bluuebunny/crossref_metadata_2025 huggingface dataset:
Buoy‐Based Detection of Low‐Energy Cosmic‐Ray Neutrons to Monitor the Influence of Atmospheric, Geomagnetic, and Heliospheric Effects
Authors: Schrön Martin , Rasche Daniel , Weimar Jannis , Köhli Markus , Herbst Konstantin , Boehrer Bertram , Hertle Lasse , Kögler Simon , Zacharias Steffen
Published: June 2024

Cosmic radiation on Earth responds to heliospheric, geomagnetic, atmospheric, and lithospheric changes. In order to use its signal for soil hydrological monitoring, the signal of thermal and epithermal neutron detectors needs to be corrected for external influencing factors. However, theories about the neutron response to soil water, air pressure, air humidity, and incoming cosmic radiation are still under debate. To challenge these theories, we isolated the neutron response from almost any terrestrial changes by operating a bare and a moderated neutron detector in a buoy on a lake in Germany from July 15 to 02 December 2014. We found that the count rate over water has been better predicted by a theory from Köhli et al. (2021, https://doi.org/10.3389/frwa.2020.544847) compared to the traditional approach from Desilets et al. (2010, https://doi.org/10.1029/2009wr008726). We further found strong linear correlation parameters to air pressure (β = 0.0077 mb−1) and air humidity (α = 0.0054 m3/g) for epithermal neutrons, while thermal neutrons responded with α = 0.0023 m3/g. Both approaches, from Rosolem et al. (2013, https://doi.org/10.1175/jhm‐d‐12‐0120.1) and from Köhli et al. (2021, https://doi.org/10.3389/frwa.2020.544847), were similarly able to remove correlations of epithermal neutrons to air humidity. Correction for incoming radiation proved to be necessary for both thermal and epithermal neutrons, for which we tested different neutron monitor stations and correction methods. Here, the approach from Zreda et al. (2012, https://doi.org/10.5194/hess‐16‐4079‐2012) worked best with the Jungfraujoch monitor in Switzerland, while the approach from McJannet and Desilets (2023, https://doi.org/10.1029/2022wr033889) was able to adequately rescale data from more remote neutron monitors. However, no approach was able to sufficiently remove the signal from a major Forbush decrease event on 13 September, to which thermal and epithermal neutrons showed a comparatively strong response. The buoy detector experiment provided a unique data set for empirical testing of traditional and new theories on Cosmic‐Ray Neutron Sensing. It could serve as a local alternative to reference data from remote neutron monitors.
An Examination of the Wrangel Island Sea Ice Thickness Dipole
Authors: Ross Spenser , Moore G. W. K. , Laidre Kristin L.
Published: June 2024

The Beaufort Sea High is a high‐pressure system located in the Beaufort Sea that influences ocean circulation in the western Arctic known as the Beaufort Gyre. Wrangel Island, located in the western Chukchi Sea, typically experiences easterly sea ice motion due to the Beaufort Gyre. We find that under these climatological conditions, moving ice is blocked by the island and accumulates on its eastern side, while ice on its western side continues to drift leaving an area of open water and reduced ice thickness along the western side of the island. This results in an ice thickness dipole across the island. A reversal in the atmospheric circulation across the western Arctic results in a dipole with the opposing sign. We find the dipole is present throughout the year and is strongest in January when the difference in ice thickness between the eastern and western sides of the island is approximately 1 m. During the spring, it is associated with the transient opening of a polynya to the west of the island. The dipole is the result of opposing ice divergence and convergence across the western Arctic and may impact ocean circulation and ecosystems within the Chukchi Sea.
Turbulence Over Camarinal Sill and Its Impact on Water Mixing—Strait of Gibraltar
Authors: Roustan Jean‐Baptiste , Bouruet‐Aubertot Pascale , Bordois Lucie , Cuypers Yannis , Carton Xavier , Dumas Franck , Auclair Francis
Published: June 2024

Straits and narrows are the place of intensified turbulent mixing. Deep understanding of the turbulent dynamics at these locations is of crucial importance as it conditions the properties of the water masses flowing in the open ocean. A new extensive field experiment, PROTEVS GIB20, with high frequency measurements has been conducted in the Strait of Gibraltar. It allows us to infer dissipation rates of the turbulent kinetic energy, ϵ, from two consistent methods. The range of ϵ is depicted for the different processes which developed in the vicinity of Camarinal Sill, the main topographic feature of the Strait of Gibraltar. It evidences that the bottom boundary layer, hydraulic jumps and large overturns are the main loci of intensified turbulence reaching 10−3W.kg−1. The variability of the turbulence is mainly controlled by semi‐diurnal, diurnal and fortnightly tidal oscillations. Spatially, the western flank of Camarinal Sill is evidenced as the hotspot for turbulent mixing. We confirm a weak variation of the spatially averaged vertically integrated turbulent dissipation rate. This result needs to be qualified in view of the differentiated impact of the various processes on adjacent water masses. The dynamics of the spring tide directly mix Atlantic and Mediterranean waters, resulting in a large spreading of the T‐S diagram.
Extreme Planktic Foraminiferal Dwarfism Across the ETM2 in the Tethys Realm in Response to Warming
Authors: D’Onofrio R. , Barrett R. , Schmidt D. N. , Fornaciari E. , Giusberti L. , Frijia G. , Adatte T. , Sabatino N. , Monsuru A. , Brombin V. , Luciani V.
Published: June 2024

Pronounced warming negatively impacts ecosystem resilience in modern oceans. To offer a long‐term geological perspective of the calcareous plankton response to global warming, we present an integrated record, from two Tethyan sections (northeastern Italy), of the planktic foraminiferal and calcareous nannofossil response to the Eocene Thermal Maximum 2 hyperthermal (ETM2, ∼54 Ma). Our study reveals pronounced changes in assemblage composition and a striking dwarfing of planktic foraminiferal tests of up to 40% during the event, impacting both surface and deeper dwellers. The increased abundance of small placoliths among calcareous nannofossils is interpreted as community size reduction. Literature and our foraminiferal size data from Sites 1263 and 1209 (Atlantic and Pacific Oceans) highlights that the pronounced dwarfism is restricted to the Tethyan area. The ETM2 is characterized by warm sea surface temperatures as indicated by our δ18O data, but this warming is of global extent and cannot explain the unique dwarfism. Excluding evolutionary modifications, other potential drivers of dwarfism (eutrophication, deoxygenation, metabolic adaptation) cannot explain the exceptional dwarfism by themselves. The smallest sizes are in close temporal association with peaks in volcanic derived Hg/Th‐Hg/Rb recorded just before and at the ETM2 which could not have been brought into our sections through weathering. In contrast, size reductions are absent below and above the ETM2 at Hg peaks where δ18O data do not show warm conditions. We speculate that the local input of toxic metals from submarine volcanic emissions could have acted synergistically to warming, causing the unique dwarfism.
Thank You to Our 2023 Reviewers
Authors: Parrish Julia , Schensul Jean , Beveridge Claire , Buchanan Paula , Gupta Shobhana , Haklay Muki , Pandya Rajul , Roop Heidi , Semmens Kate , Shukla Roopam
Published: June 2024

The editors of the Community Science Exchange want to say a big thank you to the 29 reviewers for reviewing for Community Science in 2023. Peer‐review is essential to the process of doing and publishing scientific findings, and will be a pillar of our successful expansion of science by, with and for communities into mainstream science. Many papers start with an inquiry, allowing us to assist prospective authors in inclusion of community voice. These consultations also allow us to respect reviewers' time as we only send papers for review that meet our criteria.
Finally, Hawaii Gets Its Own Climate Divisions
Authors: Kornei Katherine
Published: June 2024

Researchers have analyzed precipitation patterns in the 50th state to define a long-overdue data set that brings Hawaii into the fold of modern-day climate analyses.
Ray Tracing for Jupiter's Icy Moon Ionospheric Occultation of Jovian Auroral Radio Sources
Authors: Yasuda Rikuto , Kimura Tomoki , Misawa Hiroaki , Tsuchiya Fuminori , Cecconi Baptiste , Kasaba Yasumasa , Satoh Shinnosuke , Sakai Shotaro , Louis Corentin K.
Published: June 2024

The ionospheres of Jupiter's icy moons have been observed by in situ plasma measurements and radio science. However, their spatial structures have not yet been fully characterized. To address this, we developed a new ray tracing method for modeling the radio occultation of the ionospheres using Jovian auroral radio sources. Applying our method to Jovian auroral radio observations with the Galileo spacecraft, we derived the electron density of the ionosphere of Ganymede and Callisto. For Ganymede's ionosphere, we found that the maximum electron density on the surface was 76.5–288.5 cm−3 in the open magnetic field line regions and 5.0–20.5 cm−3 in the closed magnetic field line region during the Galileo Ganymede 01 flyby. The difference in the electron density distribution was correlated with the accessibility of Jovian magnetospheric plasma to the atmosphere and surface of the moons. These results indicated that electron‐impact ionization of the Ganymede exosphere and sputtering of the surface water ice were effective for the producing Ganymede's ionosphere. For Callisto's ionosphere, we found that the densities were approximately 350 and 12.5 cm−3 on the night side hemisphere during Callisto 09 and 30 flybys, respectively. These results combined with previous observations indicated that atmospheric production through sublimation controlled the ionospheric density of Callisto. This method is also applicable to upcoming Jovian radio observation data from the Jupiter Icy Moon Explorer, JUICE.
Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex
Authors: Williams Barnabas G. , King Lloyd D. W. , Pulido David , Quinkert Doris , Lias Amelia M. , Silk Sarah E. , Ragotte Robert J. , Davies Hannah , Barrett Jordan R. , McHugh Kirsty , Rigby Cassandra A. , Alanine Daniel G. W. , Barfod Lea , Shea Michael W. , Cowley Li An , Dabbs Rebecca A. , Pattinson David J. , Douglas Alexander D. , Lyth Oliver R. , Illingworth Joseph J. , Jin Jing , Carnrot Cecilia , Kotraiah Vinayaka , Christen Jayne M. , Noe Amy R. , MacGill Randall S. , King C. Richter , Birkett Ashley J. , Soisson Lorraine A. , Skinner Katherine , Miura Kazutoyo , Long Carole A. , Higgins Matthew K. , Draper Simon J.
Published: June 2024

Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric “RCR-complex”. We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically. However, immunisation of female rats with the RCR-complex fails to outperform RH5 alone due to immuno-dominance of RIPR coupled with inferior potency of anti-RIPR polyclonal IgG. We identify that all growth-inhibitory antibody epitopes of RIPR cluster within the C-terminal EGF-like domains and that a fusion of these domains to CyRPA, called “R78C”, combined with RH5, improves the level of in vitro parasite growth inhibition compared to RH5 alone. These preclinical data justify the advancement of the RH5.1 + R78C/Matrix-M™ vaccine candidate to Phase 1 clinical trial.
Parvalbumin-expressing basal forebrain neurons mediate learning from negative experience
Authors: Hegedüs Panna , Király Bálint , Schlingloff Dániel , Lyakhova Victoria , Velencei Anna , Szabó Írisz , Mayer Márton I. , Zelenak Zsofia , Nyiri Gábor , Hangya Balázs
Published: June 2024

Parvalbumin (PV)-expressing GABAergic neurons of the basal forebrain (BFPVNs) were proposed to serve as a rapid and transient arousal system, yet their exact role in awake behaviors remains unclear. We performed bulk calcium measurements and electrophysiology with optogenetic tagging from the horizontal limb of the diagonal band of Broca (HDB) while male mice were performing an associative learning task. BFPVNs responded with a distinctive, phasic activation to punishment, but showed slower and delayed responses to reward and outcome-predicting stimuli. Optogenetic inhibition during punishment impaired the formation of cue-outcome associations, suggesting a causal role of BFPVNs in associative learning. BFPVNs received strong inputs from the hypothalamus, the septal complex and the median raphe region, while they synapsed on diverse cell types in key limbic structures, where they broadcasted information about aversive stimuli. We propose that the arousing effect of BFPVNs is recruited by aversive stimuli to serve crucial associative learning functions.
Kriging-based surrogate data-enriching artificial neural network prediction of strength and permeability of permeable cement-stabilized base
Authors: Wang Xiaoming , Xiao Yuanjie , Li Wenqi , Wang Meng , Zhou Yanbin , Chen Yuliang , Li Zhiyong
Published: June 2024

Limited test data hinder the accurate prediction of mechanical strength and permeability of permeable cement-stabilized base materials (PCBM). Here we show a kriging-based surrogate model assisted artificial neural network (KS-ANN) framework that integrates laboratory testing, mathematical modeling, and machine learning. A statistical distribution model was established from limited test data to enrich the dataset through the combination of markov chain monte carlo simulation and kriging-based surrogate modeling. Subsequently, an artificial neural network (ANN) model was trained using the enriched dataset. The results demonstrate that the well-trained KS-ANN model effectively captures the actual data distribution characteristics. The accurate prediction of the mechanical strength and permeability of PCBM under the constraint of limited data validates the effectiveness of the proposed framework. As compared to traditional ANN models, the KS-ANN model improves the prediction accuracy of PCBM’s mechanical strength by 21%. Based on the accurate prediction of PCBM’s mechanical strength and permeability by the KS-ANN model, an optimization function was developed to determine the optimal cement content and compaction force range of PCBM, enabling it to concurrently satisfy the requirements of mechanical strength and permeability. This study provides a cost-effective and rapid solution for evaluating the performance and optimizing the design of PCBM and similar materials.
Nondiffracting supertoroidal pulses and optical “Kármán vortex streets”
Authors: Shen Yijie , Papasimakis Nikitas , Zheludev Nikolay I.
Published: June 2024

Supertoroidal light pulses, as space-time nonseparable electromagnetic waves, exhibit unique topological properties including skyrmionic configurations, fractal-like singularities, and energy backflow in free space, which however do not survive upon propagation. Here, we introduce the non-diffracting supertoroidal pulses (NDSTPs) with propagation-robust skyrmionic and vortex field configurations that persists over arbitrary propagation distances. Intriguingly, the field structure of NDSTPs has a similarity with the von Kármán vortex street, a pattern of swirling vortices in fluid and gas dynamics with staggered singularities that can stably propagate forward. NDSTPs will be of interest as directed channels for information and energy transfer applications.
Identifying critical features of iron phosphate particle for lithium preference
Authors: Yan Gangbin , Wei Jialiang , Apodaca Emory , Choi Suin , Eng Peter J. , Stubbs Joanne E. , Han Yu , Zou Siqi , Bera Mrinal K. , Wu Ronghui , Karapetrova Evguenia , Zhou Hua , Chen Wei , Liu Chong
Published: June 2024

One-dimensional (1D) olivine iron phosphate (FePO4) is widely proposed for electrochemical lithium (Li) extraction from dilute water sources, however, significant variations in Li selectivity were observed for particles with different physical attributes. Understanding how particle features influence Li and sodium (Na) co-intercalation is crucial for system design and enhancing Li selectivity. Here, we investigate a series of FePO4 particles with various features and revealed the importance of harnessing kinetic and chemo-mechanical barrier difference between lithiation and sodiation to promote selectivity. The thermodynamic preference of FePO4 provides baseline of selectivity while the particle features are critical to induce different kinetic pathways and barriers, resulting in different Li to Na selectivity from 6.2 × 102 to 2.3 × 104. Importantly, we categorize the FePO4 particles into two groups based on their distinctly paired phase evolutions upon lithiation and sodiation, and generate quantitative correlation maps among Li preference, morphological features, and electrochemical properties. By selecting FePO4 particles with specific features, we demonstrate fast (636 mA/g) Li extraction from a high Li source (1: 100 Li to Na) with (96.6 ± 0.2)% purity, and high selectivity (2.3 × 104) from a low Li source (1: 1000 Li to Na) with (95.8 ± 0.3)% purity in a single step.
Easy-to-actuate multi-compatible truss structures with prescribed reconfiguration
Authors: Ai Lin , Yin Shukun , He Weixia , Zhang Peidong , Li Yang
Published: June 2024

Multi-stable structures attract great interest because they possess special energy landscapes with domains of attraction around the stable states. Consequently, multi-stable structures have the potential to achieve prescribed reconfiguration with only a few lightweight actuators (such as shape-memory alloy springs), and do not need constant actuation to be locked at a stable state. However, most existing multi-stability designs are based on assembling bi-stable unit cells, which contain multitudes of distractive stable states, diminishing the feasibility of reconfiguration actuation. Another type is by introducing prestress together with kinematic symmetry or nonlinearity to achieve multi-stability, but the resultant structure often suffers the lack of stiffness. To help address these challenges, we firstly introduce the constraints that a truss structure is simultaneously compatible at multiple (more than two) prescribed states. Then, we solve for the design of multi-stable truss structures, named multi-compatible structures in this paper, where redundant stable states are limited. Secondly, we explore minimum energy paths connecting the designed stable states, and compute for a simple and inaccurate pulling actuation guiding the structure to transform along the computed paths. Finally, we fabricated four prototypes to demonstrate that prescribed reconfigurations with easy-actuation have been achieved and applied a quadra-stable structure to the design of a variable stiffness gripper. Altogether, our full-cycle design approach contains multi-stability design, stiffness design, minimum-energy-path finding, and pulling actuation design, which highlights the potential for designing morphing structures with lightweight actuation for practical applications.
A YAP-centered mechanotransduction loop drives collective breast cancer cell invasion
Authors: Khalil Antoine A. , Smits Daan , Haughton Peter D. , Koorman Thijs , Jansen Karin A. , Verhagen Mathijs P. , van der Net Mirjam , van Zwieten Kitty , Enserink Lotte , Jansen Lisa , El-Gammal Abdelrahman G. , Visser Daan , Pasolli Milena , Tak Max , Westland Denise , van Diest Paul J. , Moelans Cathy B. , Roukens M. Guy , Tavares Sandra , Fortier Anne-Marie , Park Morag , Fodde Riccardo , Gloerich Martijn , Zwartkruis Fried. J. T. , Derksen Patrick WB. , de Rooij Johan
Published: June 2024

Dense and aligned Collagen I fibers are associated with collective cancer invasion led by protrusive tumor cells, leader cells. In some breast tumors, a population of cancer cells (basal-like cells) maintain several epithelial characteristics and express the myoepithelial/basal cell marker Keratin 14 (K14). Emergence of leader cells and K14 expression are regarded as interconnected events triggered by Collagen I, however the underlying mechanisms remain unknown. Using breast carcinoma organoids, we show that Collagen I drives a force-dependent loop, specifically in basal-like cancer cells. The feed-forward loop is centered around the mechanotransducer Yap and independent of K14 expression. Yap promotes a transcriptional program that enhances Collagen I alignment and tension, which further activates Yap. Active Yap is detected in invading breast cancer cells in patients and required for collective invasion in 3D Collagen I and in the mammary fat pad of mice. Our work uncovers an essential function for Yap in leader cell selection during collective cancer invasion.
ASXLs binding to the PHD2/3 fingers of MLL4 provides a mechanism for the recruitment of BAP1 to active enhancers
Authors: Zhang Yi , Xie Guojia , Lee Ji-Eun , Zandian Mohamad , Sudarshan Deepthi , Estavoyer Benjamin , Benz Caroline , Viita Tiina , Asgaritarghi Golareh , Lachance Catherine , Messmer Clémence , Simonetti Leandro , Sinha Vikrant Kumar , Lambert Jean-Philippe , Chen Yu-Wen , Wang Shu-Ping , Ivarsson Ylva , Affar El Bachir , Côté Jacques , Ge Kai , Kutateladze Tatiana G.
Published: June 2024

The human methyltransferase and transcriptional coactivator MLL4 and its paralog MLL3 are frequently mutated in cancer. MLL4 and MLL3 monomethylate histone H3K4 and contain a set of uncharacterized PHD fingers. Here, we report a novel function of the PHD2 and PHD3 (PHD2/3) fingers of MLL4 and MLL3 that bind to ASXL2, a component of the Polycomb repressive H2AK119 deubiquitinase (PR-DUB) complex. The structure of MLL4 PHD2/3 in complex with the MLL-binding helix (MBH) of ASXL2 and mutational analyses reveal the molecular mechanism which is conserved in homologous ASXL1 and ASXL3. The native interaction of the Trithorax MLL3/4 complexes with the PR-DUB complex in vivo depends solely on MBH of ASXL1/2, coupling the two histone modifying activities. ChIP-seq analysis in embryonic stem cells demonstrates that MBH of ASXL1/2 is required for the deubiquitinase BAP1 recruitment to MLL4-bound active enhancers. Our findings suggest an ASXL1/2-dependent functional link between the MLL3/4 and PR-DUB complexes.
Realization of 2D multiferroic with strong magnetoelectric coupling by intercalation: a first-principles high-throughput prediction
Authors: Zhao Ying , Wang Yanxia , Yang Yue , Zhao Jijun , Jiang Xue
Published: June 2024

The discovery of novel two-dimensional (2D) multiferroic materials is attractive due to their potential for the realization of information storage and logic devices. Although many approaches have been explored to simultaneously introduce ferromagnetic (FM) and ferroelectric (FE) orders into a 2D material, the resulting systems are often plagued by weak magnetoelectric (ME) coupling or limited room-temperature stability. Here, we present a superlattice strategy to construct non-centrosymmetric AM2X4 multiferroic monolayers, i.e., intercalating transition metal ions (A) into the tetragonal-like vacancies of transition metal dichalcogenide bilayers (MX2). Starting from 960 intercalated AM2X4 compounds, our high-throughput calculations have identified 21 multiferroics with robust magnetic order, large FE polarization, low transition barrier, high FE/FM transition temperature, and strong ME coupling. According to the origin of magnetism, we have classified them into twelve type-a, seven type-b, and two type-c multiferroics, which exhibit different ME coupling behavior. During the switching of polarization, the reversal of skyrmions chirality, the transition of the magnetic ground state from FM to antiferromagnetic, and the changes in spin-polarized electron distribution were observed in type-a, type-b, and type-c 2D multiferroic materials, respectively. These results substantially expand the family of 2D ferroic materials and pave an avenue for designing and implementing nonvolatile logic and memory devices.
Systematic assessment of long-read RNA-seq methods for transcript identification and quantification
Authors: Pardo-Palacios Francisco J. , Wang Dingjie , Reese Fairlie , Diekhans Mark , Carbonell-Sala Sílvia , Williams Brian , Loveland Jane E. , De María Maite , Adams Matthew S. , Balderrama-Gutierrez Gabriela , Behera Amit K. , Gonzalez Martinez Jose M. , Hunt Toby , Lagarde Julien , Liang Cindy E. , Li Haoran , Meade Marcus Jerryd , Moraga Amador David A. , Prjibelski Andrey D. , Birol Inanc , Bostan Hamed , Brooks Ashley M. , Çelik Muhammed Hasan , Chen Ying , Du Mei R. M. , Felton Colette , Göke Jonathan , Hafezqorani Saber , Herwig Ralf , Kawaji Hideya , Lee Joseph , Li Jian-Liang , Lienhard Matthias , Mikheenko Alla , Mulligan Dennis , Nip Ka Ming , Pertea Mihaela , Ritchie Matthew E. , Sim Andre D. , Tang Alison D. , Wan Yuk Kei , Wang Changqing , Wong Brandon Y. , Yang Chen , Barnes If , Berry Andrew E. , Capella-Gutierrez Salvador , Cousineau Alyssa , Dhillon Namrita , Fernandez-Gonzalez Jose M. , Ferrández-Peral Luis , Garcia-Reyero Natàlia , Götz Stefan , Hernández-Ferrer Carles , Kondratova Liudmyla , Liu Tianyuan , Martinez-Martin Alessandra , Menor Carlos , Mestre-Tomás Jorge , Mudge Jonathan M. , Panayotova Nedka G. , Paniagua Alejandro , Repchevsky Dmitry , Ren Xingjie , Rouchka Eric , Saint-John Brandon , Sapena Enrique , Sheynkman Leon , Smith Melissa Laird , Suner Marie-Marthe , Takahashi Hazuki , Youngworth Ingrid A. , Carninci Piero , Denslow Nancy D. , Guigó Roderic , Hunter Margaret E. , Maehr Rene , Shen Yin , Tilgner Hagen U. , Wold Barbara J. , Vollmers Christopher , Frankish Adam , Au Kin Fai , Sheynkman Gloria M. , Mortazavi Ali , Conesa Ana , Brooks Angela N.
Published: June 2024

The Long-read RNA-Seq Genome Annotation Assessment Project Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. Using different protocols and sequencing platforms, the consortium generated over 427 million long-read sequences from complementary DNA and direct RNA datasets, encompassing human, mouse and manatee species. Developers utilized these data to address challenges in transcript isoform detection, quantification and de novo transcript detection. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. Incorporating additional orthogonal data and replicate samples is advised when aiming to detect rare and novel transcripts or using reference-free approaches. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.
Field experiment on the effect of musical street performance/busking on public space perception as mediated by street audience experience
Authors: Ho Robbie , Szubielska Magdalena
Published: June 2024

Street performance or busking is common in public spaces. The literature highlights two psychological issues: the effect of street performance on public space perception and the complexity of the appreciation of street performance, regarded as street audience experience (SAE). The present study aims at verifying the effect of street performance on public space perception, while examining SAE as a mediator of this effect. We conducted a between-subjects field experiment (a quasi-experiment; N = 292) in Hong Kong. Participants assessed a public space without (control) or with (experimental) musical busking on essentialism, anti-essentialism, sonic restorativeness, and overall liking. In the experimental condition, unengaged passersby and engaged audience further evaluated SAE factors of emotion, intellect, novelty, place, interaction, and technique, and outcomes of overall satisfaction and donation worth. The public space with busking was perceived as significantly more sonically restorative. Engaged audience perceived the space as significantly more essentialist, anti-essentialist, sonically restorative, and likeable. Engaged audience also experienced more positive SAE and outcome variables. SAE fully mediated the effects of street performance on public space perception and outcome variables, respectively. These findings support the positive impact of street performance, which may enhance city inhabitants’ well-being.
Systemic inflammation, oxidative damage and neurocognition predict telomere length in a transdiagnostic sample stratified by global DNA methylation levels
Authors: Sánchez-Ortí Joan Vicent , Correa-Ghisays Patricia , Balanzá-Martínez Vicent , Macías Saint-Gerons Diego , Berenguer-Pascual Ester , Romá-Mateo Carlos , Victor Víctor M. , Forés-Martos Jaume , San-Martin Constanza , Selva-Vera Gabriel , Tabarés-Seisdedos Rafael
Published: June 2024

Epigenetic mechanisms contribute to the maintenance of both type 2 diabetes mellitus (T2DM) and psychiatric disorders. Emerging evidence suggests that molecular pathways and neurocognitive performance regulate epigenetic dynamics in these disorders. The current combined and transdiagnostic study investigated whether inflammatory, oxidative stress, adhesion molecule, neurocognitive and functional performance are significant predictors of telomere dynamics in a sample stratified by global DNA methylation levels. Peripheral blood inflammation, oxidative stress and adhesion molecule biomarkers and neurocognitive function were assessed twice over a 1-year period in 80 individuals, including 16 with schizophrenia (SZ), 16 with bipolar disorder (BD), 16 with major depressive disorder (MDD), 15 with T2DM, and 17 healthy controls (HCs). Leukocyte telomere length (LTL) was measured by qRT-PCR using deoxyribonucleic acid (DNA) extracted from peripheral blood samples. A posteriori, individuals were classified based on their global methylation score (GMS) at baseline into two groups: the below-average methylation (BM) and above-average methylation (AM) groups. Hierarchical and k-means clustering methods, mixed one-way analysis of variance and linear regression analyses were performed. Overall, the BM group showed a significantly higher leukocyte telomere length (LTL) than the AM group at both time points (p = 0.02; η2p = 0.06). Moreover, the BM group had significantly lower levels of tumor necrosis factor alpha (TNF-α) (p = 0.03; η2p = 0.06) and C-reactive protein (CRP) (p = 0.03; η2p = 0.06) than the AM group at the 1-year follow-up. Across all participants, the regression models showed that oxidative stress (reactive oxygen species [ROS]) (p = 0.04) and global cognitive score [GCS] (p = 0.02) were significantly negatively associated with LTL, whereas inflammatory (TNF-α) (p = 0.04), adhesion molecule biomarkers (inter cellular adhesion molecule [ICAM]) (p = 0.009), and intelligence quotient [IQ] (p = 0.03) were significantly positively associated with LTL. Moreover, the model predictive power was increased when tested in both groups separately, explaining 15.8% and 28.1% of the LTL variance at the 1-year follow-up for the AM and BM groups, respectively. Heterogeneous DNA methylation in individuals with T2DM and severe mental disorders seems to support the hypothesis that epigenetic dysregulation occurs in a transdiagnostic manner. Our results may help to elucidate the interplay between epigenetics, molecular processes and neurocognitive function in these disorders. DNA methylation and LTL are potential therapeutic targets for transdiagnostic interventions to decrease the risk of comorbidities.
In silico design of peptide inhibitors for Dengue virus to treat Dengue virus-associated infections
Authors: Ajmal Amar , Shahab Muhammad , Waqas Muhammad , Zheng Guojun , Zulfat Maryam , Bin Jardan Yousef A. , Wondmie Gezahign Fentahun , Bourhia Mohammed , Ali Ijaz
Published: June 2024

Dengue virus is a single positive-strand RNA virus that is composed of three structural proteins including capsid, envelope, and precursor membrane while seven non-structural proteins (NS1, NS2A, NS2B, NS3A, NS3B, NS4, and NS5). Dengue is a viral infection caused by the dengue virus (DENV). DENV infections are asymptomatic or produce only mild illness. However, DENV can occasionally cause more severe cases and even death. There is no specific treatment for dengue virus infections. Therapeutic peptides have several important advantages over proteins or antibodies: they are small in size, easy to synthesize, and have the ability to penetrate the cell membranes. They also have high activity, specificity, affinity, and less toxicity. Based on the known peptide inhibitor, the current study designs peptide inhibitors for dengue virus envelope protein using an alanine and residue scanning technique. By replacing I21 with Q21, L14 with H14, and V28 with K28, the binding affinity of the peptide inhibitors was increased. The newly designed peptide inhibitors with single residue mutation improved the binding affinity of the peptide inhibitors. The inhibitory capability of the new promising peptide inhibitors was further confirmed by the utilization of MD simulation and free binding energy calculations. The molecular dynamics simulation demonstrated that the newly engineered peptide inhibitors exhibited greater stability compared to the wild-type peptide inhibitors. According to the binding free energies MM(GB)SA of these developed peptides, the first peptide inhibitor was the most effective against the dengue virus envelope protein. All peptide derivatives had higher binding affinities for the envelope protein and have the potential to treat dengue virus-associated infections. In this study, new peptide inhibitors were developed for the dengue virus envelope protein based on the already reported peptide inhibitor.
Cell-specific models of hiPSC-CMs developed by the gradient-based parameter optimization method fitting two different action potential waveforms
Authors: Zhang Yixin , Toyoda Futoshi , Himeno Yukiko , Noma Akinori , Amano Akira
Published: June 2024

Parameter optimization (PO) methods to determine the ionic current composition of experimental cardiac action potential (AP) waveform have been developed using a computer model of cardiac membrane excitation. However, it was suggested that fitting a single AP record in the PO method was not always successful in providing a unique answer because of a shortage of information. We found that the PO method worked perfectly if the PO method was applied to a pair of a control AP and a model output AP in which a single ionic current out of six current species, such as IKr, ICaL, INa, IKs, IKur or IbNSC was partially blocked in silico. When the target was replaced by a pair of experimental control and IKr-blocked records of APs generated spontaneously in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), the simultaneous fitting of the two waveforms by the PO method was hampered to some extent by the irregular slow fluctuations in the Vm recording and/or sporadic alteration in AP configurations in the hiPSC-CMs. This technical problem was largely removed by selecting stable segments of the records for the PO method. Moreover, the PO method was made fail-proof by running iteratively in identifying the optimized parameter set to reconstruct both the control and the IKr-blocked AP waveforms. In the lead potential analysis, the quantitative ionic mechanisms deduced from the optimized parameter set were totally consistent with the qualitative view of ionic mechanisms of AP so far described in physiological literature.
Leukocyte filtration and leukocyte modulation therapy during extracorporeal cardiopulmonary resuscitation in a porcine model of prolonged cardiac arrest
Authors: VanZalen Jensyn J. , Nakashima Takahiro , Phillips Annie , Hill Joseph E. , Westover Angela J. , Lou Liandi , Liao Jinhui , Mergos Joshua , Fogo Garrett , Sanderson Thomas H. , Stacey William C. , Tiba Mohamad Hakam , Humes David H. , Bartlett Robert H. , Rojas-Peña Alvaro , Neumar Robert W.
Published: June 2024

Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a feasible and effective rescue strategy for prolonged cardiac arrest (CA). However, prolonged total body ischemia and reperfusion can cause microvascular occlusion that prevents organ reperfusion and recovery of function. One hypothesized mechanism of microvascular “no-reflow” is leukocyte adhesion and formation of neutrophil extracellular traps. In this study we tested the hypothesis that a leukocyte filter (LF) or leukocyte modulation device (L-MOD) could reduce NETosis and improve recovery of heart and brain function in a swine model of prolonged cardiac arrest treated with ECPR. Thirty-six swine (45.5 ± 2.5 kg, evenly distributed sex) underwent 8 min of untreated ventricular fibrillation CA followed by 30 min of mechanical CPR with subsequent 8 h of ECPR. Two females were later excluded from analysis due to CPR complications. Swine were randomized to standard care (Control group), LF, or L-MOD at the onset of CPR. NET formation was quantified by serum dsDNA and citrullinated histone as well as immunofluorescence staining of the heart and brain for citrullinated histone in the microvasculature. Primary outcomes included recovery of cardiac function based on cardiac resuscitability score (CRS) and recovery of neurologic function based on the somatosensory evoked potential (SSEP) N20 cortical response. In this model of prolonged CA treated with ECPR we observed significant increases in serum biomarkers of NETosis and immunohistochemical evidence of microvascular NET formation in the heart and brain that were not reduced by LF or L-MOD therapy. Correspondingly, there were no significant differences in CRS and SSEP recovery between Control, LF, and L-MOD groups 8 h after ECPR onset (CRS = 3.1 ± 2.7, 3.7 ± 2.6, and 2.6 ± 2.6 respectively; p = 0.606; and SSEP = 27.9 ± 13.0%, 36.7 ± 10.5%, and 31.2 ± 9.8% respectively, p = 0.194). In this model of prolonged CA treated with ECPR, the use of LF or L-MOD therapy during ECPR did not reduce microvascular NETosis or improve recovery of myocardial or brain function. The causal relationship between microvascular NETosis, no-reflow, and recovery of organ function after prolonged cardiac arrest treated with ECPR requires further investigation.
Oxidative modification of miR-30c promotes cardiac fibroblast proliferation via CDKN2C mismatch
Authors: Chang Wenguang , Xiao Dandan , Fang Xinyu , Wang Jianxun
Published: June 2024

The response of cardiac fibroblast proliferation to detrimental stimuli is one of the main pathological factors causing heart remodeling. Reactive oxygen species (ROS) mediate the proliferation of cardiac fibroblasts. However, the exact molecular mechanism remains unclear. In vivo, we examined the oxidative modification of miRNAs with miRNA immunoprecipitation with O8G in animal models of cardiac fibrosis induced by Ang II injection or ischemia‒reperfusion injury. Furthermore, in vitro, we constructed oxidation-modified miR-30c and investigated its effects on the proliferation of cardiac fibroblasts. Additionally, luciferase reporter assays were used to identify the target of oxidized miR-30c. We found that miR-30c oxidation was modified by Ang II and PDGF treatment and mediated by excess ROS. We demonstrated that oxidative modification of G to O8G occurred at positions 4 and 5 of the 5′ end of miR-30c (4,5-oxo-miR-30c), and this modification promoted cardiac fibroblast proliferation. Furthermore, CDKN2C is a negative regulator of cardiac fibroblast proliferation. 4,5-oxo-miR-30c misrecognizes CDKN2C mRNA, resulting in a reduction in protein expression. Oxidized miR-30c promotes cardiac fibroblast proliferation by mismatch mRNA of CDKN2C.
Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on hippocampal long-term potentiation at perforant pathway-dentate gyrus synapses in prenatal valproic acid-induced rat model of autism
Authors: Gholipour Parsa , Ebrahimi Zahra , Mohammadkhani Reihaneh , Ghahremani Reza , Salehi Iraj , Sarihi Abdolrahman , Komaki Alireza , Karimi Seyed Asaad
Published: June 2024

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition characterized by social interaction deficits, communication impairments, repetitive behaviors, and sensory sensitivities. While the etiology of ASD is multifaceted, abnormalities in glutamatergic neurotransmission and synaptic plasticity have been implicated. This study investigated the role of metabotropic glutamate receptor 8 (mGlu8) in modulating long-term potentiation (LTP) in a rat model of ASD induced by prenatal valproic acid (VPA) exposure. To induce an animal model with autism-like characteristics, pregnant rats received an intraperitoneal injection of 500 mg/kg of sodium valproate (NaVPA) on embryonic day 12.5. High-frequency stimulation was applied to the perforant path-dentate gyrus (PP-DG) synapse to induce LTP, while the mGlu8 receptor agonist (S)-3,4-dicarboxyphenylglycine (DCPG) was administered into the DG. The results revealed that VPA-exposed rats exhibited reduced LTP compared to controls. DCPG had contrasting effects, inhibiting LTP in controls and enhancing it in VPA-exposed rats. Moreover, reduced social novelty preference index (SNPI) in VPA-exposed rats was reversed by intra-DG administration of S-3,4-DCPG. In conclusion, our study advances our understanding of the complex relationship between glutamatergic neurotransmission, synaptic plasticity, and VPA-induced autism model. The findings suggest that mGlu8 receptor dysfunction plays a role in the impaired synaptic plasticity seen in ASD.
Potential therapeutic targets of gastric cancer explored under endogenous network modeling of clinical data
Authors: Zhang Xile , Chen Yong-Cong , Yao Mengchao , Xiong Ruiqi , Liu Bingya , Zhu Xiaomei , Ao Ping
Published: June 2024

Improvement in the survival rate of gastric cancer, a prevalent global malignancy and the leading cause of cancer-related mortality calls for more avenues in molecular therapy. This work aims to comprehend drug resistance and explore multiple-drug combinations for enhanced therapeutic treatment. An endogenous network modeling clinic data with core gastric cancer molecules, functional modules, and pathways is constructed, which is then transformed into dynamics equations for in-silicon studies. Principal component analysis, hierarchical clustering, and K-means clustering are utilized to map the attractor domains of the stochastic model to the normal and pathological phenotypes identified from the clinical data. The analyses demonstrate gastric cancer as a cluster of stable states emerging within the stochastic dynamics and elucidate the cause of resistance to anti-VEGF monotherapy in cancer treatment as the limitation of the single pathway in preventing cancer progression. The feasibility of multiple objectives of therapy targeting specified molecules and/or pathways is explored. This study verifies the rationality of the platform of endogenous network modeling, which contributes to the development of cross-functional multi-target combinations in clinical trials.
Attention spotlight in V1-based cortico-cortical interactions in human visual hierarchy
Authors: Zhang Yanyu , Zhang Xilin , Lu Xincheng , Chen Nihong
Published: June 2024

Attention is often viewed as a mental spotlight, which can be scaled like a zoom lens at specific spatial locations and features a center-surround gradient. Here, we demonstrate a neural signature of attention spotlight in signal transmission along the visual hierarchy. fMRI background connectivity analysis was performed between retinotopic V1 and downstream areas to characterize the spatial distribution of inter-areal interaction under two attentional states. We found that, compared to diffused attention, focal attention sharpened the spatial gradient in the strength of the background connectivity. Dynamic causal modeling analysis further revealed the effect of attention in both the feedback and feedforward connectivity between V1 and extrastriate cortex. In a context which induced a strong effect of crowding, the effect of attention in the background connectivity profile diminished. Our findings reveal a context-dependent attention prioritization in information transmission via modulating the recurrent processing across the early stages in human visual cortex.
Artificial intelligence-based radiographic extent analysis to predict tuberculosis treatment outcomes: a multicenter cohort study
Authors: Kim Hyung-Jun , Kwak Nakwon , Yoon Soon Ho , Park Nanhee , Kim Young Ran , Lee Jae Ho , Lee Ji Yeon , Park Youngmok , Kang Young Ae , Kim Saerom , Mok Jeongha , Kim Joong-Yub , Jeon Doosoo , Lee Jung-Kyu , Yim Jae-Joon
Published: June 2024

Predicting outcomes in pulmonary tuberculosis is challenging despite effective treatments. This study aimed to identify factors influencing treatment success and culture conversion, focusing on artificial intelligence (AI)-based chest X-ray analysis and Xpert MTB/RIF assay cycle threshold (Ct) values. In this retrospective study across six South Korean referral centers (January 1 to December 31, 2019), we included adults with rifampicin-susceptible pulmonary tuberculosis confirmed by Xpert assay from sputum samples. We analyzed patient characteristics, AI-based tuberculosis extent scores from chest X-rays, and Xpert Ct values. Of 230 patients, 206 (89.6%) achieved treatment success. The median age was 61 years, predominantly male (76.1%). AI-based radiographic tuberculosis extent scores (median 7.5) significantly correlated with treatment success (odds ratio [OR] 0.938, 95% confidence interval [CI] 0.895–0.983) and culture conversion at 8 weeks (liquid medium: OR 0.911, 95% CI 0.853–0.973; solid medium: OR 0.910, 95% CI 0.850–0.973). Sputum smear positivity was 49.6%, with a median Ct of 26.2. However, Ct values did not significantly correlate with major treatment outcomes. AI-based radiographic scoring at diagnosis is a significant predictor of treatment success and culture conversion in pulmonary tuberculosis, underscoring its potential in personalized patient management.