bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resveratrol protects osteocytes against oxidative stress in ovariectomized rats through AMPK/JNK1-dependent pathway leading to promotion of autophagy and inhibition of apoptosis
Authors: Wei Liwei , Chai Shuang , Yue Chen , Zhang Hong , Li Jitian , Qin Na 
Published: January 2023

AbstractA large number of studies in recent years indicate that osteocytes are the orchestrators of bone remodeling by regulating both osteoblast and osteoclast activities. Oxidative stress-induced osteocyte apoptosis plays critical roles in the pathological processes of postmenopausal osteoporosis. Resveratrol is a natural polyphenolic compound that ameliorates postmenopausal osteoporosis. However, whether resveratrol regulates osteocyte apoptosis via autophagy remains largely unknown. The effects of resveratrol on regulating osteocyte apoptosis and autophagy were analyzed both in vivo and in vitro. In vitro, cultured MLO-Y4 cells were exposed to H2O2 with or without resveratrol. In vivo, an ovariectomy-induced osteoporosis model was constructed in rats with or without daily intraperitoneal injection of 10 mg/kg body weight resveratrol. It was found that resveratrol attenuated H2O2-induced apoptosis through activating autophagy in cultured MLO-Y4 cells, which was mediated by the dissociation of Beclin-1/Bcl-2 complex in AMPK/JNK1-dependent pathway, ultimately regulating osteocytes function. Furthermore, it was shown that resveratrol treatment reduced osteocytes oxidative stress, inhibited osteocytes apoptosis and promoted autophagy in ovariectomized rats. Our study suggests that resveratrol protects against oxidative stress by restoring osteocytes autophagy and alleviating apoptosis via AMPK/JNK1 activation, therefore dissociating Bcl-2 from Beclin-1.
Polycomb deficiency drives a FOXP2-high aggressive state targetable by epigenetic inhibitors
Authors: Chen Fan , Byrd Aria L. , Liu Jinpeng , Flight Robert M. , DuCote Tanner J. , Naughton Kassandra J. , Song Xiulong , Edgin Abigail R. , Lukyanchuk Alexsandr , Dixon Danielle T. , Gosser Christian M. , Esoe Dave-Preston , Jayswal Rani D. , Orkin Stuart H. , Moseley Hunter N. B. , Wang Chi , Brainson Christine Fillmore 
Published: January 2023

AbstractInhibitors of the Polycomb Repressive Complex 2 (PRC2) histone methyltransferase EZH2 are approved for certain cancers, but realizing their wider utility relies upon understanding PRC2 biology in each cancer system. Using a genetic model to delete Ezh2 in KRAS-driven lung adenocarcinomas, we observed that Ezh2 haplo-insufficient tumors were less lethal and lower grade than Ezh2 fully-insufficient tumors, which were poorly differentiated and metastatic. Using three-dimensional cultures and in vivo experiments, we determined that EZH2-deficient tumors were vulnerable to H3K27 demethylase or BET inhibitors. PRC2 loss/inhibition led to de-repression of FOXP2, a transcription factor that promotes migration and stemness, and FOXP2 could be suppressed by BET inhibition. Poorly differentiated human lung cancers were enriched for an H3K27me3-low state, representing a subtype that may benefit from BET inhibition as a single therapy or combined with additional EZH2 inhibition. These data highlight diverse roles of PRC2 in KRAS-driven lung adenocarcinomas, and demonstrate the utility of three-dimensional cultures for exploring epigenetic drug sensitivities for cancer.
Selective CO2 electrolysis to CO using isolated antimony alloyed copper
Authors: Li Jiawei , Zeng Hongliang , Dong Xue , Ding Yimin , Hu Sunpei , Zhang Runhao , Dai Yizhou , Cui Peixin , Xiao Zhou , Zhao Donghao , Zhou Liujiang , Zheng Tingting , Xiao Jianping , Zeng Jie , Xia Chuan 
Published: January 2023

AbstractRenewable electricity-powered CO evolution from CO2emissions is a promising first step in the sustainable production of commodity chemicals, but performing electrochemical CO2reduction economically at scale is challenging since only noble metals, for example, gold and silver, have shown high performance for CO2-to-CO. Cu is a potential catalyst to achieve CO2reduction to CO at the industrial scale, but the C-C coupling process on Cu significantly depletes CO* intermediates, thus limiting the CO evolution rate and producing many hydrocarbon and oxygenate mixtures. Herein, we tune the CO selectivity of Cu by alloying a second metal Sb into Cu, and report an antimony-copper single-atom alloy catalyst (Sb1Cu) of isolated Sb-Cu interfaces that catalyzes the efficient conversion of CO2-to-CO with a Faradaic efficiency over 95%. The partial current density reaches 452 mA cm−2with approximately 91% CO Faradaic efficiency, and negligible C2+products are observed. In situ spectroscopic measurements and theoretical simulations reason that the atomic Sb-Cu interface in Cu promotes CO2adsorption/activation and weakens the binding strength of CO*, which ends up with enhanced CO selectivity and production rates.
Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis
Authors: Pei Fei , Ma Li , Jing Junjun , Feng Jifan , Yuan Yuan , Guo Tingwei , Han Xia , Ho Thach-Vu , Lei Jie , He Jinzhi , Zhang Mingyi , Chen Jian-Fu , Chai Yang 
Published: January 2023

AbstractMesenchymal stem cells (MSCs) reside in microenvironments, referred to as niches, which provide structural support and molecular signals. Sensory nerves are niche components in the homeostasis of tissues such as skin, bone marrow and hematopoietic system. However, how the sensory nerve affects the behavior of MSCs remains largely unknown. Here we show that the sensory nerve is vital for mesenchymal tissue homeostasis and maintenance of MSCs in the continuously growing adult mouse incisor. Loss of sensory innervation leads to mesenchymal disorder and a decrease in MSCs. Mechanistically, FGF1 from the sensory nerve directly acts on MSCs by binding to FGFR1 and activates the mTOR/autophagy axis to sustain MSCs. Modulation of mTOR/autophagy restores the MSCs and rescues the mesenchymal tissue disorder of Fgfr1 mutant mice. Collectively, our study provides insights into the role of sensory nerves in the regulation of MSC homeostasis and the mechanism governing it.
The rocky road to organics needs drying
Authors: Andreani Muriel , Montagnac Gilles , Fellah Clémentine , Hao Jihua , Vandier Flore , Daniel Isabelle , Pisapia Céline , Galipaud Jules , Lilley Marvin D. , Früh Green Gretchen L. , Borensztajn Stéphane , Ménez Bénédicte 
Published: January 2023

AbstractHow simple abiotic organic compounds evolve toward more complex molecules of potentially prebiotic importance remains a missing key to establish where life possibly emerged. The limited variety of abiotic organics, their low concentrations and the possible pathways identified so far in hydrothermal fluids have long hampered a unifying theory of a hydrothermal origin for the emergence of life on Earth. Here we present an alternative road to abiotic organic synthesis and diversification in hydrothermal environments, which involves magmatic degassing and water-consuming mineral reactions occurring in mineral microcavities. This combination gathers key gases (N2, H2, CH4, CH3SH) and various polyaromatic materials associated with nanodiamonds and mineral products of olivine hydration (serpentinization). This endogenous assemblage results from re-speciation and drying of cooling C–O–S–H–N fluids entrapped below 600 °C–2 kbars in rocks forming the present-day oceanic lithosphere. Serpentinization dries out the system toward macromolecular carbon condensation, while olivine pods keep ingredients trapped until they are remobilized for further reactions at shallower levels. Results greatly extend our understanding of the forms of abiotic organic carbon available in hydrothermal environments and open new pathways for organic synthesis encompassing the role of minerals and drying. Such processes are expected in other planetary bodies wherever olivine-rich magmatic systems get cooled down and hydrated.
A generative deep learning framework for inverse design of compositionally complex bulk metallic glasses
Authors: Zhou Ziqing , Shang Yinghui , Liu Xiaodi , Yang Yong 
Published: January 2023

AbstractThe design of bulk metallic glasses (BMGs) via machine learning (ML) has been a topic of active research recently. However, the prior ML models were mostly built upon supervised learning algorithms with human inputs to navigate the high dimensional compositional space, which becomes inefficient with the increasing compositional complexity in BMGs. Here, we develop a generative deep-learning framework to directly generate compositionally complex BMGs, such as high entropy BMGs. Our framework is built on the unsupervised Generative Adversarial Network (GAN) algorithm for data generation and the supervised Boosted Trees algorithm for data evaluation. We studied systematically the confounding effect of various data descriptors and the literature data on the effectiveness of our framework both numerically and experimentally. Most importantly, we demonstrate that our generative deep learning framework is capable of producing composition-property mappings, therefore paving the way for the inverse design of BMGs.
Correspondence analysis for dimension reduction, batch integration, and visualization of single-cell RNA-seq data
Authors: Hsu Lauren L. , Culhane Aedín C. 
Published: January 2023

AbstractEffective dimension reduction is essential for single cell RNA-seq (scRNAseq) analysis. Principal component analysis (PCA) is widely used, but requires continuous, normally-distributed data; therefore, it is often coupled with log-transformation in scRNAseq applications, which can distort the data and obscure meaningful variation. We describe correspondence analysis (CA), a count-based alternative to PCA. CA is based on decomposition of a chi-squared residual matrix, avoiding distortive log-transformation. To address overdispersion and high sparsity in scRNAseq data, we propose five adaptations of CA, which are fast, scalable, and outperform standard CA and glmPCA, to compute cell embeddings with more performant or comparable clustering accuracy in 8 out of 9 datasets. In particular, we find that CA with Freeman–Tukey residuals performs especially well across diverse datasets. Other advantages of the CA framework include visualization of associations between genes and cell populations in a “CA biplot,” and extension to multi-table analysis; we introducecorralmfor integrative multi-table dimension reduction of scRNAseq data. We implement CA for scRNAseq data incorral, an R/Bioconductor package which interfaces directly with single cell classes in Bioconductor. Switching from PCA to CA is achieved through a simple pipeline substitution and improves dimension reduction of scRNAseq datasets.
SLC11A2: a promising biomarker and therapeutic target in ovarian cancer
Authors: Tian Liming , Li Xuemei , Lai Huiling , Sun Tingting , Li Xiaohui , Wu Linxiang , Wu Chuling , Yao Shuzhong , Ren Yufeng , He Shasha , Yang Guofen 
Published: January 2023

AbstractOvarian cancer has the highest mortality rate among gynecologic tumors, with a 5-year survival rate of less than 25%. There is an urgent need for early diagnosis and new drugs to reduce the disease burden of ovarian cancer. The aim of this study was to investigate the effectiveness of SLC11A2 as a therapeutic target and marker for ovarian cancer. Expression data of SLC11A2 were obtained from public databases. Then, the biological functions of SLC11A2 were validated in four ovarian cancer cell lines. Finally, we collected ovarian cancer clinical tissues, serum, and plasma exosomes and used immunohistochemistry, Elisa, and liquid chromatography-mass spectrometry (LC–MS) to validate the test efficacy of SLC11A2. The results showed that ovarian cancers with high SLC11A2 mRNA expression had shorter 5-year PFS and MST. Knockdown of SLC11A2 reduced ovarian cancer migration and increased cisplatin-induced apoptosis. Serum SLC11A2 may help improve the detection rate of ovarian cancer.
Evaluation of emphysema on thoracic low-dose CTs through attention-based multiple instance deep learning
Authors: Fuhrman Jordan , Yip Rowena , Zhu Yeqing , Jirapatnakul Artit C. , Li Feng , Henschke Claudia I. , Yankelevitz David F. , Giger Maryellen L. 
Published: January 2023

AbstractIn addition to lung cancer, other thoracic abnormalities, such as emphysema, can be visualized within low-dose CT scans that were initially obtained in cancer screening programs, and thus, opportunistic evaluation of these diseases may be highly valuable. However, manual assessment for each scan is tedious and often subjective, thus we have developed an automatic, rapid computer-aided diagnosis system for emphysema using attention-based multiple instance deep learning and 865 LDCTs. In the task of determining if a CT scan presented with emphysema or not, our novel Transfer AMIL approach yielded an area under the ROC curve of 0.94 ± 0.04, which was a statistically significant improvement compared to other methods evaluated in our study following the Delong Test with correction for multiple comparisons. Further, from our novel attention weight curves, we found that the upper lung demonstrated a stronger influence in all scan classes, indicating that the model prioritized upper lobe information. Overall, our novel Transfer AMIL method yielded high performance and provided interpretable information by identifying slices that were most influential to the classification decision, thus demonstrating strong potential for clinical implementation.
Deterministic and probabilistic regularities underlying risky choices are acquired in a changing decision context
Authors: Kóbor Andrea , Tóth-Fáber Eszter , Kardos Zsófia , Takács Ádám , Éltető Noémi , Janacsek Karolina , Csépe Valéria , Nemeth Dezso 
Published: January 2023

AbstractPredictions supporting risky decisions could become unreliable when outcome probabilities temporarily change, making adaptation more challenging. Therefore, this study investigated whether sensitivity to the temporal structure in outcome probabilities can develop and remain persistent in a changing decision environment. In a variant of the Balloon Analogue Risk Task with 90 balloons, outcomes (rewards or balloon bursts) were predictable in the task’s first and final 30 balloons and unpredictable in the middle 30 balloons. The temporal regularity underlying the predictable outcomes differed across three experimental conditions. In the deterministic condition, a repeating three-element sequence dictated the maximum number of pumps before a balloon burst. In the probabilistic condition, a single probabilistic regularity ensured that burst probability increased as a function of pumps. In the hybrid condition, a repeating sequence of three different probabilistic regularities increased burst probabilities. In every condition, the regularity was absent in the middle 30 balloons. Participants were not informed about the presence or absence of the regularity. Sensitivity to both the deterministic and hybrid regularities emerged and influenced risk taking. Unpredictable outcomes of the middle phase did not deteriorate this sensitivity. In conclusion, humans can adapt their risky choices in a changing decision environment by exploiting the statistical structure that controls how the environment changes.
Visuospatial information foraging describes search behavior in learning latent environmental features
Authors: Barack David L. , Bakkour Akram , Shohamy Daphna , Salzman C. Daniel 
Published: January 2023

AbstractIn the real world, making sequences of decisions to achieve goals often depends upon the ability to learn aspects of the environment that are not directly perceptible. Learning these so-called latent features requires seeking information about them. Prior efforts to study latent feature learning often used single decisions, used few features, and failed to distinguish between reward-seeking and information-seeking. To overcome this, we designed a task in which humans and monkeys made a series of choices to search for shapes hidden on a grid. On our task, the effects of reward and information outcomes from uncovering parts of shapes could be disentangled. Members of both species adeptly learned the shapes and preferred to select tiles expected to be informative earlier in trials than previously rewarding ones, searching a part of the grid until their outcomes dropped below the average information outcome—a pattern consistent with foraging behavior. In addition, how quickly humans learned the shapes was predicted by how well their choice sequences matched the foraging pattern, revealing an unexpected connection between foraging and learning. This adaptive search for information may underlie the ability in humans and monkeys to learn latent features to support goal-directed behavior in the long run.
Synthetic two-species allodiploid and three-species allotetraploid Saccharomyces hybrids with euploid (complete) parental subgenomes
Authors: Antunovics Zsuzsa , Szabo Adrienn , Heistinger Lina , Mattanovich Diethard , Sipiczki Matthias 
Published: January 2023

AbstractCombination of the genomes of Saccharomyces species has great potential for the construction of new industrial strains as well as for the study of the process of speciation. However, these species are reproductively isolated by a double sterility barrier. The first barrier is mainly due to the failure of the chromosomes to pair in allodiploid meiosis. The second barrier ensures that the hybrid remains sterile even after genome duplication, an event that can restore fertility in plant interspecies hybrids. The latter is attributable to the autodiploidisation of the allotetraploid meiosis that results in sterile allodiploid spores (return to the first barrier). Occasionally, mating-competent alloaneuploid spores arise by malsegregation of MAT-carrying chromosomes. These can mate with cells of a third species resulting in aneuploid zygotes having at least one incomplete subgenome. Here we report on the construction of euploid three-species hybrids by making use of “rare mating” between a sterile S. kudriavzevii x S. uvarum allodiploid hybrid and a diploid S. cerevisiae strain. The hybrids have allotetraploid 2nScnSk nSu genomes consisting of complete sets of parental chromosomes. This is the first report on the production of euploid three-species Saccharomyces hybrids by natural mating, without genetic manipulation. The hybrids provide possibilities for studying the interactions of three allospecific genomes and their orthologous genes present in the same cell.
Codon modification of Tuba1a alters mRNA levels and causes a severe neurodevelopmental phenotype in mice
Authors: Leca Ines , Phillips Alexander William , Ushakova Lyubov , Cushion Thomas David , Keays David Anthony 
Published: January 2023

AbstractThe tubulinopathies are an umbrella of rare diseases that result from mutations in tubulin genes and are frequently characterised by severe brain malformations. The characteristics of a given disease reflect the expression pattern of the transcript, the function of a given tubulin gene, and the role microtubules play in a particular cell type. Mouse models have proved to be valuable tools that have provided insight into the molecular and cellular mechanisms that underlie the disease state. In this manuscript we compare two Tuba1a mouse models, both of which express wild-type TUBA1A protein but employ different codon usage. We show that modification of the Tuba1a mRNA sequence results in homozygous lethality and a severe neurodevelopmental phenotype. This is associated with a decrease in the number of post-mitotic neurons, PAX6 positive progenitors, and an increase in the number of apoptotic cells. We attribute this to a decrease in the stability of the modified Tuba1a transcript, and the absence of compensation by the other neurogenic tubulins. Our findings highlight the importance of maintaining the wild-type coding sequence when engineering mouse lines and the impact of synonymous genetic variation.
Analyses of binding partners and functional domains for the developmentally essential protein Hmx3a/HMX3
Authors: Haws William , England Samantha , Grieb Ginny , Susana Gabriela , Hernandez Sophie , Mirer Hunter , Lewis Katharine 
Published: January 2023

AbstractHMX3 is a homeodomain protein with essential roles in CNS and ear development. Homeodomains are DNA-binding domains and hence homeodomain-containing proteins are usually assumed to be transcription factors. However, intriguingly, our recent data suggest that zebrafish Hmx3a may not require its homeodomain to function, raising the important question of what molecular interactions mediate its effects. To investigate this, we performed a yeast two-hybrid screen and identified 539 potential binding partners of mouse HMX3. Using co-immunoprecipitation, we tested whether a prioritized subset of these interactions are conserved in zebrafish and found that Tle3b, Azin1b, Prmt2, Hmgb1a, and Hmgn3 bind Hmx3a. Next, we tested whether these proteins bind the products of four distinct hmx3a mutant alleles that all lack the homeodomain. Embryos homozygous for two of these alleles develop abnormally and die, whereas zebrafish homozygous for the other two alleles are viable. We found that all four mutations abrogate binding to Prmt2 and Tle3b, whereas Azin1b binding was preserved in all cases. Interestingly, Hmgb1a and Hmgn3 had more affinity for products of the viable mutant alleles. These data shed light on how HMX3/Hmx3a might function at a molecular level and identify new targets for future study in these vital developmental processes.
Clonal population expansion of Staphylococcus aureus occurs due to escape from a finite number of intraphagocyte niches
Authors: Pidwill Grace R. , Pyrah Josie F. , Sutton Joshua A. F. , Best Alex , Renshaw Stephen A. , Foster Simon J. 
Published: January 2023

AbstractStaphylococcus aureus is a human commensal and also an opportunist pathogen causing life threatening infections. During S. aureus disease, the abscesses that characterise infection can be clonal, whereby a large bacterial population is founded by a single or few organisms. Our previous work has shown that macrophages are responsible for restricting bacterial growth such that a population bottleneck occurs and clonality can emerge. A subset of phagocytes fail to control S. aureus resulting in bacterial division, escape and founding of microabscesses that can seed other host niches. Here we investigate the basis for clonal microabscess formation, using in vitro and in silico models of S. aureus macrophage infection. Macrophages that fail to control S. aureus are characterised by formation of intracellular bacterial masses, followed by cell lysis. High-resolution microscopy reveals that most macrophages had internalised only a single S. aureus, providing a conceptual framework for clonal microabscess generation, which was supported by a stochastic individual-based, mathematical model. Once a threshold of masses was reached, increasing the number of infecting bacteria did not result in greater mass numbers, despite enhanced phagocytosis. This suggests a finite number of permissive, phagocyte niches determined by macrophage associated factors. Increased understanding of the parameters of infection dynamics provides avenues for development of rational control measures.