bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metrological complementarity reveals the Einstein-Podolsky-Rosen paradox
Authors: Yadin Benjamin , Fadel Matteo , Gessner Manuel 
Published: April 2021

AbstractThe Einstein-Podolsky-Rosen (EPR) paradox plays a fundamental role in our understanding of quantum mechanics, and is associated with the possibility of predicting the results of non-commuting measurements with a precision that seems to violate the uncertainty principle. This apparent contradiction to complementarity is made possible by nonclassical correlations stronger than entanglement, called steering. Quantum information recognises steering as an essential resource for a number of tasks but, contrary to entanglement, its role for metrology has so far remained unclear. Here, we formulate the EPR paradox in the framework of quantum metrology, showing that it enables the precise estimation of a local phase shift and of its generating observable. Employing a stricter formulation of quantum complementarity, we derive a criterion based on the quantum Fisher information that detects steering in a larger class of states than well-known uncertainty-based criteria. Our result identifies useful steering for quantum-enhanced precision measurements and allows one to uncover steering of non-Gaussian states in state-of-the-art experiments.
The VRNetzer platform enables interactive network analysis in Virtual Reality
Authors: Pirch Sebastian , Müller Felix , Iofinova Eugenia , Pazmandi Julia , Hütter Christiane V. R. , Chiettini Martin , Sin Celine , Boztug Kaan , Podkosova Iana , Kaufmann Hannes , Menche Jörg 
Published: April 2021

AbstractNetworks provide a powerful representation of interacting components within complex systems, making them ideal for visually and analytically exploring big data. However, the size and complexity of many networks render static visualizations on typically-sized paper or screens impractical, resulting in proverbial ‘hairballs’. Here, we introduce a Virtual Reality (VR) platform that overcomes these limitations by facilitating the thorough visual, and interactive, exploration of large networks. Our platform allows maximal customization and extendibility, through the import of custom code for data analysis, integration of external databases, and design of arbitrary user interface elements, among other features. As a proof of concept, we show how our platform can be used to interactively explore genome-scale molecular networks to identify genes associated with rare diseases and understand how they might contribute to disease development. Our platform represents a general purpose, VR-based data exploration platform for large and diverse data types by providing an interface that facilitates the interaction between human intuition and state-of-the-art analysis methods.
Imaging the response to DNA damage in heterochromatin domains reveals core principles of heterochromatin maintenance
Authors: Fortuny Anna , Chansard Audrey , Caron Pierre , Chevallier Odile , Leroy Olivier , Renaud Olivier , Polo Sophie E. 
Published: April 2021

AbstractHeterochromatin is a critical chromatin compartment, whose integrity governs genome stability and cell fate transitions. How heterochromatin features, including higher-order chromatin folding and histone modifications associated with transcriptional silencing, are maintained following a genotoxic stress challenge is unknown. Here, we establish a system for targeting UV damage to pericentric heterochromatin in mammalian cells and for tracking the heterochromatin response to UV in real time. We uncover profound heterochromatin compaction changes during repair, orchestrated by the UV damage sensor DDB2, which stimulates linker histone displacement from chromatin. Despite massive heterochromatin unfolding, heterochromatin-specific histone modifications and transcriptional silencing are maintained. We unveil a central role for the methyltransferase SETDB1 in the maintenance of heterochromatic histone marks after UV. SETDB1 coordinates histone methylation with new histone deposition in damaged heterochromatin, thus protecting cells from genome instability. Our data shed light on fundamental molecular mechanisms safeguarding higher-order chromatin integrity following DNA damage.
Estimating the effect of social inequalities on the mitigation of COVID-19 across communities in Santiago de Chile
Authors: Gozzi Nicolò , Tizzoni Michele , Chinazzi Matteo , Ferres Leo , Vespignani Alessandro , Perra Nicola 
Published: April 2021

AbstractWe study the spatio-temporal spread of SARS-CoV-2 in Santiago de Chile using anonymized mobile phone data from 1.4 million users, 22% of the whole population in the area, characterizing the effects of non-pharmaceutical interventions (NPIs) on the epidemic dynamics. We integrate these data into a mechanistic epidemic model calibrated on surveillance data. As of August 1, 2020, we estimate a detection rate of 102 cases per 1000 infections (90% CI: [95–112 per 1000]). We show that the introduction of a full lockdown on May 15, 2020, while causing a modest additional decrease in mobility and contacts with respect to previous NPIs, was decisive in bringing the epidemic under control, highlighting the importance of a timely governmental response to COVID-19 outbreaks. We find that the impact of NPIs on individuals’ mobility correlates with the Human Development Index of comunas in the city. Indeed, more developed and wealthier areas became more isolated after government interventions and experienced a significantly lower burden of the pandemic. The heterogeneity of COVID-19 impact raises important issues in the implementation of NPIs and highlights the challenges that communities affected by systemic health and social inequalities face adapting their behaviors during an epidemic.
Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer’s disease-like pathology
Authors: Baglietto-Vargas David , Forner Stefania , Cai Lena , Martini Alessandra C. , Trujillo-Estrada Laura , Swarup Vivek , Nguyen Marie Minh Thu , Do Huynh Kelly , Javonillo Dominic I. , Tran Kristine Minh , Phan Jimmy , Jiang Shan , Kramár Enikö A. , Nuñez-Diaz Cristina , Balderrama-Gutierrez Gabriela , Garcia Franklin , Childs Jessica , Rodriguez-Ortiz Carlos J. , Garcia-Leon Juan Antonio , Kitazawa Masashi , Shahnawaz Mohammad , Matheos Dina P. , Ma Xinyi , Da Cunha Celia , Walls Ken C. , Ager Rahasson R. , Soto Claudio , Gutierrez Antonia , Moreno-Gonzalez Ines , Mortazavi Ali , Tenner Andrea J. , MacGregor Grant R. , Wood Marcelo , Green Kim N. , LaFerla Frank M. 
Published: April 2021

AbstractThe majority of Alzheimer’s disease (AD) cases are late-onset and occur sporadically, however most mouse models of the disease harbor pathogenic mutations, rendering them better representations of familial autosomal-dominant forms of the disease. Here, we generated knock-in mice that express wildtype human Aβ under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Aβ sequence to its wild-type human counterpart leads to age-dependent impairments in cognition and synaptic plasticity, brain volumetric changes, inflammatory alterations, the appearance of Periodic Acid-Schiff (PAS) granules and changes in gene expression. In addition, when exon 14 encoding the Aβ sequence was flanked by loxP sites we show that Cre-mediated excision of exon 14 ablates hAβ expression, rescues cognition and reduces the formation of PAS granules.
CRISPR-based genome editing in primary human pancreatic islet cells
Authors: Bevacqua Romina J. , Dai Xiaoqing , Lam Jonathan Y. , Gu Xueying , Friedlander Mollie S. H. , Tellez Krissie , Miguel-Escalada Irene , Bonàs-Guarch Silvia , Atla Goutham , Zhao Weichen , Kim Seung Hyun , Dominguez Antonia A. , Qi Lei S. , Ferrer Jorge , MacDonald Patrick E. , Kim Seung K. 
Published: April 2021

AbstractGene targeting studies in primary human islets could advance our understanding of mechanisms driving diabetes pathogenesis. Here, we demonstrate successful genome editing in primary human islets using clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9). CRISPR-based targeting efficiently mutated protein-coding exons, resulting in acute loss of islet β-cell regulators, like the transcription factor PDX1 and the KATP channel subunit KIR6.2, accompanied by impaired β-cell regulation and function. CRISPR targeting of non-coding DNA harboring type 2 diabetes (T2D) risk variants revealed changes in ABCC8, SIX2 and SIX3 expression, and impaired β-cell function, thereby linking regulatory elements in these target genes to T2D genetic susceptibility. Advances here establish a paradigm for genetic studies in human islet cells, and reveal regulatory and genetic mechanisms linking non-coding variants to human diabetes risk.
Arginine is an epigenetic regulator targeting TEAD4 to modulate OXPHOS in prostate cancer cells
Authors: Chen Chia-Lin , Hsu Sheng-Chieh , Chung Tan-Ya , Chu Cheng-Ying , Wang Hung-Jung , Hsiao Pei-Wen , Yeh Shauh-Der , Ann David K. , Yen Yun , Kung Hsing-Jien 
Published: April 2021

AbstractArginine plays diverse roles in cellular physiology. As a semi-essential amino acid, arginine deprivation has been used to target cancers with arginine synthesis deficiency. Arginine-deprived cancer cells exhibit mitochondrial dysfunction, transcriptional reprogramming and eventual cell death. In this study, we show in prostate cancer cells that arginine acts as an epigenetic regulator to modulate histone acetylation, leading to global upregulation of nuclear-encoded oxidative phosphorylation (OXPHOS) genes. TEAD4 is retained in the nucleus by arginine, enhancing its recruitment to the promoter/enhancer regions of OXPHOS genes and mediating coordinated upregulation in a YAP1-independent but mTOR-dependent manner. Arginine also activates the expression of lysine acetyl-transferases and increases overall levels of acetylated histones and acetyl-CoA, facilitating TEAD4 recruitment. Silencing of TEAD4 suppresses OXPHOS functions and prostate cancer cell growth in vitro and in vivo. Given the strong correlation of TEAD4 expression and prostate carcinogenesis, targeting TEAD4 may be beneficially used to enhance arginine-deprivation therapy and prostate cancer therapy.
Neural network based 3D tracking with a graphene transparent focal stack imaging system
Authors: Zhang Dehui , Xu Zhen , Huang Zhengyu , Gutierrez Audrey Rose , Blocker Cameron J. , Liu Che-Hung , Lien Miao-Bin , Cheng Gong , Liu Zhe , Chun Il Yong , Fessler Jeffrey A. , Zhong Zhaohui , Norris Theodore B. 
Published: April 2021

AbstractRecent years have seen the rapid growth of new approaches to optical imaging, with an emphasis on extracting three-dimensional (3D) information from what is normally a two-dimensional (2D) image capture. Perhaps most importantly, the rise of computational imaging enables both new physical layouts of optical components and new algorithms to be implemented. This paper concerns the convergence of two advances: the development of a transparent focal stack imaging system using graphene photodetector arrays, and the rapid expansion of the capabilities of machine learning including the development of powerful neural networks. This paper demonstrates 3D tracking of point-like objects with multilayer feedforward neural networks and the extension to tracking positions of multi-point objects. Computer simulations further demonstrate how this optical system can track extended objects in 3D, highlighting the promise of combining nanophotonic devices, new optical system designs, and machine learning for new frontiers in 3D imaging.
Brockarchaeota, a novel archaeal phylum with unique and versatile carbon cycling pathways
Authors: De Anda Valerie , Chen Lin-Xing , Dombrowski Nina , Hua Zheng-Shuang , Jiang Hong-Chen , Banfield Jillian F. , Li Wen-Jun , Baker Brett J. 
Published: April 2021

AbstractGeothermal environments, such as hot springs and hydrothermal vents, are hotspots for carbon cycling and contain many poorly described microbial taxa. Here, we reconstructed 15 archaeal metagenome-assembled genomes (MAGs) from terrestrial hot spring sediments in China and deep-sea hydrothermal vent sediments in Guaymas Basin, Gulf of California. Phylogenetic analyses of these MAGs indicate that they form a distinct group within the TACK superphylum, and thus we propose their classification as a new phylum, ‘Brockarchaeota’, named after Thomas Brock for his seminal research in hot springs. Based on the MAG sequence information, we infer that some Brockarchaeota are uniquely capable of mediating non-methanogenic anaerobic methylotrophy, via the tetrahydrofolate methyl branch of the Wood-Ljungdahl pathway and reductive glycine pathway. The hydrothermal vent genotypes appear to be obligate fermenters of plant-derived polysaccharides that rely mostly on substrate-level phosphorylation, as they seem to lack most respiratory complexes. In contrast, hot spring lineages have alternate pathways to increase their ATP yield, including anaerobic methylotrophy of methanol and trimethylamine, and potentially use geothermally derived mercury, arsenic, or hydrogen. Their broad distribution and their apparent anaerobic metabolic versatility indicate that Brockarchaeota may occupy previously overlooked roles in anaerobic carbon cycling.
Frustration-driven magnetic fluctuations as the origin of the low-temperature skyrmion phase in Co7Zn7Mn6
Authors: Ukleev V. , Karube K. , Derlet P. M. , Wang C. N. , Luetkens H. , Morikawa D. , Kikkawa A. , Mangin-Thro L. , Wildes A. R. , Yamasaki Y. , Yokoyama Y. , Yu L. , Piamonteze C. , Jaouen N. , Tokunaga Y. , Rønnow H. M. , Arima T. , Tokura Y. , Taguchi Y. , White J. S. 
Published: April 2021

AbstractIn chiral cubic helimagnets, phases of magnetic skyrmions—topologically protected spin whirls—are stabilized by thermal fluctuations over a narrow region directly below the magnetic ordering temperature Tc. Due to often being touted for use in applications, there is a high demand to identify new ways to stabilize equilibrium skyrmion phases far below Tc where they may display an enhanced robustness against external perturbation due to a larger magnetic order parameter. Here, from quantum beam experiments on the chiral magnet Co7Zn7Mn6, we unveil a direct correlation between the stability of its second skyrmion phase-stable far from Tc, and a concomitant enhancement of an underlying magnetic fluctuation rate that is driven by geometric magnetic frustration. The influences of other leading skyrmion stability mechanisms, such as those derived from thermal fluctuations and low T cubic anisotropies, are shown to be weak in this system. We therefore advance the existence of a fundamental mechanism for stabilizing topological skyrmions in Co7Zn7Mn6 chiral magnet that draws upon magnetic frustration as the key ingredient.
A multiple species, continent-wide, million-phenotype agronomic plant dataset
Authors: Newman Saul Justin , Furbank Robert T. 
Published: April 2021

AbstractA critical shortage of ‘big’ agronomic data is placing an unnecessary constraint on the conduct of public agronomic research, imparting barriers to model development and testing. Here, we address this problem by providing a large non-relational database of agronomic trials, linked to intensive management and observational data, run under a unified experimental framework. The National Variety Trials (NVTs) represent a decade-long experimental trial network, conducted across thousands of Australian field sites using highly standardised randomised controlled designs. The NVTs contain over a million machine-measured phenotypic observations, aggregated from density-controlled populations containing hundreds of millions of plants and thousands of released plant varieties. These data are linked to hundreds of thousands of metadata observations including standardised soil tests, fertiliser and pesticide input data, crop rotation data, prior farm management practices, and in-field sensors. Finally, these data are linked to a suite of ground and remote sensing observations, arranged into interpolated daily- and ten-day aggregated time series, to capture the substantial diversity in vegetation and environmental patterns across the continent-spanning NVT network.
Elevated expression of the adhesion GPCR ADGRL4/ELTD1 promotes endothelial sprouting angiogenesis without activating canonical GPCR signalling
Authors: Favara David M. , Liebscher Ines , Jazayeri Ali , Nambiar Madhulika , Sheldon Helen , Banham Alison H. , Harris Adrian L. 
Published: April 2021

AbstractADGRL4/ELTD1 is an orphan adhesion GPCR (aGPCR) expressed in endothelial cells that regulates tumour angiogenesis. The majority of aGPCRs are orphan receptors. The Stachel Hypothesis proposes a mechanism for aGPCR activation, in which aGPCRs contain a tethered agonist (termed Stachel) C-terminal to the GPCR-proteolytic site (GPS) cleavage point which, when exposed, initiates canonical GPCR signalling. This has been shown in a growing number of aGPCRs. We tested this hypothesis on ADGRL4/ELTD1 by designing full length (FL) and C-terminal fragment (CTF) ADGRL4/ELTD1 constructs, and a range of potential Stachel peptides. Constructs were transfected into HEK293T cells and HTRF FRET, luciferase-reporter and Alphascreen GPCR signalling assays were performed. A stable ADGRL4/ELTD1 overexpressing HUVEC line was additionally generated and angiogenesis assays, signalling assays and transcriptional profiling were performed. ADGRL4/ELTD1 has the lowest GC content in the aGPCR family and codon optimisation significantly increased its expression. FL and CTF ADGRL4/ELTD1 constructs, as well as Stachel peptides, did not activate canonical GPCR signalling. Furthermore, stable overexpression of ADGRL4/ELTD1 in HUVECs induced sprouting angiogenesis, lowered in vitro anastomoses, and decreased proliferation, without activating canonical GPCR signalling or MAPK/ERK, PI3K/AKT, JNK, JAK/HIF-1α, beta catenin or STAT3 pathways. Overexpression upregulated ANTXR1, SLC39A6, HBB, CHRNA, ELMOD1, JAG1 and downregulated DLL4, KIT, CCL15, CYP26B1. ADGRL4/ELTD1 specifically regulates the endothelial tip-cell phenotype through yet undefined signalling pathways.
Effects of family planning on fertility behaviour across the demographic transition
Authors: Kramer Karen L. , Hackman Joe , Schacht Ryan , Davis Helen E. 
Published: April 2021

AbstractThe adoption of contraception often coincides with market integration and has transformative effects on fertility behavior. Yet many parents in small-scale societies make decisions about whether and when to adopt family planning in an environment where the payoffs to have smaller families are uncertain. Here we track the fertility of Maya women across 90 years, spanning the transition from natural to contracepting fertility. We first situate the uncertainty in which fertility decisions are made and model how childbearing behaviors respond. We find that contraception, a key factor in cultural transmission models of fertility decline, initially has little effect on family size as women appear to hedge their bets and adopt fertility control only at the end of their reproductive careers. Family planning is, however, associated with the spread of lower fertility in later cohorts. Distinguishing influences on the origin versus spread of a behaviour provides valuable insight into causal factors shaping individual and normative changes in fertility.
Nine residues in HLA-DQ molecules determine with susceptibility and resistance to type 1 diabetes among young children in Sweden
Authors: Zhao Lue Ping , Papadopoulos George K. , Moustakas Antonis K. , Bondinas George P. , Carlsson Annelie , Larsson Helena Elding , Ludvigsson Johnny , Marcus Claude , Persson Martina , Samuelsson Ulf , Wang Ruihan , Pyo Chul-Woo , Geraghty Daniel E. , Lernmark Åke 
Published: April 2021

AbstractHLA-DQ molecules account over 50% genetic risk of type 1 diabetes (T1D), but little is known about associated residues. Through next generation targeted sequencing technology and deep learning of DQ residue sequences, the aim was to uncover critical residues and their motifs associated with T1D. Our analysis uncovered (αa1, α44, α157, α196) and (β9, β30, β57, β70, β135) on the HLA-DQ molecule. Their motifs captured all known susceptibility and resistant T1D associations. Three motifs, “DCAA-YSARD” (OR = 2.10, p = 1.96*10−20), “DQAA-YYARD” (OR = 3.34, 2.69*10−72) and “DQDA-YYARD” (OR = 3.71, 1.53*10−6) corresponding to DQ2.5 and DQ8.1 (the latter two motifs) associated with susceptibility. Ten motifs were significantly associated with resistance to T1D. Collectively, homozygous DQ risk motifs accounted for 43% of DQ-T1D risk, while homozygous DQ resistant motifs accounted for 25% protection to DQ-T1D risk. Of the identified nine residues five were within or near anchoring pockets of the antigenic peptide (α44, β9, β30, β57 and β70), one was the N-terminal of the alpha chain (αa1), one in the CD4-binding region (β135), one in the putative cognate TCR-induced αβ homodimerization process (α157), and one in the intra-membrane domain of the alpha chain (α196). Finding these critical residues should allow investigations of fundamental properties of host immunity that underlie tolerance to self and organ-specific autoimmunity.
Liver fat scores do not reflect interventional changes in liver fat content induced by high-protein diets
Authors: Kabisch Stefan , Markova Mariya , Hornemann Silke , Sucher Stephanie , Pivovarova-Ramich Olga , Machann Jürgen , Hierholzer Johannes , Rohn Sascha , Pfeiffer Andreas F. H. 
Published: April 2021

AbstractNon-alcoholic fatty liver disease (NAFLD) is common in Metabolic Syndrome and type 2 diabetes (T2DM), driven by energy imbalance, saturated fats and simple carbohydrates. NAFLD requires screening and monitoring for late complications. Liver fat indices may predict NAFLD avoiding expensive or invasive gold-standard methods, but they are poorly validated for use in interventional settings. Recent data indicate a particular insensitivity to weight-independent liver fat reduction. We evaluated 31 T2DM patients, completing a randomized intervention study on isocaloric high-protein diets. We assessed anthropometric measures, intrahepatic lipid (IHL) content and serum liver enzymes, allowing AUROC calculations as well as cross-sectional and longitudinal Spearman correlations between the fatty liver index, the NAFLD-liver fat score, the Hepatosteatosis Index, and IHL. At baseline, all indices predicted NAFLD with moderate accuracy (AUROC 0.731–0.770), supported by correlation analyses. Diet-induced IHL changes weakly correlated with changes of waist circumference, but no other index component or the indices themselves. Liver fat indices may help to easily detect NAFLD, allowing cost-effective allocation of further diagnostics to patients at high risk. IHL reduction by weight-independent diets is not reflected by a proportional change in liver fat scores. Further research on the development of treatment-sensitive indices is required.Trial registration: The trial was registered at clinicaltrials.gov: NCT02402985.