bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic variation, genetic advance, heritability and correlation analysis of phenotypic traits in tetraploid wheat (Triticum turgidum spp.) landraces and some improved cultivars of Ethiopia
Authors: Fufa Miheretu , Gedebo Andargachew , Leta Tesfaye , Lule Dagnachew
Published: January 2024

Tetraploid wheat species from Ethiopia hold ample genetic variation, which could provide a source for improvement of wheat. A total of 196 Ethiopian tetraploid wheat (Triticum turgidum spp.) accessions, including 174 landraces and 22 improved cultivars, were evaluated at Sinana and Debrezeit to assess morphological variation, genetic advance, heritability and correlation based on 11 phenotypic traits. Except for spike length, highly significant variation (P < 0.001) among genotypes for all traits was observed. The observed mean and range values of the phenotypic traits revealed high variability in the accessions. Phenotypic coefficient of variation (PCV) and genotypic coefficient of variation (GCV) values were high for grain yield, biomass yield and harvest index. Seed yield showed highly significant (P < 0.001) negative correlation with days to booting and days to maturity and positive correlation with all traits. The estimates of heritability (H2) for grain yield and the number of spikelets per spike respectively ranged from 41.78 to 84.62%. The genetic advance as a percentage of mean was low for the number of seeds per spikelet, days to booting and days to maturity; intermediate for plant height, thousand kernel weight and spike length and high for the number of spikelets per spike, the number of effective tillers per plant, grain yield, biomass yield and harvest index, respectively. The number of spikelets per spike gave a high value of genetic advance and heritability implying high genetic gain from its selection.
The myth of the Others: Western representations of the Dan people and boat clusters in the island city of Guangzhou, China (1842–1900)
Authors: Lin Tingcong , Su Ping
Published: January 2024

This article studies Western (primarily Anglophone) representations of the Dan people (boat people) and the boat clusters on which they lived, relative to the mainland, in the island city of Guangzhou, focusing on 1842–1900. A change occurred over time, as the Dan went from being in close interaction with Westerners prior to the Opium Wars to being peripheral to Western interests and activities. This shift is evident in Western writings, and negative representations of the Dan came to dominate in the late nineteenth century. This mirrored changing sociospatial power relations between Westerners and the terrestrial Chinese, as Westerners increasingly gained access to the onshore city of Guangzhou itself, in part from the colonial island enclave of Shamian. Changing crosscultural interactions affected how the Chinese Others were perceived and ultimately how the Chinese whole was intertextually constructed in Western colonial discourse.
EU Trade Policy between Constitutional Openness and Strategic Autonomy
Authors: Kübek Gesa , Mancini Isabella
Published: January 2024

From ‘strategic autonomy’ to ‘open strategic autonomy’ in the 2021 EU Trade Policy Review – questioning the added value of the qualifier ‘open’ – legal exploration of ‘openness’ in EU external trade – identification of constitutional norms of ‘openness’ in the Treaties – strong constitutional preference for openness – discretion for trade liberalisation and multilateralism and international cooperation but strict obligation for compliance with international law – reviewing recent EU trade instruments in light of these norms – rise in unilateral trade policy instruments adopted since 2021 in pursuit of open strategic autonomy – instruments seeking to restore reciprocity in international trade relations – instruments using access to the internal market as a lever for achieving global sustainability goals – instruments preserving EU security through trade – problematic tensions with international law – very limited ‘openness’ in ‘open strategic autonomy’.
Design and realization of a compact substrate integrated coaxial line butler matrix for beamforming applications
Authors: Idury Satya Krishna , Delmonte Nicoló , Silvestri Lorenzo , Bozzi Maurizio , Mukherjee Soumava
Published: January 2024

This article presents the modeling and realization of a compact substrate integrated coaxial line (SICL) based butler matrix operating at 5 GHz for beam-forming applications. The proposed 4 × 4 butler matrix is developed using SICL-based hybrid coupler, crossover, and phase shifter. A compact 90∘ coupler comprising of center tapped unequal stubs is designed to enhance the size reduction as well as to extend the out of band rejection. Wideband SICL-based crossover operating from DC to 10 GHz is conceived for the proposed butler matrix using a plated through hole as transition. The SICL crossover features very high measured isolation of 65 dB owing to the reduction in coupling between the two signal paths within a lateral footprint of only 0.034 $\lambda_g^2$. A meandered SICL-based line is used in order to provide the necessary 45∘ and 0∘ phase shift to realize the butler matrix. The fully shielded and self-packaged compact 4 × 4 SICL-based butler matrix is fabricated and experimentally validated to operate at 5 GHz.
Substorm Driven Chorus Waves: Decay Timescales and Implications for Pulsating Aurora
Authors: Troyer Riley N. , Jaynes Allison N. , Hartley David P. , Meredith Nigel P. , Hua Man , Bortnik Jacob
Published: January 2024

Energetic electron precipitation (EEP) associated with pulsating aurora can transfer greater than 30 keV electrons from the outer radiation belt region into the upper atmosphere and can deplete atmospheric ozone via collisions that produce NOx and HOx molecules. Our knowledge of exactly how EEP occurs is incomplete. Previous studies have shown that pitch angle scattering between electrons and lower‐band chorus waves can cause pulsating aurora associated with EEP and that substorms play an important role. In this work, we quantify the timescale of chorus wave decay following substorms and compare that to previously determined timescales. We find that the chorus decay e‐folding time varies based on magnetic local time (MLT), magnetic latitude, and wave frequency. The shortest timescales occur for lower‐band chorus in the 21 to 9 MLT region and compares, within uncertainty, to the energetic pulsating aurora timescale of Troyer et al. (2022, https://doi.org/10.3389/fspas.2022.1032552) for energetic pulsating aurora. We are able to further support this connection by modeling our findings in a quasi‐linear diffusion simulation. These results provide observations of how chorus waves behave after substorms and add additional statistical evidence linking energetic pulsating aurora to substorm driven lower‐band chorus waves.
Effects of Urbanization in China on the East Asian Summer Monsoon as Revealed by Two Global Climate Models
Authors: Liu Shu , Wang Yong , Zhang Guang J. , Gong Peng , Wei Linyi , He Yujun , Li Lijuan , Wang Bin
Published: January 2024

The East Asian summer monsoon (EASM), vulnerable to anthropogenic activities, exerts profound impacts on precipitation in East Asia. In recent decades, China has been experiencing rapid urbanization. It has not yet reached a consensus on its influences on EASM. Here, we introduce satellite‐derived urban impervious areas of China during 1985–2017 into two global climate models with contrasting biases of climatological EASM simulation. Both models consistently show that urbanization weakens EASM by increasing surface friction drag. The increased surface roughness reduces climatological southerly winds in the concentrated urbanization area. As a result, moisture convergence occurs south of the concentrated urbanization area with ascending motion, while moisture divergence with descending motion appears to the north, resulting in the precipitation anomalies of “southern flood and northern drought.” The dominant role of urban dynamic forcing in regulating EASM is confirmed by reducing urban roughness to the level of croplands in sensitivity experiments. As urban dynamic forcing is largely mitigated, the urbanization impact mainly driven by urban thermal forcing conversely strengthens EASM due to enhanced land‐sea thermal contrast via urbanization‐induced warming. Spatial patterns and magnitudes of the urbanization‐induced EASM weakening vary between the two models due to disparities in their simulations of urban thermodynamic forcing and atmospheric adjustments. These results underscore the robust weakening effect of urbanization on EASM by urban friction drag and document uncertainties in the related spatial pattern and magnitude resulting from model discrepancies.
Changes of Atlantic Multidecadal Variability During the Medieval Climate Anomaly and Little Ice Age and Associated Causes
Authors: Miao Jiapeng , Ge Yucen , Jiang Dabang
Published: January 2024

This study investigates changes in the period, amplitude, and spatial pattern of Atlantic Multidecadal Variability (AMV) during the Medieval Climate Anomaly (MCA; 950–1250) and Little Ice Age (LIA; 1450–1850) by analyzing simulations from the Community Earth System Model‐Last Millennium Ensemble. During the MCA, the AMV indices from ensemble members display periods of 30–50 years and their amplitudes decrease by 16%–26% for the 25th–75th percentile range relative to last millennium. During the LIA, periods of 25 and 35–50 years and increase of amplitudes (5%–13%) are found in ensemble members. The AMV shows horseshoe patterns during both periods, with a stronger subtropical warming center during the MCA than during the LIA. Further analysis indicates that AMV changes are mainly derived from their externally forced components, especially the volcanic forcing induced ones. However, internally generated parts of AMVs change little during the two periods.
Subsurface Redox Interactions Regulate Ebullitive Methane Flux in Heterogeneous Mississippi River Deltaic Wetland
Authors: Wang Jiaze , O'Meara Theresa , LaFond‐Hudson Sophie , He Songjie , Maiti Kanchan , Ward Eric J. , Sulman Benjamin N.
Published: January 2024

As interfaces connecting terrestrial and ocean ecosystems, coastal wetlands develop temporally and spatially complex redox conditions, which drive uncertainties in greenhouse gas emission as well as the total carbon budget of the coastal ecosystem. To evaluate the role of complex redox reactions in methane emission from coastal wetlands, a coupled reactive‐transport model was configured to represent subsurface biogeochemical cycles of carbon, nitrogen, and sulfur, along with production and transport of multiple gas species through diffusion and ebullition. This model study was conducted at multiple sites along a salinity gradient in the Barataria Basin at the Mississippi River Deltaic Plain. Over a freshwater to saline gradient, simulated total flux of methane was primarily controlled by its subsurface production and consumption, which were determined by redox reactions directly (e.g., methanogenesis, methanotrophy) and indirectly (e.g., competition with sulfate reduction) under aerobic and/or anaerobic conditions. At fine spatiotemporal scales, surface methane fluxes were also strongly dependent on transport processes, with episodic ebullitive fluxes leading to higher spatial and temporal variability compared to the gradient‐driven diffusion flux. Ebullitive methane fluxes were determined by methane fraction in total ebullitive gas and the frequency of ebullitive events, both of which varied with subsurface methane concentrations and other gas species. Although ebullition thresholds are constrained by local physical factors, this study indicates that redox interactions not only determine gas composition in ebullitive fluxes but can also regulate ebullition frequency through gas production.
Toward a New Flood Assessment Paradigm: From Exceedance Probabilities to the Expected Maximum Floods and Damages
Authors: Todini E. , Reggiani P.
Published: January 2024

To assess flood risks, we seek to estimate the probability distribution of the worst possible single‐event over a contiguous period of N years rather than the cumulative losses expected over a planning horizon. For this we use the probability distribution FN of extreme flood events over a multi‐year period, which is different from using the conventional single‐valued exceedance probability of 1/N years. FN can be used to estimate the hazard and then proceed to the estimation of risk, which we define as the “largest expected damage” over the set period. It also allows for a more coherent determination of design values, which descend from fully acknowledging the aleatoric uncertainty of the underlying natural river flow process. The epistemic uncertainty is removed by marginalizing the aleatoric‐epistemic uncertainty joint distribution over the parameter space. The advantage of the proposed Bayesian approach, which can be summarized in 12 steps, is demonstrated for the 2021 River Ahr flood in Germany, which caused casualties and huge material damage. Adopting the multi‐year maxima extreme value distribution can potentially lead to the reclassification of vulnerability levels for flood‐prone areas and reconsideration of current policy‐making and flood risk communication.
Can a Sparse Network of Cosmic Ray Neutron Sensors Improve Soil Moisture and Evapotranspiration Estimation at the Larger Catchment Scale?
Authors: Li Fang , Bogena Heye Reemt , Bayat Bagher , Kurtz Wolfgang , Hendricks Franssen Harrie‐Jan
Published: January 2024

Cosmic‐ray neutron sensors (CRNS) fill the gap between locally measured in‐situ soil moisture (SM) and remotely sensed SM by providing accurate SM estimation at the field scale. This is promising for improving hydrologic model predictions, as CRNS can provide valuable information on SM in the root zone at the typical scale of a model grid cell. In this study, SM measurements from a network of 12 CRNS in the Rur catchment (Germany) were assimilated into the Terrestrial System Modeling Platform (TSMP) to investigate its potential for improving SM, evapotranspiration (ET) and river discharge characterization and estimating soil hydraulic parameters at the larger catchment scale. The data assimilation (DA) experiments (with and without parameter estimation) were conducted in both a wet year (2016) and a dry year (2018) with the ensemble Kalman filter (EnKF), and later verified with an independent year (2017) without DA. The results show that SM characterization was significantly improved at measurement locations (with up to 60% root mean square error (RMSE) reduction), and that joint state‐parameter estimation improved SM simulation more than state estimation alone (more than 15% additional RMSE reduction). Jackknife experiments showed that SM at verification locations had lower and different improvements in the wet and dry years (an RMSE reduction of 40% in 2016 and 16% in 2018). In addition, SM assimilation was found to improve ET characterization to a much lesser extent, with a 15% RMSE reduction of monthly ET in the wet year and 9% in the dry year.
Caspase cleavage of RIPK3 after Asp333 is dispensable for mouse embryogenesis
Authors: Newton Kim , Wickliffe Katherine E. , Maltzman Allie , Dugger Debra L. , Webster Joshua D. , Guo Hongyan , Dixit Vishva M.
Published: January 2024

The proteolytic activity of caspase-8 suppresses lethal RIPK1-, RIPK3- and MLKL-dependent necroptosis during mouse embryogenesis. Caspase-8 is reported to cleave RIPK3 in addition to the RIPK3-interacting kinase RIPK1, but whether cleavage of RIPK3 is crucial for necroptosis suppression is unclear. Here we show that caspase-8-driven cleavage of endogenous mouse RIPK3 after Asp333 is dependent on downstream caspase-3. Consistent with RIPK3 cleavage being a consequence of apoptosis rather than a critical brake on necroptosis, Ripk3D333A/D333A knock-in mice lacking the Asp333 cleavage site are viable and develop normally. Moreover, in contrast to mice lacking caspase-8 in their intestinal epithelial cells, Ripk3D333A/D333A mice do not exhibit increased sensitivity to high dose tumor necrosis factor (TNF). Ripk3D333A/D333A macrophages died at the same rate as wild-type (WT) macrophages in response to TNF plus cycloheximide, TNF plus emricasan, or infection with murine cytomegalovirus (MCMV) lacking M36 and M45 to inhibit caspase-8 and RIPK3 activation, respectively. We conclude that caspase cleavage of RIPK3 is dispensable for mouse development, and that cleavage of caspase-8 substrates, including RIPK1, is sufficient to prevent necroptosis.
Distinct mesenchymal cell states mediate prostate cancer progression
Authors: Pakula Hubert , Omar Mohamed , Carelli Ryan , Pederzoli Filippo , Fanelli Giuseppe Nicolò , Pannellini Tania , Socciarelli Fabio , Van Emmenis Lucie , Rodrigues Silvia , Fidalgo-Ribeiro Caroline , Nuzzo Pier Vitale , Brady Nicholas J. , Dinalankara Wikum , Jere Madhavi , Valencia Itzel , Saladino Christopher , Stone Jason , Unkenholz Caitlin , Garner Richard , Alexanderani Mohammad K. , Khani Francesca , de Almeida Francisca Nunes , Abate-Shen Cory , Greenblatt Matthew B. , Rickman David S. , Barbieri Christopher E. , Robinson Brian D. , Marchionni Luigi , Loda Massimo
Published: January 2024

In the complex tumor microenvironment (TME), mesenchymal cells are key players, yet their specific roles in prostate cancer (PCa) progression remain to be fully deciphered. This study employs single-cell RNA sequencing to delineate molecular changes in tumor stroma that influence PCa progression and metastasis. Analyzing mesenchymal cells from four genetically engineered mouse models (GEMMs) and correlating these findings with human tumors, we identify eight stromal cell populations with distinct transcriptional identities consistent across both species. Notably, stromal signatures in advanced mouse disease reflect those in human bone metastases, highlighting periostin’s role in invasion and differentiation. From these insights, we derive a gene signature that predicts metastatic progression in localized disease beyond traditional Gleason scores. Our results illuminate the critical influence of stromal dynamics on PCa progression, suggesting new prognostic tools and therapeutic targets.
Developmental basis of SHH medulloblastoma heterogeneity
Authors: Gold Maxwell P. , Ong Winnie , Masteller Andrew M. , Ghasemi David R. , Galindo Julie Anne , Park Noel R. , Huynh Nhan C. , Donde Aneesh , Pister Veronika , Saurez Raul A. , Vladoiu Maria C. , Hwang Grace H. , Eisemann Tanja , Donovan Laura K. , Walker Adam D. , Benetatos Joseph , Dufour Christelle , Garzia Livia , Segal Rosalind A. , Wechsler-Reya Robert J. , Mesirov Jill P. , Korshunov Andrey , Pajtler Kristian W. , Pomeroy Scott L. , Ayrault Olivier , Davidson Shawn M. , Cotter Jennifer A. , Taylor Michael D. , Fraenkel Ernest
Published: January 2024

Many genes that drive normal cellular development also contribute to oncogenesis. Medulloblastoma (MB) tumors likely arise from neuronal progenitors in the cerebellum, and we hypothesized that the heterogeneity observed in MBs with sonic hedgehog (SHH) activation could be due to differences in developmental pathways. To investigate this question, here we perform single-nucleus RNA sequencing on highly differentiated SHH MBs with extensively nodular histology and observed malignant cells resembling each stage of canonical granule neuron development. Through innovative computational approaches, we connect these results to published datasets and find that some established molecular subtypes of SHH MB appear arrested at different developmental stages. Additionally, using multiplexed proteomic imaging and MALDI imaging mass spectrometry, we identify distinct histological and metabolic profiles for highly differentiated tumors. Our approaches are applicable to understanding the interplay between heterogeneity and differentiation in other cancers and can provide important insights for the design of targeted therapies.
Electrically and mechanically driven rotation of polar spirals in a relaxor ferroelectric polymer
Authors: Guo Mengfan , Xu Erxiang , Huang Houbing , Guo Changqing , Chen Hetian , Chen Shulin , He Shan , Zhou Le , Ma Jing , Shen Zhonghui , Xu Ben , Yi Di , Gao Peng , Nan Ce-Wen , Mathur Neil. D. , Shen Yang
Published: January 2024

Topology created by quasi-continuous spatial variations of a local polarization direction represents an exotic state of matter, but field-driven manipulation has been hitherto limited to creation and destruction. Here we report that relatively small electric or mechanical fields can drive the non-volatile rotation of polar spirals in discretized microregions of the relaxor ferroelectric polymer poly(vinylidene fluoride-ran-trifluoroethylene). These polar spirals arise from the asymmetric Coulomb interaction between vertically aligned helical polymer chains, and can be rotated in-plane through various angles with robust retention. Given also that our manipulation of topological order can be detected via infrared absorption, our work suggests a new direction for the application of complex materials.
Deletion of Aurora kinase A prevents the development of polycystic kidney disease in mice
Authors: Tham Ming Shen , Cottle Denny L. , Zylberberg Allara K. , Short Kieran M. , Jones Lynelle K. , Chan Perkin , Conduit Sarah E. , Dyson Jennifer M. , Mitchell Christina A. , Smyth Ian M.
Published: January 2024

Aurora Kinase A (AURKA) promotes cell proliferation and is overexpressed in different types of polycystic kidney disease (PKD). To understand AURKA’s role in regulating renal cyst development we conditionally deleted the gene in mouse models of Autosomal Dominant PKD (ADPKD) and Joubert Syndrome, caused by Polycystin 1 (Pkd1) and Inositol polyphosphate-5-phosphatase E (Inpp5e) mutations respectively. We show that while Aurka is dispensable for collecting duct development and homeostasis, its deletion prevents cyst formation in both disease models. Cross-comparison of transcriptional changes implicated AKT signaling in cyst prevention and we show that (i) AURKA and AKT physically interact, (ii) AURKA regulates AKT activity in a kinase-independent manner and (iii) inhibition of AKT can reduce disease severity. AKT activation also regulates Aurka expression, creating a feed-forward loop driving renal cystogenesis. We find that the AURKA kinase inhibitor Alisertib stabilises the AURKA protein, agonizing its cystogenic functions. These studies identify AURKA as a master regulator of renal cyst development in different types of PKD, functioning in-part via AKT.
Analysis of rare Parkinson’s disease variants in millions of people
Authors: Pitz Vanessa , Makarious Mary B. , Bandres-Ciga Sara , Iwaki Hirotaka ,   23andMe Research Team, Aslibekyan Stella , Auton Adam , Babalola Elizabeth , Bell Robert K. , Bielenberg Jessica , Bryc Katarzyna , Bullis Emily , Coker Daniella , Partida Gabriel Cuellar , Dhamija Devika , Das Sayantan , Elson Sarah L. , Eriksson Nicholas , Filshtein Teresa , Fitch Alison , Fletez-Brant Kipper , Fontanillas Pierre , Freyman Will , Granka Julie M. , Hernandez Alejandro , Hicks Barry , Hinds David A. , Jewett Ethan M. , Jiang Yunxuan , Kukar Katelyn , Kwong Alan , Lin Keng-Han , Llamas Bianca A. , Lowe Maya , McCreight Jey C. , McIntyre Matthew H. , Micheletti Steven J. , Moreno Meghan E. , Nandakumar Priyanka , Nguyen Dominique T. , Noblin Elizabeth S. , O’Connell Jared , Petrakovitz Aaron A. , Poznik G. David , Reynoso Alexandra , Schumacher Morgan , Shastri Anjali J. , Shelton Janie F. , Shi Jingchunzi , Shringarpure Suyash , Su Qiaojuan Jane , Tat Susana A. , Tchakouté Christophe Toukam , Tran Vinh , Tung Joyce Y. , Wang Xin , Wang Wei , Weldon Catherine H. , Wilton Peter , Wong Corinna D. , Singleton Andrew B. , Nalls Mike , Heilbron Karl , Blauwendraat Cornelis
Published: January 2024

Although many rare variants have been reportedly associated with Parkinson’s disease (PD), many have not been replicated or have failed to replicate. Here, we conduct a large-scale replication of rare PD variants. We assessed a total of 27,590 PD cases, 6701 PD proxies, and 3,106,080 controls from three data sets: 23andMe, Inc., UK Biobank, and AMP-PD. Based on well-known PD genes, 834 variants of interest were selected from the ClinVar annotated 23andMe dataset. We performed a meta-analysis using summary statistics of all three studies. The meta-analysis resulted in five significant variants after Bonferroni correction, including variants in GBA1 and LRRK2. Another eight variants are strong candidate variants for their association with PD. Here, we provide the largest rare variant meta-analysis to date, providing information on confirmed and newly identified variants for their association with PD using several large databases. Additionally we also show the complexities of studying rare variants in large-scale cohorts.
The motivating effect of monetary over psychological incentives is stronger in WEIRD cultures
Authors: Medvedev Danila , Davenport Diag , Talhelm Thomas , Li Yin
Published: January 2024

Motivating effortful behaviour is a problem employers, governments and nonprofits face globally. However, most studies on motivation are done in Western, educated, industrialized, rich and democratic (WEIRD) cultures. We compared how hard people in six countries worked in response to monetary incentives versus psychological motivators, such as competing with or helping others. The advantage money had over psychological interventions was larger in the United States and the United Kingdom than in China, India, Mexico and South Africa (N = 8,133). In our last study, we randomly assigned cultural frames through language in bilingual Facebook users in India (N = 2,065). Money increased effort over a psychological treatment by 27% in Hindi and 52% in English. These findings contradict the standard economic intuition that people from poorer countries should be more driven by money. Instead, they suggest that the market mentality of exchanging time and effort for material benefits is most prominent in WEIRD cultures.
Real-time single-proton counting with transmissive perovskite nanocrystal scintillators
Authors: Mi Zhaohong , Bian Hongyu , Yang Chengyuan , Dou Yanxin , Bettiol Andrew A. , Liu Xiaogang
Published: January 2024

High-sensitivity radiation detectors for energetic particles are essential for advanced applications in particle physics, astronomy and cancer therapy. Current particle detectors use bulk crystals, and thin-film organic scintillators have low light yields and limited radiation tolerance. Here we present transmissive thin scintillators made from CsPbBr3 nanocrystals, designed for real-time single-proton counting. These perovskite scintillators exhibit exceptional sensitivity, with a high light yield (~100,000 photons per MeV) when subjected to proton beams. This enhanced sensitivity is attributed to radiative emission from biexcitons generated through proton-induced upconversion and impact ionization. These scintillators can detect as few as seven protons per second, a sensitivity level far below the rates encountered in clinical settings. The combination of rapid response (~336 ps) and pronounced ionostability enables diverse applications, including single-proton tracing, patterned irradiation and super-resolution proton imaging. These advancements have the potential to improve proton dosimetry in proton therapy and radiography.
A palmitoyl transferase chemical–genetic system to map ZDHHC-specific S-acylation
Authors: Ocasio Cory A. , Baggelaar Marc P. , Sipthorp James , Losada de la Lastra Ana , Tavares Manuel , Volarić Jana , Soudy Christelle , Storck Elisabeth M. , Houghton Jack W. , Palma-Duran Susana A. , MacRae James I. , Tomić Goran , Carr Lotte , Downward Julian , Eggert Ulrike S. , Tate Edward W.
Published: January 2024

The 23 human zinc finger Asp-His-His-Cys motif-containing (ZDHHC) S-acyltransferases catalyze long-chain S-acylation at cysteine residues across an extensive network of hundreds of proteins important for normal physiology or dysregulated in disease. Here we present a technology to directly map the protein substrates of a specific ZDHHC at the whole-proteome level, in intact cells. Structure-guided engineering of paired ZDHHC ‘hole’ mutants and ‘bumped’ chemically tagged fatty acid probes enabled probe transfer to specific protein substrates with excellent selectivity over wild-type ZDHHCs. Chemical–genetic systems were exemplified for five human ZDHHCs (3, 7, 11, 15 and 20) and applied to generate de novo ZDHHC substrate profiles, identifying >300 substrates and S-acylation sites for new functionally diverse proteins across multiple cell lines. We expect that this platform will elucidate S-acylation biology for a wide range of models and organisms.
Engineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo
Authors: An Meirui , Raguram Aditya , Du Samuel W. , Banskota Samagya , Davis Jessie R. , Newby Gregory A. , Chen Paul Z. , Palczewski Krzysztof , Liu David R.
Published: January 2024

Prime editing enables precise installation of genomic substitutions, insertions and deletions in living systems. Efficient in vitro and in vivo delivery of prime editing components, however, remains a challenge. Here we report prime editor engineered virus-like particles (PE-eVLPs) that deliver prime editor proteins, prime editing guide RNAs and nicking single guide RNAs as transient ribonucleoprotein complexes. We systematically engineered v3 and v3b PE-eVLPs with 65- to 170-fold higher editing efficiency in human cells compared to a PE-eVLP construct based on our previously reported base editor eVLP architecture. In two mouse models of genetic blindness, single injections of v3 PE-eVLPs resulted in therapeutically relevant levels of prime editing in the retina, protein expression restoration and partial visual function rescue. Optimized PE-eVLPs support transient in vivo delivery of prime editor ribonucleoproteins, enhancing the potential safety of prime editing by reducing off-target editing and obviating the possibility of oncogenic transgene integration.
A pairwise cytokine code explains the organism-wide response to sepsis
Authors: Takahama Michihiro , Patil Ashwini , Richey Gabriella , Cipurko Denis , Johnson Katherine , Carbonetto Peter , Plaster Madison , Pandey Surya , Cheronis Katerina , Ueda Tatsuki , Gruenbaum Adam , Kawamoto Tadafumi , Stephens Matthew , Chevrier Nicolas
Published: January 2024

Sepsis is a systemic response to infection with life-threatening consequences. Our understanding of the molecular and cellular impact of sepsis across organs remains rudimentary. Here, we characterize the pathogenesis of sepsis by measuring dynamic changes in gene expression across organs. To pinpoint molecules controlling organ states in sepsis, we compare the effects of sepsis on organ gene expression to those of 6 singles and 15 pairs of recombinant cytokines. Strikingly, we find that the pairwise effects of tumor necrosis factor plus interleukin (IL)-18, interferon-gamma or IL-1β suffice to mirror the impact of sepsis across tissues. Mechanistically, we map the cellular effects of sepsis and cytokines by computing changes in the abundance of 195 cell types across 9 organs, which we validate by whole-mouse spatial profiling. Our work decodes the cytokine cacophony in sepsis into a pairwise cytokine message capturing the gene, cell and tissue responses of the host to the disease.
Unsupervised and supervised discovery of tissue cellular neighborhoods from cell phenotypes
Authors: Hu Yuxuan , Rong Jiazhen , Xu Yafei , Xie Runzhi , Peng Jacqueline , Gao Lin , Tan Kai
Published: January 2024

It is poorly understood how different cells in a tissue organize themselves to support tissue functions. We describe the CytoCommunity algorithm for the identification of tissue cellular neighborhoods (TCNs) based on cell phenotypes and their spatial distributions. CytoCommunity learns a mapping directly from the cell phenotype space to the TCN space using a graph neural network model without intermediate clustering of cell embeddings. By leveraging graph pooling, CytoCommunity enables de novo identification of condition-specific and predictive TCNs under the supervision of sample labels. Using several types of spatial omics data, we demonstrate that CytoCommunity can identify TCNs of variable sizes with substantial improvement over existing methods. By analyzing risk-stratified colorectal and breast cancer data, CytoCommunity revealed new granulocyte-enriched and cancer-associated fibroblast-enriched TCNs specific to high-risk tumors and altered interactions between neoplastic and immune or stromal cells within and between TCNs. CytoCommunity can perform unsupervised and supervised analyses of spatial omics maps and enable the discovery of condition-specific cell–cell communication patterns across spatial scales.
Unraveling the function and structure impact of deleterious missense SNPs in the human OX1R receptor by computational analysis
Authors: Farajzadeh-Dehkordi Mahvash , Mafakher Ladan , Harifi Abbas , Haghdoost-Yazdi Hashem , Piri Hossein , Rahmani Babak
Published: January 2024

The orexin/hypocretin receptor type 1 (OX1R) plays a crucial role in regulating various physiological functions, especially feeding behavior, addiction, and reward. Genetic variations in the OX1R have been associated with several neurological disorders. In this study, we utilized a combination of sequence and structure-based computational tools to identify the most deleterious missense single nucleotide polymorphisms (SNPs) in the OX1R gene. Our findings revealed four highly conserved and structurally destabilizing missense SNPs, namely R144C, I148N, S172W, and A297D, located in the GTP-binding domain. Molecular dynamics simulations analysis demonstrated that all four most detrimental mutant proteins altered the overall structural flexibility and dynamics of OX1R protein, resulting in significant changes in the structural organization and motion of the protein. These findings provide valuable insights into the impact of missense SNPs on OX1R function loss and their potential contribution to the development of neurological disorders, thereby guiding future research in this field.
Effect of wooden floorboards on the vibration of timber floor
Authors: Hassan Osama A. B.
Published: January 2024

This study is aimed at investigating those parameters related to timber flooring that can affect the acceptability of vibration behaviour of a timber floor in a residential building in view of the criteria stated in Eurocode EC5. The timber floor investigated is made of OSB/3 floorboards and timber joists. The parameters that are investigated in this study are thickness of flooring, floor joist span, joist spacing and connection of floorboards to the joists. In this context, two cases are considered. First: the flooring is nailed or screwed to the joists and no composite action or interaction is obtained between joists and floorboards. Second: the flooring is glued sufficiently to the joists and full interaction is obtained. The result suggests that glued floorboards perform much better with respect to natural frequency, static deflection and peak floor velocity than nailed or screwed floorboards. In almost all cases of glued floorboards, the result complies fully with the Eurocode 5 design vibration requirements. However, as floor lengths increase, the static deflection will increase beyond the allowable limit, especially for relatively thin floor panels and relatively widely spread joists. For both cases, increasing floorboards thickness and decreasing the joist span by adding more beams can yield even better results to satisfy the requirement of vibration comfort.
Distribution of global sea turtle nesting explained from regional-scale coastal characteristics
Authors: Christiaanse Jakob C. , Antolínez José A. A. , Luijendijk Arjen P. , Athanasiou Panagiotis , Duarte Carlos M. , Aarninkhof Stefan
Published: January 2024

Climate change and human activity threaten sea turtle nesting beaches through increased flooding and erosion. Understanding the environmental characteristics that enable nesting can aid to preserve and expand these habitats. While numerous local studies exist, a comprehensive global analysis of environmental influences on the distribution of sea turtle nesting habitats remains largely unexplored. Here, we relate the distribution of global sea turtle nesting to 22 coastal indicators, spanning hydrodynamic, atmospheric, geophysical, habitat, and human processes. Using state-of-the-art global datasets and a novel 50-km-resolution hexagonal coastline grid (Coastgons), we employ machine learning to identify spatially homogeneous patterns in the indicators and correlate these to the occurrence of nesting grounds. Our findings suggest sea surface temperature, tidal range, extreme surges, and proximity to coral and seagrass habitats significantly influence global nesting distribution. Low tidal ranges and low extreme surges appear to be particularly favorable for individual species, likely due to reduced nest flooding. Other indicators, previously reported as influential (e.g., precipitation and wind speed), were not as important in our global-scale analysis. Finally, we identify new, potentially suitable nesting regions for each species. On average, $$23\%$$

23
%

of global coastal regions between $$-39^\circ$$

-

39
∘

and $$48^\circ$$

48
∘

latitude could be suitable for nesting, while only $$7\%$$

7
%

is currently used by turtles, showing that the realized niche is significantly smaller than the fundamental niche, and that there is potential for sea turtles to expand their nesting habitat. Our results help identify suitable nesting conditions, quantify potential hazards to global nesting habitats, and lay a foundation for nature-based solutions to preserve and potentially expand these habitats.
Behavioural factors matter for the adoption of climate-smart agriculture
Authors: Tabe-Ojong Martin Paul Jr , Kedinga Marvin Ebot , Gebrekidan Bisrat Haile
Published: January 2024

Increasing agricultural productivity while ensuring environmental sustainability are two important targets in achieving the sustainable development goals under climatic shocks. In this regard, different climate-smart agricultural (CSA) practices have been recommended and promoted to meet these goals and targets. However, the adoption of these practices remains low and variable. For the most part, low adoption has been attributed to external factors. Behavioural and psychological factors also matter but have received little empirical and policy attention. In this study, we examine the relationship between aspirations, aspiration gaps, and the adoption of CSA practices such as crop rotation, intercropping, fallowing, and organic soil amendments. Employing parametric and non-parametric estimation techniques on a pooled farm household survey from Cameroon and Kenya, we show that aspirations are associated with the use of crop rotation and organic soil amendments. We also investigate the theorized non-monotonic inverse U-shaped relationship between aspiration gaps and investments. We find evidence of this relationship for the adoption of these CSA practices, suggesting an aspiration failure for smallholder farmers. These results imply that aspirations that are ahead but not too far ahead of the current state serve as the best incentives for stimulating the adoption of CSA practices. Employing the multivariate probit model, we further highlight interdependencies in the use of these CSA practices. Specifically, we underscore significant complementarities, suggesting the bundled use of these practices. Overall, the analysis demonstrates that aspirations matter for farmer decision-making with many implications for agricultural, food, and environmental policies.
Analysis of compression damage pattern and strength influencing factors in graphite-tailing-filled soilbags
Authors: Gao Jian , Du Changbo , Xu Zhan , Yi Fu
Published: January 2024

To realize the resourceful use of soilbags filled with graphite tailings, their load-bearing and deformation characteristics must be fully understood. In this study, the following results were obtained by performing geometric testing of water-filled sealing bags and uniaxial compression tests of soilbags filled with graphite tailings. The volume of the soilbag expressed in rectangular form was approximately 0.773 times the actual volume. The types of compression damage to soilbags can be defined as surface damage and overall damage. The surface damage load increases with decreasing filling density and decreases with decreasing soilbag size. Moreover, the higher the tensile capacity of the soilbag material and the lower the friction between the soilbags, the greater the surface damage load. The overall damage load increased with an increase in the tensile strength of the soilbag material and decreased with an increase in the degree of filling; the overall damage load was greater for large-sized soilbags at high degrees of filling. Thus, the existing theoretical calculation method cannot accurately calculate the damage load of soilbags filled with graphite tailings, and the test results deviate from the theoretical calculation results, with the latter showing an increasing damage load with a decreasing filling degree.
Dosimetric characterization of a novel UHDR megavoltage X-ray source for FLASH radiobiological experiments
Authors: Esplen Nolan , Egoriti Luca , Planche Thomas , Rädel Stephanie , Koay Hui-Wen , Humphries Brandon , Ren Xi , Ford Nancy , Hoehr Cornelia , Gottberg Alexander , Bazalova-Carter Magdalena
Published: January 2024

A first irradiation platform capable of delivering 10 MV X-ray beams at ultra-high dose rates (UHDR) has been developed and characterized for FLASH radiobiological research at TRIUMF. Delivery of both UHDR (FLASH mode) and low dose-rate conventional (CONV mode) irradiations was demonstrated using a common source and experimental setup. Dose rates were calculated using film dosimetry and a non-intercepting beam monitoring device; mean values for a 100 μA pulse (peak) current were nominally 82.6 and 4.40 × 10−2 Gy/s for UHDR and CONV modes, respectively. The field size for which > 40 Gy/s could be achieved exceeded 1 cm down to a depth of 4.1 cm, suitable for total lung irradiations in mouse models. The calculated delivery metrics were used to inform subsequent pre-clinical treatments. Four groups of 6 healthy male C57Bl/6J mice were treated using thoracic irradiations to target doses of either 15 or 30 Gy using both FLASH and CONV modes. Administration of UHDR X-ray irradiation to healthy mouse models was demonstrated for the first time at the clinically-relevant beam energy of 10 MV.
Subcortical responses to music and speech are alike while cortical responses diverge
Authors: Shan Tong , Cappelloni Madeline S. , Maddox Ross K.
Published: January 2024

Music and speech are encountered daily and are unique to human beings. Both are transformed by the auditory pathway from an initial acoustical encoding to higher level cognition. Studies of cortex have revealed distinct brain responses to music and speech, but differences may emerge in the cortex or may be inherited from different subcortical encoding. In the first part of this study, we derived the human auditory brainstem response (ABR), a measure of subcortical encoding, to recorded music and speech using two analysis methods. The first method, described previously and acoustically based, yielded very different ABRs between the two sound classes. The second method, however, developed here and based on a physiological model of the auditory periphery, gave highly correlated responses to music and speech. We determined the superiority of the second method through several metrics, suggesting there is no appreciable impact of stimulus class (i.e., music vs speech) on the way stimulus acoustics are encoded subcortically. In this study’s second part, we considered the cortex. Our new analysis method resulted in cortical music and speech responses becoming more similar but with remaining differences. The subcortical and cortical results taken together suggest that there is evidence for stimulus-class dependent processing of music and speech at the cortical but not subcortical level.
Dietary oleic acid intake increases the proportion of type 1 and 2X muscle fibers in mice
Authors: Komiya Yusuke , Iseki Shugo , Ochiai Masaru , Takahashi Yume , Yokoyama Issei , Suzuki Takahiro , Tatsumi Ryuichi , Sawano Shoko , Mizunoya Wataru , Arihara Keizo
Published: January 2024

Skeletal muscle is one of the largest metabolic tissues in mammals and is composed of four different types of muscle fibers (types 1, 2A, 2X, and 2B); however, type 2B is absent in humans. Given that slow-twitch fibers are superior to fast-twitch fibers in terms of oxidative metabolism and are rich in mitochondria, shift of muscle fiber types in direction towards slower fiber types improves metabolic disorders and endurance capacity. We previously had reported that oleic acid supplementation increases type 1 fiber formation in C2C12 myotubes; however, its function still remains unclear. This study aimed to determine the effect of oleic acid on the muscle fiber types and endurance capacity. An in vivo mouse model was used, and mice were fed a 10% oleic acid diet for 4 weeks. Two different skeletal muscles, slow soleus muscle with the predominance of slow-twitch fibers and fast extensor digitorum longus (EDL) muscle with the predominance of fast-twitch fibers, were used. We found that dietary oleic acid intake improved running endurance and altered fiber type composition of muscles, the proportion of type 1 and 2X fibers increased in the soleus muscle and type 2X increased in the EDL muscle. The fiber type shift in the EDL muscle was accompanied by an increased muscle TAG content. In addition, blood triacylglycerol (TAG) and non-esterified fatty acid levels decreased during exercise. These changes suggested that lipid utilization as an energy substrate was enhanced by oleic acid. Increased proliferator-activated receptor γ coactivator-1β protein levels were observed in the EDL muscle, which potentially enhanced the fiber type transitions towards type 2X and muscle TAG content. In conclusion, dietary oleic acid intake improved running endurance with the changes of muscle fiber type shares in mice. This study elucidated a novel functionality of oleic acid in skeletal muscle fiber types. Further studies are required to elucidate the underlying mechanisms. Our findings have the potential to contribute to the field of health and sports science through nutritional approaches, such as the development of supplements aimed at improving muscle function.
Named entity recognition in aerospace based on multi-feature fusion transformer
Authors: Chu Jing , Liu Yumeng , Yue Qi , Zheng Zixuan , Han Xiaokai
Published: January 2024

In recent years, along with the rapid development in the domain of artificial intelligence and aerospace, aerospace combined with artificial intelligence is the future trend. As an important basic tool for Natural Language Processing, Named Entity Recognition technology can help obtain key relevant knowledge from a large number of aerospace data. In this paper, we produced an aerospace domain entity recognition dataset containing 30 k sentences in Chinese and developed a named entity recognition model that is Multi-Feature Fusion Transformer (MFT), which combines features such as words and radicals to enhance the semantic information of the sentences. In our model, the double Feed-forward Neural Network is exploited as well to ensure MFT better performance. We use our aerospace dataset to train MFT. The experimental results show that MFT has great entity recognition performance, and the F1 score on aerospace dataset is 86.10%.