bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA helicase DDX5 modulates sorafenib sensitivity in hepatocellular carcinoma via the Wnt/β-catenin–ferroptosis axis
Authors: Li Zhili , Caron de Fromentel Claude , Kim Woojun , Wang Wen-Hung , Sun Jiazeng , Yan Bingyu , Utturkar Sagar , Lanman Nadia Atallah , Elzey Bennett D. , Yeo Yoon , Zhang Hao , Kazemian Majid , Levrero Massimo , Andrisani Ourania 
Published: November 2023

AbstractReduced expression of the RNA helicase DDX5 associated with increased hepatocellular carcinoma (HCC) tumor grade and poor patient survival following treatment with sorafenib. While immunotherapy is the first-line treatment for HCC, sorafenib and other multi-tyrosine kinase inhibitors (mTKIs) are widely used when immunotherapy is contra-indicated or fails. Herein, we elucidate the role of DDX5 in sensitizing HCC to sorafenib, offering new therapeutic strategies. Treatment of various human HCC cell lines with sorafenib/mTKIs downregulated DDX5 in vitro and in preclinical HCC models. Conversely, DDX5 overexpression reduced the viability of sorafenib-treated cells via ferroptosis, suggesting a role for DDX5 in sorafenib sensitivity. RNAseq of wild-type vs. DDX5-knockdown cells treated with or without sorafenib identified a set of common genes repressed by DDX5 and upregulated by sorafenib. This set significantly overlaps with Wnt signaling genes, including Disheveled-1 (DVL1), an indispensable Wnt activator and prognostic indicator of poor survival for sorafenib-treated patients. DDX5-knockout (DDX5KO) HCC cells exhibited DVL1 induction, Wnt/β-catenin pathway activation, and ferroptosis upon inhibition of canonical Wnt signaling. Consistently, xenograft HCC tumors exhibited reduced growth by inhibition of Wnt/β-catenin signaling via induction of ferroptosis. Significantly, overexpression of DDX5 in HCC xenografts repressed DVL1 expression and increased ferroptosis, resulting in reduced tumor growth by sorafenib. We conclude that DDX5 downregulation by sorafenib mediates adaptive resistance by activating Wnt/β-catenin signaling, leading to ferroptosis escape. Conversely, overexpression of DDX5 in vivo enhances the anti-tumor efficacy of sorafenib by suppressing Wnt/β-catenin activation and induction of ferroptosis. Thus, DDX5 overexpression in combination with mTKIs is a promising therapeutic strategy for HCC.
Marine toxin domoic acid alters nitrogen cycling in sediments
Authors: Li Zelong , Wang Jing , Yue Hao , Du Miaomiao , Jin Yuan , Fan Jingfeng 
Published: November 2023

AbstractAs a red tide algal toxin with intense neurotoxicity distributed worldwide, domoic acid (DA) has attracted increasing concerns. In this work, the integrative analysis of metagenome and metabolome are applied to investigate the impact of DA on nitrogen cycling in coastal sediments. Here we show that DA can act as a stressor to induce the variation of nitrogen (N) cycling by altering the abundance of functional genes and electron supply. Moreover, microecology theory revealed that DA can increase the role of deterministic assembly in microbial dynamic succession, resulting in the shift of niches and, ultimately, the alteration in N cycling. Notably, denitrification and Anammox, the important process for sediment N removal, are markedly limited by DA. Also, variation of N cycling implies the modification in cycles of other associated elements. Overall, DA is capable of ecosystem-level effects, which require further evaluation of its potential cascading effects.
Solving complex nanostructures with ptychographic atomic electron tomography
Authors: Pelz Philipp M. , Griffin Sinéad M. , Stonemeyer Scott , Popple Derek , DeVyldere Hannah , Ercius Peter , Zettl Alex , Scott Mary C. , Ophus Colin 
Published: November 2023

AbstractTransmission electron microscopy (TEM) is essential for determining atomic scale structures in structural biology and materials science. In structural biology, three-dimensional structures of proteins are routinely determined from thousands of identical particles using phase-contrast TEM. In materials science, three-dimensional atomic structures of complex nanomaterials have been determined using atomic electron tomography (AET). However, neither of these methods can determine the three-dimensional atomic structure of heterogeneous nanomaterials containing light elements. Here, we perform ptychographic electron tomography from 34.5 million diffraction patterns to reconstruct an atomic resolution tilt series of a double wall-carbon nanotube (DW-CNT) encapsulating a complex ZrTe sandwich structure. Class averaging the resulting tilt series images and subpixel localization of the atomic peaks reveals a Zr11Te50 structure containing a previously unobserved ZrTe2 phase in the core. The experimental realization of atomic resolution ptychographic electron tomography will allow for the structural determination of a wide range of beam-sensitive nanomaterials containing light elements.
Feasible supply of steel and cement within a carbon budget is likely to fall short of expected global demand
Authors: Watari Takuma , Cabrera Serrenho André , Gast Lukas , Cullen Jonathan , Allwood Julian 
Published: November 2023

AbstractThe current decarbonization strategy for the steel and cement industries is inherently dependent on the build-out of infrastructure, including for CO2 transport and storage, renewable electricity, and green hydrogen. However, the deployment of this infrastructure entails considerable uncertainty. Here we explore the global feasible supply of steel and cement within Paris-compliant carbon budgets, explicitly considering uncertainties in the deployment of infrastructure. Our scenario analysis reveals that despite substantial growth in recycling- and hydrogen-based production, the feasible steel supply will only meet 58–65% (interquartile range) of the expected baseline demand in 2050. Cement supply is even more uncertain due to limited mitigation options, meeting only 22–56% (interquartile range) of the expected baseline demand in 2050. These findings pose a two-fold challenge for decarbonizing the steel and cement industries: on the one hand, governments need to expand essential infrastructure rapidly; on the other hand, industries need to prepare for the risk of deployment failures, rather than solely waiting for large-scale infrastructure to emerge. Our feasible supply scenarios provide compelling evidence of the urgency of demand-side actions and establish benchmarks for the required level of resource efficiency.
CurveCurator: a recalibrated F-statistic to assess, classify, and explore significance of dose–response curves
Authors: Bayer Florian P. , Gander Manuel , Kuster Bernhard , The Matthew 
Published: November 2023

AbstractDose-response curves are key metrics in pharmacology and biology to assess phenotypic or molecular actions of bioactive compounds in a quantitative fashion. Yet, it is often unclear whether or not a measured response significantly differs from a curve without regulation, particularly in high-throughput applications or unstable assays. Treating potency and effect size estimates from random and true curves with the same level of confidence can lead to incorrect hypotheses and issues in training machine learning models. Here, we present CurveCurator, an open-source software that provides reliable dose-response characteristics by computing p-values and false discovery rates based on a recalibrated F-statistic and a target-decoy procedure that considers dataset-specific effect size distributions. The application of CurveCurator to three large-scale datasets enables a systematic drug mode of action analysis and demonstrates its scalable utility across several application areas, facilitated by a performant, interactive dashboard for fast data exploration.
Nickel/photoredox dual catalyzed arylalkylation of nonactivated alkenes
Authors: Gao Yuxi , Gao Lijuan , Zhu Endiao , Yang Yunhong , Jie Mi , Zhang Jiaqian , Pan Zhiqiang , Xia Chengfeng 
Published: November 2023

AbstractAlkene dicarbofunctionalization is an efficient strategy and operation-economic fashion for introducing complexity in molecules. A nickel/photoredox dual catalyzed arylalkylation of nonactivated alkenes for the simultaneous construction of one C(sp3)−C(sp3) bond and one C(sp3)−C(sp2) bond has been developed. The mild catalytic method provided valuable indanethylamine derivatives with wide substrate scope and good functional group compatibility. An enantioselective dicarbofunctionalization was also achieved with pyridine-oxazoline as a ligand. The efficiency of metallaphotoredox dicarbofunctionalization was demonstrated for the concise synthesis of pharmaceutically active compounds.
Demographics and risk of isolation due to sea level rise in the United States
Authors: Best Kelsea , He Qian , Reilly Allison C. , Niemeier Deb A. , Anderson Mitchell , Logan Tom 
Published: November 2023

AbstractWithin coastal communities, sea level rise (SLR) will result in widespread intermittent flooding and long-term inundation. Inundation effects will be evident, but isolation that arises from the loss of accessibility to critical services due to inundation of transportation networks may be less obvious. We examine who is most at risk of isolation due to SLR, which can inform community adaptation plans and help ensure that existing social vulnerabilities are not exacerbated. Combining socio-demographic data with an isolation metric, we identify social and economic disparities in risk of isolation under different SLR scenarios (1-10 ft) for the coastal U.S. We show that Black and Hispanic populations face a disproportionate risk of isolation at intermediate levels of SLR (4 ft and greater). Further, census tracts with higher rates of renters and older adults consistently face higher risk of isolation. These insights point to significant inequity in the burdens associated with SLR.
Estrogen receptor-positive breast cancer and adverse outcome in BRCA2 mutation carriers and young non-carrier patients
Authors: Vidarsdottir Linda , Olafsdottir Elinborg J. , Barkardottir Rosa B. , Bjarnadottir Olöf , Jonasson Jon G. , Sigurdsson Stefan , Tryggvadottir Laufey 
Published: November 2023

AbstractEstrogen receptor-positive (ER+) breast cancer generally confers a more favorable prognosis than ER-negative cancer, however, a different picture is emerging for BRCA2 mutation carriers and young patients. We used nationwide data from population-based registries to study prognostic effects in those two groups. Of all 2817 eligible women diagnosed with breast cancer in Iceland during 1980–2004, 85% had been tested for the Icelandic 999del5 BRCA2 (c.771_775delTCAAA) founder pathogenic variant. We compared breast cancer-specific survival, effects of ER status, other clinical parameters, and treatment, between three mutually exclusive groups: BRCA2-carriers, non-carriers diagnosed 40 years or younger, and older non-carriers. Prevalence of the BRCA2 mutation among tested patients <=40 years of age was 21.0%, but it was 5.4% among women diagnosed >40 years of age. For ER+ cancer, breast cancer-specific 15-year survival was 49.7%, 55.2%, and 74.7%, among BRCA2-carriers, young and older non-carriers, respectively, whereas for ER-negative cancer, survival was similar (64.0–69.3%) for all three groups. Neither BRCA2 carriers nor young non-carriers did tumor grade 3 predict worse survival than did tumor grade 1. The adverse outcome for the young cases cannot be explained by BRCA2 mutations, as carriers were excluded from the group. Those two clinically important patient groups need special attention with respect to treatment choices, in particular, if diagnosed with ER+ tumors. It is thus advisable to have knowledge of BRCA2 status when treatment decisions are made. Finally, it is important to understand the biological basis for the specific nature of ER+ tumors in young women and BRCA2 carriers.
ERα/PR crosstalk is altered in the context of the ERα Y537S mutation and contributes to endocrine therapy-resistant tumor proliferation
Authors: Huggins Rosemary J. , Greene Geoffrey L. 
Published: November 2023

AbstractThe constitutively active ESR1 Y537S mutation is associated with endocrine therapy (ET) resistance and progression of metastatic breast cancer through its effects on estrogen receptor (ERα) gene regulatory functions. However, the complex relationship between ERα and the progesterone receptor (PR), known as ERα/PR crosstalk, has yet to be characterized in the context of the ERα Y537S mutation. Using proximity ligation assays, we identify an increased physical interaction of ERα and PR in the context of the ERα Y537S mutation, including in the nucleus where this interaction may translate to altered gene expression. As such, more than 30 genes were differentially expressed in both patient tumor and cell line data (MCF7 and/or T47D cells) in the context of the ERα Y537S mutation compared to ERα WT. Of these, IRS1 stood out as a gene of interest, and ERα and PR occupancy at chromatin binding sites along IRS1 were uniquely altered in the context of ERα Y537S. Furthermore, siRNA knockdown of IRS1 or treatment with the IRS1 inhibitor NT-157 had a significant anti-proliferative effect in ERα Y537S cell lines, implicating IRS1 as a potential therapeutic target for restoring treatment sensitivity to patients with breast cancers harboring ERα Y537S mutations.
Pangenome analysis reveals genomic variations associated with domestication traits in broomcorn millet
Authors: Chen Jinfeng , Liu Yang , Liu Minxuan , Guo Wenlei , Wang Yongqiang , He Qiang , Chen Weiyao , Liao Yi , Zhang Wei , Gao Yuanzhu , Dong Kongjun , Ren Ruiyu , Yang Tianyu , Zhang Liyuan , Qi Mingyu , Li Zhiguang , Zhao Min , Wang Haigang , Wang Junjie , Qiao Zhijun , Li Haiquan , Jiang Yanmiao , Liu Guoqing , Song Xiaoqiang , Deng Yarui , Li Hai , Yan Feng , Dong Yang , Li Qingquan , Li Tao , Yang Wenyao , Cui Jianghui , Wang Hongru , Zhou Yongfeng , Zhang Xiaoming , Jia Guanqing , Lu Ping , Zhi Hui , Tang Sha , Diao Xianmin 
Published: November 2023

AbstractBroomcorn millet (Panicum miliaceum L.) is an orphan crop with the potential to improve cereal production and quality, and ensure food security. Here we present the genetic variations, population structure and diversity of a diverse worldwide collection of 516 broomcorn millet genomes. Population analysis indicated that the domesticated broomcorn millet originated from its wild progenitor in China. We then constructed a graph-based pangenome of broomcorn millet based on long-read de novo genome assemblies of 32 representative accessions. Our analysis revealed that the structural variations were highly associated with transposable elements, which influenced gene expression when located in the coding or regulatory regions. We also identified 139 loci associated with 31 key domestication and agronomic traits, including candidate genes and superior haplotypes, such as LG1, for panicle architecture. Thus, the study’s findings provide foundational resources for developing genomics-assisted breeding programs in broomcorn millet.
Chromosome-level genome assembly of the flower thrips Frankliniella intonsa
Authors: Zhang Zhijun , Bao Jiandong , Chen Qizhang , He Jianyun , Li Xiaowei , Zhang Jiahui , Liu Zhixing , Wu Yixuan , Li Xuesheng , Wang Yunsheng , Lu Yaobin 
Published: November 2023

AbstractAs an economically important insect pest, the flower thrips Frankliniella intonsa (Trybom) causes great damage to host plants by directly feeding and indirectly transmitting various pathogenic viruses. The lack of a well-assembled genomic resource has hindered our understanding of the genetic basis and evolution of F. intonsa. In this study, we used Oxford Nanopore Technology (ONT) long reads and High-through chromosome conformation capture (Hi-C) linked reads to construct a high-quality reference genome assembly of F. intonsa, with a total size of 225.5 Mb and a contig N50 of 3.37 Mb. By performing the Hi-C analysis, we anchored 91.68% of the contigs into 15 pseudochromosomes. Genomic annotation uncovered 17,581 protein-coding genes and identified 20.09% of the sequences as repeat elements. BUSCO analysis estimated over 98% of genome completeness. Our study is at the first time to report the chromosome-scale genome for the species of the genus Frankliniella. It provides a valuable genomic resource for further biological research and pest management of the thrips.
The time and place of origin of South Caucasian languages: insights into past human societies, ecosystems and human population genetics
Authors: Gavashelishvili Alexander , Chukhua Merab , Sakhltkhutsishvili Kakhi , Koptekin Dilek , Somel Mehmet 
Published: November 2023

AbstractThis study re-examines the linguistic phylogeny of the South Caucasian linguistic family (aka the Kartvelian linguistic family) and attempts to identify its Urheimat. We apply Bayesian phylogenetics to infer a dated phylogeny of the South Caucasian languages. We infer the Urheimat and the reasons for the split of the Kartvelian languages by taking into consideration (1) the past distribution ranges of wildlife elements whose names can be traced back to proto-Kartvelian roots, (2) the distribution ranges of past cultures and (3) the genetic variations of past and extant human populations. Our best-fit Bayesian phylogenetic model is in agreement with the widely accepted topology suggested by previous studies. However, in contrast to these studies, our model suggests earlier mean split dates, according to which the divergence between Svan and Karto-Zan occurred in the early Copper Age, while Georgian and Zan diverged in the early Iron Age. The split of Zan into Megrelian and Laz is widely attributed to the spread of Georgian and/or Georgian speakers in the seventh-eighth centuries CE. Our analyses place the Kartvelian Urheimat in an area that largely intersects the Colchis glacial refugium in the South Caucasus. The divergence of Kartvelian languages is strongly associated with differences in the rate of technological expansions in relation to landscape heterogeneity, as well as the emergence of state-run communities. Neolithic societies could not colonize dense forests, whereas Copper Age societies made limited progress in this regard, but not to the same degree of success achieved by Bronze and Iron Age societies. The paper also discusses the importance of glacial refugia in laying the foundation for linguistic families and where Indo-European languages might have originated.
Characterization and nutritional valorization of agricultural waste corncobs from Italian maize landraces through the growth of medicinal mushrooms
Authors: Castorina G. , Cappa C. , Negrini N. , Criscuoli F. , Casiraghi M. C. , Marti A. , Rollini M. , Consonni G. , Erba D. 
Published: November 2023

AbstractThe research investigates the potential use of maize cobs (or corncobs) from five genotypes, including the B73 inbred line and four locally cultivated landraces from Northern Italy, as substrate for implementing Solid State fermentation processes with four Medicinal Mushrooms (MMs). The corncobs were characterized based on their proximate composition, lignin, phenolics content (both free and bound), and total antioxidant capacity. Among the MMs tested, Pleurotus ostreatus and Ganoderma annularis demonstrated the most robust performance. Their growth was parametrized using Image Analysis technique, and chemical composition of culture samples was characterized compared to that of corncobs alone. In all culture samples, the growth of MMs led to a significant reduction (averaging 40%) in the total phenolics contents compared to that measured in corncobs alone. However, the high content of free phenolics in the cobs negatively impacted the growth of P. ostreatus. The final MM-corncob matrix exhibited reduced levels of free sugars and starch (≤ 2.2% DW, as a sum) and increased levels of proteins (up to 5.9% DW) and soluble dietary fiber (up to 5.0% DW), with a notable trend toward higher levels of β-glucan compared to corncobs alone. This research paves the way for the use of this matrix as an active ingredient to enhance the nutritional value of food preparations.
Assessment of the utility of underwater hyperspectral imaging for surveying and monitoring coral reef ecosystems
Authors: Mills Matthew S. , Ungermann Mischa , Rigot Guy , den Haan Joost , Leon Javier X. , Schils Tom 
Published: November 2023

AbstractTechnological innovations that improve the speed, scale, reproducibility, and accuracy of monitoring surveys will allow for a better understanding of the global decline in tropical reef health. The DiveRay, a diver-operated hyperspectral imager, and a complementary machine learning pipeline to automate the analysis of hyperspectral imagery were developed for this purpose. To evaluate the use of a hyperspectral imager underwater, the automated classification of benthic taxa in reef communities was tested. Eight reefs in Guam were surveyed and two approaches for benthic classification were employed: high taxonomic resolution categories and broad benthic categories. The results from the DiveRay surveys were validated against data from concurrently conducted photoquadrat surveys to determine their accuracy and utility as a proxy for reef surveys. The high taxonomic resolution classifications did not reliably predict benthic communities when compared to those obtained by standard photoquadrat analysis. At the level of broad benthic categories, however, the hyperspectral results were comparable to those of the photoquadrat analysis. This was particularly true when estimating scleractinian coral cover, which was accurately predicted for six out of the eight sites. The annotation libraries generated for this study were insufficient to train the model to fully account for the high biodiversity on Guam’s reefs. As such, prediction accuracy is expected to improve with additional surveying and image annotation. This study is the first to directly compare the results from underwater hyperspectral scanning with those from traditional photoquadrat survey techniques across multiple sites with two levels of identification resolution and different degrees of certainty. Our findings show that dependent on a well-annotated library, underwater hyperspectral imaging can be used to quickly, repeatedly, and accurately monitor and map dynamic benthic communities on tropical reefs using broad benthic categories.
Integration of motion information in illusory motion perceived in stationary patterns
Authors: Kobayashi Taisuke , Watanabe Eiji 
Published: November 2023

AbstractIllusory motion is a phenomenon in which stationary images with repeating luminance gradient patterns appear to be moving. In this study, we conducted experiments focusing on illusory motion to verify the hypothetical rule that velocity information, extracted from local luminance patterns, is integrated by summation in visual information processing. This rule is based on the hypothesis of velocity integration, and could estimate perceived velocity of stimulus. The summation rule was evaluated by a psychophysical experiment. Our results showed that the summation rule unbiasedly predicted perceived velocity, suggesting that an algorithm for integrating velocity information in illusory motion is based on the summation rule. These results would contribute to understanding of the spatial integration of local motion signals in visual information processing.