bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non‐Linear Climate Change Impacts on Crop Yields May Mislead Stakeholders
Authors: Ruane Alex C. , Phillips Meridel , Jägermeyr Jonas , Müller Christoph 
Published: April 2024

AbstractWe utilize a global warming level (GWL) lens to evaluate global and regional patterns of agricultural impacts as global surface temperature increases, providing a unique perspective on the experience of stakeholders with continued warming in the 21st century. We analyze crop productivity outputs from 11 crop models simulating 5 climate models under 3 emissions scenarios across 4 crops within the AgMIP/ISIMIP Phase 3 ensemble. We categorize regional productivity changes (without adaptation) into 9 characteristic climate change response patterns, identifying consistent increases and decreases as well as non‐linear (peak or dip) responses indicative of inflection points reversing trends as GWLs increase. Many maize regions and pockets of wheat, rice and soybean show peak decrease patterns where initial increases may lull stakeholders into complacency or maladaptation before productivity shifts to losses at higher GWLs. Although the GWL perspective has proven useful in connecting diverse climate models and emissions scenarios, we identify multiple pitfalls that recommend proceeding with caution when applying this approach to climate impacts. Chief among these is that carbon dioxide (CO2) concentrations at any GWL depend on a climate model's transient climate response (TCR). Higher CO2 concentrations generally benefit crop productivity, so this leads to more pessimistic agricultural projections for so‐called “hot” models and can skew multi‐model ensemble results as models with high TCR are disproportionately likely to reach higher GWLs. While there are strong connections between many climatic impact‐drivers and GWLs, vulnerability and exposure components of food system risk are strongly dependent on development pathways.
Fluorescence in situ hybridization reveals the evolutionary biology of minor clone of gain/amp(1q) in multiple myeloma
Authors: Cui Jian , Liu Yuntong , Lv Rui , Yan Wenqiang , Xu Jingyu , Li Lingna , Du Chenxing , Yu Tengteng , Zhang Shuaishuai , Deng Shuhui , Sui Weiwei , Hao Mu , Yi Shuhua , Zou Dehui , Qiu Lugui , Xu Yan , An Gang 
Published: April 2024

AbstractGrowing evidence suggests that gain or amplification [gain/amp(1q)] accumulates during disease progression of multiple myeloma (MM). Previous investigations have indicated that small gain/amp(1q) subclones present at the time of diagnosis may evolve into dominant clones upon MM relapse. However, the influence of a minor clone of gain/amp(1q) on MM survival, as well as the correlation between different clonal sizes of gain/amp(1q) and the chromosomal instability (CIN) of MM, remains poorly understood. In this study, we analyzed fluorescence in situ hybridization (FISH) results of 998 newly diagnosed MM (NDMM) patients. 513 patients were detected with gain/amp(1q) at diagnosis. Among these 513 patients, 55 had a minor clone (≤20%) of gain/amp(1q). Patients with a minor clone of gain/amp(1q) displayed similar survival outcomes compared to those without gain/amp(1q). Further analysis demonstrated patients with a minor clone of gain/amp(1q) exhibited a clonal architecture similar to those without gain/amp(1q). Lastly, our results showed a significant increase in the clonal size of the minor clone of gain/amp(1q), frequently observed in MM. These findings suggested that a minor clone of gain/amp(1q) might represent an earlier stage in the pathogenesis of gain/amp(1q) and propose a “two-step” process in the clonal size changes of gain/amp(1q) in MM.
RUVBL1 ubiquitination by DTL promotes RUVBL1/2-β-catenin-mediated transcriptional regulation of NHEJ pathway and enhances radiation resistance in breast cancer
Authors: Tian Jie , Wen Mingxin , Gao Peng , Feng Maoxiao , Wei Guangwei 
Published: April 2024

AbstractRadiotherapy effectiveness in breast cancer is limited by radioresistance. Nevertheless, the mechanisms behind radioresistance are not yet fully understood. RUVBL1 and RUVBL2, referred to as RUVBL1/2, are crucial AAA+ ATPases that act as co-chaperones and are connected to cancer. Our research revealed that RUVBL1, also known as pontin/TIP49, is excessively expressed in MMTV-PyMT mouse models undergoing radiotherapy, which is considered a murine spontaneous breast-tumor model. Our findings suggest that RUVBL1 enhances DNA damage repair and radioresistance in breast cancer cells both in vitro and in vivo. Mechanistically, we discovered that DTL, also known as CDT2 or DCAF2, which is a substrate adapter protein of CRL4, promotes the ubiquitination of RUVBL1 and facilitates its binding to RUVBL2 and transcription cofactor β-catenin. This interaction, in turn, attenuates its binding to acetyltransferase Tat-interacting protein 60 (TIP60), a comodulator of nuclear receptors. Subsequently, ubiquitinated RUVBL1 promotes the transcriptional regulation of RUVBL1/2-β-catenin on genes associated with the non-homologous end-joining (NHEJ) repair pathway. This process also attenuates TIP60-mediated H4K16 acetylation and the homologous recombination (HR) repair process. Expanding upon the prior study’s discoveries, we exhibited that the ubiquitination of RUVBL1 by DTL advances the interosculation of RUVBL1/2-β-catenin. And, it then regulates the transcription of NHEJ repair pathway protein. Resulting in an elevated resistance of breast cancer cells to radiation therapy. From the aforementioned, it is evident that targeting DTL-RUVBL1/2-β-catenin provides a potential radiosensitization approach when treating breast cancer.
Kinetic trapping organizes actin filaments within liquid-like protein droplets
Authors: Chandrasekaran Aravind , Graham Kristin , Stachowiak Jeanne C. , Rangamani Padmini 
Published: April 2024

AbstractSeveral actin-binding proteins (ABPs) phase separate to form condensates capable of curating the actin network shapes. Here, we use computational modeling to understand the principles of actin network organization within VASP condensate droplets. Our simulations reveal that the different actin shapes, namely shells, rings, and mixture states are highly dependent on the kinetics of VASP-actin interactions, suggesting that they arise from kinetic trapping. Specifically, we show that reducing the residence time of VASP on actin filaments reduces degree of bundling, thereby promoting assembly of shells rather than rings. We validate the model predictions experimentally using a VASP-mutant with decreased bundling capability. Finally, we investigate the ring opening within deformed droplets and found that the sphere-to-ellipsoid transition is favored under a wide range of filament lengths while the ellipsoid-to-rod transition is only permitted when filaments have a specific range of lengths. Our findings highlight key mechanisms of actin organization within phase-separated ABPs.
Introgression and disruption of migration routes have shaped the genetic integrity of wildebeest populations
Authors: Liu Xiaodong , Lin Long , Sinding Mikkel-Holger S. , Bertola Laura D. , Hanghøj Kristian , Quinn Liam , Garcia-Erill Genís , Rasmussen Malthe Sebro , Schubert Mikkel , Pečnerová Patrícia , Balboa Renzo F. , Li Zilong , Heaton Michael P. , Smith Timothy P. L. , Pinto Rui Resende , Wang Xi , Kuja Josiah , Brüniche-Olsen Anna , Meisner Jonas , Santander Cindy G. , Ogutu Joseph O. , Masembe Charles , da Fonseca Rute R. , Muwanika Vincent , Siegismund Hans R. , Albrechtsen Anders , Moltke Ida , Heller Rasmus 
Published: April 2024

AbstractThe blue wildebeest (Connochaetes taurinus) is a keystone species in savanna ecosystems from southern to eastern Africa, and is well known for its spectacular migrations and locally extreme abundance. In contrast, the black wildebeest (C. gnou) is endemic to southern Africa, barely escaped extinction in the 1900s and is feared to be in danger of genetic swamping from the blue wildebeest. Despite the ecological importance of the wildebeest, there is a lack of understanding of how its unique migratory ecology has affected its gene flow, genetic structure and phylogeography. Here, we analyze whole genomes from 121 blue and 22 black wildebeest across the genus’ range. We find discrete genetic structure consistent with the morphologically defined subspecies. Unexpectedly, our analyses reveal no signs of recent interspecific admixture, but rather a late Pleistocene introgression of black wildebeest into the southern blue wildebeest populations. Finally, we find that migratory blue wildebeest populations exhibit a combination of long-range panmixia, higher genetic diversity and lower inbreeding levels compared to neighboring populations whose migration has recently been disrupted. These findings provide crucial insights into the evolutionary history of the wildebeest, and tangible genetic evidence for the negative effects of anthropogenic activities on highly migratory ungulates.
Precision ion separation via self-assembled channels
Authors: Hong Shanshan , Di Vincenzo Maria , Tiraferri Alberto , Bertozzi Erica , Górecki Radosław , Davaasuren Bambar , Li Xiang , Nunes Suzana P. 
Published: April 2024

AbstractSelective nanofiltration membranes with accurate molecular sieving offer a solution to recover rare metals and other valuable elements from brines. However, the development of membranes with precise sub-nanometer pores is challenging. Here, we report a scalable approach for membrane fabrication in which functionalized macrocycles are seamlessly oriented via supramolecular interactions during the interfacial polycondensation on a polyacrylonitrile support layer. The rational incorporation of macrocycles enables the formation of nanofilms with self-assembled channels holding precise molecular sieving capabilities and a threshold of 6.6 ångström, which corresponds to the macrocycle cavity size. The resulting membranes provide a 100-fold increase in selectivity for Li+/Mg2+ separation, outperforming commercially available and state-of-the-art nanocomposite membranes for lithium recovery. Their performance is further assessed in high-recovery tests under realistic nanofiltration conditions using simulated brines or concentrated seawater with various Li+ levels and demonstrates their remarkable potential in ion separation and Li+ recovery applications.
Collective relational inference for learning heterogeneous interactions
Authors: Han Zhichao , Fink Olga , Kammer David S. 
Published: April 2024

AbstractInteracting systems are ubiquitous in nature and engineering, ranging from particle dynamics in physics to functionally connected brain regions. Revealing interaction laws is of fundamental importance but also particularly challenging due to underlying configurational complexities. These challenges become exacerbated for heterogeneous systems that are prevalent in reality, where multiple interaction types coexist simultaneously and relational inference is required. Here, we propose a probabilistic method for relational inference, which possesses two distinctive characteristics compared to existing methods. First, it infers the interaction types of different edges collectively by explicitly encoding the correlation among incoming interactions with a joint distribution, and second, it allows handling systems with variable topological structure over time. We evaluate the proposed methodology across several benchmark datasets and demonstrate that it outperforms existing methods in accurately inferring interaction types. The developed methodology constitutes a key element for understanding interacting systems and may find application in graph structure learning.
Tension activation of mechanosensitive two-pore domain K+ channels TRAAK, TREK-1, and TREK-2
Authors: Sorum Ben , Docter Trevor , Panico Vincent , Rietmeijer Robert A. , Brohawn Stephen G. 
Published: April 2024

AbstractTRAAK, TREK-1, and TREK-2 are mechanosensitive two-pore domain K+ (K2P) channels that contribute to action potential propagation, sensory transduction, and muscle contraction. While structural and functional studies have led to models that explain their mechanosensitivity, we lack a quantitative understanding of channel activation by membrane tension. Here, we define the tension response of mechanosensitive K2Ps using patch-clamp recording and imaging. All are low-threshold mechanosensitive channels (T10%/50% 0.6-2.7 / 4.4-6.4 mN/m) with distinct response profiles. TRAAK is most sensitive, TREK-1 intermediate, and TREK-2 least sensitive. TRAAK and TREK-1 are activated broadly over a range encompassing nearly all physiologically relevant tensions. TREK-2, in contrast, activates over a narrower range like mechanosensitive channels Piezo1, MscS, and MscL. We further show that low-frequency, low-intensity focused ultrasound increases membrane tension to activate TRAAK and MscS. This work provides insight into tension gating of mechanosensitive K2Ps relevant to understanding their physiological roles and potential applications for ultrasonic neuromodulation.
PRPF8-mediated dysregulation of hBrr2 helicase disrupts human spliceosome kinetics and 5´-splice-site selection causing tissue-specific defects
Authors: Atkinson Robert , Georgiou Maria , Yang Chunbo , Szymanska Katarzyna , Lahat Albert , Vasconcelos Elton J. R. , Ji Yanlong , Moya Molina Marina , Collin Joseph , Queen Rachel , Dorgau Birthe , Watson Avril , Kurzawa-Akanbi Marzena , Laws Ross , Saxena Abhijit , Shyan Beh Chia , Siachisumo Chileleko , Goertler Franziska , Karwatka Magdalena , Davey Tracey , Inglehearn Chris F. , McKibbin Martin , Lührmann Reinhard , Steel David H. , Elliott David J. , Armstrong Lyle , Urlaub Henning , Ali Robin R. , Grellscheid Sushma-Nagaraja , Johnson Colin A. , Mozaffari-Jovin Sina , Lako Majlinda 
Published: April 2024

AbstractThe carboxy-terminus of the spliceosomal protein PRPF8, which regulates the RNA helicase Brr2, is a hotspot for mutations causing retinitis pigmentosa-type 13, with unclear role in human splicing and tissue-specificity mechanism. We used patient induced pluripotent stem cells-derived cells, carrying the heterozygous PRPF8 c.6926 A > C (p.H2309P) mutation to demonstrate retinal-specific endophenotypes comprising photoreceptor loss, apical-basal polarity and ciliary defects. Comprehensive molecular, transcriptomic, and proteomic analyses revealed a role of the PRPF8/Brr2 regulation in 5’-splice site (5’SS) selection by spliceosomes, for which disruption impaired alternative splicing and weak/suboptimal 5’SS selection, and enhanced cryptic splicing, predominantly in ciliary and retinal-specific transcripts. Altered splicing efficiency, nuclear speckles organisation, and PRPF8 interaction with U6 snRNA, caused accumulation of active spliceosomes and poly(A)+ mRNAs in unique splicing clusters located at the nuclear periphery of photoreceptors. Collectively these elucidate the role of PRPF8/Brr2 regulatory mechanisms in splicing and the molecular basis of retinal disease, informing therapeutic approaches.
Probing the tunable multi-cone band structure in Bernal bilayer graphene
Authors: Seiler Anna M. , Jacobsen Nils , Statz Martin , Fernandez Noelia , Falorsi Francesca , Watanabe Kenji , Taniguchi Takashi , Dong Zhiyu , Levitov Leonid S. , Weitz R. Thomas 
Published: April 2024

AbstractBernal bilayer graphene (BLG) offers a highly flexible platform for tuning the band structure, featuring two distinct regimes. One is a tunable band gap induced by large displacement fields. Another is a gapless metallic band occurring at low fields, featuring rich fine structure consisting of four linearly dispersing Dirac cones and van Hove singularities. Even though BLG has been extensively studied experimentally, the evidence of this band structure is still elusive, likely due to insufficient energy resolution. Here, we use Landau levels as markers of the energy dispersion and analyze the Landau level spectrum in a regime where the cyclotron orbits of electrons or holes in momentum space are small enough to resolve the distinct mini Dirac cones. We identify the presence of four Dirac cones and map out topological transitions induced by displacement field. By clarifying the low-energy properties of BLG bands, these findings provide a valuable addition to the toolkit for graphene electronics.
A hippocampus-accumbens code guides goal-directed appetitive behavior
Authors: Barnstedt Oliver , Mocellin Petra , Remy Stefan 
Published: April 2024

AbstractThe dorsal hippocampus (dHPC) is a key brain region for the expression of spatial memories, such as navigating towards a learned reward location. The nucleus accumbens (NAc) is a prominent projection target of dHPC and implicated in value-based action selection. Yet, the contents of the dHPC→NAc information stream and their acute role in behavior remain largely unknown. Here, we found that optogenetic stimulation of the dHPC→NAc pathway while mice navigated towards a learned reward location was both necessary and sufficient for spatial memory-related appetitive behaviors. To understand the task-relevant coding properties of individual NAc-projecting hippocampal neurons (dHPC→NAc), we used in vivo dual-color two-photon imaging. In contrast to other dHPC neurons, the dHPC→NAc subpopulation contained more place cells, with enriched spatial tuning properties. This subpopulation also showed enhanced coding of non-spatial task-relevant behaviors such as deceleration and appetitive licking. A generalized linear model revealed enhanced conjunctive coding in dHPC→NAc neurons which improved the identification of the reward zone. We propose that dHPC routes specific reward-related spatial and behavioral state information to guide NAc action selection.
A facile one step route that introduces functionality to polymer powders for laser sintering
Authors: Krumins Eduards , Crawford Liam A. , Rogers David M. , Machado Fabricio , Taresco Vincenzo , East Mark , Irving Samuel H. , Fowler Harriet R. , Jiang Long , Starr Nichola , Parmenter Christopher D. J. , Kortsen Kristoffer , Cuzzucoli Crucitti Valentina , Avery Simon V. , Tuck Christopher J. , Howdle Steven M. 
Published: April 2024

AbstractLaser Sintering (LS) is a type of Additive Manufacturing (AM) exploiting laser processing of polymeric particles to produce 3D objects. Because of its ease of processability and thermo-physical properties, polyamide-12 (PA-12) represents ~95% of the polymeric materials used in LS. This constrains the functionality of the items produced, including limited available colours. Moreover, PA-12 objects tend to biofoul in wet environments. Therefore, a key challenge is to develop an inexpensive route to introduce desirable functionality to PA-12. We report a facile, clean, and scalable approach to modification of PA-12, exploiting supercritical carbon dioxide (scCO2) and free radical polymerizations to yield functionalised PA-12 materials. These can be easily printed using commercial apparatus. We demonstrate the potential by creating coloured PA-12 materials and show that the same approach can be utilized to create anti-biofouling objects. Our approach to functionalise materials could open significant new applications for AM.
Epidemiological, clinical, and genomic landscape of coccidioidomycosis in northeastern Brazil
Authors: Eulálio Kelsen Dantas , Kollath Daniel R. , Martins Liline Maria Soares , Filho Antonio de Deus , Cavalcanti Maria do Amparo Salmito , Moreira Lucas Machado , Tenório Bernardo Guerra , Alves Lucas Gomes de Brito , Yamauchi Danielle , Barrozo Ligia Vizeu , Thompson III George R. , Nacher Mathieu , Stajich Jason E. , Benard Gil , Bagagli Eduardo , Felipe Maria Sueli Soares , Barker Bridget M. , Trilles Luciana , Teixeira Marcus de Melo 
Published: April 2024

AbstractCoccidioidomycosis, listed as a priority mycosis by the WHO, is endemic in the United States but often overlooked in Central and South America. Employing a multi-institutional approach, we investigate how disease characteristics, pathogen genetic variation, and environmental factors impact coccidioidomycosis epidemiology and outcomes in South America. We identified 292 cases (1978–2021) and 42 outbreaks in Piauí and Maranhão states, Brazil, the largest series outside the US/Mexico epidemic zone. The male-to-female ratio was 57.4:1 and the most common activity was armadillo hunting (91.1%) 4 to 30 days before symptom onset. Most patients (92.8%) exhibited typical acute pulmonary disease, with cough (93%), fever (90%), and chest pain (77%) as predominant symptoms. The case fatality rate was 8%. Our negative binomial regression model indicates that reduced precipitation levels in the current (p = 0.015) and preceding year (p = 0.001) predict heightened incidence. Unlike other hotspots, acidic soil characterizes this region. Brazilian strains differ genomically from other C. posadasii lineages. Northeastern Brazil presents a distinctive coccidioidomycosis profile, with armadillo hunters facing elevated risks. Low annual rainfall emerges as a key factor in increasing cases. A unique C. posadasii lineage in Brazil suggests potential differences in environmental, virulence, and/or pathogenesis traits compared to other Coccidioides genotypes.
Annelid adult cell type diversity and their pluripotent cellular origins
Authors: Álvarez-Campos Patricia , García-Castro Helena , Emili Elena , Pérez-Posada Alberto , del Olmo Irene , Peron Sophie , Salamanca-Díaz David A. , Mason Vincent , Metzger Bria , Bely Alexandra E. , Kenny Nathan J. , Özpolat B. Duygu , Solana Jordi 
Published: April 2024

AbstractMany annelids can regenerate missing body parts or reproduce asexually, generating all cell types in adult stages. However, the putative adult stem cell populations involved in these processes, and the diversity of cell types generated by them, are still unknown. To address this, we recover 75,218 single cell transcriptomes of the highly regenerative and asexually-reproducing annelid Pristina leidyi. Our results uncover a rich cell type diversity including annelid specific types as well as novel types. Moreover, we characterise transcription factors and gene networks that are expressed specifically in these populations. Finally, we uncover a broadly abundant cluster of putative stem cells with a pluripotent signature. This population expresses well-known stem cell markers such as vasa, piwi and nanos homologues, but also shows heterogeneous expression of differentiated cell markers and their transcription factors. We find conserved expression of pluripotency regulators, including multiple chromatin remodelling and epigenetic factors, in piwi+ cells. Finally, lineage reconstruction analyses reveal computational differentiation trajectories from piwi+ cells to diverse adult types. Our data reveal the cell type diversity of adult annelids by single cell transcriptomics and suggest that a piwi+ cell population with a pluripotent stem cell signature is associated with adult cell type differentiation.
Systematic investigation of chemo-immunotherapy synergism to shift anti-PD-1 resistance in cancer
Authors: Wang Yue , Pattarayan Dhamotharan , Huang Haozhe , Zhao Yueshan , Li Sihan , Wang Yifei , Zhang Min , Li Song , Yang Da 
Published: April 2024

AbstractChemo-immunotherapy combinations have been regarded as one of the most practical ways to improve immunotherapy response in cancer patients. In this study, we integrate the transcriptomics data from anti-PD-1-treated tumors and compound-treated cancer cell lines to systematically screen for chemo-immunotherapy synergisms in silico. Through analyzing anti-PD-1 induced expression changes in patient tumors, we develop a shift ability score to measure if a chemotherapy or a small molecule inhibitor treatment can shift anti-PD-1 resistance in tumor cells. By applying shift ability analysis to 41,321 compounds and 16,853 shRNA treated cancer cell lines transcriptomic data, we characterize the landscape of chemo-immunotherapy synergism and experimentally validated a mitochondrial RNA-dependent mechanism for drug-induced immune activation in tumor. Our study represents an effort to mechanistically characterize chemo-immunotherapy synergism and will facilitate future pre-clinical and clinical studies.