bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of immune checkpoint inhibitors: insights into the regulation of circular RNAS involved in cancer hallmarks
Authors: Meng Lingjiao , Wu Haotian , Wu Jiaxiang , Ding Ping’an , He Jinchen , Sang Meixiang , Liu Lihua 
Published: January 2024

AbstractCurrent treatment strategies for cancer, especially advanced cancer, are limited and unsatisfactory. One of the most substantial advances in cancer therapy, in the last decades, was the discovery of a new layer of immunotherapy approach, immune checkpoint inhibitors (ICIs), which can specifically activate immune cells by targeting immune checkpoints. Immune checkpoints are a type of immunosuppressive molecules expressed on immune cells, which can regulate the degree of immune activation and avoid autoimmune responses. ICIs, such as anti-PD-1/PD-L1 drugs, has shown inspiring efficacy and broad applicability across various cancers. Unfortunately, not all cancer patients benefit remarkably from ICIs, and the overall response rates to ICIs remain relatively low for most cancer types. Moreover, the primary and acquired resistance to ICIs pose serious challenges to the clinical application of cancer immunotherapy. Thus, a deeper understanding of the molecular biological properties and regulatory mechanisms of immune checkpoints is urgently needed to improve clinical options for current therapies. Recently, circular RNAs (circRNAs) have attracted increasing attention, not only due to their involvement in various aspects of cancer hallmarks, but also for their impact on immune checkpoints in shaping the tumor immune microenvironment. In this review, we systematically summarize the current status of immune checkpoints in cancer and the existing regulatory roles of circRNAs on immune checkpoints. Meanwhile, we also aim to settle the issue in an evidence-oriented manner that circRNAs involved in cancer hallmarks regulate the effects and resistance of ICIs by targeting immune checkpoints.
Hydrogenative degradation of PEG-functionalized lignin
Authors: Kusumoto Shuhei , Higashi Takuya , Matsumoto Yusuke , Yamada Tatsuhiko , Nozaki Kyoko 
Published: January 2024

AbstractThe valorization of lignin to value-added basic chemicals is one of the most important technologies for efficient carbon recycling. While many catalytic systems have been developed for cleavage of monolignol linkages, especially for β-O-4 structures, the low solubility of lignin, which originates from its complicated polymeric structure, often makes it difficult to apply these catalytic process to degradation of real lignin-derived materials. Here, we investigated the degradation of poly(ethylene glycol)-modified lignin with transition metal complexes. Monolignols (4-methyl, 4-ethyl- and 4-propyl-guaiacol) were obtained as the degradation products. Although low solubility after detachment of the PEG moiety hampered efficient degradation, the addition of PEG for in situ protection of the hydroxy group was effective in maintaining the lignin solubility and improving the monolignol yields.
DCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance
Authors: Schröder Martin , Renatus Martin , Liang Xiaoyou , Meili Fabian , Zoller Thomas , Ferrand Sandrine , Gauter Francois , Li Xiaoyan , Sigoillot Frederic , Gleim Scott , Stachyra Therese-Marie , Thomas Jason R. , Begue Damien , Khoshouei Maryam , Lefeuvre Peggy , Andraos-Rey Rita , Chung BoYee , Ma Renate , Pinch Benika , Hofmann Andreas , Schirle Markus , Schmiedeberg Niko , Imbach Patricia , Gorses Delphine , Calkins Keith , Bauer-Probst Beatrice , Maschlej Magdalena , Niederst Matt , Maher Rob , Henault Martin , Alford John , Ahrne Erik , Tordella Luca , Hollingworth Greg , Thomä Nicolas H. , Vulpetti Anna , Radimerski Thomas , Holzer Philipp , Carbonneau Seth , Thoma Claudio R. 
Published: January 2024

AbstractTargeted protein degradation (TPD) mediates protein level through small molecule induced redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal degradation. TPD has recently emerged as a key modality in drug discovery. So far only a few ligases have been utilized for TPD. Interestingly, the workhorse ligase CRBN has been observed to be downregulated in settings of resistance to immunomodulatory inhibitory drugs (IMiDs). Here we show that the essential E3 ligase receptor DCAF1 can be harnessed for TPD utilizing a selective, non-covalent DCAF1 binder. We confirm that this binder can be functionalized into an efficient DCAF1-BRD9 PROTAC. Chemical and genetic rescue experiments validate specific degradation via the CRL4DCAF1 E3 ligase. Additionally, a dasatinib-based DCAF1 PROTAC successfully degrades cytosolic and membrane-bound tyrosine kinases. A potent and selective DCAF1-BTK-PROTAC (DBt-10) degrades BTK in cells with acquired resistance to CRBN-BTK-PROTACs while the DCAF1-BRD9 PROTAC (DBr-1) provides an alternative strategy to tackle intrinsic resistance to VHL-degrader, highlighting DCAF1-PROTACS as a promising strategy to overcome ligase mediated resistance in clinical settings.
Oligodendrocyte calcium signaling promotes actin-dependent myelin sheath extension
Authors: Iyer Manasi , Kantarci Husniye , Cooper Madeline H. , Ambiel Nicholas , Novak Sammy Weiser , Andrade Leonardo R. , Lam Mable , Jones Graham , Münch Alexandra E. , Yu Xinzhu , Khakh Baljit S. , Manor Uri , Zuchero J. Bradley 
Published: January 2024

AbstractMyelin is essential for rapid nerve signaling and is increasingly found to play important roles in learning and in diverse diseases of the CNS. Morphological parameters of myelin such as sheath length are thought to precisely tune conduction velocity, but the mechanisms controlling sheath morphology are poorly understood. Local calcium signaling has been observed in nascent myelin sheaths and can be modulated by neuronal activity. However, the role of calcium signaling in sheath formation remains incompletely understood. Here, we use genetic tools to attenuate oligodendrocyte calcium signaling during myelination in the developing mouse CNS. Surprisingly, genetic calcium attenuation does not grossly affect the number of myelinated axons or myelin thickness. Instead, calcium attenuation causes myelination defects resulting in shorter, dysmorphic sheaths. Mechanistically, calcium attenuation reduces actin filaments in oligodendrocytes, and an intact actin cytoskeleton is necessary and sufficient to achieve accurate myelin morphology. Together, our work reveals a cellular mechanism required for accurate CNS myelin formation and may provide mechanistic insight into how oligodendrocytes respond to neuronal activity to sculpt and refine myelin sheaths.
Improving deep neural network generalization and robustness to background bias via layer-wise relevance propagation optimization
Authors: Bassi Pedro R. A. S. , Dertkigil Sergio S. J. , Cavalli Andrea 
Published: January 2024

AbstractFeatures in images’ backgrounds can spuriously correlate with the images’ classes, representing background bias. They can influence the classifier’s decisions, causing shortcut learning (Clever Hans effect). The phenomenon generates deep neural networks (DNNs) that perform well on standard evaluation datasets but generalize poorly to real-world data. Layer-wise Relevance Propagation (LRP) explains DNNs’ decisions. Here, we show that the optimization of LRP heatmaps can minimize the background bias influence on deep classifiers, hindering shortcut learning. By not increasing run-time computational cost, the approach is light and fast. Furthermore, it applies to virtually any classification architecture. After injecting synthetic bias in images’ backgrounds, we compared our approach (dubbed ISNet) to eight state-of-the-art DNNs, quantitatively demonstrating its superior robustness to background bias. Mixed datasets are common for COVID-19 and tuberculosis classification with chest X-rays, fostering background bias. By focusing on the lungs, the ISNet reduced shortcut learning. Thus, its generalization performance on external (out-of-distribution) test databases significantly surpassed all implemented benchmark models.
Severe 21st-century ocean acidification in Antarctic Marine Protected Areas
Authors: Nissen Cara , Lovenduski Nicole S. , Brooks Cassandra M. , Hoppema Mario , Timmermann Ralph , Hauck Judith 
Published: January 2024

AbstractAntarctic coastal waters are home to several established or proposed Marine Protected Areas (MPAs) supporting exceptional biodiversity. Despite being threatened by anthropogenic climate change, uncertainties remain surrounding the future ocean acidification (OA) of these waters. Here we present 21st-century projections of OA in Antarctic MPAs under four emission scenarios using a high-resolution ocean–sea ice–biogeochemistry model with realistic ice-shelf geometry. By 2100, we project pH declines of up to 0.36 (total scale) for the top 200 m. Vigorous vertical mixing of anthropogenic carbon produces severe OA throughout the water column in coastal waters of proposed and existing MPAs. Consequently, end-of-century aragonite undersaturation is ubiquitous under the three highest emission scenarios. Given the cumulative threat to marine ecosystems by environmental change and activities such as fishing, our findings call for strong emission-mitigation efforts and further management strategies to reduce pressures on ecosystems, such as the continuation and expansion of Antarctic MPAs.
Redirecting antibody responses from egg-adapted epitopes following repeat vaccination with recombinant or cell culture-based versus egg-based influenza vaccines
Authors: Liu Feng , Gross F. Liaini , Joshi Sneha , Gaglani Manjusha , Naleway Allison L. , Murthy Kempapura , Groom Holly C. , Wesley Meredith G. , Edwards Laura J. , Grant Lauren , Kim Sara S. , Sambhara Suryaprakash , Gangappa Shivaprakash , Tumpey Terrence , Thompson Mark G. , Fry Alicia M. , Flannery Brendan , Dawood Fatimah S. , Levine Min Z. 
Published: January 2024

AbstractRepeat vaccination with egg-based influenza vaccines could preferentially boost antibodies targeting the egg-adapted epitopes and reduce immunogenicity to circulating viruses. In this randomized trial (Clinicaltrials.gov: NCT03722589), sera pre- and post-vaccination with quadrivalent inactivated egg-based (IIV4), cell culture-based (ccIIV4), and recombinant (RIV4) influenza vaccines were collected from healthcare personnel (18-64 years) in 2018−19 (N = 723) and 2019−20 (N = 684) influenza seasons. We performed an exploratory analysis. Vaccine egg-adapted changes had the most impact on A(H3N2) immunogenicity. In year 1, RIV4 induced higher neutralizing and total HA head binding antibodies to cell- A(H3N2) virus than ccIIV4 and IIV4. In year 2, among the 7 repeat vaccination arms (IIV4-IIV4, IIV4-ccIIV4, IIV4-RIV4, RIV4-ccIIV4, RIV4-RIV4, ccIIV4-ccIIV4 and ccIIV4-RIV4), repeat vaccination with either RIV4 or ccIIV4 further improved antibody responses to circulating viruses with decreased neutralizing antibody egg/cell ratio. RIV4 also had higher post-vaccination A(H1N1)pdm09 and A(H3N2) HA stalk antibodies in year 1, but there was no significant difference in HA stalk antibody fold rise among vaccine groups in either year 1 or year 2. Multiple seasons of non-egg-based vaccination may be needed to redirect antibody responses from immune memory to egg-adapted epitopes and re-focus the immune responses towards epitopes on the circulating viruses to improve vaccine effectiveness.
Drosophila activins adapt gut size to food intake and promote regenerative growth
Authors: Christensen Christian F. , Laurichesse Quentin , Loudhaief Rihab , Colombani Julien , Andersen Ditte S. 
Published: January 2024

AbstractRapidly renewable tissues adapt different strategies to cope with environmental insults. While tissue repair is associated with increased intestinal stem cell (ISC) proliferation and accelerated tissue turnover rates, reduced calorie intake triggers a homeostasis-breaking process causing adaptive resizing of the gut. Here we show that activins are key drivers of both adaptive and regenerative growth. Activin-β (Actβ) is produced by stem and progenitor cells in response to intestinal infections and stimulates ISC proliferation and turnover rates to promote tissue repair. Dawdle (Daw), a divergent Drosophila activin, signals through its receptor, Baboon, in progenitor cells to promote their maturation into enterocytes (ECs). Daw is dynamically regulated during starvation-refeeding cycles, where it couples nutrient intake with progenitor maturation and adaptive resizing of the gut. Our results highlight an activin-dependent mechanism coupling nutrient intake with progenitor-to-EC maturation to promote adaptive resizing of the gut and further establish activins as key regulators of adult tissue plasticity.
Mapping expectancy-based appetitive placebo effects onto the brain in women
Authors: Khalid Iraj , Rodrigues Belina , Dreyfus Hippolyte , Frileux Solène , Meissner Karin , Fossati Philippe , Hare Todd Anthony , Schmidt Liane 
Published: January 2024

AbstractSuggestions about hunger can generate placebo effects on hunger experiences. But, the underlying neurocognitive mechanisms are unknown. Here, we show in 255 women that hunger expectancies, induced by suggestion-based placebo interventions, determine hunger sensations and economic food choices. Functional magnetic resonance imaging in a subgroup (n = 57/255) provides evidence that the strength of expecting the placebo to decrease hunger moderates medial prefrontal cortex activation at the time of food choice and attenuates ventromedial prefrontal cortex (vmPFC) responses to food value. Dorsolateral prefrontal cortex activation linked to interference resolution formally mediates the suggestion-based placebo effects on hunger. A drift-diffusion model characterizes this effect by showing that the hunger suggestions bias participants’ food choices and how much they weigh tastiness against the healthiness of food, which further moderates vmPFC–dlPFC psychophysiological interactions when participants expect decreased hunger. Thus, suggestion-induced beliefs about hunger shape hunger addressing economic choices through cognitive regulation of value computation within the prefrontal cortex.
Spin-related Cu-Co pair to increase electrochemical ammonia generation on high-entropy oxides
Authors: Sun Shengnan , Dai Chencheng , Zhao Peng , Xi Shibo , Ren Yi , Tan Hui Ru , Lim Poh Chong , Lin Ming , Diao Caozheng , Zhang Danwei , Wu Chao , Yu Anke , Koh Jie Cheng Jackson , Lieu Wei Ying , Seng Debbie Hwee Leng , Sun Libo , Li Yuke , Tan Teck Leong , Zhang Jia , Xu Zhichuan J. , Seh Zhi Wei 
Published: January 2024

AbstractThe electrochemical conversion of nitrate to ammonia is a way to eliminate nitrate pollutant in water. Cu-Co synergistic effect was found to produce excellent performance in ammonia generation. However, few studies have focused on this effect in high-entropy oxides. Here, we report the spin-related Cu-Co synergistic effect on electrochemical nitrate-to-ammonia conversion using high-entropy oxide Mg0.2Co0.2Ni0.2Cu0.2Zn0.2O. In contrast, the Li-incorporated MgCoNiCuZnO exhibits inferior performance. By correlating the electronic structure, we found that the Co spin states are crucial for the Cu-Co synergistic effect for ammonia generation. The Cu-Co pair with a high spin Co in Mg0.2Co0.2Ni0.2Cu0.2Zn0.2O can facilitate ammonia generation, while a low spin Co in Li-incorporated MgCoNiCuZnO decreases the Cu-Co synergistic effect on ammonia generation. These findings offer important insights in employing the synergistic effect and spin states inside for selective catalysis. It also indicates the generality of the magnetic effect in ammonia synthesis between electrocatalysis and thermal catalysis.
Helical-caging enables single-emitted large asymmetric full-color circularly polarized luminescence
Authors: Zhou Yajie , Wang Yaxin , Song Yonghui , Zhao Shanshan , Zhang Mingjiang , Li Guangen , Guo Qi , Tong Zhi , Li Zeyi , Jin Shan , Yao Hong-Bin , Zhu Manzhou , Zhuang Taotao 
Published: January 2024

AbstractColorful circularly polarized luminescence materials are desired for 3D displays, information security and asymmetric synthesis, in which single-emitted materials are ideal owing to self-absorption avoidance, evenly entire-visible-spectrum-covered photon emission and facile device fabrication. However, restricted by the synthesis of chiral broad-luminescent emitters, the realization and application of high-performing single-emitted full-color circularly polarized luminescence is in its infancy. Here, we disclose a single-emitted full-color circularly polarized luminescence system (spiral full-color emission generator), composed of whole-vis-spectrum emissive quantum dots and chiral liquid crystals. The system achieves a maximum luminescence dissymmetry factor of 0.8 and remains an order of 10−1 in visible region by tuning its photonic bandgap. We then expand it to a series of desired customized-color circularly polarized luminescence, build chiral devices and further demonstrate the working scenario in the photoinduced enantioselective polymerization. This work contributes to the design and synthesis of efficient chiroptical materials, device fabrication and photoinduced asymmetric synthesis.
A compendium of genetic regulatory effects across pig tissues
Authors: Teng Jinyan , Gao Yahui , Yin Hongwei , Bai Zhonghao , Liu Shuli , Zeng Haonan ,   The PigGTEx Consortium, Bai Lijing , Cai Zexi , Zhao Bingru , Li Xiujin , Xu Zhiting , Lin Qing , Pan Zhangyuan , Yang Wenjing , Yu Xiaoshan , Guan Dailu , Hou Yali , Keel Brittney N. , Rohrer Gary A. , Lindholm-Perry Amanda K. , Oliver William T. , Ballester Maria , Crespo-Piazuelo Daniel , Quintanilla Raquel , Canela-Xandri Oriol , Rawlik Konrad , Xia Charley , Yao Yuelin , Zhao Qianyi , Yao Wenye , Yang Liu , Li Houcheng , Zhang Huicong , Liao Wang , Chen Tianshuo , Karlskov-Mortensen Peter , Fredholm Merete , Amills Marcel , Clop Alex , Giuffra Elisabetta , Wu Jun , Cai Xiaodian , Diao Shuqi , Pan Xiangchun , Wei Chen , Li Jinghui , Cheng Hao , Wang Sheng , Su Guosheng , Sahana Goutam , Lund Mogens Sandø , Dekkers Jack C. M. , Kramer Luke , Tuggle Christopher K. , Corbett Ryan , Groenen Martien A. M. , Madsen Ole , Gòdia Marta , Rocha Dominique , Charles Mathieu , Li Cong-jun , Pausch Hubert , Hu Xiaoxiang , Frantz Laurent , Luo Yonglun , Lin Lin , Zhou Zhongyin , Zhang Zhe , Chen Zitao , Cui Leilei , Xiang Ruidong , Shen Xia , Li Pinghua , Huang Ruihua , Tang Guoqing , Li Mingzhou , Zhao Yunxiang , Yi Guoqiang , Tang Zhonglin , Jiang Jicai , Zhao Fuping , Yuan Xiaolong , Liu Xiaohong , Chen Yaosheng , Xu Xuewen , Zhao Shuhong , Zhao Pengju , Haley Chris , Zhou Huaijun , Wang Qishan , Pan Yuchun , Ding Xiangdong , Ma Li , Li Jiaqi , Navarro Pau , Zhang Qin , Li Bingjie , Tenesa Albert , Li Kui , Liu George E. , Zhang Zhe , Fang Lingzhao 
Published: January 2024

AbstractThe Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.
Structural insights into the activation and inhibition of CXC chemokine receptor 3
Authors: Jiao Haizhan , Pang Bin , Liu Aijun , Chen Qiang , Pan Qi , Wang Xiankun , Xu Yunong , Chiang Ying-Chih , Ren Ruobing , Hu Hongli 
Published: January 2024

AbstractThe chemotaxis of CD4+ type 1 helper cells and CD8+ cytotoxic lymphocytes, guided by interferon-inducible CXC chemokine 9–11 (CXCL9–11) and CXC chemokine receptor 3 (CXCR3), plays a critical role in type 1 immunity. Here we determined the structures of human CXCR3–DNGi complexes activated by chemokine CXCL11, peptidomimetic agonist PS372424 and biaryl-type agonist VUF11222, and the structure of inactive CXCR3 bound to noncompetitive antagonist SCH546738. Structural analysis revealed that PS372424 shares a similar orthosteric binding pocket to the N terminus of CXCL11, while VUF11222 buries deeper and activates the receptor in a distinct manner. We showed an allosteric binding site between TM5 and TM6, accommodating SCH546738 in the inactive CXCR3. SCH546738 may restrain the receptor at an inactive state by preventing the repacking of TM5 and TM6. By revealing the binding patterns and the pharmacological properties of the four modulators, we present the activation mechanisms of CXCR3 and provide insights for future drug development.
A biologging database of mobulid rays from the Gulf of California, Mexico
Authors: Zilliacus Kelly M. , O’Sullivan John , Galván-Magña Felipe , McKinzie Megan K. , Croll Donald A. 
Published: January 2024

AbstractWe initiated a tagging program in 2004 to determine the large-scale and long-term movement patterns of three species of Mobulid Ray (Mobula mobular, M. munkiana, M. thurstoni). Between 2004 and 2014 we deployed 48 pop-up archival (PAT) tags that recorded temperature, pressure, and light level. Pressure and light level records were then used to calculate animal depth and geolocation. Transmitted and when available recovered raw data files from successful deployments (n = 45) were auto-ingested from the manufacturer into the United States Animal Telemetry Network’s (ATN) Data Assembly Center (DAC). Through the ATN DAC, all necessary metadata were compiled, dataset was prepped for release, and derived geolocation trajectories (n = 43) were visualized within their public facing data portal. These data and the full metadata records are available for download from the ATN portal as well as permanently archived under the DataONE Research Workspace member node.
The 100-protein NMR spectra dataset: A resource for biomolecular NMR data analysis
Authors: Klukowski Piotr , Damberger Fred F. , Allain Frédéric H.-T. , Iwai Hideo , Kadavath Harindranath , Ramelot Theresa A. , Montelione Gaetano T. , Riek Roland , Güntert Peter 
Published: January 2024

AbstractMultidimensional NMR spectra are the basis for studying proteins by NMR spectroscopy and crucial for the development and evaluation of methods for biomolecular NMR data analysis. Nevertheless, in contrast to derived data such as chemical shift assignments in the BMRB and protein structures in the PDB databases, this primary data is in general not publicly archived. To change this unsatisfactory situation, we present a standardized set of solution NMR data comprising 1329 2–4-dimensional NMR spectra and associated reference (chemical shift assignments, structures) and derived (peak lists, restraints for structure calculation, etc.) annotations. With the 100-protein NMR spectra dataset that was originally compiled for the development of the ARTINA deep learning-based spectra analysis method, 100 protein structures can be reproduced from their original experimental data. The 100-protein NMR spectra dataset is expected to help the development of computational methods for NMR spectroscopy, in particular machine learning approaches, and enable consistent and objective comparisons of these methods.