bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bulk valley transport and Berry curvature spreading at the edge of flat bands
Authors: Sinha Subhajit , Adak Pratap Chandra , Surya Kanthi R. S. , Chittari Bheema Lingam , Sangani L. D. Varma , Watanabe Kenji , Taniguchi Takashi , Jung Jeil , Deshmukh Mandar M. 
Published: November 2020

Abstract2D materials based superlattices have emerged as a promising platform to modulate band structure and its symmetries. In particular, moiré periodicity in twisted graphene systems produces flat Chern bands. The recent observation of anomalous Hall effect (AHE) and orbital magnetism in twisted bilayer graphene has been associated with spontaneous symmetry breaking of such Chern bands. However, the valley Hall state as a precursor of AHE state, when time-reversal symmetry is still protected, has not been observed. Our work probes this precursor state using the valley Hall effect. We show that broken inversion symmetry in twisted double bilayer graphene (TDBG) facilitates the generation of bulk valley current by reporting experimental evidence of nonlocal transport in a nearly flat band system. Despite the spread of Berry curvature hotspots and reduced quasiparticle velocities of the carriers in these flat bands, we observe large nonlocal voltage several micrometers away from the charge current path — this persists when the Fermi energy lies inside a gap with large Berry curvature. The high sensitivity of the nonlocal voltage to gate tunable carrier density and gap modulating perpendicular electric field makes TDBG an attractive platform for valley-twistronics based on flat bands.
cAMP-dependent regulation of HCN4 controls the tonic entrainment process in sinoatrial node pacemaker cells
Authors: Fenske Stefanie , Hennis Konstantin , Rötzer René D. , Brox Verena F. , Becirovic Elvir , Scharr Andreas , Gruner Christian , Ziegler Tilman , Mehlfeld Verena , Brennan Jaclyn , Efimov Igor R. , Pauža Audrys G. , Moser Markus , Wotjak Carsten T. , Kupatt Christian , Gönner Rasmus , Zhang Rai , Zhang Henggui , Zong Xiangang , Biel Martin , Wahl-Schott Christian 
Published: November 2020

AbstractIt is highly debated how cyclic adenosine monophosphate-dependent regulation (CDR) of the major pacemaker channel HCN4 in the sinoatrial node (SAN) is involved in heart rate regulation by the autonomic nervous system. We addressed this question using a knockin mouse line expressing cyclic adenosine monophosphate-insensitive HCN4 channels. This mouse line displayed a complex cardiac phenotype characterized by sinus dysrhythmia, severe sinus bradycardia, sinus pauses and chronotropic incompetence. Furthermore, the absence of CDR leads to inappropriately enhanced heart rate responses of the SAN to vagal nerve activity in vivo. The mechanism underlying these symptoms can be explained by the presence of nonfiring pacemaker cells. We provide evidence that a tonic and mutual interaction process (tonic entrainment) between firing and nonfiring cells slows down the overall rhythm of the SAN. Most importantly, we show that the proportion of firing cells can be increased by CDR of HCN4 to efficiently oppose enhanced responses to vagal activity. In conclusion, we provide evidence for a novel role of CDR of HCN4 for the central pacemaker process in the sinoatrial node.
ArfB can displace mRNA to rescue stalled ribosomes
Authors: Carbone Christine E. , Demo Gabriel , Madireddy Rohini , Svidritskiy Egor , Korostelev Andrei A. 
Published: November 2020

AbstractRibosomes stalled during translation must be rescued to replenish the pool of translation-competent ribosomal subunits. Bacterial alternative rescue factor B (ArfB) releases nascent peptides from ribosomes stalled on mRNAs truncated at the A site, allowing ribosome recycling. Prior structural work revealed that ArfB recognizes such ribosomes by inserting its C-terminal α-helix into the vacant mRNA tunnel. In this work, we report that ArfB can efficiently recognize a wider range of mRNA substrates, including longer mRNAs that extend beyond the A-site codon. Single-particle cryo-EM unveils that ArfB employs two modes of function depending on the mRNA length. ArfB acts as a monomer to accommodate a shorter mRNA in the ribosomal A site. By contrast, longer mRNAs are displaced from the mRNA tunnel by more than 20 Å and are stabilized in the intersubunit space by dimeric ArfB. Uncovering distinct modes of ArfB function resolves conflicting biochemical and structural studies, and may lead to re-examination of other ribosome rescue pathways, whose functions depend on mRNA lengths.
Behavior control of membrane-less protein liquid condensates with metal ion-induced phase separation
Authors: Hong Kibeom , Song Daesun , Jung Yongwon 
Published: November 2020

AbstractPhase separation of specific biomolecules into liquid droplet-like condensates is a key mechanism to form membrane-less organelles, which spatio-temporally organize diverse biochemical processes in cells. To investigate the working principles of these biomolecular condensates as dynamic reaction centers, precise control of diverse condensate properties is essential. Here, we design a strategy for metal ion-induced clustering of minimal protein modules to produce liquid protein condensates, the properties of which can be widely varied by simple manipulation of the protein clustering systems. The droplet forming-minimal module contains only a single receptor protein and a binding ligand peptide with a hexahistidine tag for divalent metal ion-mediated clustering. A wide range of protein condensate properties such as droplet forming tendency, droplet morphology, inside protein diffusivity, protein recruitment, and droplet density can be varied by adjusting the nature of receptor/ligand pairs or used metal ions, metal/protein ratios, incubation time, binding motif variation on recruited proteins, and even spacing between receptor/ligand pairs and the hexahistidine tag. We also demonstrate metal-ion-induced protein phase separation in cells. The present phase separation strategy provides highly versatile protein condensates, which will greatly facilitate investigation of molecular and structural codes of droplet-forming proteins and the monitoring of biomolecular behaviors inside diverse protein condensates.
Functional characterization of SMARCA4 variants identified by targeted exome-sequencing of 131,668 cancer patients
Authors: Fernando Tharu M. , Piskol Robert , Bainer Russell , Sokol Ethan S. , Trabucco Sally E. , Zhang Qing , Trinh Huong , Maund Sophia , Kschonsak Marc , Chaudhuri Subhra , Modrusan Zora , Januario Thomas , Yauch Robert L. 
Published: November 2020

AbstractGenomic studies performed in cancer patients and tumor-derived cell lines have identified a high frequency of alterations in components of the mammalian switch/sucrose non-fermentable (mSWI/SNF or BAF) chromatin remodeling complex, including its core catalytic subunit, SMARCA4. Cells exhibiting loss of SMARCA4 rely on its paralog, SMARCA2, making SMARCA2 an attractive therapeutic target. Here we report the genomic profiling of solid tumors from 131,668 cancer patients, identifying 9434 patients with one or more SMARCA4 gene alterations. Homozygous SMARCA4 mutations were highly prevalent in certain tumor types, notably non-small cell lung cancer (NSCLC), and associated with reduced survival. The large sample size revealed previously uncharacterized hotspot missense mutations within the SMARCA4 helicase domain. Functional characterization of these mutations demonstrated markedly reduced remodeling activity. Surprisingly, a few SMARCA4 missense variants partially or fully rescued paralog dependency, underscoring that careful selection criteria must be employed to identify patients with inactivating, homozygous SMARCA4 missense mutations who may benefit from SMARCA2-targeted therapy.
Genealogy of the neurodegenerative diseases based on a meta-analysis of age-stratified incidence data
Authors: Gerovska Daniela , Irizar Haritz , Otaegi David , Ferrer Isidre , López de Munain Adolfo , Araúzo-Bravo Marcos J. 
Published: November 2020

AbstractWhile the central common feature of the neurodegenerative diseases (NDs) is the accumulation of misfolded proteins, they share other pathogenic mechanisms. However, we miss an explanation for the onset of the NDs. The mechanisms through which genetic mutations, present from conception are expressed only after several decades of life are unknown. We aim to find clues on the complexity of the disease onset trigger of the different NDs expressed in the number of steps of factors related to a disease. We collected brain autopsies on diseased patients with NDs, and found a dynamic increase of the ND multimorbidity with the advance of age. Together with the observation that the NDs accumulate multiple misfolded proteins, and the same misfolded proteins are involved in more than one ND, motivated us to propose a model for a genealogical tree of the NDs. To collect the dynamic data needed to build the tree, we used a Big-data approach that searched automatically epidemiological datasets for age-stratified incidence of NDs. Based on meta-analysis of over 400 datasets, we developed an algorithm that checks whether a ND follows a multistep model, finds the number of steps necessary for the onset of each ND, finds the number of common steps with other NDs and the number of specific steps of each ND, and builds with these findings a parsimony tree of the genealogy of the NDs. The tree discloses three types of NDs: the stem NDs with less than 3 steps; the trunk NDs with 5 to 6 steps; and the crown NDs with more than 7 steps. The tree provides a comprehensive understanding of the relationship across the different NDs, as well as a mathematical framework for dynamic adjustment of the genealogical tree of the NDs with the appearance of new epidemiological studies and the addition of new NDs to the model, thus setting the basis for the search for the identity and order of these steps. Understanding the complexity, or number of steps, of factors related to disease onset trigger is important prior deciding to study single factors for a multiple steps disease.
Metabolic comparison of polycystic ovarian syndrome and control women in Middle Eastern and UK Caucasian populations
Authors: Butler Alexandra E. , Abouseif Ahmed , Dargham Soha R. , Sathyapalan Thozhukat , Atkin Stephen L. 
Published: November 2020

AbstractTo determine if metabolic characteristics differed in women with and without polycystic ovary syndrome (PCOS) between a Caucasian and Middle East population. Comparative cross-sectional analysis. Demographic and metabolic data from Middle Eastern women from Qatar Biobank (97 with PCOS, 622 controls) were compared to a Caucasian PCOS biobank in Hull UK (108 with PCOS, 69 controls). In both populations, PCOS women showed a worse cardiovascular risk profile of increased systolic and diastolic blood pressure, increased C-reactive protein (CRP), reduced HDL, insulin resistance as well as increased androgens compared to their respective controls without PCOS. UK women without PCOS had higher systolic and diastolic blood pressures, and increased testosterone results (p < 0.01) compared to Middle Eastern women without PCOS who had higher inflammatory markers (WBC and CRP), HDL and insulin resistance (p < 0.001). UK PCOS women had a higher body mass index, systolic and diastolic blood pressures, triglycerides (p < 0.01), whilst Middle Eastern PCOS women showed increased testosterone, free androgen index, HDL and CRP (P < 0.01). There was no difference in insulin or insulin resistance between the two PCOS cohorts. This study highlights ethnic population differences because, whilst cardiovascular risk indices were increased for both PCOS cohorts, this may be for different reasons: BMI, waist and hip measurements, systolic and diastolic blood pressure, and triglycerides were higher in the UK cohort whilst testosterone, HDL and CRP were higher in the Middle East population. Insulin resistance did not differ between the two PCOS populations despite differences in BMI.
Assessment of body composition in obese patients undergoing one anastomosis gastric bypass: cross-sectional study
Authors: Jimenez Jose-Maria , Ruiz-Tovar Jaime , López María , Marc-Hernandez Artur , Carbajo Miguel-Angel , Cao Maria-Jose , Garcia Sara , Castro Maria-Jose 
Published: November 2020

AbstractBariatric surgery is the most effective long-term treatment to obesity, and it is necessary to assess changes in body composition and to be able to establish better follow-up of patients. Cross-sectional, observational study in patients undergoing One Anastomosis Gastric Bypass (OAGB) bariatric surgery. We analysed changes in weight and body composition during the first postoperative year. 405 patients (68.9% women. 31.1% men), mean age 44 years, mean weight 110.02 kg, Body Mass Index (BMI) 39.76 kg/m2, height 1.66 m. The variables analyzed were substantially decreased compared to the preoperative values one year after surgery in every case: weight (110.02 ± 22.03 kg vs. 69.36 ± 13.60 kg), BMI (39.76 ± 6.65 vs. 24.52 ± 3. 76), fat free mass (61.12 ± 12.43 kg vs. 53.61 ± 11.61 kg), fat mass (50.44 ± 14.36 kg vs. 15.74 ± 6.74 kg), bone mass (58.06 ± 11.85 kg vs. 50.92 ± 11.06 kg) and water (45.08 ± 9.99 kg vs. 37.39 ± 9.23 kg), P < 0.001. The results show noticeable improvements in weight reduction and changes in body composition, and will contribute to develop a thorough understanding of both of them, contributing also to perform a better patients’ follow-up.
Deep learning method for comet segmentation and comet assay image analysis
Authors: Hong Yiyu , Han Hyo-Jeong , Lee Hannah , Lee Donghwan , Ko Junsu , Hong Zhen-yu , Lee Ji-Young , Seok Ju-Hyung , Lim Hee Seon , Son Woo-Chan , Sohn Insuk 
Published: November 2020

AbstractComet assay is a widely used method, especially in the field of genotoxicity, to quantify and measure DNA damage visually at the level of individual cells with high sensitivity and efficiency. Generally, computer programs are used to analyze comet assay output images following two main steps. First, each comet region must be located and segmented, and next, it is scored using common metrics (e.g., tail length and tail moment). Currently, most studies on comet assay image analysis have adopted hand-crafted features rather than the recent and effective deep learning (DL) methods. In this paper, however, we propose a DL-based baseline method, called DeepComet, for comet segmentation. Furthermore, we created a trainable and testable comet assay image dataset that contains 1037 comet assay images with 8271 manually annotated comet objects. From the comet segmentation test results with the proposed dataset, the DeepComet achieves high average precision (AP), which is an essential metric in image segmentation and detection tasks. A comparative analysis was performed between the DeepComet and the state-of-the-arts automatic comet segmentation programs on the dataset. Besides, we found that the DeepComet records high correlations with a commercial comet analysis tool, which suggests that the DeepComet is suitable for practical application.
Assessment of hemodynamic responses to exercise in aortic coarctation using MRI-ergometry in combination with computational fluid dynamics
Authors: Schubert Charlotte , Brüning Jan , Goubergrits Leonid , Hennemuth Anja , Berger Felix , Kühne Titus , Kelm Marcus 
Published: November 2020

AbstractIn patients with aortic coarctation it would be desirable to assess pressure gradients as well as information about blood flow profiles at rest and during exercise. We aimed to assess the hemodynamic responses to physical exercise by combining MRI-ergometry with computational fluid dynamics (CFD). MRI was performed on 20 patients with aortic coarctation (13 men, 7 women, mean age 21.5 ± 13.7 years) at rest and during ergometry. Peak systolic pressure gradients, wall shear stress (WSS), secondary flow degree (SFD) and normalized flow displacement (NFD) were calculated using CFD. Stroke volume was determined based on MRI. On average, the pressure gradient was 18.0 ± 16.6 mmHg at rest and increased to 28.5 ± 22.6 mmHg (p < 0.001) during exercise. A significant increase in cardiac index was observed (p < 0.001), which was mainly driven by an increase in heart rate (p < 0.001). WSS significantly increased during exercise (p = 0.006), whereas SFD and NFD remained unchanged. The combination of MRI-ergometry with CFD allows assessing pressure gradients as well as flow profiles during physical exercise. This concept has the potential to serve as an alternative to cardiac catheterization with pharmacological stress testing and provides hemodynamic information valuable for studying the pathophysiology of aortic coarctation.
Positron annihilation spectroscopy study of radiation-induced defects in W and Fe irradiated with neutrons with different spectra
Authors: Ogorodnikova O. V. , Majerle M. , Čížek J. , Simakov S. , Gann V. V. , Hruška P. , Kameník J. , Pospíšil J. , Štefánik M. , Vinš M. 
Published: November 2020

AbstractThe paper presents new knowledge on primary defect formation in tungsten (W) and iron (Fe) irradiated by fission and high-energy neutrons at near-room temperature. Using a well-established method of positron-annihilation lifetime-spectroscopy (PALS), it was found that irradiation of W in the fission reactor and by high-energy neutrons from the p(35 MeV)-Be generator leads to the formation of small radiation-induced vacancy clusters with comparable mean size. In the case of Fe, smaller mean size of primary radiation-induced vacancy clusters was measured after irradiation with fission neutrons compared to irradiation with high-energy neutrons from the p(35 MeV)-Be generator. It was found that one of the reasons of the formation of the larger size of the defects with lower density in Fe is lower flux in the case of irradiation with high-energy neutrons from the p(35 MeV)-Be source. The second reason is enhanced defect agglomeration and recombination within the energetic displacement cascade at high energy primary knock-on-atoms (PKAs). This is consistent with the concept of the athermal recombination corrected (arc-dpa) model, although the measured dpa cross-section of both fission neutrons and wide-spectrum high-energy neutrons in W is between the conventional Norgett–Robinson–Torrens (NRT-dpa) and arc-dpa predictions. This means that the physics of the primary radiation effects in materials is still not fully known and requires further study through a combination of modeling and experimental efforts. The present data serve as a basis for the development of an improved concept of the displacement process.
Desacetyl-α-MSH and α-MSH have sex specific interactions with diet to influence mouse gut morphology, metabolites and microbiota
Authors: Sun Bo , Vatanen Tommi , Jayasinghe Thilini N. , McKenzie Elizabeth , Murphy Rinki , O’Sullivan Justin M. 
Published: November 2020

AbstractThe melanocortin peptides have an important role in regulating body weight and appetite. Mice that lack the desacetyl-α-MSH and α-MSH peptides (Pomctm1/tm1) develop obesity. This effect is exacerbated by a high fat diet (HFD). However, development of obesity in femalePomctm1/tm1mice during chronic HFD conditions is not fully accounted for by the increased energy intake. We hypothesized that the protection against chronic HFD-induced obesity imparted by MSH peptides in females is mediated by sex-specific alterations in the gut structure and gut microbiota. We determined that female WT mice had reduced jejunum villus length and increased crypt depth in response to chronic HFD. WT males andPomctm1/tm1mice lacked this adaptation to a chronic HFD. BothPomctm1/tm1genotype and chronic HFD were significantly associated with gut microbiota composition. Sex-specific associations betweenPomctm1/tm1genotype and gut microbiota were observed in the presence of a chronic HFD.Pomctm1/tm1females had significantly reduced fecal acetate and propionate concentrations when compared to WT females. We conclude that MSH peptides influence jejunum villus length, crypt depth and the structure of the gut microbiota. These effects favor reduced nutrient absorption and occur in addition to the recognized roles of desacetyl-α-MSH and α-MSH peptides in appetite control.
Integrating large mammal behaviour and traffic flow to determine traversability of roads with heterogeneous traffic on a Central Indian Highway
Authors: Saxena Akanksha , Chatterjee Nilanjan , Rajvanshi Asha , Habib Bilal 
Published: November 2020

AbstractRoads impact wildlife in multiple ways, most conspicuous amongst which are animal-vehicle collisions (AVCs). Mitigation measures to reduce AVCs at the local scale are often centred on species-specific crossing zones and collision hotspots. However, at the road network scale, consideration of interactions among road, species and traffic characteristics influencing AVC occurrence is required to design effective mitigation strategies. We modelled traversability—the probability of an animal successfully crossing a road- across an Indian highway for six large mammal species under different scenarios of road and traffic characteristics. Among the study species, group-living and slow-moving animals had higher AVC probabilities that increased significantly with increasing traffic volume and proportions of heavy vehicles in the traffic flow. The risk of AVC was higher for species that were active near roadside habitat during peak traffic hours. Our approach could help identify roads that pose potential mortality risks to animals using empirical data on animal and traffic characteristics. Results suggest that regulating traffic volume and heterogeneity on existing road stretches could potentially reduce animal mortality and barrier effect. Mitigation on roads expected to carry heavy traffic loads passing through ecologically-sensitive areas should be prioritised to ensure traversability for animal communities.
Muometric positioning system (μPS) with cosmic muons as a new underwater and underground positioning technique
Authors: Tanaka Hiroyuki K. M. 
Published: November 2020

AbstractThus far, underwater and underground positioning techniques have been limited to those using classical waves (sound waves, electromagnetic waves or their combination). However, the positioning accuracy is strongly affected by the conditions of media they propagate (temperature, salinity, density, elastic constants, opacity, etc.). In this work, we developed a precise and entirely new three-dimensional positioning technique with cosmic muons. This muonic technique is totally unaffected by the media condition and can be universally implemented anywhere on the globe without a signal transmitter. Results of our laboratory-based experiments and simulations showed that, for example, plate-tectonics-driven seafloor motion and magma-driven seamount deformation can be detected with the μPS.