bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trabectedin derails transcription-coupled nucleotide excision repair to induce DNA breaks in highly transcribed genes
Authors: Son Kook , Takhaveev Vakil , Mor Visesato , Yu Hobin , Dillier Emma , Zilio Nicola , Püllen Nikolai J. L. , Ivanov Dmitri , Ulrich Helle D. , Sturla Shana J. , Schärer Orlando D. 
Published: February 2024

AbstractMost genotoxic anticancer agents fail in tumors with intact DNA repair. Therefore, trabectedin, anagent more toxic to cells with active DNA repair, specifically transcription-coupled nucleotide excision repair (TC-NER), provides therapeutic opportunities. To unlock the potential of trabectedin and inform its application in precision oncology, an understanding of the mechanism of the drug’s TC-NER-dependent toxicity is needed. Here, we determine that abortive TC-NER of trabectedin-DNA adducts forms persistent single-strand breaks (SSBs) as the adducts block the second of the two sequential NER incisions. We map the 3’-hydroxyl groups of SSBs originating from the first NER incision at trabectedin lesions, recording TC-NER on a genome-wide scale. Trabectedin-induced SSBs primarily occur in transcribed strands of active genes and peak near transcription start sites. Frequent SSBs are also found outside gene bodies, connecting TC-NER to divergent transcription from promoters. This work advances the use of trabectedin for precision oncology and for studying TC-NER and transcription.
The Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation
Authors: Nelson Christopher B. , Rogers Samuel , Roychoudhury Kaushik , Tan Yaw Sing , Atkinson Caroline J. , Sobinoff Alexander P. , Tomlinson Christopher G. , Hsu Anton , Lu Robert , Dray Eloise , Haber Michelle , Fletcher Jamie I. , Cesare Anthony J. , Hegde Rashmi S. , Pickett Hilda A. 
Published: February 2024

AbstractThe Eyes Absent proteins (EYA1-4) are a biochemically unique group of tyrosine phosphatases known to be tumour-promoting across a range of cancer types. To date, the targets of EYA phosphatase activity remain largely uncharacterised. Here, we identify Polo-like kinase 1 (PLK1) as an interactor and phosphatase substrate of EYA4 and EYA1, with pY445 on PLK1 being the primary target site. Dephosphorylation of pY445 in the G2 phase of the cell cycle is required for centrosome maturation, PLK1 localization to centrosomes, and polo-box domain (PBD) dependent interactions between PLK1 and PLK1-activation complexes. Molecular dynamics simulations support the rationale that pY445 confers a structural impairment to PBD-substrate interactions that is relieved by EYA-mediated dephosphorylation. Depletion of EYA4 or EYA1, or chemical inhibition of EYA phosphatase activity, dramatically reduces PLK1 activation, causing mitotic defects and cell death. Overall, we have characterized a phosphotyrosine signalling network governing PLK1 and mitosis.
High-spin Co3+ in cobalt oxyhydroxide for efficient water oxidation
Authors: Zhang Xin , Zhong Haoyin , Zhang Qi , Zhang Qihan , Wu Chao , Yu Junchen , Ma Yifan , An Hang , Wang Hao , Zou Yiming , Diao Caozheng , Chen Jingsheng , Yu Zhi Gen , Xi Shibo , Wang Xiaopeng , Xue Junmin 
Published: February 2024

AbstractCobalt oxyhydroxide (CoOOH) is a promising catalytic material for oxygen evolution reaction (OER). In the traditional CoOOH structure, Co3+ exhibits a low-spin state configuration ($${t}_{2{{{{{\rm{g}}}}}}}^{6}{e}_{{{{{{\rm{g}}}}}}}^{0}$$

t

2
g

6

e

g

0

), with electron transfer occurring in face-to-face $${t}_{2{{{{{\rm{g}}}}}}}^{*}$$

t

2
g

*

orbitals. In this work, we report the successful synthesis of high-spin state Co3+ CoOOH structure, by introducing coordinatively unsaturated Co atoms. As compared to the low-spin state CoOOH, electron transfer in the high-spin state CoOOH occurs in apex-to-apex $${e}_{{{{{{\rm{g}}}}}}}^{*}$$

e

g

*

orbitals, which exhibits faster electron transfer ability. As a result, the high-spin state CoOOH performs superior OER activity with an overpotential of 226 mV at 10 mA cm−2, which is 148 mV lower than that of the low-spin state CoOOH. This work emphasizes the effect of the spin state of Co3+ on OER activity of CoOOH based electrocatalysts for water splitting, and thus provides a new strategy for designing highly efficient electrocatalysts.
Electrocatalytic water oxidation with manganese phosphates
Authors: Yang Shujiao , Yue Kaihang , Liu Xiaohan , Li Sisi , Zheng Haoquan , Yan Ya , Cao Rui , Zhang Wei 
Published: February 2024

AbstractAs inspired by the Mn4CaO5 oxygen evolution center in nature, Mn-based electrocatalysts have received overwhelming attention for water oxidation. However, the understanding of the detailed reaction mechanism has been a long-standing problem. Herein, homologous KMnPO4 and KMnPO4•H2O with 4-coordinated and 6-coordinated Mn centers, respectively, are prepared. The two catalysts constitute an ideal platform to study the structure-performance correlation. The presence of Mn(III), Mn(IV), and Mn(V) intermediate species are identified during water oxidation. The Mn(V)=O species is demonstrated to be the substance for O−O bond formation. In KMnPO4•H2O, the Mn coordination structure did not change significantly during water oxidation. In KMnPO4, the Mn coordination structure changed from 4-coordinated [MnO4] to 5-coordinated [MnO5] motif, which displays a triangular biconical configuration. The structure flexibility of [MnO5] is thermodynamically favored in retaining Mn(III)−OH and generating Mn(V)=O. The Mn(V)=O species is at equilibrium with Mn(IV)=O, the concentration of which determines the intrinsic activity of water oxidation. This study provides a clear picture of water oxidation mechanism on Mn-based systems.
Adipocyte p53 coordinates the response to intermittent fasting by regulating adipose tissue immune cell landscape
Authors: Reinisch Isabel , Michenthaler Helene , Sulaj Alba , Moyschewitz Elisabeth , Krstic Jelena , Galhuber Markus , Xu Ruonan , Riahi Zina , Wang Tongtong , Vujic Nemanja , Amor Melina , Zenezini Chiozzi Riccardo , Wabitsch Martin , Kolb Dagmar , Georgiadi Anastasia , Glawitsch Lisa , Heitzer Ellen , Schulz Tim J. , Schupp Michael , Sun Wenfei , Dong Hua , Ghosh Adhideb , Hoffmann Anne , Kratky Dagmar , Hinte Laura C. , von Meyenn Ferdinand , Heck Albert J. R. , Blüher Matthias , Herzig Stephan , Wolfrum Christian , Prokesch Andreas 
Published: February 2024

AbstractIn obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, the impact of fasting regimens on the regulation of AT immune infiltration is still elusive. Here we show that intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, this increase in LAM abundance is strongly p53 dependent and partly mediated by p53-driven adipocyte apoptosis. Adipocyte-specific deletion of p53 prevents LAM accumulation during IF, increases the catabolic state of adipocytes, and enhances systemic metabolic flexibility and insulin sensitivity. Finally, in cohorts of obese/diabetic patients, we describe a p53 polymorphism that links to efficacy of a fasting-mimicking diet and that the expression of p53 and TREM2 in AT negatively correlates with maintaining weight loss after bariatric surgery. Overall, our results demonstrate that p53 signalling in adipocytes dictates LAM accumulation in AT under IF and modulates fasting effectiveness in mice and humans.
High resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing
Authors: Wu Haojia , Dixon Eryn E. , Xuanyuan Qiao , Guo Juanru , Yoshimura Yasuhiro , Debashish Chitnis , Niesnerova Anezka , Xu Hao , Rouault Morgane , Humphreys Benjamin D. 
Published: February 2024

AbstractEmerging spatially resolved transcriptomics technologies allow for the measurement of gene expression in situ at cellular resolution. We apply direct RNA hybridization-based in situ sequencing (dRNA HybISS, Cartana part of 10xGenomics) to compare male and female healthy mouse kidneys and the male kidney injury and repair timecourse. A pre-selected panel of 200 genes is used to identify cell state dynamics patterns during injury and repair. We develop a new computational pipeline, CellScopes, for the rapid analysis, multi-omic integration and visualization of spatially resolved transcriptomic datasets. The resulting dataset allows us to resolve 13 kidney cell types within distinct kidney niches, dynamic alterations in cell state over the course of injury and repair and cell-cell interactions between leukocytes and kidney parenchyma. At late timepoints after injury, C3+ leukocytes are enriched near pro-inflammatory, failed-repair proximal tubule cells. Integration of snRNA-seq dataset from the same injury and repair samples also allows us to impute the spatial localization of genes not directly measured by dRNA HybISS.
Evaluation of single-sample network inference methods for precision oncology
Authors: Deschildre Joke , Vandemoortele Boris , Loers Jens Uwe , De Preter Katleen , Vermeirssen Vanessa 
Published: February 2024

AbstractA major challenge in precision oncology is to detect targetable cancer vulnerabilities in individual patients. Modeling high-throughput omics data in biological networks allows identifying key molecules and processes of tumorigenesis. Traditionally, network inference methods rely on many samples to contain sufficient information for learning, resulting in aggregate networks. However, to implement patient-tailored approaches in precision oncology, we need to interpret omics data at the level of individual patients. Several single-sample network inference methods have been developed that infer biological networks for an individual sample from bulk RNA-seq data. However, only a limited comparison of these methods has been made and many methods rely on ‘normal tissue’ samples as reference, which are not always available. Here, we conducted an evaluation of the single-sample network inference methods SSN, LIONESS, SWEET, iENA, CSN and SSPGI using transcriptomic profiles of lung and brain cancer cell lines from the CCLE database. The methods constructed functional gene networks with distinct network characteristics. Hub gene analyses revealed different degrees of subtype-specificity across methods. Single-sample networks were able to distinguish between tumor subtypes, as exemplified by node strength clustering, enrichment of known subtype-specific driver genes among hubs and differential node strength. We also showed that single-sample networks correlated better to other omics data from the same cell line as compared to aggregate networks. We conclude that single-sample network inference methods can reflect sample-specific biology when ‘normal tissue’ samples are absent and we point out peculiarities of each method.
Intranasal vaccine for Lyme disease provides protection against tick transmitted Borrelia burgdorferi beyond one year
Authors: Gingerich Maria Cristina , Nair Nisha , Azevedo Jose F. , Samanta Kamalika , Kundu Suman , He Biao , Gomes-Solecki Maria 
Published: February 2024

AbstractStrategies for disease control are necessary to reduce incidence of Lyme Disease (LD) including development of safe vaccines for human use. Parainfluenza virus 5 (PIV5) vector has an excellent safety record in animals and PIV5-vectored vaccines are currently under clinical development. We constructed PIV5-vectored LD vaccine candidates expressing OspA from B. burgdorferi (OspAB31) and a chimeric protein containing sequences from B. burgdorferi and B. afzelii (OspABPBPk). Immunogenicity and vaccine efficacy were analyzed in C3H-HeN mice after prime-boost intranasal vaccination with live PIV5-OspAB31 or PIV5-OspABPBPk, subcutaneous (s.c.) vaccination with rOspAB31+Alum, and the respective controls. Mice vaccinated intranasally with live PIV5-AB31 or PIV5-ABPBPk had higher endpoint titers of serum antibody against OspAB31 at 6- and 12- months post vaccination, compared to mice vaccinated s.c. with rOspAB31. Neutralization activity of antibody was maintained up to 18-months post-immunization, with the response greater in live PIV5-delivered OspA vaccines, than that induced by s.c. rOspAB31. Challenge with infected ticks carrying 10-19 strains of B. burgdorferi performed at 4-, 9- or 15-months post-immunization showed increased breakthrough infections in mice vaccinated with s.c. rOspAB31 compared to intranasal PIV5-AB31 or PIV5-ABPBPk at 9- and 15-months, as determined by quantification of serologic antibodies to B. burgdorferi proteins as well as flaB DNA in tissues, and by visualization of motile B. burgdorferi in culture of tissues under dark field microscope. These findings indicate that immunization of mice with PIV5 delivered OspA generates immune responses that produce longer-lasting protection ( > 1 year) against tick-transmitted B. burgdorferi than a parenteral recombinant OspA vaccine.
Zika purified inactivated virus (ZPIV) vaccine reduced vertical transmission in pregnant immunocompetent mice
Authors: Kim In-Jeong , Tighe Michael P. , Lanthier Paula A. , Clark Madeline J. , De La Barrera Rafael A. , Dussupt Vincent , Mendez-Rivera Letzibeth , Krebs Shelly J. , Travis Kelsey L. , Low-Beer Timothy C. , Cookenham Tres S. , Lanzer Kathleen G. , Bernacki Derek T. , Szaba Frank M. , Schneck Amanda A. , Ward Jerrold , Thomas Stephen J. , Modjarrad Kayvon , Blackman Marcia A. 
Published: February 2024

AbstractZika virus (ZIKV) is a significant threat to pregnant women and their fetuses as it can cause severe birth defects and congenital neurodevelopmental disorders, referred to as congenital Zika syndrome (CZS). Thus, a safe and effective ZIKV vaccine for pregnant women to prevent in utero ZIKV infection is of utmost importance. Murine models of ZIKV infection are limited by the fact that immunocompetent mice are resistant to ZIKV infection. As such, interferon-deficient mice have been used in some preclinical studies to test the efficacy of ZIKV vaccine candidates against lethal virus challenge. However, interferon-deficient mouse models have limitations in assessing the immunogenicity of vaccines, necessitating the use of immunocompetent mouse pregnancy models. Using the human stat2 knock-in (hSTAT2KI) mouse pregnancy model, we show that vaccination with a purified formalin-inactivated Zika virus (ZPIV) vaccine prior to pregnancy successfully prevented vertical transmission. In addition, maternal immunity protected offspring against postnatal challenge for up to 28 days. Furthermore, passive transfer of human IgG purified from hyper-immune sera of ZPIV vaccinees prevented maternal and fetal ZIKV infection, providing strong evidence that the neutralizing antibody response may serve as a meaningful correlate of protection.
Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression
Authors: Hu Junyi , Wang Shao-Gang , Hou Yaxin , Chen Zhaohui , Liu Lilong , Li Ruizhi , Li Nisha , Zhou Lijie , Yang Yu , Wang Liping , Wang Liang , Yang Xiong , Lei Yichen , Deng Changqi , Li Yang , Deng Zhiyao , Ding Yuhong , Kuang Yingchun , Yao Zhipeng , Xun Yang , Li Fan , Li Heng , Hu Jia , Liu Zheng , Wang Tao , Hao Yi , Jiao Xuanmao , Guan Wei , Tao Zhen , Ren Shancheng , Chen Ke 
Published: February 2024

AbstractClear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.
RANKL blockade for erosive hand osteoarthritis: a randomized placebo-controlled phase 2a trial
Authors: Wittoek Ruth , Verbruggen Gust , Vanhaverbeke Tine , Colman Roos , Elewaut Dirk 
Published: February 2024

AbstractErosive hand osteoarthritis (OA) is a prevalent and disabling disease with limited treatment options. Here we present the results of a monocentric, placebo-controlled, double-blind, randomized phase 2a clinical trial with denosumab, a receptor activator of nuclear factor-κB ligand inhibitor, evaluating the effects on structure modification in erosive hand OA. Patients were randomized to 48 weeks treatment with denosumab 60 mg every 3 months (n = 51, 41 females) or placebo (n = 49, 37 females). The primary (radiographic) endpoint was the change in the total Ghent University Scoring System (GUSS) at week 24, where positive changes correspond to remodeling and negative changes to erosive progression. Secondary endpoints were the change in the GUSS at week 48 and the number of new erosive joints at week 48 by the anatomical phase scoring system. Baseline mean GUSS (standard deviation) of target joints was 155.9 (69.3) in the denosumab group and 158.7 (46.8) in the placebo group. The primary endpoint was met with an estimated difference between groups of 8.9 (95% confidence interval (CI) 1.0 to 16.9; P = 0.024) at week 24. This effect was confirmed at week 48 (baseline adjusted GUSS (standard error of the mean) denosumab and placebo were 163.5 (2.9) and 149.2 (3.9), respectively; with an estimated difference between groups of 14.3 (95% CI 4.6 to 24.0; P = 0.003)). At patient level, more new erosive joints were developed in the placebo group compared with denosumab at week 48 (odds ratio 0.24 (95% CI 0.08 to 0.72); P = 0.009). More adverse events occurred in the placebo group (125 events in 44 patients (90%)) compared with the denosumab group (97 events in 41 patients (80%)). These results demonstrate that denosumab has structure modifying effects in erosive hand OA by inducing remodeling and preventing new erosive joints. EU Clinical Trials Register identifier 2015-003223-53.
Transitioning from MODIS to VIIRS Global Water Reservoir Product
Authors: Shah Deep , Zhang Shuai , Sarkar Sudipta , Davidson Carol , Zhang Rui , Zhao Maosheng , Devadiga Sadashiva , Noojipady Praveen , Román Miguel O. , Gao Huilin 
Published: February 2024

AbstractReservoirs play a crucial role in regulating water availability and enhancing water security. Here, we develop NASA’s Visible Infrared Imaging Radiometer Suite (VIIRS) based Global Water Reservoir (GWR) product, consisting of measurements of reservoir area, elevation, storage, evaporation rate, and evaporation loss for 164 large global reservoirs. The dataset is available at 8-day and monthly temporal resolutions. Since the Moderate Resolution Imaging Spectroradiometer (MODIS) is close to the end of its life, we further evaluated the consistency between MODIS and VIIRS-based GWR to ensure continuity to the 20+ year MODIS GWR product. Independent assessment of VIIRS reservoir storage (8-day) retrievals against in-situ measurements shows an average of R2 = 0.84, RMSE = 0.47 km3, and NRMSE = 16.45%. The evaporation rate has an average of R2 = 0.56, RMSE = 1.32 mm/day, and NRMSE = 28.14%. Furthermore, results show good consistency (R2 ≥ 0.90) between the VIIRS and MODIS-based product components, confirming that long-term data continuity can be achieved. This dataset can provide valuable insights for long-term trend analysis, hydrological modeling, and understanding hydroclimatic extremes in the context of reservoirs.
Assessment of Self-report, Palpation, and Surface Electromyography Dataset During Isometric Muscle Contraction
Authors: Lim Jihoon , Lu Lei , Goonewardena Kusal , Liu Jefferson Zhe , Tan Ying 
Published: February 2024

AbstractMeasuring muscle fatigue involves assessing various components within the motor system. While subjective and sensor-based measures have been proposed, a comprehensive comparison of these assessment measures is currently lacking. This study aims to bridge this gap by utilizing three commonly used measures: participant self-reported perceived muscle fatigue scores, a sports physiotherapist’s manual palpation-based muscle tightness scores, and surface electromyography sensors. Compensatory muscle fatigue occurs when one muscle group becomes fatigued, leading to the involvement and subsequent fatigue of other muscles as they compensate for the workload. The evaluation of compensatory muscle fatigue focuses on nine different upper body muscles selected by the sports physiotherapist. With a cohort of 30 male subjects, this study provides a valuable dataset for researchers and healthcare practitioners in sports science, rehabilitation, and human performance. It enables the exploration and comparison of diverse methods for evaluating different muscles in isometric contraction.
Metabolism Regimes in Regulated Rivers of the Illinois River Basin, USA
Authors: Harvey Judson W. , Choi Jay , Quion Katherine 
Published: February 2024

AbstractMetabolism estimates organic carbon accumulation by primary productivity and removal by respiration. In rivers it is relevant to assessing trophic status and threats to river health such as hypoxia as well as greenhouse gas fluxes. We estimated metabolism in 17 rivers of the Illinois River basin (IRB) for a total of 15,176 days, or an average of 2.5 years per site. Daily estimates of gross primary productivity (GPP), ecosystem respiration (ER), net ecosystem productivity (NEP), and the air-water gas exchange rate constant (K600) are reported, along with ancillary data such as river temperature and saturated dissolved oxygen concentration, barometric pressure, and river depth and discharge. Workflows for metabolism estimation and quality assurance are described including a new method for estimating river depth. IRB rivers are dominantly heterotrophic; however, autotrophy was common in river locations coinciding with reported harmful algal blooms (HABs) events. Metabolism of these regulated Midwestern U.S. rivers can help assess the causes and consequences of excessive algal blooms in rivers and their role in river ecological health.
High-resolution Annual Dynamic dataset of Curve Number from 2008 to 2021 over Conterminous United States
Authors: Wu Qiong , Ramirez Avila John J. , Yang Jia , Ji Cunxiong , Fang Shanmin 
Published: February 2024

AbstractThe spatial distribution and data quality of curve number (CN) values determine the performance of hydrological estimations. However, existing CN datasets are constrained by universal-applicability hypothesis, medium resolution, and imbalance between specificity CN tables to generalized land use/land cover (LULC) maps, which hinder their applicability and predictive accuracy. A new annual CN dataset named CUSCN30, featuring an enhanced resolution of 30 meters and accounting for temporal variations in climate and LULC in the continental United States (CONUS) between 2008 and 2021, was developed in this study. CUSCN30 demonstrated good performance in surface runoff estimation using CN method when compared to observed surface runoff for the selected watersheds. Compared with existing CN datasets, CUSCN30 exhibits the highest accuracy in runoff estimation for both normal and extreme rainfall events. In addition, CUSCN30, with its high spatial resolution, better captures the spatial heterogeneity of watersheds. This developed CN dataset can be used as input for hydrological models or machine learning algorithms to simulate rainfall-runoff across multiple spatiotemporal scales.