bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic and genetic basis of single-strand templated repair at Cas12a-induced DNA breaks in Chlamydomonas reinhardtii
Authors: Ferenczi Aron , Chew Yen Peng , Kroll Erika , von Koppenfels Charlotte , Hudson Andrew , Molnar Attila 
Published: November 2021

AbstractSingle-stranded oligodeoxynucleotides (ssODNs) are widely used as DNA repair templates in CRISPR/Cas precision genome editing. However, the underlying mechanisms of single-strand templated DNA repair (SSTR) are inadequately understood, constraining rational improvements to precision editing. Here we study SSTR at CRISPR/Cas12a-induced DNA double-strand breaks (DSBs) in the eukaryotic model green microalga Chlamydomonas reinhardtii. We demonstrate that ssODNs physically incorporate into the genome during SSTR at Cas12a-induced DSBs. This process is genetically independent of the Rad51-dependent homologous recombination and Fanconi anemia pathways, is strongly antagonized by non-homologous end-joining, and is mediated almost entirely by the alternative end-joining enzyme polymerase θ. These findings suggest differences in SSTR between C. reinhardtii and animals. Our work illustrates the promising potentially of C. reinhardtii as a model organism for studying nuclear DNA repair.
Site-controlled telecom-wavelength single-photon emitters in atomically-thin MoTe2
Authors: Zhao Huan , Pettes Michael T. , Zheng Yu , Htoon Han 
Published: November 2021

AbstractQuantum emitters (QEs) in two-dimensional transition metal dichalcogenides (2D TMDCs) have advanced to the forefront of quantum communication and transduction research. To date, QEs capable of operating in O-C telecommunication bands have not been demonstrated in TMDCs. Here we report site-controlled creation of telecom QEs emitting over the 1080 to 1550 nm telecommunication wavelength range via coupling of 2D molybdenum ditelluride (MoTe2) to strain inducing nano-pillar arrays. Hanbury Brown and Twiss experiments conducted at 10 K reveal clear photon antibunching with 90% single-photon purity. The photon antibunching can be observed up to liquid nitrogen temperature (77 K). Polarization analysis further reveals that while some QEs display cross-linearly polarized doublets with ~1 meV splitting resulting from the strain induced anisotropic exchange interaction, valley degeneracy is preserved in other QEs. Valley Zeeman splitting as well as restoring of valley symmetry in cross-polarized doublets are observed under 8 T magnetic field.
Soft fibers with magnetoelasticity for wearable electronics
Authors: Zhao Xun , Zhou Yihao , Xu Jing , Chen Guorui , Fang Yunsheng , Tat Trinny , Xiao Xiao , Song Yang , Li Song , Chen Jun 
Published: November 2021

AbstractMagnetoelastic effect characterizes the change of materials’ magnetic properties under mechanical deformation, which is conventionally observed in some rigid metals or metal alloys. Here we show magnetoelastic effect can also exist in 1D soft fibers with stronger magnetomechanical coupling than that in traditional rigid counterparts. This effect is explained by a wavy chain model based on the magnetic dipole-dipole interaction and demagnetizing factor. To facilitate practical applications, we further invented a textile magnetoelastic generator (MEG), weaving the 1D soft fibers with conductive yarns to couple the observed magnetoelastic effect with magnetic induction, which paves a new way for biomechanical-to-electrical energy conversion with short-circuit current density of 0.63 mA cm−2, internal impedance of 180 Ω, and intrinsic waterproofness. Textile MEG was demonstrated to convert the arterial pulse into electrical signals with a low detection limit of 0.05 kPa, even with heavy perspiration or in underwater situations without encapsulations.
The genetic architecture of DNA replication timing in human pluripotent stem cells
Authors: Ding Qiliang , Edwards Matthew M. , Wang Ning , Zhu Xiang , Bracci Alexa N. , Hulke Michelle L. , Hu Ya , Tong Yao , Hsiao Joyce , Charvet Christine J. , Ghosh Sulagna , Handsaker Robert E. , Eggan Kevin , Merkle Florian T. , Gerhardt Jeannine , Egli Dieter , Clark Andrew G. , Koren Amnon 
Published: November 2021

AbstractDNA replication follows a strict spatiotemporal program that intersects with chromatin structure but has a poorly understood genetic basis. To systematically identify genetic regulators of replication timing, we exploited inter-individual variation in human pluripotent stem cells from 349 individuals. We show that the human genome’s replication program is broadly encoded in DNA and identify 1,617 cis-acting replication timing quantitative trait loci (rtQTLs) – sequence determinants of replication initiation. rtQTLs function individually, or in combinations of proximal and distal regulators, and are enriched at sites of histone H3 trimethylation of lysines 4, 9, and 36 together with histone hyperacetylation. H3 trimethylation marks are individually repressive yet synergistically associate with early replication. We identify pluripotency-related transcription factors and boundary elements as positive and negative regulators of replication timing, respectively. Taken together, human replication timing is controlled by a multi-layered mechanism with dozens of effectors working combinatorially and following principles analogous to transcription regulation.
Magneto-transport evidence for strong topological insulator phase in ZrTe5
Authors: Wang Jingyue , Jiang Yuxuan , Zhao Tianhao , Dun Zhiling , Miettinen Anna L. , Wu Xiaosong , Mourigal Martin , Zhou Haidong , Pan Wei , Smirnov Dmitry , Jiang Zhigang 
Published: November 2021

AbstractThe identification of a non-trivial band topology usually relies on directly probing the protected surface/edge states. But, it is difficult to achieve electronically in narrow-gap topological materials due to the small (meV) energy scales. Here, we demonstrate that band inversion, a crucial ingredient of the non-trivial band topology, can serve as an alternative, experimentally accessible indicator. We show that an inverted band can lead to a four-fold splitting of the non-zero Landau levels, contrasting the two-fold splitting (spin splitting only) in the normal band. We confirm our predictions in magneto-transport experiments on a narrow-gap strong topological insulator, zirconium pentatelluride (ZrTe5), with the observation of additional splittings in the quantum oscillations and also an anomalous peak in the extreme quantum limit. Our work establishes an effective strategy for identifying the band inversion as well as the associated topological phases for future topological materials research.
Recursive evolution of spin-wave multiplets in magnonic crystals of antidot-lattice fractals
Authors: Park Gyuyoung , Yang Jaehak , Kim Sang-Koog 
Published: November 2021

AbstractWe explored spin-wave multiplets excited in a different type of magnonic crystal composed of ferromagnetic antidot-lattice fractals, by means of micromagnetic simulations with a periodic boundary condition. The modeling of antidot-lattice fractals was designed with a series of self-similar antidot-lattices in an integer Hausdorff dimension. As the iteration level increased, multiple splits of the edge and center modes of quantized spin-waves in the antidot-lattices were excited due to the fractals’ inhomogeneous and asymmetric internal magnetic fields. It was found that a recursive development (Fn = Fn−1 + Gn−1) of geometrical fractals gives rise to the same recursive evolution of spin-wave multiplets.
Gastrocnemius medialis contractile behavior during running differs between simulated Lunar and Martian gravities
Authors: Richter Charlotte , Braunstein Bjoern , Staeudle Benjamin , Attias Julia , Suess Alexander , Weber Tobias , Mileva Katya N. , Rittweger Joern , Green David A. , Albracht Kirsten 
Published: November 2021

AbstractThe international partnership of space agencies has agreed to proceed forward to the Moon sustainably. Activities on the Lunar surface (0.16 g) will allow crewmembers to advance the exploration skills needed when expanding human presence to Mars (0.38 g). Whilst data from actual hypogravity activities are limited to the Apollo missions, simulation studies have indicated that ground reaction forces, mechanical work, muscle activation, and joint angles decrease with declining gravity level. However, these alterations in locomotion biomechanics do not necessarily scale to the gravity level, the reduction in gastrocnemius medialis activation even appears to level off around 0.2 g, while muscle activation pattern remains similar. Thus, it is difficult to predict whether gastrocnemius medialis contractile behavior during running on Moon will basically be the same as on Mars. Therefore, this study investigated lower limb joint kinematics and gastrocnemius medialis behavior during running at 1 g, simulated Martian gravity, and simulated Lunar gravity on the vertical treadmill facility. The results indicate that hypogravity-induced alterations in joint kinematics and contractile behavior still persist between simulated running on the Moon and Mars. This contrasts with the concept of a ceiling effect and should be carefully considered when evaluating exercise prescriptions and the transferability of locomotion practiced in Lunar gravity to Martian gravity.
Spatial distribution of conspecific genotypes within chimeras of the branching coral Stylophora pistillata
Authors: Guerrini Gabriele , Shefy Dor , Douek Jacob , Shashar Nadav , Goulet Tamar L. , Rinkevich Baruch 
Published: November 2021

AbstractChimerism is a coalescence of conspecific genotypes. Although common in nature, fundamental knowledge, such as the spatial distribution of the genotypes within chimeras, is lacking. Hence, we investigated the spatial distribution of conspecific genotypes within the brooding coral Stylophora pistillata, a common species throughout the Indo-Pacific and Red Sea. From eight gravid colonies, we collected planula larvae that settled in aggregates, forming 2–3 partner chimeras. Coral chimeras grew in situ for up to 25 months. Nine chimeras (8 kin, 1 non-related genotypes) were sectioned into 7–17 fragments (6–26 polyps/fragment), and genotyped using eight microsatellite loci. The discrimination power of each microsatellite-locus was evaluated with 330 ‘artificial chimeras,’ made by mixing DNA from three different S. pistillata genotypes in pairwise combinations. In 68% of ‘artificial chimeras,’ the second genotype was detected if it constituted 5–30% of the chimera. Analyses of S. pistillata chimeras revealed that: (a) chimerism is a long-term state; (b) conspecifics were intermixed (not separate from one another); (c) disproportionate distribution of the conspecifics occurred; (d) cryptic chimerism (chimerism not detected via a given microsatellite) existed, alluding to the underestimation of chimerism in nature. Mixed chimerism may affect ecological/physiological outcomes for a chimera, especially in clonal organisms, and challenges the concept of individuality, affecting our understanding of the unit of selection.
Kinetics of antibody response in critically ill patients with Middle East respiratory syndrome and association with mortality and viral clearance
Authors: Arabi Yaseen M , Hajeer Ali H. , Balkhy Hanan , Al Johani Sameera , Sadat Musharaf , Al-Dawood Abdulaziz , Abu Taleb Alanoud , Jose Jesna , Al Qasim Eman , Al Ajlan Abdulaziz 
Published: November 2021

AbstractThe objective of this study is to examine the IgG antibody response in critically ill patients with the Middle East respiratory syndrome (MERS) and to examine the association of early antibody response with mortality and viral clearance. We collected blood samples from 40 consecutive real-time reverse transcription-polymerase chain reaction (rRT-PCR) confirmed critically ill MERS patients on ICU days 1, 3, 7, 14 and 28. MERS-CoV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), using wells coated with MERS-CoV S1 antigen. Patients were admitted to ICU after a median (Q1, Q3) of 9 (4, 13) days from onset of symptoms with an admission Sequential Organ Failure Assessment (SOFA) score of 11 (6.5, 12). Among the study cohort, 38 patients (95%) received invasive ventilation, 35 (88%) vasopressors, 21 (53%) renal replacement therapy and 17 (43%) corticosteroids. Median (Q1,Q3) ELISA optical density (OD) ratio significantly increased with time (p < 0.001) from 0.11 (0.07, 1.43) on day 1; to 0.69 (0.11, 2.08) on day 3, 2.72 (1.84, 3.54) on day 7, 2.51 (0.35, 3.35) on day 14 and 3.77 (3.70, 3.84) on day 28. Early antibody response (day 1–3) was observed in 13/39 patients (33%) and was associated with lower mortality (hazard ratio: 0.31, 95% CI 0.10, 0.96, p = 0.04) but was not associated with faster clearance of MERS-CoV RNA. In conclusion, among critically ill patients with MERS, early antibody response was associated with lower mortality but not with faster clearance of MERS-CoV RNA. These findings have important implications for understanding pathogenesis and potential immunotherapy.
Large-scale genetic investigation reveals genetic liability to multiple complex traits influencing a higher risk of ADHD
Authors: García-Marín Luis M. , Campos Adrián I. , Cuéllar-Partida Gabriel , Medland Sarah E. , Kollins Scott H. , Rentería Miguel E. 
Published: November 2021

AbstractAttention Deficit-Hyperactivity Disorder (ADHD) is a complex psychiatric and neurodevelopmental disorder that develops during childhood and spans into adulthood. ADHD’s aetiology is complex, and evidence about its cause and risk factors is limited. We leveraged genetic data from genome-wide association studies (GWAS) and performed latent causal variable analyses using a hypothesis-free approach to infer causal associations between 1387 complex traits and ADHD. We identified 37 inferred potential causal associations with ADHD risk. Our results reveal that genetic variants associated with iron deficiency anemia (ICD10), obesity, type 2 diabetes, synovitis and tenosynovitis (ICD10), polyarthritis (ICD10), neck or shoulder pain, and substance use in adults display partial genetic causality on ADHD risk in children. Genetic variants associated with ADHD have a partial genetic causality increasing the risk for chronic obstructive pulmonary disease and carpal tunnel syndrome. Protective factors for ADHD risk included genetic variants associated with the likelihood of participating in socially supportive and interactive activities. Our results show that genetic liability to multiple complex traits influences a higher risk for ADHD, highlighting the potential role of cardiometabolic phenotypes and physical pain in ADHD’s aetiology. These findings have the potential to inform future clinical studies and development of interventions.
A molecular spectroscopy approach for the investigation of early phase ochronotic pigment development in Alkaptonuria
Authors: Bernini Andrea , Petricci Elena , Atrei Andrea , Baratto Maria Camilla , Manetti Fabrizio , Santucci Annalisa 
Published: November 2021

AbstractAlkaptonuria (AKU), a rare genetic disorder, is characterized by the accumulation of homogentisic acid (HGA) in organs due to a deficiency in functional levels of the enzyme homogentisate 1,2-dioxygenase (HGD), required for the breakdown of HGA, because of mutations in the HGD gene. Over time, HGA accumulation causes the formation of the ochronotic pigment, a dark deposit that leads to tissue degeneration and organ malfunction. Such behaviour can be observed also in vitro for HGA solutions or HGA-containing biofluids (e.g. urine from AKU patients) upon alkalinisation, although a comparison at the molecular level between the laboratory and the physiological conditions is lacking. Indeed, independently from the conditions, such process is usually explained with the formation of 1,4-benzoquinone acetic acid (BQA) as the product of HGA chemical oxidation, mostly based on structural similarity between HGA and hydroquinone that is known to be oxidized to the corresponding para-benzoquinone. To test such correlation, a comprehensive, comparative investigation on HGA and BQA chemical behaviours was carried out by a combined approach of spectroscopic techniques (UV spectrometry, Nuclear Magnetic Resonance, Electron Paramagnetic Resonance, Dynamic Light Scattering) under acid/base titration both in solution and in biofluids. New insights on the process leading from HGA to ochronotic pigment have been obtained, spotting out the central role of radical species as intermediates not reported so far. Such evidence opens the way for molecular investigation of HGA fate in cells and tissue aiming to find new targets for Alkaptonuria therapy.
Effect of data leakage in brain MRI classification using 2D convolutional neural networks
Authors: Yagis Ekin , Atnafu Selamawet Workalemahu , García Seco de Herrera Alba , Marzi Chiara , Scheda Riccardo , Giannelli Marco , Tessa Carlo , Citi Luca , Diciotti Stefano 
Published: November 2021

AbstractIn recent years, 2D convolutional neural networks (CNNs) have been extensively used to diagnose neurological diseases from magnetic resonance imaging (MRI) data due to their potential to discern subtle and intricate patterns. Despite the high performances reported in numerous studies, developing CNN models with good generalization abilities is still a challenging task due to possible data leakage introduced during cross-validation (CV). In this study, we quantitatively assessed the effect of a data leakage caused by 3D MRI data splitting based on a 2D slice-level using three 2D CNN models to classify patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Our experiments showed that slice-level CV erroneously boosted the average slice level accuracy on the test set by 30% on Open Access Series of Imaging Studies (OASIS), 29% on Alzheimer’s Disease Neuroimaging Initiative (ADNI), 48% on Parkinson’s Progression Markers Initiative (PPMI) and 55% on a local de-novo PD Versilia dataset. Further tests on a randomly labeled OASIS-derived dataset produced about 96% of (erroneous) accuracy (slice-level split) and 50% accuracy (subject-level split), as expected from a randomized experiment. Overall, the extent of the effect of an erroneous slice-based CV is severe, especially for small datasets.
Transcriptome profiles of Anopheles gambiae harboring natural low-level Plasmodium infection reveal adaptive advantages for the mosquito
Authors: Carr Ann L. , Rinker David C. , Dong Yuemei , Dimopoulos George , Zwiebel Laurence J. 
Published: November 2021

AbstractAnopheline mosquitoes are the sole vectors for the Plasmodium pathogens responsible for malaria, which is among the oldest and most devastating of human diseases. The continuing global impact of malaria reflects the evolutionary success of a complex vector-pathogen relationship that accordingly has been the long-term focus of both debate and study. An open question in the biology of malaria transmission is the impact of naturally occurring low-level Plasmodium infections of the vector on the mosquito’s health and longevity as well as critical behaviors such as host-preference/seeking. To begin to answer this, we have completed a comparative RNAseq-based transcriptome profile study examining the effect of biologically salient, salivary gland transmission-stage Plasmodium infection on the molecular physiology of Anopheles gambiae s.s. head, sensory appendages, and salivary glands. When compared with their uninfected counterparts, Plasmodium infected mosquitoes exhibit increased transcript abundance of genes associated with olfactory acuity as well as a range of synergistic processes that align with increased fitness based on both anti-aging and reproductive advantages. Taken together, these data argue against the long-held paradigm that malaria infection is pathogenic for anophelines and, instead suggests there are biological and evolutionary advantages for the mosquito that drive the preservation of its high vectorial capacity.
Contact ability based topology control for predictable delay-tolerant networks
Authors: Chen Hongsheng , Wu Chunhui 
Published: November 2021

AbstractIn predictable delay tolerant networks (PDTNs), the network topology is known a priori or can be predicted over time, such as space planet networks and vehicular networks based on public buses or trains. Due to the intermittent connectivity, network partitioning, and long delays in PDTNs, most of the researchers mainly focuses on routing and data access research. However, topology control can improve energy effectiveness and increase the communication capacity, thus how to maintain the dynamic topology of PDTNs becomes crucial. In this paper, a contact ability based topology control method for PDTNs is proposed. First, the contact ability is calculated using our contact ability calculation model, and then the PDTNs is modeled as an undirected weighted contact graph which includes spatial and contact ability information. The topology control problem is defined as constructing a minimum spanning tree (MST) that the contact ability of the MST is maximized. We propose two algorithms based on undirected weighted contact graph to solve the defined problem, and compare them with the latest method in terms of energy cost and contact ability. Extensive simulation experiments demonstrate that the proposed algorithms can guarantee data transmission effectively, and reduce the network energy consumption significantly.
Complete model-free sliding mode control (CMFSMC)
Authors: Zhu Quanmin 
Published: November 2021

AbstractThis study presents a complete model-free sliding mode control (CMFSMC) framework for the control of continuous-time non-affine nonlinear dynamic systems with unknown models. The novelty lies in the introduction of two equalities to assign the derivative of the sliding functions, which generally bridges the designs of those model-based SMC and model-free SMC. The study includes a double SMC (DSMC) design, state observer design, and desired reference state vector design (whole system performance), which all do not require plant nominal models. The preconditions required in the CMFSMC are the plant dynamic order and the boundedness of plant and disturbances. U-model based control (U-control) is incorporated to configure the whole control system, that is (1) taking model-free double SMC as a robust dynamic inverter to cancel simultaneously both nonlinearity and dynamics of the underlying plants, (2) taking a model-free state observer to estimate the state vector, (3) taking invariant controller to specify the whole control system performance in a linear output feedback control and to provide desired reference state vector. The related properties are studied to support the concept/configuration development and the analytical formulations. Simulated case studies demonstrate the developed framework and show off the transparent design procedure for applications and expansions.
A glucagon analogue decreases body weight in mice via signalling in the liver
Authors: Hinds Charlotte E. , Owen Bryn M. , Hope David C. D. , Pickford Philip , Jones Ben , Tan Tricia M. , Minnion James S. , Bloom Stephen R. 
Published: November 2021

AbstractGlucagon receptor agonists show promise as components of next generation metabolic syndrome pharmacotherapies. However, the biology of glucagon action is complex, controversial, and likely context dependent. As such, a better understanding of chronic glucagon receptor (GCGR) agonism is essential to identify and mitigate potential clinical side-effects. Herein we present a novel, long-acting glucagon analogue (GCG104) with high receptor-specificity and potent in vivo action. It has allowed us to make two important observations about the biology of sustained GCGR agonism. First, it causes weight loss in mice by direct receptor signalling at the level of the liver. Second, subtle changes in GCG104-sensitivity, possibly due to interindividual variation, may be sufficient to alter its effects on metabolic parameters. Together, these findings confirm the liver as a principal target for glucagon-mediated weight loss and provide new insights into the biology of glucagon analogues.