bluuebunny/crossref_metadata_2025_split huggingface dataset:
IKKε and TBK1 prevent RIPK1 dependent and independent inflammation
Authors: Eren Remzi Onur , Kaya Göksu Gökberk , Schwarzer Robin , Pasparakis Manolis 
Published: January 2024

AbstractTBK1 and IKKε regulate multiple cellular processes including anti-viral type-I interferon responses, metabolism and TNF receptor signaling. However, the relative contributions and potentially redundant functions of IKKε and TBK1 in cell death, inflammation and tissue homeostasis remain poorly understood. Here we show that IKKε compensates for the loss of TBK1 kinase activity to prevent RIPK1-dependent and -independent inflammation in mice. Combined inhibition of IKKε and TBK1 kinase activities caused embryonic lethality that was rescued by heterozygous expression of kinase-inactive RIPK1. Adult mice expressing kinase-inactive versions of IKKε and TBK1 developed systemic inflammation that was induced by both RIPK1-dependent and -independent mechanisms. Combined inhibition of IKKε and TBK1 kinase activities in myeloid cells induced RIPK1-dependent cell death and systemic inflammation mediated by IL-1 family cytokines. Tissue-specific studies showed that IKKε and TBK1 were required to prevent cell death and inflammation in the intestine but were dispensable for liver and skin homeostasis. Together, these findings revealed that IKKε and TBK1 exhibit tissue-specific functions that are important to prevent cell death and inflammation and maintain tissue homeostasis.
The impact of extreme heat on lake warming in China
Authors: Wang Weijia , Shi Kun , Wang Xiwen , Zhang Yunlin , Qin Boqiang , Zhang Yibo , Woolway R. Iestyn 
Published: January 2024

AbstractGlobal lake ecosystems are subjected to an increased occurrence of heat extremes, yet their impact on lake warming remains poorly understood. In this study, we employed a hybrid physically-based/statistical model to assess the contribution of heat extremes to variations in surface water temperature of 2260 lakes in China from 1985 to 2022. Our study indicates that heat extremes are increasing at a rate of about 2.08 days/decade and an intensity of about 0.03 °C/ day·decade in China. The warming rate of lake surface water temperature decreases from 0.16 °C/decade to 0.13 °C/decade after removing heat extremes. Heat extremes exert a considerable influence on long-term lake surface temperature changes, contributing 36.5% of the warming trends within the studied lakes. Given the important influence of heat extremes on the mean warming of lake surface waters, it is imperative that they are adequately accounted for in climate impact studies.
Dual-wavelength metalens enables Epi-fluorescence detection from single molecules
Authors: Barulin Aleksandr , Kim Yeseul , Oh Dong Kyo , Jang Jaehyuck , Park Hyemi , Rho Junsuk , Kim Inki 
Published: January 2024

AbstractSingle molecule fluorescence spectroscopy is at the heart of molecular biophysics research and the most sensitive biosensing assays. The growing demand for precision medicine and environmental monitoring requires the creation of miniaturized and portable sensing platforms. However, the need for highly sophisticated objective lenses has precluded the development of single molecule detection systems for truly portable devices. Here, we propose a dielectric metalens device of submicrometer thickness to excite and collect light from fluorescent molecules instead of an objective lens. The high numerical aperture, high focusing efficiency, and dual-wavelength operation of the metalens enable the implementation of fluorescence correlation spectroscopy with a single Alexa 647 molecule in the focal volume. Moreover, the metalens enables real-time monitoring of individual fluorescent nanoparticle transitions and identification of hydrodynamic diameters ranging from a few to hundreds of nanometers. This advancement in sensitivity extends the application of the metalens technology to ultracompact single-molecule sensors.
The evolution of centriole degradation in mouse sperm
Authors: Khanal Sushil , Jaiswal Ankit , Chowdanayaka Rajanikanth , Puente Nahshon , Turner Katerina , Assefa Kebron Yeshitela , Nawras Mohamad , Back Ezekiel David , Royfman Abigail , Burkett James P. , Cheong Soon Hon , Fisher Heidi S. , Sindhwani Puneet , Gray John , Ramachandra Nallur Basappa , Avidor-Reiss Tomer 
Published: January 2024

AbstractCentrioles are subcellular organelles found at the cilia base with an evolutionarily conserved structure and a shock absorber-like function. In sperm, centrioles are found at the flagellum base and are essential for embryo development in basal animals. Yet, sperm centrioles have evolved diverse forms, sometimes acting like a transmission system, as in cattle, and sometimes becoming dispensable, as in house mice. How the essential sperm centriole evolved to become dispensable in some organisms is unclear. Here, we test the hypothesis that this transition occurred through a cascade of evolutionary changes to the proteins, structure, and function of sperm centrioles and was possibly driven by sperm competition. We found that the final steps in this cascade are associated with a change in the primary structure of the centriolar inner scaffold protein FAM161A in rodents. This information provides the first insight into the molecular mechanisms and adaptive evolution underlying a major evolutionary transition within the internal structure of the mammalian sperm neck.
Cell cycle arrest induces lipid droplet formation and confers ferroptosis resistance
Authors: Lee Hyemin , Horbath Amber , Kondiparthi Lavanya , Meena Jitendra Kumar , Lei Guang , Dasgupta Shayani , Liu Xiaoguang , Zhuang Li , Koppula Pranavi , Li Mi , Mahmud Iqbal , Wei Bo , Lorenzi Philip L. , Keyomarsi Khandan , Poyurovsky Masha V. , Olszewski Kellen , Gan Boyi 
Published: January 2024

AbstractHow cells coordinate cell cycling with cell survival and death remains incompletely understood. Here, we show that cell cycle arrest has a potent suppressive effect on ferroptosis, a form of regulated cell death induced by overwhelming lipid peroxidation at cellular membranes. Mechanistically, cell cycle arrest induces diacylglycerol acyltransferase (DGAT)–dependent lipid droplet formation to sequester excessive polyunsaturated fatty acids (PUFAs) that accumulate in arrested cells in triacylglycerols (TAGs), resulting in ferroptosis suppression. Consequently, DGAT inhibition orchestrates a reshuffling of PUFAs from TAGs to phospholipids and re-sensitizes arrested cells to ferroptosis. We show that some slow-cycling antimitotic drug–resistant cancer cells, such as 5-fluorouracil–resistant cells, have accumulation of lipid droplets and that combined treatment with ferroptosis inducers and DGAT inhibitors effectively suppresses the growth of 5-fluorouracil–resistant tumors by inducing ferroptosis. Together, these results reveal a role for cell cycle arrest in driving ferroptosis resistance and suggest a ferroptosis-inducing therapeutic strategy to target slow-cycling therapy-resistant cancers.
Allosteric control of dynamin-related protein 1 through a disordered C-terminal Short Linear Motif
Authors: Pérez-Jover Isabel , Rochon Kristy , Hu Di , Mahajan Mukesh , Madan Mohan Pooja , Santos-Pérez Isaac , Ormaetxea Gisasola Julene , Martinez Galvez Juan Manuel , Agirre Jon , Qi Xin , Mears Jason A. , Shnyrova Anna V. , Ramachandran Rajesh 
Published: January 2024

AbstractThe mechanochemical GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial and peroxisomal fission, but the regulatory mechanisms remain ambiguous. Here we find that a conserved, intrinsically disordered, six-residue Short Linear Motif at the extreme Drp1 C-terminus, named CT-SLiM, constitutes a critical allosteric site that controls Drp1 structure and function in vitro and in vivo. Extension of the CT-SLiM by non-native residues, or its interaction with the protein partner GIPC-1, constrains Drp1 subunit conformational dynamics, alters self-assembly properties, and limits cooperative GTP hydrolysis, surprisingly leading to the fission of model membranes in vitro. In vivo, the involvement of the native CT-SLiM is critical for productive mitochondrial and peroxisomal fission, as both deletion and non-native extension of the CT-SLiM severely impair their progression. Thus, contrary to prevailing models, Drp1-catalyzed membrane fission relies on allosteric communication mediated by the CT-SLiM, deceleration of GTPase activity, and coupled changes in subunit architecture and assembly-disassembly dynamics.
A nanoemulsion targeting adipose hypertrophy and hyperplasia shows anti-obesity efficiency in female mice
Authors: Lu Yichao , Luo Zhenyu , Zhou Huanli , Shi Yingying , Zhu Ying , Guo Xuemeng , Huang Jiaxin , Zhang Junlei , Liu Xu , Wang Sijie , Shan Xinyu , Yin Hang , Du Yongzhong , Li Qingpo , You Jian , Luo Lihua 
Published: January 2024

AbstractObesity often leads to severe medical complications. However, existing FDA-approved medications to combat obesity have limited effectiveness in reducing adiposity and often cause side effects. These medications primarily act on the central nervous system or disrupt fat absorption through the gastrointestinal tract. Adipose tissue enlargement involves adipose hyperplasia and hypertrophy, both of which correlate with increased reactive oxygen species (ROS) and hyperactivated X-box binding protein 1 (XBP1) in (pre)adipocytes. In this study, we demonstrate that KT-NE, a nanoemulsion loaded with the XBP1 inhibitor KIRA6 and α-Tocopherol, simultaneously alleviates aberrant endoplasmic reticulum stress and oxidative stress in (pre)adipocytes. As a result, KT-NE significantly inhibits abnormal adipogenic differentiation, reduces lipid droplet accumulation, restricts lipid droplet transfer, impedes obesity progression, and lowers the risk of obesity-associated non-alcoholic fatty liver disease in female mice with obesity. Furthermore, diverse administration routes of KT-NE impact its in vivo biodistribution and contribute to localized and/or systemic anti-obesity effectiveness.
Injectable hydrogel electrodes as conduction highways to restore native pacing
Authors: Rodriguez-Rivera Gabriel J. , Post Allison , John Mathews , Buchan Skylar , Bernard Drew , Razavi Mehdi , Cosgriff-Hernandez Elizabeth 
Published: January 2024

AbstractThere is an urgent clinical need for a treatment regimen that addresses the underlying pathophysiology of ventricular arrhythmias, the leading cause of sudden cardiac death. The current report describes the design of an injectable hydrogel electrode and successful deployment in a pig model with access far more refined than any current pacing modalities allow. In addition to successful cardiac capture and pacing, analysis of surface ECG tracings and three-dimensional electroanatomic mapping revealed a QRS morphology comparable to native sinus rhythm, strongly suggesting the hydrogel electrode captures the deep septal bundle branches and Purkinje fibers. In an ablation model, electroanatomic mapping data demonstrated that the activation wavefront from the hydrogel reaches the mid-myocardium and endocardium much earlier than current single-point pacing modalities. Such uniform activation of broad swaths of tissue enables an opportunity to minimize the delayed myocardial conduction of heterogeneous tissue that underpins re-entry. Collectively, these studies demonstrate the feasibility of a new pacing modality that most closely resembles native conduction with the potential to eliminate lethal re-entrant arrhythmias and provide painless defibrillation.
A light-activatable theranostic combination for ratiometric hypoxia imaging and oxygen-deprived drug activity enhancement
Authors: Ge Lei , Tang Yikai , Wang Chongzhi , Chen Jian , Mao Hui , Jiang Xiqun 
Published: January 2024

AbstractWhile performing oxygen-related tumour treatments such as chemotherapy and photodynamic therapy, real-time monitoring hypoxia of tumour is of great value and significance. Here, we design a theranostic combination for light-activated ratiometric hypoxia imaging, hypoxia modulating and prodrug activation. This combination consisted of an oxygen-sensitive near-infrared-emitting ratiometric phosphorescence probe and a hypoxia-activated prodrug-loaded covalent organic framework. In this combination, the probe plays two roles, including quantitative monitoring of oxygen concentration by ratiometric imaging and consuming the oxygen of tumour under light excitation by photodynamic therapy. Meanwhile, the enhanced hypoxia microenvironment of tumour can raise the cytotoxicity of prodrug loaded in covalent organic framework, resulting in boosting antitumour therapeutic effects in vivo. This theranostic combination can precisely provide therapeutic regime and screen hypoxia-activated prodrugs based on real-time tumour hypoxia level, offering a strategy to develop hypoxia mediated tumour theranostics with hypoxia targeted prodrugs.
Inferring language dispersal patterns with velocity field estimation
Authors: Yang Sizhe , Sun Xiaoru , Jin Li , Zhang Menghan 
Published: January 2024

AbstractReconstructing the spatial evolution of languages can deepen our understanding of the demic diffusion and cultural spread. However, the phylogeographic approach that is frequently used to infer language dispersal patterns has limitations, primarily because the phylogenetic tree cannot fully explain the language evolution induced by the horizontal contact among languages, such as borrowing and areal diffusion. Here, we introduce the language velocity field estimation, which does not rely on the phylogenetic tree, to infer language dispersal trajectories and centre. Its effectiveness and robustness are verified through both simulated and empirical validations. Using language velocity field estimation, we infer the dispersal patterns of four agricultural language families and groups, encompassing approximately 700 language samples. Our results show that the dispersal trajectories of these languages are primarily compatible with population movement routes inferred from ancient DNA and archaeological materials, and their dispersal centres are geographically proximate to ancient homelands of agricultural or Neolithic cultures. Our findings highlight that the agricultural languages dispersed alongside the demic diffusions and cultural spreads during the past 10,000 years. We expect that language velocity field estimation could aid the spatial analysis of language evolution and further branch out into the studies of demographic and cultural dynamics.
Universal microbial reworking of dissolved organic matter along environmental gradients
Authors: Freeman Erika C. , Emilson Erik J. S. , Dittmar Thorsten , Braga Lucas P. P. , Emilson Caroline E. , Goldhammer Tobias , Martineau Christine , Singer Gabriel , Tanentzap Andrew J. 
Published: January 2024

AbstractSoils are losing increasing amounts of carbon annually to freshwaters as dissolved organic matter (DOM), which, if degraded, can offset their carbon sink capacity. However, the processes underlying DOM degradation across environments are poorly understood. Here we show DOM changes similarly along soil-aquatic gradients irrespective of environmental differences. Using ultrahigh-resolution mass spectrometry, we track DOM along soil depths and hillslope positions in forest catchments and relate its composition to soil microbiomes and physico-chemical conditions. Along depths and hillslopes, we find carbohydrate-like and unsaturated hydrocarbon-like compounds increase in abundance-weighted mass, and the expression of genes essential for degrading plant-derived carbohydrates explains >50% of the variation in abundance of these compounds. These results suggest that microbes transform plant-derived compounds, leaving DOM to become increasingly dominated by the same (i.e., universal), difficult-to-degrade compounds as degradation proceeds. By synthesising data from the land-to-ocean continuum, we suggest these processes generalise across ecosystems and spatiotemporal scales. Such general degradation patterns can help predict DOM composition and reactivity along environmental gradients to inform management of soil-to-stream carbon losses.
Projected soil carbon loss with warming in constrained Earth system models
Authors: Ren Shuai , Wang Tao , Guenet Bertrand , Liu Dan , Cao Yingfang , Ding Jinzhi , Smith Pete , Piao Shilong 
Published: January 2024

AbstractThe soil carbon-climate feedback is currently the least constrained component of global warming projections, and the major source of uncertainties stems from a poor understanding of soil carbon turnover processes. Here, we assemble data from long-term temperature-controlled soil incubation studies to show that the arctic and boreal region has the shortest intrinsic soil carbon turnover time while tropical forests have the longest one, and current Earth system models overestimate intrinsic turnover time by 30 percent across active, slow and passive carbon pools. Our constraint suggests that the global soils will switch from carbon sink to source, with a loss of 0.22–0.53 petagrams of carbon per year until the end of this century from strong mitigation to worst emission scenarios, suggesting that global soils will provide a strong positive carbon feedback on warming. Such a reversal of global soil carbon balance would lead to a reduction of 66% and 15% in the current estimated remaining carbon budget for limiting global warming well below 1.5 °C and 2 °C, respectively, rendering climate mitigation much more difficult.
CRISPR-Cas-based identification of a sialylated human milk oligosaccharides utilization cluster in the infant gut commensal Bacteroides dorei
Authors: Kijner Sivan , Ennis Dena , Shmorak Shimrit , Florentin Anat , Yassour Moran 
Published: January 2024

AbstractThe infant gut microbiome is impacted by early-life feeding, as human milk oligosaccharides (HMOs) found in breastmilk cannot be digested by infants and serve as nutrients for their gut bacteria. While the vast majority of HMO-utilization research has focused on Bifidobacterium species, recent studies have suggested additional HMO-utilizers, mostly Bacteroides, yet their utilization mechanism is poorly characterized. Here, we investigate Bacteroides dorei isolates from breastfed-infants and identify that polysaccharide utilization locus (PUL) 33 enables B. dorei to utilize sialylated HMOs. We perform transcriptional profiling and identity upregulated genes when growing on sialylated HMOs. Using CRISPR-Cas12 to knock-out four PUL33 genes, combined with complementation assays, we identify GH33 as the critical gene in PUL33 for sialylated HMO-utilization. This demonstration of an HMO-utilization system by Bacteroides species isolated from infants opens the way to further characterization of additional such systems, to better understand HMO-utilization in the infant gut.
Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification
Authors: Wang Jun , Huang Jinyong , Hu Yunlong , Guo Qianwen , Zhang Shasha , Tian Jinglin , Niu Yanqin , Ji Ling , Xu Yuzhong , Tang Peijun , He Yaqin , Wang Yuna , Zhang Shuya , Yang Hao , Kang Kang , Chen Xinchun , Li Xinying , Yang Ming , Gou Deming 
Published: January 2024

AbstractCell-free RNAs (cfRNAs) offer an opportunity to detect diseases from a transcriptomic perspective, however, existing techniques have fallen short in generating a comprehensive cell-free transcriptome profile. We develop a sensitive library preparation method that is robust down to 100 µl input plasma to analyze cfRNAs independent of their 5’-end modifications. We show that it outperforms adapter ligation-based method in detecting a greater number of cfRNA species. We perform transcriptome-wide characterizations in 165 lung cancer, 30 breast cancer, 37 colorectal cancer, 55 gastric cancer, 15 liver cancer, and 133 cancer-free participants and demonstrate its ability to identify transcriptomic changes occurring in early-stage tumors. We also leverage machine learning analyses on the differentially expressed cfRNA signatures and reveal their robust performance in cancer detection and classification. Our work sets the stage for in-depth study of the cfRNA repertoire and highlights the value of cfRNAs as cancer biomarkers in clinical applications.
Molecular mechanism of antihistamines recognition and regulation of the histamine H1 receptor
Authors: Wang Dandan , Guo Qiong , Wu Zhangsong , Li Ming , He Binbin , Du Yang , Zhang Kaiming , Tao Yuyong 
Published: January 2024

AbstractHistamine receptors are a group of G protein-coupled receptors (GPCRs) that play important roles in various physiological and pathophysiological conditions. Antihistamines that target the histamine H1 receptor (H1R) have been widely used to relieve the symptoms of allergy and inflammation. Here, to uncover the details of the regulation of H1R by the known second-generation antihistamines, thereby providing clues for the rational design of newer antihistamines, we determine the cryo-EM structure of H1R in the apo form and bound to different antihistamines. In addition to the deep hydrophobic cavity, we identify a secondary ligand-binding site in H1R, which potentially may support the introduction of new derivative groups to generate newer antihistamines. Furthermore, these structures show that antihistamines exert inverse regulation by utilizing a shared phenyl group that inserts into the deep cavity and block the movement of the toggle switch residue W4286.48. Together, these results enrich our understanding of GPCR modulation and facilitate the structure-based design of novel antihistamines.
Bioinspired structural hydrogels with highly ordered hierarchical orientations by flow-induced alignment of nanofibrils
Authors: Zhu Shuihong , Wang Sen , Huang Yifan , Tang Qiyun , Fu Tianqi , Su Riyan , Fan Chaoyu , Xia Shuang , Lee Pooi See , Lin Youhui 
Published: January 2024

AbstractNatural structural materials often possess unique combinations of strength and toughness resulting from their complex hierarchical assembly across multiple length scales. However, engineering such well-ordered structures in synthetic materials via a universal and scalable manner still poses a grand challenge. Herein, a simple yet versatile approach is proposed to design hierarchically structured hydrogels by flow-induced alignment of nanofibrils, without high time/energy consumption or cumbersome postprocessing. Highly aligned fibrous configuration and structural densification are successfully achieved in anisotropic hydrogels under ambient conditions, resulting in desired mechanical properties and damage-tolerant architectures, for example, strength of 14 ± 1 MPa, toughness of 154 ± 13 MJ m−3, and fracture energy of 153 ± 8 kJ m−2. Moreover, a hydrogel mesoporous framework can deliver ultra-fast and unidirectional water transport (maximum speed at 65.75 mm s−1), highlighting its potential for water purification. This scalable fabrication explores a promising strategy for developing bioinspired structural hydrogels, facilitating their practical applications in biomedical and engineering fields.