadband time-dependent signals. Here, we derive a frequency-dependent photonic sensor transfer function that accounts for thermo-optical dynamics and quantitatively describes the measured broadband optomechanical signal from an integrated photonic atomic force microscopy nanomechanical probe. Using this transfer function, the probe can be operated in the high optical power, strongly thermo-optically nonlinear regime, accurately measuring low- and intermediate-frequency components of a dynamic signal while reaching a sensitivity of 0.7 fm/Hz1/2 at high frequencies, an improvement of ≈10× relative to the best performance in the linear regime. Counterintuitively, we discover that a higher transduction gain and sensitivity are achieved with lower quality-factor optical modes for low signal frequencies. Not limited to optomechanical transducers, the derived transfer function is generally valid for describing the small-signal dynamic responses of a broad range of technologically important photonic sensors subject to the thermo-optical effect.
Assessment of suicide attempt and death in bipolar affective disorder: a combined clinical and genetic approach
Authors: Monson Eric T. , Shabalin Andrey A. , Docherty Anna R. , DiBlasi Emily , Bakian Amanda V. , Li Qingqin S. , Gray Douglas , Keeshin Brooks , Crowell Sheila E. , Mullins Niamh , Willour Virginia L. , Coon Hilary 
Published: July 2021

AbstractBipolar disorder (BP) suicide death rates are 10–30 times greater than the general population, likely arising from environmental and genetic risk factors. Though suicidal behavior in BP has been investigated, studies have not addressed combined clinical and genetic factors specific to suicide death. To address this gap, a large, harmonized BP cohort was assessed to identify clinical risk factors for suicide death and attempt which then directed testing of underlying polygenic risks. 5901 individuals of European ancestry were assessed: 353 individuals with BP and 2498 without BP who died from suicide (BPS and NBPS, respectively) from a population-derived sample along with a volunteer-derived sample of 799 individuals with BP and a history of suicide attempt (BPSA), 824 individuals with BP and no prior attempts (BPNSA), and 1427 individuals without several common psychiatric illnesses per self-report (C). Clinical and subsequent directed genetic analyses utilized multivariable logistic models accounting for critical covariates and multiple testing. There was overrepresentation of diagnosis of PTSD (OR = 4.9, 95%CI: 3.1–7.6) in BPS versus BPSA, driven by female subjects. PRS assessments showed elevations in BPS including PTSD (OR = 1.3, 95%CI:1.1–1.5, versus C), female-derived ADHD (OR = 1.2, 95%CI:1.1–1.4, versus C), and male insomnia (OR = 1.4, 95%CI: 1.1–1.7, versus BPSA). The results provide support from genetic and clinical standpoints for dysregulated traumatic response particularly increasing risk of suicide death among individuals with BP of Northern European ancestry. Such findings may direct more aggressive treatment and prevention of trauma sequelae within at-risk bipolar individuals.
A MYBL2 complex for RRM2 transactivation and the synthetic effect of MYBL2 knockdown with WEE1 inhibition against colorectal cancer
Authors: Liu Qian , Guo Lijuan , Qi Hongyan , Lou Meng , Wang Rui , Hai Boning , Xu Kailun , Zhu Lijun , Ding Yongfeng , Li Chen , Xie Lingdan , Shen Jing , Xiang Xueping , Shao Jimin 
Published: July 2021

AbstractRibonucleotide reductase (RR) is a unique enzyme for the reduction of NDPs to dNDPs, the building blocks for DNA synthesis and thus essential for cell proliferation. Pan-cancer profiling studies showed that RRM2, the small subunit M2 of RR, is abnormally overexpressed in multiple types of cancers; however, the underlying regulatory mechanisms in cancers are still unclear. In this study, through searching in cancer-omics databases and immunohistochemistry validation with clinical samples, we showed that the expression of MYBL2, a key oncogenic transcriptional factor, was significantly upregulated correlatively with RRM2 in colorectal cancer (CRC). Ectopic expression and knockdown experiments indicated that MYBL2 was essential for CRC cell proliferation, DNA synthesis, and cell cycle progression in an RRM2-dependent manner. Mechanistically, MYBL2 directly bound to the promoter of RRM2 gene and promoted its transcription during S-phase together with TAF15 and MuvB components. Notably, knockdown of MYBL2 sensitized CRC cells to treatment with MK-1775, a clinical trial drug for inhibition of WEE1, which is involved in a degradation pathway of RRM2. Finally, mouse xenograft experiments showed that the combined suppression of MYBL2 and WEE1 synergistically inhibited CRC growth with a low systemic toxicity in vivo. Therefore, we propose a new regulatory mechanism for RRM2 transcription for CRC proliferation, in which MYBL2 functions by constituting a dynamic S-phase transcription complex following the G1/early S-phase E2Fs complex. Doubly targeting the transcription and degradation machines of RRM2 could produce a synthetic inhibitory effect on RRM2 level with a novel potential for CRC treatment.
Exosomes secreted by palmitic acid-treated hepatocytes promote LX-2 cell activation by transferring miRNA-107
Authors: Wang Wei , Li Fangfang , Lai Xiaoyang , Liu Han , Wu Shuting , Han Yunqin , Shen Yunfeng 
Published: July 2021

AbstractActivation of hepatic stellate cells (HSCs) is a key inducer of liver fibrogenesis in nonalcoholic fatty liver disease (NAFLD). Exosomes play an important role between hepatocytes and HSCs. This study aims to explore the role of exosomes derived from palmitic acid (PA)-treated hepatocytes in regulating HSCs (LX-2 cell) proliferation and activation and the underlying mechanisms. Exosomes were isolated from PA-treated human normal hepatocytes and incubated with LX-2 cells. Cell Counting Kit-8 (CCK-8) was performed to determine LX-2 cell proliferation, and the expression of fibrosis markers α-smooth muscle actin (α-SMA) and collagen type 1 α1 (CoL1A1) were examined to evaluateLX-2 cell activation. PA induced hepatocytes to release more exosomes enriched in miR-107. Mechanically, on the one hand, exosomes from PA-treated hepatocytes shuttled miR-107 to LX-2 cells, where miR-107 activated Wnt signaling by targeting DKK1 and thereby induced LX-2 cell activation; on the other hand, PA-treated hepatocytes derived exosomes also delivered miR-107 to CD4 + T lymphocytes, where miR-107 elevated IL-9 expression by targeting Foxp1, which bound to the IL-9 promoter in CD4 + T cells and suppressed Th9 cell differentiation and reduced IL-9 expression, and thus promoted LX-2 cell activation by activating Raf/MEK/ERK signaling pathway.
Spatial coherence of light inside three-dimensional media
Authors: Leonetti Marco , Pattelli Lorenzo , De Panfilis Simone , Wiersma Diederik S. , Ruocco Giancarlo 
Published: July 2021

AbstractSpeckle is maybe the most fundamental interference effect of light in disordered media, giving rise to fascinating physical phenomena and cutting edge applications. While speckle formed outside a sample is easily measured and analysed, true bulk speckle, as formed inside random media, is difficult to investigate directly due to the obvious issue of physical access. Furthermore, its proper theoretical description poses enormous challenges. Here we report on the first direct measurements of spatially resolved intensity correlations of light inside a disordered medium, using embedded DNA strings decorated with emitters separated by a controlled nanometric distance. Our method provides in situ access to fundamental properties of bulk speckles as their size and polarization degrees of freedom, both of which are found to deviate significantly from theoretical predictions. The deviations are explained, by comparison with rigorous numerical calculations, in terms of correlations among polarization components and non-universal near-field contributions at the nanoscale.
Spectral index-flux relation for investigating the origins of steep decay in γ-ray bursts
Authors: Ronchini Samuele , Oganesyan Gor , Branchesi Marica , Ascenzi Stefano , Bernardini Maria Grazia , Brighenti Francesco , Dall’Osso Simone , D’Avanzo Paolo , Ghirlanda Giancarlo , Ghisellini Gabriele , Ravasio Maria Edvige , Salafia Om Sharan 
Published: July 2021

Abstractγ-ray bursts (GRBs) are short-lived transients releasing a large amount of energy (1051 − 1053 erg) in the keV-MeV energy range. GRBs are thought to originate from internal dissipation of the energy carried by ultra-relativistic jets launched by the remnant of a massive star’s death or a compact binary coalescence. While thousands of GRBs have been observed over the last thirty years, we still have an incomplete understanding of where and how the radiation is generated in the jet. Here we show a relation between the spectral index and the flux found by investigating the X-ray tails of bright GRB pulses via time-resolved spectral analysis. This relation is incompatible with the long standing scenario which invokes the delayed arrival of photons from high-latitude parts of the jet. While the alternative scenarios cannot be firmly excluded, the adiabatic cooling of the emitting particles is the most plausible explanation for the discovered relation, suggesting a proton-synchrotron origin of the GRB emission.
The molecular basis for SARS-CoV-2 binding to dog ACE2
Authors: Zhang Zengyuan , Zhang Yanfang , Liu Kefang , Li Yan , Lu Qiong , Wang Qingling , Zhang Yuqin , Wang Liang , Liao Hanyi , Zheng Anqi , Ma Sufang , Fan Zheng , Li Huifang , Huang Weijin , Bi Yuhai , Zhao Xin , Wang Qihui , Gao George F. , Xiao Haixia , Tong Zhou , Qi Jianxun , Sun Yeping 
Published: July 2021

AbstractSARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.
Whole-genome profiling of nasopharyngeal carcinoma reveals viral-host co-operation in inflammatory NF-κB activation and immune escape
Authors: Bruce Jeff P. , To Ka-Fai , Lui Vivian W. Y. , Chung Grace T. Y. , Chan Yuk-Yu , Tsang Chi Man , Yip Kevin Y. , Ma Brigette B. Y. , Woo John K. S. , Hui Edwin P. , Mak Michael K. F. , Lee Sau-Dan , Chow Chit , Velapasamy Sharmila , Or Yvonne Y. Y. , Siu Pui Kei , El Ghamrasni Samah , Prokopec Stephenie , Wu Man , Kwan Johnny S. H. , Liu Yuchen , Chan Jason Y. K. , van Hasselt C. Andrew , Young Lawrence S. , Dawson Christopher W. , Paterson Ian C. , Yap Lee-Fah , Tsao Sai-Wah , Liu Fei-Fei , Chan Anthony T. C. , Pugh Trevor J. , Lo Kwok-Wai 
Published: July 2021

AbstractInterplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.
Precise spatiotemporal control of voltage-gated sodium channels by photocaged saxitoxin
Authors: Elleman Anna V. , Devienne Gabrielle , Makinson Christopher D. , Haynes Allison L. , Huguenard John R. , Du Bois J. 
Published: July 2021

AbstractHere we report the pharmacologic blockade of voltage-gated sodium ion channels (NaVs) by a synthetic saxitoxin derivative affixed to a photocleavable protecting group. We demonstrate that a functionalized saxitoxin (STX-eac) enables exquisite spatiotemporal control of NaVs to interrupt action potentials in dissociated neurons and nerve fiber bundles. The photo-uncaged inhibitor (STX-ea) is a nanomolar potent, reversible binder of NaVs. We use STX-eac to reveal differential susceptibility of myelinated and unmyelinated axons in the corpus callosum to NaV-dependent alterations in action potential propagation, with unmyelinated axons preferentially showing reduced action potential fidelity under conditions of partial NaV block. These results validate STX-eac as a high precision tool for robust photocontrol of neuronal excitability and action potential generation.