bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractIn 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

AbstractMany 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

AbstractTopology 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

AbstractAurora 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

AbstractAlthough 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

AbstractMotivating 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

AbstractHigh-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

AbstractThe 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

AbstractPrime 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

AbstractSepsis 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

AbstractIt 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

AbstractThe 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

AbstractThis 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

AbstractClimate 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

AbstractIncreasing 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.