bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically predicted physical activity levels are associated with lower colorectal cancer risk: a Mendelian randomisation study
Authors: Zhang Xiaomeng , Theodoratou Evropi , Li Xue , Farrington Susan M. , Law Philip J. , Broderick Peter , Walker Marion , Klimentidis Yann C. , Rees Jessica M. B. , Houlston Richard S. , Tomlinson Ian P. M. , Burgess Stephen , Campbell Harry , Dunlop Malcolm G. , Timofeeva Maria 
Published: January 2021

Abstract
Background
We conducted a Mendelian randomisation (MR) study to investigate whether physical activity (PA) causes a reduction of colorectal cancer risk and to understand the contributions of effects mediated through changes in body fat.

Methods
Common genetic variants associated with self-reported moderate-to-vigorous PA (MVPA), acceleration vector magnitude PA (AMPA) and sedentary time were used as instrumental variables. To control for confounding effects of obesity, we included instrumental variables for body mass index (BMI), body fat percentage, waist circumference and arm, trunk and leg fat ratios. We analysed the effect of these instrumental variables in a colorectal cancer genome-wide association study comprising 31,197 cases and 61,770 controls of European ancestry by applying two-sample and multivariable MR study designs.

Results
We found decreased colorectal cancer risk for genetically represented measures of MVPA and AMPA that were additional to effects mediated through genetic measures of obesity. Odds ratio and 95% confidence interval (CI) per standard deviation increase in MVPA and AMPA was 0.56 (0.31, 1.01) and 0.60 (0.41, 0.88), respectively. No association has been found between sedentary time and colorectal cancer risk. The proportion of effect mediated through BMI was 2% (95% CI: 0, 14) and 32% (95% CI: 12, 46) for MVPA and AMPA, respectively.

Conclusion
These findings provide strong evidence to reinforce public health measures on preventing colorectal cancer that promote PA at a population level regardless of body fatness.
The noncanonical role of the protease cathepsin D as a cofilin phosphatase
Authors: Liu Yi-Jun , Zhang Ting , Chen Sicong , Cheng Daxiao , Wu Cunjin , Wang Xingyue , Duan Duo , Zhu Liya , Lou Huifang , Gong Zhefeng , Wang Xiao-Dong , Ho Margaret S. , Duan Shumin 
Published: January 2021

AbstractCathepsin D (cathD) is traditionally regarded as a lysosomal protease that degrades substrates in acidic compartments. Here we report cathD plays an unconventional role as a cofilin phosphatase orchestrating actin remodeling. In neutral pH environments, the cathD precursor directly dephosphorylates and activates the actin-severing protein cofilin independent of its proteolytic activity, whereas mature cathD degrades cofilin in acidic pH conditions. During development, cathD complements the canonical cofilin phosphatase slingshot and regulates the morphogenesis of actin-based structures. Moreover, suppression of cathD phosphatase activity leads to defective actin organization and cytokinesis failure. Our findings identify cathD as a dual-function molecule, whose functional switch is regulated by environmental pH and its maturation state, and reveal a novel regulatory role of cathD in actin-based cellular processes.
Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome
Authors: Lu J. Yuyang , Chang Lei , Li Tong , Wang Ting , Yin Yafei , Zhan Ge , Han Xue , Zhang Ke , Tao Yibing , Percharde Michelle , Wang Liang , Peng Qi , Yan Pixi , Zhang Hui , Bi Xianju , Shao Wen , Hong Yantao , Wu Zhongyang , Ma Runze , Wang Peizhe , Li Wenzhi , Zhang Jing , Chang Zai , Hou Yingping , Zhu Bing , Ramalho-Santos Miguel , Li Pilong , Xie Wei , Na Jie , Sun Yujie , Shen Xiaohua 
Published: January 2021

AbstractOrganization of the genome into euchromatin and heterochromatin appears to be evolutionarily conserved and relatively stable during lineage differentiation. In an effort to unravel the basic principle underlying genome folding, here we focus on the genome itself and report a fundamental role for L1 (LINE1 or LINE-1) and B1/Alu retrotransposons, the most abundant subclasses of repetitive sequences, in chromatin compartmentalization. We find that homotypic clustering of L1 and B1/Alu demarcates the genome into grossly exclusive domains, and characterizes and predicts Hi-C compartments. Spatial segregation of L1-rich sequences in the nuclear and nucleolar peripheries and B1/Alu-rich sequences in the nuclear interior is conserved in mouse and human cells and occurs dynamically during the cell cycle. In addition, de novo establishment of L1 and B1 nuclear segregation is coincident with the formation of higher-order chromatin structures during early embryogenesis and appears to be critically regulated by L1 and B1 transcripts. Importantly, depletion of L1 transcripts in embryonic stem cells drastically weakens homotypic repeat contacts and compartmental strength, and disrupts the nuclear segregation of L1- or B1-rich chromosomal sequences at genome-wide and individual sites. Mechanistically, nuclear co-localization and liquid droplet formation of L1 repeat DNA and RNA with heterochromatin protein HP1α suggest a phase-separation mechanism by which L1 promotes heterochromatin compartmentalization. Taken together, we propose a genetically encoded model in which L1 and B1/Alu repeats blueprint chromatin macrostructure. Our model explains the robustness of genome folding into a common conserved core, on which dynamic gene regulation is overlaid across cells.
Gate-tunable photodetector and ambipolar transistor implemented using a graphene/MoSe2 barristor
Authors: Oh Gwangtaek , Jeon Ji Hoon , Kim Young Chul , Ahn Yeong Hwan , Park Bae Ho 
Published: January 2021

AbstractNext-generation electronic and optoelectronic devices require a high-quality channel layer. Graphene is a good candidate because of its high carrier mobility and unique ambipolar transport characteristics. However, the on/off ratio and photoresponsivity of graphene are typically low. Transition metal dichalcogenides (e.g., MoSe2) are semiconductors with high photoresponsivity but lower mobility than that of graphene. Here, we propose a graphene/MoSe2 barristor with a high-k ion-gel gate dielectric. It shows a high on/off ratio (3.3 × 104) and ambipolar behavior that is controlled by an external bias. The barristor exhibits very high external quantum efficiency (EQE, 66.3%) and photoresponsivity (285.0 mA/W). We demonstrate that an electric field applied to the gate electrode substantially modulates the photocurrent of the barristor, resulting in a high gate tuning ratio (1.50 μA/V). Therefore, this barristor shows potential for use as an ambipolar transistor with a high on/off ratio and a gate-tunable photodetector with a high EQE and responsivity.
Integrated neuromorphic computing networks by artificial spin synapses and spin neurons
Authors: Yang Seungmo , Shin Jeonghun , Kim Taeyoon , Moon Kyoung-Woong , Kim Jaewook , Jang Gabriel , Hyeon Da Seul , Yang Jungyup , Hwang Chanyong , Jeong YeonJoo , Hong Jin Pyo 
Published: January 2021

AbstractOne long-standing goal in the emerging neuromorphic field is to create a reliable neural network hardware implementation that has low energy consumption, while providing massively parallel computation. Although diverse oxide-based devices have made significant progress as artificial synaptic and neuronal components, these devices still need further optimization regarding linearity, symmetry, and stability. Here, we present a proof-of-concept experiment for integrated neuromorphic computing networks by utilizing spintronics-based synapse (spin-S) and neuron (spin-N) devices, along with linear and symmetric weight responses for spin-S using a stripe domain and activation functions for spin-N. An integrated neural network of electrically connected spin-S and spin-N successfully proves the integration function for a simple pattern classification task. We simulate a spin-N network using the extracted device characteristics and demonstrate a high classification accuracy (over 93%) for the spin-S and spin-N optimization without the assistance of additional software or circuits required in previous reports. These experimental studies provide a new path toward establishing more compact and efficient neural network systems with optimized multifunctional spintronic devices.
Enhanced piezoelectricity from highly polarizable oriented amorphous fractions in biaxially oriented poly(vinylidene fluoride) with pure β crystals
Authors: Huang Yanfei , Rui Guanchun , Li Qiong , Allahyarov Elshad , Li Ruipeng , Fukuto Masafumi , Zhong Gan-Ji , Xu Jia-Zhuang , Li Zhong-Ming , Taylor Philip L. , Zhu Lei 
Published: January 2021

AbstractPiezoelectric polymers hold great potential for various electromechanical applications, but only show low performance, with |d33 | < 30 pC/N. We prepare a highly piezoelectric polymer (d33 = −62 pC/N) based on a biaxially oriented poly(vinylidene fluoride) (BOPVDF, crystallinity = 0.52). After unidirectional poling, macroscopically aligned samples with pure β crystals are achieved, which show a high spontaneous polarization (Ps) of 140 mC/m2. Given the theoretical limit of Ps,β = 188 mC/m2 for the neat β crystal, the high Ps cannot be explained by the crystalline-amorphous two-phase model (i.e., Ps,β = 270 mC/m2). Instead, we deduce that a significant amount (at least 0.25) of an oriented amorphous fraction (OAF) must be present between these two phases. Experimental data suggest that the mobile OAF resulted in the negative and high d33 for the poled BOPVDF. The plausibility of this conclusion is supported by molecular dynamics simulations.
Benchmarking monolayer MoS2 and WS2 field-effect transistors
Authors: Sebastian Amritanand , Pendurthi Rahul , Choudhury Tanushree H. , Redwing Joan M. , Das Saptarshi 
Published: January 2021

AbstractHere we benchmark device-to-device variation in field-effect transistors (FETs) based on monolayer MoS2 and WS2 films grown using metal-organic chemical vapor deposition process. Our study involves 230 MoS2 FETs and 160 WS2 FETs with channel lengths ranging from 5 μm down to 100 nm. We use statistical measures to evaluate key FET performance indicators for benchmarking these two-dimensional (2D) transition metal dichalcogenide (TMD) monolayers against existing literature as well as ultra-thin body Si FETs. Our results show consistent performance of 2D FETs across 1 × 1 cm2 chips owing to high quality and uniform growth of these TMDs followed by clean transfer onto device substrates. We are able to demonstrate record high carrier mobility of 33 cm2 V−1 s−1 in WS2 FETs, which is a 1.5X improvement compared to the best reported in the literature. Our experimental demonstrations confirm the technological viability of 2D FETs in future integrated circuits.
The oncogenicity of tumor-derived mutant p53 is enhanced by the recruitment of PLK3
Authors: Vaughan Catherine A. , Singh Shilpa , Subler Mark A. , Windle Jolene J. , Inoue Kazushi , Fry Elizabeth A. , Pillappa Raghavendra , Grossman Steven R. , Windle Brad , Andrew Yeudall W. , Deb Swati Palit , Deb Sumitra 
Published: January 2021

Abstractp53 mutations with single amino acid changes in cancer often lead to dominant oncogenic changes. Here, we have developed a mouse model of gain-of-function (GOF) p53-driven lung cancer utilizing conditionally active LSL p53-R172H and LSL K-Ras-G12D knock-in alleles that can be activated by Cre in lung club cells. Mutation of the p53 transactivation domain (TAD) (p53-L25Q/W26S/R172H) eliminating significant transactivation activity resulted in loss of tumorigenicity, demonstrating that transactivation mediated by or dependent on TAD is required for oncogenicity by GOF p53. GOF p53 TAD mutations significantly reduce phosphorylation of nearby p53 serine 20 (S20), which is a target for PLK3 phosphorylation. Knocking out PLK3 attenuated S20 phosphorylation along with transactivation and oncogenicity by GOF p53, indicating that GOF p53 exploits PLK3 to trigger its transactivation capability and exert oncogenic functions. Our data show a mechanistic involvement of PLK3 in mutant p53 pathway of oncogenesis.
Structural basis for a complex I mutation that blocks pathological ROS production
Authors: Yin Zhan , Burger Nils , Kula-Alwar Duvaraka , Aksentijević Dunja , Bridges Hannah R. , Prag Hiran A. , Grba Daniel N. , Viscomi Carlo , James Andrew M. , Mottahedin Amin , Krieg Thomas , Murphy Michael P. , Hirst Judy 
Published: January 2021

AbstractMitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia–reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease-causing mtDNA point mutation encoding the P25L substitution in the ND6 subunit of complex I. The cryo-EM structure of ND6-P25L complex I revealed subtle structural changes that facilitate rapid conversion to the “deactive” state, usually formed only after prolonged inactivity. Despite its tendency to adopt the “deactive” state, the mutant complex is fully active for NADH oxidation, but cannot generate ROS by reverse electron transfer (RET). ND6-P25L mitochondria function normally, except for their lack of RET ROS production, and ND6-P25L mice are protected against cardiac IR injury in vivo. Thus, this single point mutation in complex I, which does not affect oxidative phosphorylation but renders the complex unable to catalyse RET, demonstrates the pathological role of ROS production by RET during IR injury.
Topological optical differentiator
Authors: Zhu Tengfeng , Guo Cheng , Huang Junyi , Wang Haiwen , Orenstein Meir , Ruan Zhichao , Fan Shanhui 
Published: January 2021

AbstractOptical computing holds significant promise of information processing with ultrahigh speed and low power consumption. Recent developments in nanophotonic structures have generated renewed interests due to the prospects of performing analog optical computing with compact devices. As one prominent example, spatial differentiation has been demonstrated with nanophotonic structures and directly applied for edge detection in image processing. However, broadband isotropic two-dimensional differentiation, which is required in most imaging processing applications, has not been experimentally demonstrated yet. Here, we establish a connection between two-dimensional optical spatial differentiation and a nontrivial topological charge in the optical transfer function. Based on this connection, we experimentally demonstrate an isotropic two-dimensional differentiation with a broad spectral bandwidth, by using the simplest photonic device, i.e. a single unpatterned interface. Our work indicates that exploiting concepts from topological photonics can lead to new opportunities in optical computing.
Microthermal-induced subcellular-targeted protein damage in cells on plasmonic nanosilver-modified surfaces evokes a two-phase HSP-p97/VCP response
Authors: Mistrik Martin , Skrott Zdenek , Muller Petr , Panacek Ales , Hochvaldova Lucie , Chroma Katarina , Buchtova Tereza , Vandova Veronika , Kvitek Libor , Bartek Jiri 
Published: January 2021

AbstractDespite proteotoxic stress and heat shock being implicated in diverse pathologies, currently no methodology to inflict defined, subcellular thermal damage exists. Here, we present such a single-cell method compatible with laser-scanning microscopes, adopting the plasmon resonance principle. Dose-defined heat causes protein damage in subcellular compartments, rapid heat-shock chaperone recruitment, and ensuing engagement of the ubiquitin–proteasome system, providing unprecedented insights into the spatiotemporal response to thermal damage relevant for degenerative diseases, with broad applicability in biomedicine. Using this versatile method, we discover that HSP70 chaperone and its interactors are recruited to sites of thermally damaged proteins within seconds, and we report here mechanistically important determinants of such HSP70 recruitment. Finally, we demonstrate a so-far unsuspected involvement of p97(VCP) translocase in the processing of heat-damaged proteins. Overall, we report an approach to inflict targeted thermal protein damage and its application to elucidate cellular stress-response pathways that are emerging as promising therapeutic targets.
Acoustic spectral hole-burning in a two-level system ensemble
Authors: Andersson G. , Bilobran A. L. O. , Scigliuzzo M. , de Lima M. M. , Cole J. H. , Delsing P. 
Published: January 2021

AbstractMicroscopic two-level system (TLS) defects at dielectric surfaces and interfaces are among the dominant sources of loss in superconducting quantum circuits, and their properties have been extensively probed using superconducting resonators and qubits. We report on spectroscopy of TLSs coupling to the strain field in a surface acoustic wave (SAW) resonator. The narrow free spectral range of the resonator allows for two-tone spectroscopy where a strong pump is applied at one resonance, while a weak signal is used to probe a different mode. We map the spectral hole burnt by the pump tone as a function of frequency and extract parameters of the TLS ensemble. Our results suggest that detuned acoustic pumping can be used to enhance the coherence of superconducting devices by saturating TLSs.
Burkholderia pseudomallei OMVs derived from infection mimicking conditions elicit similar protection to a live-attenuated vaccine
Authors: Baker Sarah M. , Settles Erik W. , Davitt Christopher , Gellings Patrick , Kikendall Nicole , Hoffmann Joseph , Wang Yihui , Bitoun Jacob , Lodrigue Kasi-Russell , Sahl Jason W. , Keim Paul , Roy Chad , McLachlan James , Morici Lisa A. 
Published: January 2021

AbstractBurkholderia pseudomallei is a Gram-negative, facultative intracellular bacillus that causes the disease melioidosis. B. pseudomallei expresses a number of proteins that contribute to its intracellular survival in the mammalian host. We previously demonstrated that immunization with OMVs derived from B. pseudomallei grown in nutrient-rich media protects mice against lethal disease. Here, we evaluated if OMVs derived from B. pseudomallei grown under macrophage-mimicking growth conditions could be enriched with intracellular-stage proteins in order to improve the vaccine. We show that OMVs produced in this manner (M9 OMVs) contain proteins associated with intracellular survival yet are non-toxic to living cells. Immunization of mice provides significant protection against pulmonary infection similar to that achieved with a live attenuated vaccine and is associated with increased IgG, CD4+, and CD8+ T cells. OMVs possess inherent adjuvanticity and drive DC activation and maturation. These results indicate that M9 OMVs constitute a new promising vaccine against melioidosis.
Management of congenital nephrotic syndrome: consensus recommendations of the ERKNet-ESPN Working Group
Authors: Boyer Olivia , Schaefer Franz , Haffner Dieter , Bockenhauer Detlef , Hölttä Tuula , Bérody Sandra , Webb Hazel , Heselden Marie , Lipska-Zie˛tkiewicz Beata S. , Ozaltin Fatih , Levtchenko Elena , Vivarelli Marina 
Published: January 2021

AbstractCongenital nephrotic syndrome (CNS) is a heterogeneous group of disorders characterized by nephrotic-range proteinuria, hypoalbuminaemia and oedema, which manifest in utero or during the first 3 months of life. The main cause of CNS is genetic defects in podocytes; however, it can also be caused, in rare cases, by congenital infections or maternal allo-immune disease. Management of CNS is very challenging because patients are prone to severe complications, such as haemodynamic compromise, infections, thromboses, impaired growth and kidney failure. In this consensus statement, experts from the European Reference Network for Kidney Diseases (ERKNet) and the European Society for Paediatric Nephrology (ESPN) summarize the current evidence and present recommendations for the management of CNS, including the use of renin–angiotensin system inhibitors, diuretics, anticoagulation and infection prophylaxis. Therapeutic management should be adapted to the clinical severity of the condition with the aim of maintaining intravascular euvolaemia and adequate nutrition, while preventing complications and preserving central and peripheral vessels. We do not recommend performing routine early nephrectomies but suggest that they are considered in patients with severe complications despite optimal conservative treatment, and before transplantation in patients with persisting nephrotic syndrome and/or a WT1-dominant pathogenic variant.
An Indo-Pacific coral spawning database
Authors: Baird Andrew H. , Guest James R. , Edwards Alasdair J. , Bauman Andrew G. , Bouwmeester Jessica , Mera Hanaka , Abrego David , Alvarez-Noriega Mariana , Babcock Russel C. , Barbosa Miguel B. , Bonito Victor , Burt John , Cabaitan Patrick C. , Chang Ching-Fong , Chavanich Suchana , Chen Chaolun A. , Chen Chieh-Jhen , Chen Wei-Jen , Chung Fung-Chen , Connolly Sean R. , Cumbo Vivian R. , Dornelas Maria , Doropoulos Christopher , Eyal Gal , Eyal-Shaham Lee , Fadli Nur , Figueiredo Joana , Flot Jean-François , Gan Sze-Hoon , Gomez Elizabeth , Graham Erin M. , Grinblat Mila , Gutiérrez-Isaza Nataly , Harii Saki , Harrison Peter L. , Hatta Masayuki , Ho Nina Ann Jin , Hoarau Gaetan , Hoogenboom Mia , Howells Emily J. , Iguchi Akira , Isomura Naoko , Jamodiong Emmeline A. , Jandang Suppakarn , Keyse Jude , Kitanobo Seiya , Kongjandtre Narinratana , Kuo Chao-Yang , Ligson Charlon , Lin Che-Hung , Low Jeffrey , Loya Yossi , Maboloc Elizaldy A. , Madin Joshua S. , Mezaki Takuma , Min Choo , Morita Masaya , Moya Aurelie , Neo Su-Hwei , Nitschke Matthew R. , Nojima Satoshi , Nozawa Yoko , Piromvaragorn Srisakul , Plathong Sakanan , Puill-Stephan Eneour , Quigley Kate , Ramirez-Portilla Catalina , Ricardo Gerard , Sakai Kazuhiko , Sampayo Eugenia , Shlesinger Tom , Sikim Leony , Simpson Chris , Sims Carrie A. , Sinniger Frederic , Spiji Davies A. , Tabalanza Tracy , Tan Chung-Hong , Terraneo Tullia I. , Torda Gergely , True James , Tun Karenne , Vicentuan Kareen , Viyakarn Voranop , Waheed Zarinah , Ward Selina , Willis Bette , Woods Rachael M. , Woolsey Erika S. , Yamamoto Hiromi H. , Yusuf Syafyudin 
Published: January 2021

AbstractThe discovery of multi-species synchronous spawning of scleractinian corals on the Great Barrier Reef in the 1980s stimulated an extraordinary effort to document spawning times in other parts of the globe. Unfortunately, most of these data remain unpublished which limits our understanding of regional and global reproductive patterns. The Coral Spawning Database (CSD) collates much of these disparate data into a single place. The CSD includes 6178 observations (3085 of which were unpublished) of the time or day of spawning for over 300 scleractinian species in 61 genera from 101 sites in the Indo-Pacific. The goal of the CSD is to provide open access to coral spawning data to accelerate our understanding of coral reproductive biology and to provide a baseline against which to evaluate any future changes in reproductive phenology.