bluuebunny/crossref_metadata_2025_split huggingface dataset:
N-type fast inactivation of a eukaryotic voltage-gated sodium channel
Authors: Zhang Jiangtao , Shi Yiqiang , Fan Junping , Chen Huiwen , Xia Zhanyi , Huang Bo , Jiang Juquan , Gong Jianke , Huang Zhuo , Jiang Daohua 
Published: May 2022

AbstractVoltage-gated sodium (NaV) channels initiate action potentials. Fast inactivation of NaV channels, mediated by an Ile-Phe-Met motif, is crucial for preventing hyperexcitability and regulating firing frequency. Here we present cryo-electron microscopy structure of NaVEh from the coccolithophore Emiliania huxleyi, which reveals an unexpected molecular gating mechanism for NaV channel fast inactivation independent of the Ile-Phe-Met motif. An N-terminal helix of NaVEh plugs into the open activation gate and blocks it. The binding pose of the helix is stabilized by multiple electrostatic interactions. Deletion of the helix or mutations blocking the electrostatic interactions completely abolished the fast inactivation. These strong interactions enable rapid inactivation, but also delay recovery from fast inactivation, which is ~160-fold slower than human NaV channels. Together, our results provide mechanistic insights into fast inactivation of NaVEh that fundamentally differs from the conventional local allosteric inhibition, revealing both surprising structural diversity and functional conservation of ion channel inactivation.
Mineralogical control on methylotrophic methanogenesis and implications for cryptic methane cycling in marine surface sediment
Authors: Xiao Ke-Qing , Moore Oliver W. , Babakhani Peyman , Curti Lisa , Peacock Caroline L. 
Published: May 2022

AbstractMinerals are widely proposed to protect organic carbon from degradation and thus promote the persistence of organic carbon in soils and sediments, yet a direct link between mineral adsorption and retardation of microbial remineralisation is often presumed and a mechanistic understanding of the protective preservation hypothesis is lacking. We find that methylamines, the major substrates for cryptic methane production in marine surface sediment, are strongly adsorbed by marine sediment clays, and that this adsorption significantly reduces their concentrations in the dissolved pool (up to 40.2 ± 0.2%). Moreover, the presence of clay minerals slows methane production and reduces final methane produced (up to 24.9 ± 0.3%) by a typical methylotrophic methanogen—Methanococcoides methylutens TMA-10. Near edge X-ray absorption fine structure spectroscopy shows that reversible adsorption and occlusive protection of methylamines in clay interlayers are responsible for the slow-down and reduction in methane production. Here we show that mineral-OC interactions strongly control methylotrophic methanogenesis and potentially cryptic methane cycling in marine surface sediments.
Histone H1 binding to nucleosome arrays depends on linker DNA length and trajectory
Authors: Dombrowski Marco , Engeholm Maik , Dienemann Christian , Dodonova Svetlana , Cramer Patrick 
Published: May 2022

AbstractThroughout the genome, nucleosomes often form regular arrays that differ in nucleosome repeat length (NRL), occupancy of linker histone H1 and transcriptional activity. Here, we report cryo-EM structures of human H1-containing tetranucleosome arrays with four physiologically relevant NRLs. The structures show a zig-zag arrangement of nucleosomes, with nucleosomes 1 and 3 forming a stack. H1 binding to stacked nucleosomes depends on the NRL, whereas H1 always binds to the non-stacked nucleosomes 2 and 4. Short NRLs lead to altered trajectories of linker DNA, and these altered trajectories sterically impair H1 binding to the stacked nucleosomes in our structures. As the NRL increases, linker DNA trajectories relax, enabling H1 contacts and binding. Our results provide an explanation for why arrays with short NRLs are depleted of H1 and suited for transcription, whereas arrays with long NRLs show full H1 occupancy and can form transcriptionally silent heterochromatin regions.
A benchmark dataset for Hydrogen Combustion
Authors: Guan Xingyi , Das Akshaya , Stein Christopher J. , Heidar-Zadeh Farnaz , Bertels Luke , Liu Meili , Haghighatlari Mojtaba , Li Jie , Zhang Oufan , Hao Hongxia , Leven Itai , Head-Gordon Martin , Head-Gordon Teresa 
Published: May 2022

AbstractThe generation of reference data for deep learning models is challenging for reactive systems, and more so for combustion reactions due to the extreme conditions that create radical species and alternative spin states during the combustion process. Here, we extend intrinsic reaction coordinate (IRC) calculations with ab initio MD simulations and normal mode displacement calculations to more extensively cover the potential energy surface for 19 reaction channels for hydrogen combustion. A total of ∼290,000 potential energies and ∼1,270,000 nuclear force vectors are evaluated with a high quality range-separated hybrid density functional, ωB97X-V, to construct the reference data set, including transition state ensembles, for the deep learning models to study hydrogen combustion reaction.
Quantifying yeast colony morphologies with feature engineering from time-lapse photography
Authors: Goldschmidt Andy , Kunert-Graf James , Scott Adrian C. , Tan Zhihao , Dudley Aimée M. , Kutz J. Nathan 
Published: May 2022

AbstractBaker’s yeast (Saccharomyces cerevisiae) is a model organism for studying the morphology that emerges at the scale of multi-cell colonies. To look at how morphology develops, we collect a dataset of time-lapse photographs of the growth of different strains of S. cerevisiae. We discuss the general statistical challenges that arise when using time-lapse photographs to extract time-dependent features. In particular, we show how texture-based feature engineering and representative clustering can be successfully applied to categorize the development of yeast colony morphology using our dataset. The Local binary pattern (LBP) from image processing is used to score the surface texture of colonies. This texture score develops along a smooth trajectory during growth. The path taken depends on how the morphology emerges. A hierarchical clustering of the colonies is performed according to their texture development trajectories. The clustering method is designed for practical interpretability; it obtains the best representative colony image for any hierarchical cluster.
Fundamental aspects of long-acting tenofovir alafenamide delivery from subdermal implants for HIV prophylaxis
Authors: Gunawardana Manjula , Remedios-Chan Mariana , Sanchez Debbie , Webster Simon , Castonguay Amalia E. , Webster Paul , Buser Christopher , Moss John A. , Trinh MyMy , Beliveau Martin , Hendrix Craig W. , Marzinke Mark A. , Tuck Michael , Caprioli Richard M. , Reyzer Michelle L. , Kuo Joseph , Gallay Philippe A. , Baum Marc M. 
Published: May 2022

AbstractGlobal efforts aimed at preventing human immunodeficiency virus type one (HIV-1) infection in vulnerable populations appear to be stalling, limiting our ability to control the epidemic. Long-acting, controlled drug administration from subdermal implants holds significant potential by reducing the compliance burden associated with frequent dosing. We, and others, are exploring the development of complementary subdermal implant technologies delivering the potent prodrug, tenofovir alafenamide (TAF). The current report addresses knowledge gaps in the preclinical pharmacology of long-acting, subdermal TAF delivery using several mouse models. Systemic drug disposition during TAF implant dosing was explained by a multi-compartment pharmacokinetic (PK) model. Imaging mass spectrometry was employed to characterize the spatial distribution of TAF and its principal five metabolites in local tissues surrounding the implant. Humanized mouse studies determined the effective TAF dose for preventing vaginal and rectal HIV-1 acquisition. Our results represent an important step in the development of a safe and effective TAF implant for HIV-1 prevention.
99mTc-NTP 15-5 is a companion radiotracer for assessing joint functional response to sprifermin (rhFGF-18) in a murine osteoarthritis model
Authors: Briat Arnaud , Jacques Claire , Malige Mélodie , Sudre Laure , Nourissat Geoffroy , Auzeloux Philippe , Guehring Hans , Cachin Florent , Berenbaum Francis , Miot-Noirault Elisabeth 
Published: May 2022

AbstractWith the emergence of disease modifying osteoarthritis drugs (DMOAD), imaging methods to quantitatively demonstrate their efficacy and to monitor osteoarthritis progression at the functional level are urgently needed. Our group showed that articular cartilage can be quantitatively assessed in nuclear medicine imaging by our radiotracer 99mTc-NTP 15-5 targeting cartilage proteoglycans. In this work, surgically induced DMM mice were treated with sprifermin or saline. We investigated cartilage remodelling in the mice knees by 99mTc-NTP 15-5 SPECT-CT imaging over 24 weeks after surgery, as wells as proteoglycan biochemical assays. OA alterations were scored by histology according to OARSI guidelines. A specific accumulation of 99mTc-NTP 15-5 in cartilage joints was evidenced in vivo by SPECT-CT imaging as early as 30 min post-iv injection. In DMM, 99mTc-NTP 15-5 accumulation in cartilage within the operated joints, relative to contralateral ones, was observed to initially increase then decrease as pathology progressed. Under sprifermin, 99mTc-NTP 15-5 uptake in pathological knees was significantly increased compared to controls, at 7-, 12- and 24-weeks, and consistent with proteoglycan increase measured 5 weeks post-surgery, as a sign of cartilage matrix remodelling. Our work highlights the potential of 99mTc-NTP 15-5 as an imaging-based companion to monitor cartilage remodelling in OA and DMOAD response.
A novel ATG5 interaction with Ku70 potentiates DNA repair upon genotoxic stress
Authors: Demirbag-Sarikaya Sinem , Akkoc Yunus , Turgut Sıla , Erbil-Bilir Secil , Kocaturk Nur Mehpare , Dengjel Joern , Gozuacik Devrim 
Published: May 2022

AbstractThe maintenance of cellular homeostasis in living organisms requires a balance between anabolic and catabolic reactions. Macroautophagy (autophagy herein) is determined as one of the major catabolic reactions. Autophagy is an evolutionarily conserved stress response pathway that is activated by various insults including DNA damage. All sorts of damage to DNA potentially cause loss of genetic information and trigger genomic instability. Most of these lesions are repaired by the activation of DNA damage response following DNA repair mechanisms. Here we describe, a novel protein complex containing the autophagy protein ATG5 and the non-homologous end-joining repair system proteins. We discovered for the first time that ATG5 interacted with both Ku80 (XRCC5) and Ku70 (XRCC6). This novel interaction is facilitated mainly via Ku70. Our results suggest that this interaction is dynamic and enhanced upon genotoxic stresses. Strikingly, we identified that ATG5-Ku70 interaction is necessary for DNA repair and effective recovery from genotoxic stress. Therefore, our results are demonstrating a novel, direct, dynamic, and functional interaction between ATG5 and Ku70 proteins that plays a crucial role in DNA repair under genotoxic stress conditions.
Overnutrition is a significant component of food waste and has a large environmental impact
Authors: Franco Silvio , Barbanera Marco , Moscetti Roberto , Cicatiello Clara , Secondi Luca , Massantini Riccardo 
Published: May 2022

AbstractFood waste and obesity and overweight conditions are both linked to the unsustainability of current food systems. This article argues that overnutrition should be considered a form of food waste and it provides a first estimation of the quantity of food over-consumed in Italy. This is done by calculating the excess calories consumed by obese and overweight people and converting them into food quantities by comparison with a typical Italian diet. The total quantity of food consumed in excess by Italian citizens due to overnutrition is calculated as 1.553 million tonnes per year, which is comparable to the current national household food waste assessments. The environmental impact arising from production and consumption of this food accounts for 6.15 Mt of CO2-eq per year, as estimated by a Life Cycle Analysis conducted on the 46 food categories which compose the typical Italian diet. Overnutrition in the South-Islands regions of Italy exerts the largest impact (31.6%), followed by the North-West (26.6%), the Centre (22.2%), and the North-East (19.1%).
Interdisk spacing effect on resonant properties of Ge disk lattices on Si substrates
Authors: Shklyaev A. A. , Utkin D. E. , Tsarev A. V. , Kuznetsov S. A. , Anikin K. V. , Latyshev A. V. 
Published: May 2022

AbstractThe light reflection properties of Ge disk lattices on Si substrates are studied as a function of the disk height and the gap width between disks. The interdisk spacing effect is observed even at such large gap widths as 500 nm. The gap width decrease leads to the appearance of the reflection minimum in the short wavelength region relative to one originated from the magnetic and electric dipole resonances in individual Ge disks, thereby essentially widening the antireflection properties. This minimum becomes significantly deeper at small gap widths. The observed behavior is associated with the features of the resonant fields around closely spaced disks according to numerical simulation data. The result shows the importance of using structures with geometrical parameters providing the short-wavelength minimum. This can essentially enhance their other resonant properties, which are widely used for applications, in particular, based on collective lattice resonances.
Changing surface ocean circulation caused the local demise of echinoid Scaphechinus mirabilis in Taiwan during the Pleistocene–Holocene transition
Authors: Ho Sze Ling , Wang Jia-Kang , Lin Yu-Jou , Lin Ching-Ren , Lee Chen-Wei , Hsu Chia-Hsin , Chang Lo-Yu , Wu To-Hsiang , Tseng Chien-Chia , Wu Hsiao-Jou , John Cédric M. , Oji Tatsuo , Liu Tsung-Kwei , Chen Wen-Shan , Li Peter , Fang Jiann-Neng , Lin Jih-Pai 
Published: May 2022

AbstractAbundant fossil specimens of Scaphechinus mirabilis, now occurring mostly in temperate waters, have been found in the Toukoshan Formation (Pleistocene) in Miaoli County, Taiwan. Environmental changes leading to its extirpation (local extinction) have thus far been elusive. Here, we reconstruct past environmental and oceanic conditions off northwest Taiwan by analyzing clumped isotopes, as well as stable oxygen isotopes, of well-preserved fossil echinoid tests collected from the Toukoshan Formation. Radiocarbon dates suggest that these samples are from Marine Isotope Stage 3 (MIS 3). Paleotemperature estimates based on clumped isotopes indicate that fossil echinoids were living in oceanic conditions that range from 9 to 14 °C on average, comparable with the estimate derived for a modern sample from Mutsu Bay, Japan. Notably, this temperature range is ~ 10 °C colder than today’s conditions off northwest Taiwan. The substantially lower temperatures during ~ 30 ka (MIS 3) compared to the modern conditions might be due to the rerouting of surface currents off northwest Taiwan when the sea level was ~ 60 m lower than today, in addition to the cooling caused by a lower atmospheric CO2 level during the Last Glacial Period. Colder waters brought here by the China Coastal Current (CCC) and the existence of shallow subtidal zones termed “Miaoli Bay” (mainly located in the present-day Miaoli county) during MIS 3 plausibly sustained generations of S. mirabilis, yielding tens of thousands of fossil specimens in the well-preserved fossil beds. The likely extirpation driver is the drastic change from a temperate climate to much warmer conditions in the shallow sea during the Pleistocene–Holocene transition.
Micro-computed tomography assessment of bone structure in aging mice
Authors: Shim Junbo , Iwaya Chihiro , Ambrose Catherine G. , Suzuki Akiko , Iwata Junichi 
Published: May 2022

AbstractHigh-resolution computed tomography (CT) is widely used to assess bone structure under physiological and pathological conditions. Although the analytic protocols and parameters for micro-CT (μCT) analyses in mice are standardized for long bones, vertebrae, and the palms in aging mice, they have not yet been established for craniofacial bones. In this study, we conducted a morphometric assessment of craniofacial bones, in comparison with long bones, in aging mice. Although age-related changes were observed in the microarchitecture of the femur, tibia, vertebra, and basisphenoid bone, and were more pronounced in females than in males, the microarchitecture of both the interparietal bone and body of the mandible, which develop by intramembranous ossification, was less affected by age and sex. By contrast, the condyle of the mandible was more affected by aging in males compared to females. Taken together, our results indicate that mouse craniofacial bones are uniquely affected by age and sex.
Urban seismic resilience mapping: a transportation network in Istanbul, Turkey
Authors: Byun Ji-Eun , D’Ayala Dina 
Published: May 2022

AbstractWhen a seismic event occurs, transportation networks play a critical role in undertaking emergency activities such as evacuation and relief supply. Accordingly, to secure their functionality, it is essential to accurately assess their resilience. In particular, this study performs a rigorous probabilistic analysis on the seismic resilience of a transportation network in Istanbul, Turkey. The analysis accuracy is enhanced by considering, along with the structural damage of roadways, the additional disruption mode of network performance caused by the debris falling from damaged objects in their vicinity. Moreover, we obtain the results as a map of resilience measure, which enables us to investigate the disruption inequality across the study area and identify critical factors that govern the system resilience. To enable such sophisticated probabilistic analysis, a Bayesian network (BN) model is developed that involves various types of information from the hazard process to the performance of structures and systems. Then, the BN is quantified by identifying and compiling a comprehensive list of datasets. Thereby, this study analyses large-scale systems involving thousands of structures, while providing general probabilistic models and data schema that can be employed for other transportation networks.
Normal and tangential forces combine to convey contact pressure during dynamic tactile stimulation
Authors: Gueorguiev David , Lambert Julien , Thonnard Jean-Louis , Kuchenbecker Katherine J. 
Published: May 2022

AbstractHumans need to accurately process the contact forces that arise as they perform everyday haptic interactions such as sliding the fingers along a surface to feel for bumps, sticky regions, or other irregularities. Several different mechanisms are possible for how the forces on the skin could be represented and integrated in such interactions. In this study, we used a force-controlled robotic platform and simultaneous ultrasonic modulation of the finger-surface friction to independently manipulate the normal and tangential forces during passive haptic stimulation by a flat surface. To assess whether the contact pressure on their finger had briefly increased or decreased during individual trials in this broad stimulus set, participants did not rely solely on either the normal force or the tangential force. Instead, they integrated tactile cues induced by both components. Support-vector-machine analysis classified physical trial data with up to 75% accuracy and suggested a linear perceptual mechanism. In addition, the change in the amplitude of the force vector predicted participants’ responses better than the change of the coefficient of dynamic friction, suggesting that intensive tactile cues are meaningful in this task. These results provide novel insights about how normal and tangential forces shape the perception of tactile contact.
Signal-in-space range error and positioning accuracy of BDS-3
Authors: Liu Weiping , Jiao Bo , Hao Jinming , Lv Zhiwei , Xie Jiantao , Liu Jing 
Published: May 2022

AbstractBeing the first mixed-constellation global navigation system, the global BeiDou navigation system (BDS-3) designs new signals, the service performance of which has attracted extensive attention. In the present study, the Signal-in-space range error (SISRE) computation method for different types of navigation satellites was presented. The differential code bias (DCB) correction method for BDS-3 new signals was deduced. Based on these, analysis and evaluation were done by adopting the actual measured data after the official launching of BDS-3. The results showed that BDS-3 performed better than the regional navigation satellite system (BDS-2) in terms of SISRE. Specifically, the SISRE of the BDS-3 medium earth orbit (MEO) satellites reached 0.52 m, slightly inferior compared to 0.4 m from Galileo, marginally better than 0.59 m from GPS, and significantly better than 2.33 m from GLONASS. The BDS-3 inclined geostationary orbit (IGSO) satellites achieved the SISRE of 0.90 m, on par with that (0.92 m) of the QZSS IGSO satellites. However, the average SISRE of BDS-3 geostationary earth orbit (GEO) satellites was 1.15 m, which was marginally inferior to that of the QZSS GEO satellite (0.91 m). In terms of positioning accuracy, the new signals B1C and B2a are considered together with the transition signals B1I and B3I. The overall three-dimensional single-frequency standard point positioning (SPP) accuracy of BDS-3 B1C, B2a, B1I, and B3I gained an accuracy level better than 5 m. Moreover, the B1I signal exhibited the best positioning accuracy in the Asian-Pacific region, while the B1C signal set forth the best positioning accuracy in the other regions. Owing to the advantage in signal frequency, the dual-frequency SPP accuracy of B1C + B2a surpassed that of the transitional signal of B1I + B3I. Since there are more visible satellites in Asia–Pacific, the positioning accuracy of BDS-3 was moderately superior to that of GPS. The precise point positioning (PPP) accuracy of BDS-3 B1C + B2a or B1I + B3I converged to the order of centimeters, marginally inferior to that of the GPS L1 + L2. However, these three combinations had a similar convergence time of approximately 30 min.