bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment of closed 35S ribosomal RNA gene chromatin in stationary Saccharomyces cerevisiae cells
Authors: Babl Virginia , Girke Philipp , Kruse Sebastian , Pinz Sophia , Hannig Katharina , Schächner Christopher , Hergert Kristin , Wittner Manuel , Seufert Wolfgang , Milkereit Philipp , Tschochner Herbert , Griesenbeck Joachim 
Published: October 2024

Abstract
As a first step in eukaryotic ribosome biogenesis RNA polymerase (Pol) I synthesizes a large ribosomal RNA (rRNA) precursor from multicopy rRNA gene loci. This process is essential for cellular growth and regulated in response to the cell’s physiological state. rRNA gene transcription is downregulated upon growth to stationary phase in the yeast Saccharomyces cerevisiae. This reduction correlates with characteristic changes in rRNA gene chromatin structure from a transcriptionally active ‘open’ state to a non-transcribed ‘closed’ state. The conserved lysine deacetylase Rpd3 was shown to be required for this chromatin transition. We found that Rpd3 is needed for tight repression of Pol I transcription upon growth to stationary phase as a prerequisite for the establishment of the closed chromatin state. We provide evidence that Rpd3 regulates Pol I transcription by adjusting cellular levels of the Pol I preinitiation complex component core factor (CF). Importantly, our study identifies CF as the complex limiting the number of open rRNA genes in exponentially growing and stationary cells.
Revisiting the y-ome of Escherichia coli
Authors: Moore Lisa R , Caspi Ron , Boyd Dana , Berkmen Mehmet , Mackie Amanda , Paley Suzanne , Karp Peter D 
Published: October 2024

Abstract
The model organism Escherichia coli K-12 has one of the most extensively annotated genomes in terms of functional characterization, yet a significant number of genes, ∼35%, are still considered poorly characterized. Initially genes without known functional understanding were given ‘y’ gene names. However, due to inconsistency in changing ‘y’ names to non-‘y’ names over the years, gene name alone does not provide sufficient information as to the characterization level of genes. Attempts to characterize y-ome genes, i.e. those that lack experimental evidence for function, are ongoing, and recent categorization based on the level of experimental evidence has helped clarify those genes that are well characterized versus uncharacterized. EcoCyc, the most comprehensive, curated genome database for E. coli K-12 substr. MG1655, has updated this approach by expanding the categories to include Partially characterized genes using a set of computational rules that includes keywords, experimental evidence codes and Gene Ontology terms. Approximately half of the previously categorized y-ome genes are now categorized as Partially characterized, leaving 15.5% (738) as Uncharacterized genes in EcoCyc. This new categorization scheme is searchable in the EcoCyc database, will be updated as new experimental evidence is curated and provides important information for research decisions.
OrgXenomics: an integrated proteomic knowledge base for patient-derived organoid and xenograft
Authors: Zhang Yintao , Lian Xichen , Xu Hangwei , Zhu Sisi , Zhang Hao , Ni Ziheng , Fu Tingting , Liu Shuiping , Tao Lin , Zhou Ying , Zhu Feng 
Published: October 2024

Abstract
Patient-derived models (PDMs, particularly organoids and xenografts) are irreplaceable tools for precision medicine, from target development to lead identification, then to preclinical evaluation, and finally to clinical decision-making. So far, PDM-based proteomics has emerged to be one of the cutting-edge directions and massive data have been accumulated. However, such PDM-based proteomic data have not been provided by any of the available databases, and proteomics profiles of all proteins in proteomic study are also completely absent from existing databases. Herein, an integrated database named ‘OrgXenomics’ was thus developed to provide the proteomic data for PDMs, which was unique in (a) explicitly describing the establishment detail for a wide array of models, (b) systematically providing the proteomic profiles (expression/function/interaction) for all proteins in studied proteomic analysis and (c) comprehensively giving the raw data for diverse organoid/xenograft-based proteomic studies of various diseases. Our OrgXenomics was expected to server as one good complement to existing proteomic databases, and had great implication for the practice of precision medicine, which could be accessed at: https://idrblab.org/orgxenomics/
MolBiC: the cell-based landscape illustrating molecular bioactivities
Authors: Ge Yichao , Yang Mengjie , Yu Xinyuan , Zhou Ying , Zhang Yintao , Mou Minjie , Chen Zhen , Sun Xiuna , Ni Feng , Fu Tingting , Liu Shuiping , Han Lianyi , Zhu Feng 
Published: October 2024

Abstract
The measurement of cell-based molecular bioactivity (CMB) is critical for almost every step of drug development. With the booming application of AI in biomedicine, it is essential to have the CMB data to promote the learning of cell-based patterns for guiding modern drug discovery, but no database providing such information has been constructed yet. In this study, we introduce MolBiC, a knowledge base designed to describe valuable data on molecular bioactivity measured within a cellular context. MolBiC features 550 093 experimentally validated CMBs, encompassing 321 086 molecules and 2666 targets across 988 cell lines. Our MolBiC database is unique in describing the valuable data of CMB, which meets the critical demands for CMB-based big data promoting the learning of cell-based molecular/pharmaceutical pattern in drug discovery and development. MolBiC is now freely accessible without any login requirement at: https://idrblab.org/MolBiC/.
Self-assembly and condensation of intermolecular poly(UG) RNA quadruplexes
Authors: Roschdi Saeed , Montemayor Eric J , Vivek Rahul , Bingman Craig A , Butcher Samuel E 
Published: October 2024

Abstract
Poly(UG) or ‘pUG’ dinucleotide repeats are highly abundant sequences in eukaryotic RNAs. In Caenorhabditis elegans, pUGs are added to RNA 3′ ends to direct gene silencing within Mutator foci, a germ granule condensate. Here, we show that pUG RNAs efficiently self-assemble into gel condensates through quadruplex (G4) interactions. Short pUG sequences form right-handed intermolecular G4s (pUG G4s), while longer pUGs form left-handed intramolecular G4s (pUG folds). We determined a 1.05 Å crystal structure of an intermolecular pUG G4, which reveals an eight stranded G4 dimer involving 48 nucleotides, 7 different G and U quartet conformations, 7 coordinated potassium ions, 8 sodium ions and a buried water molecule. A comparison of the intermolecular pUG G4 and intramolecular pUG fold structures provides insights into the molecular basis for G4 handedness and illustrates how a simple dinucleotide repeat sequence can form complex structures with diverse topologies.
The MdERF61-mdm-miR397b-MdLAC7b module regulates apple resistance to Fusarium solani via lignin biosynthesis
Authors: Zhou Zhe , Zhang Haiqing , Yao Jia-Long , Gao Qiming , Wang Yarong , Liu Zhenzhen , Zhang Yaru , Tian Yi , Yan Zhenli , Zhu Yanmin , Zhang Hengtao 
Published: October 2024

Abstract
Apple replant disease (ARD) is a worldwide problem that threatens the industry. However, the genetic mechanism underlying plant disease resistance against ARD remains unclear. In this study, a negative regulatory microRNA in Malus domestica, mdm-miR397b, and its direct target MdLAC7b (Laccase) was selected for examination based on our previous small RNA and degradome sequencing results. Overexpressing the mdm-miR397b-MdLAC7b module altered the lignin deposition and jasmonic acid contents in apple roots, which also led to increased resistance to Fusarium solani. Additionally, Y1H library screening using mdm-miR397b promoter recombinants identified a transcription factor, MdERF61, that represses mdm-miR397b transcriptional activity by directly binding to 2 GCC-boxes in the mdm-miR397b promoter. In summary, our results suggest that the MdERF61-mdm-miR397b-MdLAC7b module plays a crucial role in apple resistance to F. solani and offers insights for enhancing plant resistance to soil-borne diseases in apples.
The Weakness of Authoritarian Regimes: Rwanda as a Difficult But Convincing Case
Authors: Longman Timothy 
Published: October 2024

Abstract
The lack of academic attention to the functioning of authoritarian regimes has allowed an erroneous impression that dictatorships are inherently strong and stable. Marie-Eve Desrosiers uses the difficult case of Rwanda, whose 1994 genocide against the Tutsi has widely been seen as a sign of state strength, to demonstrate the fragility of authoritarian rule. Looking at the First and Second Republics, which governed Rwanda from 1962 until 1994, Desrosiers explores both the vulnerability of the regimes and how they adjusted over time in attempts to strengthen control. Desrosiers argues for greater awareness of shifting strategies and changes in governance across time, what she calls “authoritarian trajectories,” to better understand how authoritarian regimes actually work and how the public responds to them. Although not focused on the 1994 genocide, Desrosiers' analysis helps explain why genocide emerged as a strategy to shore up Rwanda's failing regime.
How Do Short-Term Incentives Affect Long-Term Productivity?
Authors: Almeida Heitor , Ersahin Nuri , Fos Vyacheslav , Irani Rustom M , Kronlund Mathias 
Published: October 2024

Abstract
Previous research shows that incentives to meet short-term earnings targets can cause firms to increase share buybacks, leading to cuts in investments and employment. Using plant-level census data, we find that incentives to engage in earnings-per-share-motivated buybacks result in lower productivity at both the plant and firm level. We attribute this productivity drop to two mechanisms: reduced investment in productivity-augmenting technology, and inefficient allocation of resources across a firm’s plants. We identify multiple frictions—including labor unions, financial constraints, agency problems, and adjustment costs—that can constrain efficient reallocations across plants and thus exacerbate the consequences of firms’ short-term incentives.
Demographics and clinical features associated with abnormal small bowel motility in systemic sclerosis
Authors: Cheah Jenice X , Perin Jamie , Hughes Michael , Mecoli Christopher A , Paik Julie J , Hummers Laura K , Shah Ami A , McMahan Zsuzsanna H 
Published: October 2024

Abstract

Objective
The small bowel is affected in up to 50% of systemic sclerosis (SSc) patients, and some patients experience severe complications. Our aim was to use specific statistical methods to compare demographic and clinical features of SSc patients with and without abnormal small bowel to better characterize patients at risk for this complication.

Methods
SSc patients with gastrointestinal symptoms were prospectively enrolled and underwent a scintigraphy-based whole gut transit (WGT) study. A cross-sectional analysis was performed comparing clinical features between patients with and without abnormal small bowel transit by WGT. Univariate logistic regression models and multivariable models were used to examine the relationship between clinical features and abnormal small bowel transit.

Results
Of 130 patients enrolled in this study, 22 had abnormal small bowel transit. SSc patients with abnormal small bowel transit were more likely to be male [odds ratio (OR) = 3.70; 95% CI: 1.07, 12.50; P = 0.038] and have more severe cardiac involvement (OR = 3.98; 95% CI: 1.10, 14.38; P = 0.035), while they were less likely to have sicca symptoms (OR = 0.30; 95% CI: 0.10, 0.94; P = 0.039). In multivariable analyses, sicca symptoms (OR = 0.28; 95% CI: 0.08, 0.96; P = 0.043) remained negatively associated with abnormal small bowel transit. Additionally, SSc patients with abnormal small bowel transit had higher mortality than patients with normal small bowel transit [hazard ratio (HR) = 4.57; 95% CI: 1.58, 13.24; P = 0.005].

Conclusions
These findings suggest that patients with abnormal small bowel transit in SSc are more likely to be male, have more severe cardiac involvement, higher mortality and fewer sicca symptoms. Recognizing this patient subgroup is essential for risk stratification and optimizing clinical care.
Establishment of typical values in cerebral thrombectomy according to the stroke anatomical region and procedure clinical outcome
Authors: Lopes Rogério , Santos Joana 
Published: October 2024

Abstract
The aim of the study is to establish local diagnostic reference levels (DRLs) in cerebral thrombectomy, according to the anatomical region of ischemic stroke. This is a retrospective study from a single center involving 255 examinations. The proposed median values (P50) for thrombectomy are: 123 Gy.cm2 for air kerma-area product (PKA) and 915 mGy for air kerma (Ka,r). For middle cerebral artery (MCA) thrombectomies, the proposed DRLs are 118 Gy.cm2 for PKA and 112 Gy.cm2 for internal carotid artery (ICA). The Ka,r values for MCA and ICA are 849 and 775 mGy, respectively. It was observed that 94.9% of patients presented grade 0 on the initial modified treatment in cerebral infarction (mTICI) scale, and after thrombectomy, 63.1% of patients reached a final mTICI grade of 3. Stents were implanted in 37 patients (14.5% of cases). It was concluded that 16.1% of patients exceeded one trigger value of the Safety in Radiological Procedures' recommended parameters. Establishing DRLs is an important tool for optimizing practices and is considered a standard for quality control.
Maternal early pregnancy body mass index and risk of insomnia in the offspring
Authors: Zhu Mia Q , Cnattingius Sven , O’Brien Louise M , Villamor Eduardo 
Published: October 2024

Abstract

Study Objectives
To investigate the association between maternal early pregnancy body mass index (BMI) and risk of offspring insomnia.

Methods
We conducted a nationwide cohort study among 3 281 803 singleton live births in Sweden born 1983–2015. Using national registries with prospectively recorded information, we followed participants for an insomnia diagnosis from 2 to up to 35 years of age. We compared insomnia risks by early pregnancy BMI categories using hazard ratios (HR) with 95% confidence intervals (CI) from adjusted Cox models. To assess unmeasured shared familial confounding, we conducted sibling-controlled analyses among 1 724 473 full siblings and studied the relation of maternal full sisters’ BMI and insomnia risk in 1 185 998 offspring.

Results
There were 7154 insomnia diagnoses over a median follow-up age of 17.9 years. Compared with women with normal BMI, adjusted HR (95% CI) of offspring insomnia for early pregnancy BMI categories overweight, obesity class I, and obesity classes II or III were, respectively, 1.22 (1.14, 1.30), 1.60 (1.45, 1.77), and 2.11 (1.83, 2.45). Corresponding adjusted HR (95% CI) in sibling comparisons were, respectively, 1.32 (1.05, 1.65), 1.48 (1.03, 2.14), and 1.56 (0.91, 2.65). Associations with maternal sisters’ BMI were attenuated, suggesting a weak role for unmeasured shared factors. Other pregnancy, birth, and neonatal complications were associated with the risk of insomnia in offspring but did not substantially mediate the association.

Conclusions
The dose–response relation between maternal overweight and obesity severity with offspring insomnia risk is not fully explained by shared familial factors.
Serum glucose/potassium ratio as an indicator of early and delayed outcomes of acute carbon monoxide poisoning
Authors: Elmansy Alshaimma Mahmoud , Hannora Dalia Mustafa , Khalifa Heba K 
Published: October 2024

Abstract
Background: Carbon monoxide (CO) poisoning is a major health problem associated with a high rate of severe morbidity and mortality. Aims: This study aimed to evaluate the validity of the serum glucose/potassium (Glu/K) ratio as a quick predictor of both early and delayed unfavorable outcomes following acute CO poisoning. Patients and methods: This prospective cohort study included 136 patients with acute CO poisoning admitted at Tanta Poison Control Center, Egypt, between January 2023 and June 2024. The serum Glu/K ratio was calculated for all patients. The primary outcome was a prediction of mortality. Secondary outcomes were the prediction of delayed neurological sequelae (DNS) within six months after CO exposure, the need for mechanical ventilation, and the need for hyperbaric oxygen. A receiver operating curve analysis was applied to test the performance of the Glu/K ratio in predicting acute CO poisoning outcomes. Results: The mortality rate was 12.5% of patients with acute CO poisoning. Meanwhile, 14.7% of patients developed DNS. Furthermore, mechanical ventilation was required in 16.9% of patients. An elevated Glu/K ratio was significantly associated with the severity of acute CO poisoning. At a cut-off value of &gt;31.62, the Glu/K ratio demonstrated an AUC of 0.649 for predicting mortality. The Glu/K ratio was employed to predict DNS at a cut-off value of 33.10, with a sensitivity of 60.0%, a specificity of 82.76%, and an AUC of 0.692. Conclusions: Early Glu/K ratio may be an effective, reliable, and convenient laboratory predictor of mortality, DNS, and the need for mechanical ventilation in patients with acute CO poisoning.
Berberine and palmatine, acting as allosteric potential ligands of α7 nAChR, synergistically regulate inflammation and phagocytosis of microglial cells
Authors: Xia Yingjie , Wang Xiaoyang , Lin Shengying , Dong Tina T. X. , Tsim Karl W. K. 
Published: October 2024

AbstractBerberine and palmatine are isoquinoline quaternary alkaloids derived from Chinese medicinal herbs. These alkaloids have shown promising synergy in inhibiting acetylcholinesterase (AChE), indicating their potential in treating Alzheimer's disease (AD). Besides, the anti‐inflammatory effects of berberine and palmatine have been widely reported, although the underlying mechanism remains unclear. Here, we found that berberine and palmatine could induce calcium ion (Ca2+) influx via activating α7 nicotinic acetylcholine receptor (α7 nAChR) in cultured microglial cells, possibly serving as its allosteric potential ligands. Furthermore, we examined the synergistic anti‐inflammatory effects of berberine and palmatine in the LPS‐induced microglia, that significantly suppressed the production of TNF‐α and iNOS. Notably, this suppression was reversed by co‐treatment with a selective antagonist of α7 nAChR. Moreover, the alkaloid‐induced microglial phagocytosis was shown to be mediated by the induction of Ca2+ influx through α7 nAChR and subsequent CaMKII‐Rac1‐dependent pathway. Additionally, the combination of berberine and palmatine, at low concentration, protected against the LPS‐induced endoplasmic reticulum stress and mitochondrial dysfunction in microglia. These findings indicate the potential of berberine and palmatine, either individually or in combination, in contributing to anti‐AD drug development, which provide valuable insights into the mechanisms by which natural products, such as plant alkaloids, exert their anti‐AD effects.
LHPP deficiency aggravates liver fibrosis through TGF‐β/Smad3 signaling
Authors: Zhang Yue , Li Bi‐min , Zhang Wang , Chen Peng , Liu Linxiang , Nie Yuan , Huang Chenkai , Zhu Xuan 
Published: October 2024

AbstractLiver fibrosis is characterized by a wound‐healing response and may progress to liver cirrhosis and even hepatocellular carcinoma. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a tumor suppressor that participates in malignant diseases. However, the role of LHPP in liver fibrosis has not been determined. Herein, the function and regulatory network of LHPP were explored in liver fibrosis. The expression of LHPP in human and murine fibrotic liver tissues was assessed via immunohistochemistry and Western blot analysis. In addition, liver fibrosis was induced in wild‐type (WT) and LHPP−/− (KO) mice after carbon tetrachloride (CCl4) or thioacetamide (TAA) treatment. The effect of LHPP was systematically assessed by using specimens acquired from the above murine models. The functional role of LHPP was further explored by detecting the pathway activity of TGF‐β/Smad3 and apoptosis after interfering with LHPP in vitro. To explore whether the function of LHPP depended on the TGF‐β/Smad3 pathway in vivo, an inhibitor of the TGF‐β/Smad3 pathway was used in CCl4‐induced WT and KO mice. LHPP expression was downregulated in liver tissue samples from fibrosis patients and fibrotic mice. LHPP deficiency aggravated CCl4‐ and TAA‐induced liver fibrosis. Moreover, through immunoblot analysis, we identified the TGF‐β/Smad3 pathway as a key downstream pathway of LHPP in vivo and in vitro. The effect of LHPP deficiency was reversed by inhibiting the TGF‐β/Smad3 pathway in liver fibrosis. These results revealed that LHPP deficiency exacerbates liver fibrosis through the TGF‐β/Smad3 pathway. LHPP may be a potential therapeutic target in hepatic fibrosis.
MREDTA: A BERT and transformer‐based molecular representation encoder for predicting drug‐target binding affinity
Authors: Sun Xu , Huang Juanjuan , Fang Yabo , Jin Yixuan , Wu Jiageng , Wang Guoqing , Jia Jiwei 
Published: October 2024

AbstractDrug‐target binding affinity (DTA) prediction is vital for drug repositioning. The accuracy and generalizability of DTA models remain a major challenge. Here, we develop a model composed of BERT‐Trans Block, Multi‐Trans Block, and DTI Learning modules, referred to as Molecular Representation Encoder‐based DTA prediction (MREDTA). MREDTA has three advantages: (1) extraction of both local and global molecular features simultaneously through skip connections; (2) improved sensitivity to molecular structures through the Multi‐Trans Block; (3) enhanced generalizability through the introduction of BERT. Compared with 12 advanced models, benchmark testing of KIBA and Davis datasets demonstrated optimal performance of MREDTA. In case study, we applied MREDTA to 2034 FDA‐approved drugs for treating non‐small‐cell lung cancer (NSCLC), all of which act on mutant EGFRT790M protein. The corresponding molecular docking results demonstrated the robustness of MREDTA.
Inflammatory priming of human mesenchymal stem cells induces osteogenic differentiation via the early response gene IER3
Authors: Küppers Oliver , Ahmad Mubashir , Haffner‐Luntzer Melanie , Scharffetter‐Kochanek Karin , Ignatius Anita , Fischer Verena 
Published: October 2024

AbstractMesenchymal stem cells (MSCs) have gained tremendous interest due to their overall potent pro‐regenerative and immunomodulatory properties. In recent years, various in vitro and preclinical studies have investigated different priming (“licensing”) approaches to enhance MSC functions for specific therapeutic purposes. In this study, we primed bone marrow‐derived human MSCs (hMSCs) with an inflammation cocktail designed to mimic the elevated levels of inflammatory mediators found in serum of patients with severe injuries, such as bone fractures. We observed a significantly enhanced osteogenic differentiation potential of primed hMSCs compared to untreated controls. By RNA‐sequencing analysis, we identified the immediate early response 3 (IER3) gene as one of the top‐regulated genes upon inflammatory priming. Small interfering RNA knockdown experiments established IER3 as a novel positive regulator of osteogenic differentiation. Mechanistic analysis further revealed that IER3 deletion significantly downregulated bone marrow stromal cell antigen 2 (BST2) expression and extracellular signal‐related kinase 1/2 (ERK1/2) phosphorylation in hMSCs, suggesting that IER3 regulates osteogenic differentiation through BST2 and ERK1/2 signaling pathway activation. On the basis of these findings, we propose IER3 as a novel therapeutic target to promote hMSC osteoblastogenesis, which might be of high clinical relevance, for example, in patients with osteoporosis or compromised fracture healing.