bluuebunny/crossref_metadata_2025_split huggingface dataset:
Replication gap suppression depends on the double-strand DNA binding activity of BRCA2
Authors: Vugic Domagoj , Dumoulin Isaac , Martin Charlotte , Minello Anna , Alvaro-Aranda Lucia , Gomez-Escudero Jesus , Chaaban Rady , Lebdy Rana , von Nicolai Catharina , Boucherit Virginie , Ribeyre Cyril , Constantinou Angelos , Carreira Aura 
Published: January 2023

AbstractReplication stress (RS) is a major source of genomic instability and is intrinsic to cancer cells. RS is also the consequence of chemotherapeutic drugs for treating cancer. However, adaptation to RS is also a mechanism of resistance to chemotherapy. BRCA2 deficiency results in replication stress in human cells. BRCA2 protein’s main functions include DNA repair by homologous recombination (HR) both at induced DNA double-strand breaks (DSB) and spontaneous replicative lesions. At stalled replication forks, BRCA2 protects the DNA from aberrant nucleolytic degradation and is thought to limit the appearance of ssDNA gaps by arresting replication and via post-replicative HR. However, whether and how BRCA2 acts to limit the formation of ssDNA gaps or mediate their repair, remains ill-defined. Here, we use breast cancer variants affecting different domains of BRCA2 to shed light on this function. We demonstrate that the N-terminal DNA binding domain (NTD), and specifically, its dsDNA binding activity, is required to prevent and repair/fill-in ssDNA gaps upon nucleotide depletion but not to limit PARPi-induced ssDNA gaps. Thus, these findings suggest that nucleotide depletion and PARPi trigger gaps via distinct mechanisms and that the NTD of BRCA2 prevents nucleotide depletion-induced ssDNA gaps.
Redox-dependent Igfbp2 signaling controls Brca1 DNA damage response to govern neural stem cell fate
Authors: Shahin Weam S. , Ebed Shima O. , Tyler Scott R. , Miljkovic Branko , Choi Soon H. , Zhang Yulong , Zhou Weihong , Evans Idil A. , Yeaman Charles , Engelhardt John F. 
Published: January 2023

AbstractNeural stem cell (NSC) maintenance and functions are regulated by reactive oxygen species (ROS). However, the mechanisms by which ROS control NSC behavior remain unclear. Here we report that ROS-dependent Igfbp2 signaling controls DNA repair pathways which balance NSC self-renewal and lineage commitment. Ncf1 or Igfbp2 deficiency constrains NSCs to a self-renewing state and prevents neurosphere formation. Ncf1-dependent oxidation of Igfbp2 promotes neurogenesis by NSCs in vitro and in vivo while repressing Brca1 DNA damage response genes and inducing DNA double-strand breaks (DDSBs). By contrast, Ncf1–/– and Igfbp2–/– NSCs favor the formation of oligodendrocytes in vitro and in vivo. Notably, transient repression of Brca1 DNA repair pathway genes induces DDSBs and is sufficient to rescue the ability of Ncf1–/– and Igfbp2–/– NSCs to lineage-commit to form neurospheres and neurons. NSC lineage commitment is dependent on the oxidizable cysteine-43 residue of Igfbp2. Our study highlights the role of DNA damage/repair in orchestrating NSC fate decisions downstream of redox-regulated Igfbp2.
Epigenetic regulation of Neuregulin 1 promotes breast cancer progression associated to hyperglycemia
Authors: Lee Changhu , Kim Min , Park Chanho , Jo Woobeen , Seo Jeong Kon , Kim Sahee , Oh Jiyoung , Kim Chu-Sook , Ryu Han Suk , Lee Kyung-Hun , Park Jiyoung 
Published: January 2023

AbstractHyperglycemia is a risk factor for breast cancer-related morbidity and mortality. Hyperglycemia inducesNeuregulin 1(Nrg1) overexpression in breast cancer, which subsequently promotes tumor progression. However, molecular mechanisms underlying hyperglycemia-inducedNrg1overexpression remain poorly understood. Here, we show that hyperglycemia causes active histone modifications at theNrg1enhancer, forming enhanceosome complexes where recombination signal binding protein for immunoglobulin kappa J region (RBPJ), E1A binding protein p300 (P300), and SET domain containing 1 A (SETD1A) are recruited to upregulate Nrg1 expression. Deletions in RBPJ-binding sites causes hyperglycemia-controlledNrg1levels to be downregulated, resulting in decreased tumor growth in vitro and in vivo. Mice with modest-temporary hyperglycemia, induced by low-dose short-exposure streptozotocin, display accelerated tumor growth and lapatinib resistance, whereas combining lapatinib with N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S42 phenylglycine t-butyl ester (DAPT) ameliorates tumor growth under these modest hyperglycemic conditions by inhibiting NOTCH and EGFR superfamilies. NOTCH activity is correlated withNRG1levels, and highNRG1levels predicts poor outcomes, particularly in HER2-positive breast cancer patients. Our findings highlight the hyperglycemia-linked epigenetic modulation ofNRG1as a potential therapeutic strategy for treating breast cancer patients with diabetes.
A chromosome-level genome assembly of Plantago ovata
Authors: Herliana Lina , Schwerdt Julian G. , Neumann Tycho R. , Severn-Ellis Anita , Phan Jana L. , Cowley James M. , Shirley Neil J. , Tucker Matthew R. , Bianco-Miotto Tina , Batley Jacqueline , Watson-Haigh Nathan S. , Burton Rachel A. 
Published: January 2023

AbstractPlantago ovatais cultivated for production of its seed husk (psyllium). When wet, the husk transforms into a mucilage with properties suitable for pharmaceutical industries, utilised in supplements for controlling blood cholesterol levels, and food industries for making gluten-free products. There has been limited success in improving husk quantity and quality through breeding approaches, partly due to the lack of a reference genome. Here we constructed the first chromosome-scale reference assembly ofP. ovatausing a combination of 5.98 million PacBio and 636.5 million Hi-C reads. We also used corrected PacBio reads to estimate genome size and transcripts to generate gene models. The final assembly covers ~ 500 Mb with 99.3% gene set completeness. A total of 97% of the sequences are anchored to four chromosomes with an N50 of ~ 128.87 Mb. TheP. ovatagenome contains 61.90% repeats, where 40.04% are long terminal repeats. We identified 41,820 protein-coding genes, 411 non-coding RNAs, 108 ribosomal RNAs, and 1295 transfer RNAs. This genome will provide a resource for plant breeding programs to, for example, reduce agronomic constraints such as seed shattering, increase psyllium yield and quality, and overcome crop disease susceptibility.
SPITFIR(e): a supermaneuverable algorithm for fast denoising and deconvolution of 3D fluorescence microscopy images and videos
Authors: Prigent Sylvain , Nguyen Hoai-Nam , Leconte Ludovic , Valades-Cruz Cesar Augusto , Hajj Bassam , Salamero Jean , Kervrann Charles 
Published: January 2023

AbstractModern fluorescent microscopy imaging is still limited by the optical aberrations and the photon budget available in the specimen. A direct consequence is the necessity to develop flexible and “off-road” algorithms in order to recover structural details and improve spatial resolution, which is critical when restraining the illumination to low levels in order to limit photo-damages. Here, we report SPITFIR(e) a flexible method designed to accurately and quickly restore 2D–3D fluorescence microscopy images and videos (4D images). We designed a generic sparse-promoting regularizer to subtract undesirable out-of-focus background and we developed a primal-dual algorithm for fast optimization. SPITFIR(e) is a ”swiss-knife” method for practitioners as it adapts to any microscopy techniques, to various sources of signal degradation (noise, blur), to variable image contents, as well as to low signal-to-noise ratios. Our method outperforms existing state-of-the-art algorithms, and is more flexible than supervised deep-learning methods requiring ground truth datasets. The performance, the flexibility, and the ability to push the spatiotemporal resolution limit of sub-diffracted fluorescence microscopy techniques are demonstrated on experimental datasets acquired with various microscopy techniques from 3D spinning-disk confocal up to lattice light sheet microscopy.
Automated monitoring of honey bees with barcodes and artificial intelligence reveals two distinct social networks from a single affiliative behavior
Authors: Gernat Tim , Jagla Tobias , Jones Beryl M. , Middendorf Martin , Robinson Gene E. 
Published: January 2023

AbstractBarcode-based tracking of individuals is revolutionizing animal behavior studies, but further progress hinges on whether in addition to determining an individual’s location, specific behaviors can be identified and monitored. We achieve this goal using information from the barcodes to identify tightly bounded image regions that potentially show the behavior of interest. These image regions are then analyzed with convolutional neural networks to verify that the behavior occurred. When applied to a challenging test case, detecting social liquid transfer (trophallaxis) in the honey bee hive, this approach yielded a 67% higher sensitivity and an 11% lower error rate than the best detector for honey bee trophallaxis so far. We were furthermore able to automatically detect whether a bee donates or receives liquid, which previously required manual observations. By applying our trophallaxis detector to recordings from three honey bee colonies and performing simulations, we discovered that liquid exchanges among bees generate two distinct social networks with different transmission capabilities. Finally, we demonstrate that our approach generalizes to detecting other specific behaviors. We envision that its broad application will enable automatic, high-resolution behavioral studies that address a broad range of previously intractable questions in evolutionary biology, ethology, neuroscience, and molecular biology.
Effect and mechanism of apelin on lipopolysaccharide induced acute pulmonary vascular endothelial barrier dysfunction
Authors: Huang Tianpeng , Chen Danyang , Ye Wei , Chen Wenwen , Zhang Min , Hao Jiale , Xu Licong , Bai Xiaoqing , Mao Sunzhong 
Published: January 2023

AbstractVascular endothelial barrier dysfunction is the most prominent manifestation and important cause of mortality in infectious acute lung injury (ALI). Exogenous apelin is effective in ameliorating lipopolysaccharide (LPS)-induced inflammatory response in ALI lungs, reducing exudation of lung tissue and decreasing mortality. This study set out to investigate the association between apelin and Friend leukemia integration-1 (Fli-1) in the prevention and treatment of ALI, and to elucidate the molecular mechanism by which apelin protects the permeability of the vascular endothelial barrier. At the vivo functional level, lung wet/dry weight ratio was used to detect whole lung permeability, evans blue assay and dual fluorescent protein tracking assay were used to detect lung vascular endothelial permeability, HE staining to observe the inflammatory status of lung tissue, and immunofluorescence staining for VE-cadherin expression levels in blood vessels. The changes in inflammatory factors in bronchoalveolar lavage fluid (BALF) were detected by ELASA. Western blot was used to detect the expression level of proteins. qRT-PCR was performed to detect changes in mRNA expression of Fli-1 and adherent junction-related proteins. The correlation analysis of Fli-1 with vascular endothelial permeability and SRC showed that Fli-1 participated in the process of ALI. After preventive and therapeutic treatment of ALI mice with exogenous apelin, Fli-1, APJ, VE-cadherin, phosphorylated-VE-cadherin (p-VE-cadherin) and β-catenin were up-regulated, while SRC, phosphorylated-SRC (p-SRC), VEGF and VEGF-R were down-regulated, which indicated that the stability of vascular endothelial barrier was enhanced. With the use of Fli-1 inhibitor irinotecan, the protective effect of apelin was weakened in various functional indexes, genes and proteins. The lung was maintained at the level of the injury. Our research shows that Fli-1 is involved in the LPS-induced ALI process. The molecular mechanism for apelin in preventing endothelial barrier dysfunction in ALI is through up-regulating Fli-1, thus regulating adherens junction-related proteins, and finally recovering the endothelial barrier function.
Women with familial hypercholesterolemia phenotype are undertreated and poorly controlled compared to men
Authors: Zamora Alberto , Ramos Rafel , Comas-Cufi Marc , García-Gil María , Martí-Lluch Ruth , Plana Nuria , Alves-Cabratosa Lia , Ponjoan Anna , Rodríguez-Borjabad Celia , Ibarretxe Daiana , Roman-Degano Irene , Marrugat Jaume , Elosua Roberto , Martín-Urda Anabel , Masana Lluis 
Published: January 2023

AbstractFamilial hypercholesterolemia (FH) is an autosomal dominant disease that has a prevalence of approximately 1/250 inhabitants and is the most frequent cause of early coronary heart disease (CHD). We included 1.343.973 women and 1.210.671 men with at least one LDL-c measurement from the Catalan primary care database. We identified 14.699 subjects with Familial hypercholesterolemia-Phenotype (FH-P) based on LDL-c cut-off points by age (7.033 and 919 women, and 5.088 and 1659 men in primary and secondary prevention, respectively). Lipid lower therapy (LLT), medication possession ratio (MPR) as an indicator of adherence, and number of patients that reached their goal on lipid levels were compared by sex. In primary and secondary prevention, 69% and 54% of women (P = 0.001) and 64% and 51% of men (P = 0.001) were on low-to-moderate-potency LLT. Adherence to LLT was reduced in women older than 55 years, especially in secondary prevention (P = 0.03), where the percentage of women and men with LDL-c > 1.81 mmol/L were 99.9% and 98.9%, respectively (P = 0.001). Women with FH-P are less often treated with high-intensity LLT, less adherent to LLT, and have a lower probability of meeting their LDL-c goals than men, especially in secondary prevention.
TOR1B: a predictor of bone metastasis in breast cancer patients
Authors: Nguyen Minh Nam , Akter Salima , Akhter Hajara , Ansary Shahina , Han Sunhee , Shin Yoonhwa , Ha Joohun , Kang Insug , Kim Sung Soo , Choi Tae Gyu 
Published: January 2023

AbstractRecent therapeutic advances in breast cancer (BC) have improved survival outcomes; however, the prognosis for patients with bone metastasis (BM) remains poor. Hence, novel clinical biomarkers are needed to accurately predict BC BM as well as to promote personalized medicine. Here, we discovered a novel biomarker, TOR1B, for BM in BC patients via analysis of BC gene expression data and clinical information downloaded from open public databases. In cancer cells, we found high expression levels of TOR1B in the nucleus and endoplasmic reticulum. Regarding gene expression, the level of TOR1B was significantly upregulated in BC patients with BM (p < 0.05), and the result was externally validated. In addition, gene expression clearly demonstrated two distinct types of prognoses in ER- and PR-positive patients. In multivariate regression, the gene could be an independent predictor of BM in BC patients, i.e., a low expression level of TOR1B was associated with delayed metastasis to bone in BC patients (HR, 0.28; 95% CI 0.094–0.84). Conclusively, TOR1B might be a useful biomarker for predicting BM; specifically, patients with ER- and PR-positive subtypes would benefit from the clinical use of this promising prognostic biomarker.
Product progression: a machine learning approach to forecasting industrial upgrading
Authors: Albora Giambattista , Pietronero Luciano , Tacchella Andrea , Zaccaria Andrea 
Published: January 2023

AbstractEconomic complexity methods, and in particular relatedness measures, lack a systematic evaluation and comparison framework. We argue that out-of-sample forecast exercises should play this role, and we compare various machine learning models to set the prediction benchmark. We find that the key object to forecast is the activation of new products, and that tree-based algorithms clearly outperform both the quite strong auto-correlation benchmark and the other supervised algorithms. Interestingly, we find that the best results are obtained in a cross-validation setting, when data about the predicted country was excluded from the training set. Our approach has direct policy implications, providing a quantitative and scientifically tested measure of the feasibility of introducing a new product in a given country.
CMOS-compatible ising machines built using bistable latches coupled through ferroelectric transistor arrays
Authors: Mallick Antik , Zhao Zijian , Bashar Mohammad Khairul , Alam Shamiul , Islam Md Mazharul , Xiao Yi , Xu Yixin , Aziz Ahmedullah , Narayanan Vijaykrishnan , Ni Kai , Shukla Nikhil 
Published: January 2023

AbstractRealizing compact and scalable Ising machines that are compatible with CMOS-process technology is crucial to the effectiveness and practicality of using such hardware platforms for accelerating computationally intractable problems. Besides the need for realizing compact Ising spins, the implementation of the coupling network, which describes the spin interaction, is also a potential bottleneck in the scalability of such platforms. Therefore, in this work, we propose an Ising machine platform that exploits the novel behavior of compact bi-stable CMOS-latches (cross-coupled inverters) as classical Ising spins interacting through highly scalable and CMOS-process compatible ferroelectric-HfO2-based Ferroelectric FETs (FeFETs) which act as coupling elements. We experimentally demonstrate the prototype building blocks of this system, and evaluate the scaling behavior of the system using simulations. Our work not only provides a pathway to realizing CMOS-compatible designs but also to overcoming their scaling challenges.
Screening and validating of endogenous reference genes in Chlorella sp. TLD 6B under abiotic stress
Authors: Zhou Yongshun , Meng Fanze , Han Kai , Zhang Kaiyue , Gao Jianfeng , Chen Fulong 
Published: January 2023

AbstractChlorella sp. TLD 6B, a microalgae growing in the Taklamakan Desert, Xinjiang of China, is a good model material for studying the physiological and environmental adaptation mechanisms of plants in their arid habitats, as its adaptation to the harsh desert environment has led to its strong resistance. However, when using real-time quantitative polymerase chain reaction (RT-qPCR) to analyze the gene expression of this algae under abiotic stress, it is essential to find the suitable endogenous reference genes so to obtain reliable results. This study assessed the expression stability of 9 endogenous reference genes of Chlorella sp. TLD 6B under four abiotic stresses (drought, salt, cold and heat). These genes were selected based on the analysis results calculated by the three algorithmic procedures of geNorm, NormFinder, and BestKeeper, which were ranked by refinder. Our research showed that 18S and GTP under drought stress, 18S and IDH under salt stress, CYP and 18S under cold stress, GTP and IDH under heat stress were the most stable endogenous reference genes. Moreover, UBC and 18S were the most suitable endogenous reference gene combinations for all samples. In contrast, GAPDH and α-TUB were the two least stable endogenous reference genes in all experimental samples. Additionally, the selected genes have been verified to be durable and reliable by detecting POD and PXG3 genes using above endogenous reference genes. The identification of reliable endogenous reference genes guarantees more accurate RT-qPCR quantification for Chlorella sp. TLD 6B, facilitating functional genomics studies of deserts Chlorella as well as the mining of resistance genes.
The effects of distractors on brightness perception based on a spiking network
Authors: Liu Weisi , Liu Xinsheng 
Published: January 2023

AbstractVisual perception can be modified by the surrounding context. Particularly, experimental observations have demonstrated that visual perception and primary visual cortical responses could be modified by properties of surrounding distractors. However, the underlying mechanism remains unclear. To simulate primary visual cortical activities in this paper, we design a k-winner-take-all (k-WTA) spiking network whose responses are generated through probabilistic inference. In simulations, images with the same target and various surrounding distractors perform as stimuli. Distractors are designed with multiple varying properties, including the luminance, the sizes and the distances to the target. Simulations for each varying property are performed with other properties fixed. Each property could modify second-layer neural responses and interactions in the network. To the same target in the designed images, the modified network responses could simulate distinguishing brightness perception consistent with experimental observations. Our model provides a possible explanation of how the surrounding distractors modify primary visual cortical responses to induce various brightness perception of the given target.
On the inverse problem in optical coherence tomography
Authors: Macdonald Callum M. , Arridge Simon R. , Munro Peter R. T. 
Published: January 2023

AbstractWe examine the inverse problem of retrieving sample refractive index information in the context of optical coherence tomography. Using two separate approaches, we discuss the limitations of the inverse problem which lead to it being ill-posed, primarily as a consequence of the limited viewing angles available in the reflection geometry. This is first considered from the theoretical point of view of diffraction tomography under a weak scattering approximation. We then investigate the full non-linear inverse problem using a variational approach. This presents another illustration of the non-uniqueness of the solution, and shows that even the non-linear (strongly scattering) scenario suffers a similar fate as the linear problem, with the observable spatial Fourier components of the sample occupying a limited support. Through examples we demonstrate how the solutions to the inverse problem compare when using the variational and diffraction-tomography approaches.
Combined evaluation of audiology examination and self-reported symptoms in patients with hyperacusis
Authors: Huang Yu , Xiang Tao , Jiang Fan , Ren Jing , Xu Tao , Lai Dan 
Published: January 2023

AbstractTo investigate the application of combined audiological examination and a self-reported symptoms survey in the evaluation of hyperacusis. Patients who visited the outpatient department of Otolaryngology Head and Neck Surgery and Otological medicine, Affiliated Hospital of Southwest Medical University, from January 2019 to March 2021 were divided into a hyperacusis group and a normal control group. We measured the loudness discomfort level (LDL) and hearing threshold (HT) of the subjects and investigated their self-reported symptoms. We compared the demographic characteristics, loudness discomfort level, and hearing threshold of the two groups and analyzed the self-reported symptoms and audiological characteristics of hyperacusis. We considered 87 subjects, comprising 40 patients with hyperacusis and 47 healthy individuals. Among the hyperacusis patients, bilateral disease was predominant. Among them, 33 were females, 23 had hearing loss, and 20 had tinnitus. Patients are mainly in the 21–60 age group. Patients with hyperacusis had low discomfort thresholds at all frequencies except 500 Hz (P ≤ 0.05, mean LDL decreased by 6.14–1.37 dB HL for all frequencies). The incidences of feeling upset, pain, and anxiety or fear were 95%, 65%, and 82.5%, respectively, in patients with hyperacusis. The severity of symptoms varies between patients with hyperacusis and healthy individuals. A combination of LDL measurements and self-reported symptom surveys allows for an accurate and comprehensive assessment of hyperacusis.Trial registration: This study was retrospectively registered (TRN: ChiCTR2100047391) on June 13, 2021.