bluuebunny/crossref_metadata_2025_split huggingface dataset:
The miR-532-E2F1 feedback loop contributes to gastric cancer progression
Authors: Gao Shanting , Bu Xiaomin , Gao Yongyue , Bao Zengtao , Shi Wenchao , Luan Lipeng , Chen Huiyu , Zhang Baoming , Tian Qingshui , Guan Wenxian , Yang Liuqing 
Published: April 2022

AbstractGastric cancer (GC) ranks fourth in incidence and mortality worldwide, ascertaining the pathogenesis of GC is crucial for its treatment. E2F1, which regulates the transcription of genes encoding proteins involved in DNA repair, DNA replication, mitosis and survival of cancer patients, functions as a key regulator in GC progression. However, the underneath mechanism of these processes is not fully elucidated. Here, TCGA database analysis, microarray immunohistochemical technique and western blot showed that E2F1 was highly upregulated in clinical GC tissues and correlated with tumor malignancy. In vitro and in vivo assays confirmed the oncogenic function of E2F1. MiR-532 was decreased and negatively correlated with E2F1 in GC tissues. MiR-532 directly targeted and inhibited E2F1 expression, leading to the decrease of ASK1 and elevation of TXNIP, and affected proliferation, cell cycle, apoptosis and DNA damage in vitro and tumor growth in vivo. Moreover, E2F1 serves as a transcriptional repressor to suppress miR-532 expression and a double-negative feedback loop was formed between them. This study demonstrates the significant roles of the E2F1-miR-532 double-negative feedback loop in GC progression and may represent a potential target for GC therapy.
Dehydroepiandrosterone exacerbates nigericin-induced abnormal autophagy and pyroptosis via GPER activation in LPS-primed macrophages
Authors: Cao Ji , Li Longlong , Yao Yao , Xing Yuxiao , Ma Haitian 
Published: April 2022

AbstractAs a widely acknowledged FDA-approved dietary supplement or over-the-counter medicines, dehydroepiandrosterone (DHEA) exerts anti-inflammatory and immunomodulatory function. Pyroptosis is an important form of programmed cell death (PCD), and which acts a key role in the body’s anti-infection and inflammatory responses. But the effects and mechanisms of DHEA on pyroptosis remain unclear. Here, we found that DHEA inhibited the NLRP3 inflammasome components expression by blocking inflammatory signals in lipopolysaccharide (LPS)-primed macrophages, and prevented the bacterial toxin nigericin (Nig)-induced NLRP3 inflammasome assembly. However, DHEA exacerbated NLRP3-independent cell death in Nig-treated inflammatory macrophages. During this process, DHEA induced the abnormal autophagy, which reflected as the blocking of autophagic flux and the accumulation of autophagy receptor p62 (SQSTM1) protein. In addition, DHEA caused a burst of reactive oxygen species (ROS) and activated extracellular signal-regulated kinase (ERK) phosphorylation in LPS plus Nig-stimulated macrophages but not in LPS-treated macrophages. Mechanistically, the present study certified that the activation of G protein-coupled estrogen receptor (GPER) signal mediated the cell death induced by DHEA in Nig-stimulated inflammatory macrophages, as GPER specific inhibitor G15 alleviated the abnormal autophagy and ultimately prevented the gasdermin D (GSDMD)-mediated pyroptosis induced by DHEA. Collectively, DHEA can exacerbate Nig-induced abnormal autophagy and pyroptosis via activation of GPER in LPS-primed macrophages, which prompts us the potential application value of DHEA in anti-infection or anti-tumor immunity.
Collective interactions among organometallics are exotic bonds hidden on lab shelves
Authors: Sowlati-Hashjin Shahin , Šadek Vojtěch , Sadjadi SeyedAbdolreza , Karttunen Mikko , Martín-Pendás Angel , Foroutan-Nejad Cina 
Published: April 2022

AbstractRecent discovery of an unusual bond between Na and B in NaBH3− motivated us to look for potentially similar bonds, which remained unnoticed among systems isoelectronic with NaBH3−. Here, we report a novel family of collective interactions and a measure called exchange-correlation interaction collectivity index (ICIXC; $${ICI}\in \left[{{{{\mathrm{0,1}}}}}\right]$$
I
C
I
∈

0, 1

) to characterize the extent of collective versus pairwise bonding. Unlike conventional bonds in which ICIXC remains close to one, in collective interactions ICIXC may approach zero. We show that collective interactions are commonplace among widely used organometallics, as well as among boron and aluminum complexes with the general formula [Ma+AR3]b− (A: C, B or Al). In these species, the metal atom interacts more efficiently with the substituents (R) on the central atoms than the central atoms (A) upon forming efficient collective interactions. Furthermore, collective interactions were also found among fluorine atoms of XFn systems (X: B or C). Some of organolithium and organomagnesium species have the lowest ICIXC among the more than 100 studied systems revealing the fact that collective interactions are rather a rule than an exception among organometallic species.
Reversible Power-to-Gas systems for energy conversion and storage
Authors: Glenk Gunther , Reichelstein Stefan 
Published: April 2022

AbstractIn the transition to decarbonized energy systems, Power-to-Gas (PtG) processes have the potential to connect the existing markets for electricity and hydrogen. Specifically, reversible PtG systems can convert electricity to hydrogen at times of ample power supply, yet they can also operate in the reverse direction to deliver electricity during times when power is relatively scarce. Here we develop a model for determining when reversible PtG systems are economically viable. We apply the model to the current market environment in both Germany and Texas and find that the reversibility feature of unitized regenerative fuel cells (solid oxide) makes them already cost-competitive at current hydrogen prices, provided the fluctuations in electricity prices are as pronounced as currently observed in Texas. We further project that, due to their inherent flexibility, reversible PtG systems would remain economically viable at substantially lower hydrogen prices in the future, provided recent technological trends continue over the coming decade.
A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population
Authors: Qu Yuanyuan , Feng Jinwen , Wu Xiaohui , Bai Lin , Xu Wenhao , Zhu Lingli , Liu Yang , Xu Fujiang , Zhang Xuan , Yang Guojian , Lv Jiacheng , Chen Xiuping , Shi Guo-Hai , Wang Hong-Kai , Cao Da-Long , Xiang Hang , Li Lingling , Tan Subei , Gan Hua-Lei , Sun Meng-Hong , Qiu Jiange , Zhang Hailiang , Zhao Jian-Yuan , Ye Dingwei , Ding Chen 
Published: April 2022

AbstractClear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of renal cancer. Here we conduct a comprehensive proteogenomic analysis of 232 tumor and adjacent non-tumor tissue pairs from Chinese ccRCC patients. By comparing with tumor adjacent tissues, we find that ccRCC shows extensive metabolic dysregulation and an enhanced immune response. Molecular subtyping classifies ccRCC tumors into three subtypes (GP1–3), among which the most aggressive GP1 exhibits the strongest immune phenotype, increased metastasis, and metabolic imbalance, linking the multi-omics-derived phenotypes to clinical outcomes of ccRCC. Nicotinamide N-methyltransferase (NNMT), a one-carbon metabolic enzyme, is identified as a potential marker of ccRCC and a drug target for GP1. We demonstrate that NNMT induces DNA-dependent protein kinase catalytic subunit (DNA-PKcs) homocysteinylation, increases DNA repair, and promotes ccRCC tumor growth. This study provides insights into the biological underpinnings and prognosis assessment of ccRCC, revealing targetable metabolic vulnerabilities.
High-quality genome and methylomes illustrate features underlying evolutionary success of oaks
Authors: Sork Victoria L. , Cokus Shawn J. , Fitz-Gibbon Sorel T. , Zimin Aleksey V. , Puiu Daniela , Garcia Jesse A. , Gugger Paul F. , Henriquez Claudia L. , Zhen Ying , Lohmueller Kirk E. , Pellegrini Matteo , Salzberg Steven L. 
Published: April 2022

AbstractThe genusQuercus, which emerged ∼55 million years ago during globally warm temperatures, diversified into ∼450 extant species. We present a high-quality de novo genome assembly of a California endemic oak,Quercus lobata, revealing features consistent with oak evolutionary success. Effective population size remained large throughout history despite declining since early Miocene. Analysis of 39,373 mapped protein-coding genes outlined copious duplications consistent with genetic and phenotypic diversity, both by retention of genes created during the ancient γ whole genome hexaploid duplication event and by tandem duplication within families, including numerous resistance genes and a very large block of duplicated DUF247 genes, which have been found to be associated with self-incompatibility in grasses. An additional surprising finding is that subcontext-specific patterns of DNA methylation associated with transposable elements reveal broadly-distributed heterochromatin in intergenic regions, similar to grasses. Collectively, these features promote genetic and phenotypic variation that would facilitate adaptability to changing environments.
Generation of human islet cell type-specific identity genesets
Authors: van Gurp Léon , Fodoulian Leon , Oropeza Daniel , Furuyama Kenichiro , Bru-Tari Eva , Vu Anh Nguyet , Kaddis John S. , Rodríguez Iván , Thorel Fabrizio , Herrera Pedro L. 
Published: April 2022

AbstractGeneration of surrogate cells with stable functional identities is crucial for developing cell-based therapies. Efforts to produce insulin-secreting replacement cells to treat diabetes require reliable tools to assess islet cellular identity. Here, we conduct a thorough single-cell transcriptomics meta-analysis to identify robustly expressed markers used to build genesets describing the identity of human α-, β-, γ- and δ-cells. These genesets define islet cellular identities better than previously published genesets. We show their efficacy to outline cell identity changes and unravel some of their underlying genetic mechanisms, whether during embryonic pancreas development or in experimental setups aiming at developing glucose-responsive insulin-secreting cells, such as pluripotent stem-cell differentiation or in adult islet cell reprogramming protocols. These islet cell type-specific genesets represent valuable tools that accurately benchmark gain and loss in islet cell identity traits.
Targeting TCTP sensitizes tumor to T cell-mediated therapy by reversing immune-refractory phenotypes
Authors: Lee Hyo-Jung , Song Kwon-Ho , Oh Se Jin , Kim Suyeon , Cho Eunho , Kim Jungwon , Park Yun gyu , Lee Kyung-Mi , Yee Cassian , Song Seung-Hwa , Chang Suhwan , Choi Jungmin , Jung Sang Taek , Kim Tae Woo 
Published: April 2022

AbstractImmunotherapy has emerged as a powerful approach to cancer treatment. However, immunotherapeutic resistance limits its clinical application. Therefore, identifying immune-resistant factors, which can be targeted by clinically available drugs and it also can be a companion diagnostic marker, is needed to develop combination strategies. Here, using the transcriptome data of patients, and immune-refractory tumor models, we identify TCTP as an immune-resistance factor that correlates with clinical outcome of anti-PD-L1 therapy and confers immune-refractory phenotypes, decreased T cell trafficking to the tumor and resistance to cytotoxic T lymphocyte-mediated tumor cell killing. Mechanistically, TCTP activates the EGFR-AKT-MCL-1/CXCL10 pathway by phosphorylation-dependent interaction with Na, K ATPase. Furthermore, treatment with dihydroartenimsinin, the most effective agent impending the TCTP-mediated-refractoriness, synergizes with T cell-mediated therapy to control immune-refractory tumors. Thus, our findings suggest a role of TCTP in promoting immune-refractoriness, thereby encouraging a rationale for combination therapies to enhance the efficacy of T cell-mediated therapy.
New seasonal pattern of pollution emerges from changing North American wildfires
Authors: Buchholz Rebecca R. , Park Mijeong , Worden Helen M. , Tang Wenfu , Edwards David P. , Gaubert Benjamin , Deeter Merritt N. , Sullivan Thomas , Ru Muye , Chin Mian , Levy Robert C. , Zheng Bo , Magzamen Sheryl 
Published: April 2022

AbstractRising emissions from wildfires over recent decades in the Pacific Northwest are known to counteract the reductions in human-produced aerosol pollution over North America. Since amplified Pacific Northwest wildfires are predicted under accelerating climate change, it is essential to understand both local and transported contributions to air pollution in North America. Here, we find corresponding increases for carbon monoxide emitted from the Pacific Northwest wildfires and observe significant impacts on both local and down-wind air pollution. Between 2002 and 2018, the Pacific Northwest atmospheric carbon monoxide abundance increased in August, while other months showed decreasing carbon monoxide, so modifying the seasonal pattern. These seasonal pattern changes extend over large regions of North America, to the Central USA and Northeast North America regions, indicating that transported wildfire pollution could potentially impact the health of millions of people.
A leukemia-protective germline variant mediates chromatin module formation via transcription factor nucleation
Authors: Llimos Gerard , Gardeux Vincent , Koch Ute , Kribelbauer Judith F. , Hafner Antonina , Alpern Daniel , Pezoldt Joern , Litovchenko Maria , Russeil Julie , Dainese Riccardo , Moia Riccardo , Mahmoud Abdurraouf Mokhtar , Rossi Davide , Gaidano Gianluca , Plass Christoph , Lutsik Pavlo , Gerhauser Clarissa , Waszak Sebastian M. , Boettiger Alistair , Radtke Freddy , Deplancke Bart 
Published: April 2022

AbstractNon-coding variants coordinate transcription factor (TF) binding and chromatin mark enrichment changes over regions spanning >100 kb. These molecularly coordinated regions are named “variable chromatin modules” (VCMs), providing a conceptual framework of how regulatory variation might shape complex traits. To better understand the molecular mechanisms underlying VCM formation, here, we mechanistically dissect a VCM-modulating noncoding variant that is associated with reduced chronic lymphocytic leukemia (CLL) predisposition and disease progression. This common, germline variant constitutes a 5-bp indel that controls the activity of an AXIN2 gene-linked VCM by creating a MEF2 binding site, which, upon binding, activates a super-enhancer-like regulatory element. This triggers a large change in TF binding activity and chromatin state at an enhancer cluster spanning >150 kb, coinciding with subtle, long-range chromatin compaction and robust AXIN2 up-regulation. Our results support a model in which the indel acts as an AXIN2 VCM-activating TF nucleation event, which modulates CLL pathology.
The neural coding framework for learning generative models
Authors: Ororbia Alexander , Kifer Daniel 
Published: April 2022

AbstractNeural generative models can be used to learn complex probability distributions from data, to sample from them, and to produce probability density estimates. We propose a computational framework for developing neural generative models inspired by the theory of predictive processing in the brain. According to predictive processing theory, the neurons in the brain form a hierarchy in which neurons in one level form expectations about sensory inputs from another level. These neurons update their local models based on differences between their expectations and the observed signals. In a similar way, artificial neurons in our generative models predict what neighboring neurons will do, and adjust their parameters based on how well the predictions matched reality. In this work, we show that the neural generative models learned within our framework perform well in practice across several benchmark datasets and metrics and either remain competitive with or significantly outperform other generative models with similar functionality (such as the variational auto-encoder).
Inhibition of the succinyl dehydrogenase complex in acute myeloid leukemia leads to a lactate-fuelled respiratory metabolic vulnerability
Authors: Erdem Ayşegül , Marin Silvia , Pereira-Martins Diego A. , Geugien Marjan , Cunningham Alan , Pruis Maurien G. , Weinhäuser Isabel , Gerding Albert , Bakker Barbara M. , Wierenga Albertus T. J. , Rego Eduardo M. , Huls Gerwin , Cascante Marta , Schuringa Jan Jacob 
Published: April 2022

AbstractMetabolic programs can differ substantially across genetically distinct subtypes of acute myeloid leukemia (AML). These programs are not static entities but can change swiftly as a consequence of extracellular changes or in response to pathway-inhibiting drugs. Here, we uncover that AML patients with FLT3 internal tandem duplications (FLT3-ITD+) are characterized by a high expression of succinate-CoA ligases and high activity of mitochondrial electron transport chain (ETC) complex II, thereby driving high mitochondrial respiration activity linked to the Krebs cycle. While inhibition of ETC complex II enhances apoptosis in FLT3-ITD+ AML, cells also quickly adapt by importing lactate from the extracellular microenvironment. 13C3-labelled lactate metabolic flux analyses reveal that AML cells use lactate as a fuel for mitochondrial respiration. Inhibition of lactate transport by blocking Monocarboxylic Acid Transporter 1 (MCT1) strongly enhances sensitivity to ETC complex II inhibition in vitro as well as in vivo. Our study highlights a metabolic adaptability of cancer cells that can be exploited therapeutically.
A natural allele of OsMS1 responds to temperature changes and confers thermosensitive genic male sterility
Authors: Wu Lunying , Jing Xiaohui , Zhang Baolan , Chen Shoujun , Xu Ran , Duan Penggen , Zou Danni , Huang Shengjian , Zhou Tingbo , An Chengcai , Luo Yuehua , Li Yunhai 
Published: April 2022

AbstractChanges in ambient temperature influence crop fertility and production. Understanding of how crops sense and respond to temperature is thus crucial for sustainable agriculture. The thermosensitive genic male-sterile (TGMS) lines are widely used for hybrid rice breeding and also provide a good system to investigate the mechanisms underlying temperature sensing and responses in crops. Here, we show that OsMS1 is a histone binding protein, and its natural allele OsMS1wenmin1 confers thermosensitive male sterility in rice. OsMS1 is primarily localized in nuclei, while OsMS1wenmin1 is localized in nuclei and cytoplasm. Temperature regulates the abundances of OsMS1 and OsMS1wenmin1 proteins. The high temperature causes more reduction of OsMS1wenmin1 than OsMS1 in nuclei. OsMS1 associates with the transcription factor TDR to regulate expression of downstream genes in a temperature-dependent manner. Thus, our findings uncover a thermosensitive mechanism that could be useful for hybrid crop breeding.
A decade of cold Eurasian winters reconstructed for the early 19th century
Authors: Reichen Lukas , Burgdorf Angela-Maria , Brönnimann Stefan , Franke Jörg , Hand Ralf , Valler Veronika , Samakinwa Eric , Brugnara Yuri , Rutishauser This 
Published: April 2022

AbstractAnnual-to-decadal variability in northern midlatitude temperature is dominated by the cold season. However, climate field reconstructions are often based on tree rings that represent the growing season. Here we present cold-season (October-to-May average) temperature field reconstructions for the northern midlatitudes, 1701-1905, based on extensive phenological data (freezing and thawing dates of rivers, plant observations). Northern midlatitude land temperatures exceeded the variability range of the 18th and 19th centuries by the 1940s, to which recent warming has added another 1.5 °C. A sequences of cold winters 1808/9-1815/6 can be explained by two volcanic eruptions and unusual atmospheric flow. Weak southwesterlies over Western Europe in early winter caused low Eurasian temperatures, which persisted into spring even though the flow pattern did not. Twentieth century data and model simulations confirm this persistence and point to increased snow cover as a cause, consistent with sparse information on Eurasian snow in the early 19th century.
Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF
Authors: Aljahani Abrar , Hua Peng , Karpinska Magdalena A. , Quililan Kimberly , Davies James O. J. , Oudelaar A. Marieke 
Published: April 2022

AbstractEnhancers and promoters predominantly interact within large-scale topologically associating domains (TADs), which are formed by loop extrusion mediated by cohesin and CTCF. However, it is unclear whether complex chromatin structures exist at sub-kilobase-scale and to what extent fine-scale regulatory interactions depend on loop extrusion. To address these questions, we present an MNase-based chromosome conformation capture (3C) approach, which has enabled us to generate the most detailed local interaction data to date (20 bp resolution) and precisely investigate the effects of cohesin and CTCF depletion on chromatin architecture. Our data reveal that cis-regulatory elements have distinct internal nano-scale structures, within which local insulation is dependent on CTCF, but which are independent of cohesin. In contrast, we find that depletion of cohesin causes a subtle reduction in longer-range enhancer-promoter interactions and that CTCF depletion can cause rewiring of regulatory contacts. Together, our data show that loop extrusion is not essential for enhancer-promoter interactions, but contributes to their robustness and specificity and to precise regulation of gene expression.
Reconfigurable halide perovskite nanocrystal memristors for neuromorphic computing
Authors: John Rohit Abraham , Demirağ Yiğit , Shynkarenko Yevhen , Berezovska Yuliia , Ohannessian Natacha , Payvand Melika , Zeng Peng , Bodnarchuk Maryna I. , Krumeich Frank , Kara Gökhan , Shorubalko Ivan , Nair Manu V. , Cooke Graham A. , Lippert Thomas , Indiveri Giacomo , Kovalenko Maksym V. 
Published: April 2022

AbstractMany in-memory computing frameworks demand electronic devices with specific switching characteristics to achieve the desired level of computational complexity. Existing memristive devices cannot be reconfigured to meet the diverse volatile and non-volatile switching requirements, and hence rely on tailored material designs specific to the targeted application, limiting their universality. “Reconfigurable memristors” that combine both ionic diffusive and drift mechanisms could address these limitations, but they remain elusive. Here we present a reconfigurable halide perovskite nanocrystal memristor that achieves on-demand switching between diffusive/volatile and drift/non-volatile modes by controllable electrochemical reactions. Judicious selection of the perovskite nanocrystals and organic capping ligands enable state-of-the-art endurance performances in both modes – volatile (2 × 106 cycles) and non-volatile (5.6 × 103 cycles). We demonstrate the relevance of such proof-of-concept perovskite devices on a benchmark reservoir network with volatile recurrent and non-volatile readout layers based on 19,900 measurements across 25 dynamically-configured devices.