bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of dietary epidermal growth factor supplementation on liver antioxidant capacity of piglets with intrauterine growth retardation
Authors: Tang Xiaopeng , Xiong Kangning , Li Meijun 
Published: October 2023

Abstract
The present experiment was conducted to study the effects of dietary epidermal growth factor (EGF) supplementation on the liver antioxidant capacity of piglets with intrauterine growth retardation (IUGR). The present study consists of two experiments. In experiment 1, six normal-birth-weight (NBW) and six IUGR newborn piglets were slaughtered within 2 to 4 h after birth to compare the effects of IUGR on the liver antioxidant capacity of newborn piglets. The results showed that compared with NBW piglets, IUGR piglets had a lower birth weight and liver relative weight; IUGR piglets had a higher serum malondialdehyde (MDA) level, liver MDA level and hydrogen peroxide (H2O2) level, and had a lower liver total antioxidant capacity (T-AOC) level and glutathione peroxidase (GSH-Px) activity; IUGR trended to increase serum alanine aminotransferase activity, aspartate aminotransferase activity, and H2O2 level, and trended to decrease liver total superoxide dismutase activity. In experiment 2, six NBW piglets, and 12 IUGR piglets weaned at 21 d of age were randomly divided into the NC group (NBW piglets fed with basal diet); IC group (IUGR piglets fed with basal diet), and IE group (IUGR piglets fed with basal diet plus 2 mg/kg EGF), and feeding for 14 d. Organ index, serum parameters, liver antioxidant capacity, and liver antioxidant-related genes expression were measured. The results showed that compared to the IC group, dietary EGF supplementation (IE group) significantly reduced serum malondialdehyde level and H2O2 level, and liver protein carbonyl (PC) level and 8-hydroxydeoxyguanosine level of piglets with IUGR; dietary EGF supplementation (IE group) significantly increased serum T-AOC level, liver T-AOC level and GSH-Px activity; dietary supplemented with EGF (IE group) enhanced liver Nrf2, NQO1, HO1, and GPX1 mRNA expression compared to IC group. Pearson’s correlation analysis further showed that EGF can alleviate liver oxidative injury caused by IUGR and improve the performance of IUGR piglets. In conclusion, EGF exhibited potent protective effects on IUGR-induced liver oxidative injury, by activating the Nrf2 signaling pathway to mediate the expression of downstream antioxidant enzymes and phase II detoxification enzymes (NQO1 and HO1), thereby alleviating liver oxidative damage and promoting the growth performance of IUGR piglets.
Dynamics of mitochondrial adaptation and energy metabolism in rainbow trout (Oncorhynchus mykiss) in response to sustainable diet and temperature
Authors: Idenyi John N , Eya Jonathan C , Abanikannda Mosope F , Huber David H , Gannam Ann L , Sealey Wendy M 
Published: October 2023

Abstract
Impacts of plant-based ingredients and temperatures on energy metabolism in rainbow trout was investigated. A total of 288 fish (mean body weight: 45.6 g) were fed four isocaloric, isolipidic, and isonitrogenous diets containing 40% protein and 20% lipid and formulated as 100% animal-based protein (AP) and a blend of 50% fish oil (FO) and 50% camelina oil (CO); 100% AP and100% CO; 100% plant-based protein (PP) and a blend of 50% FO and 50% CO or 100% PP and 100% CO at 14 or 18 °C for 150 d. Diet did not significantly affect weight gain (WG) (P = 0.1902), condition factor (CF) (P = 0.0833) or specific growth rate (SGR) (P = 0.1511), but diet significantly impacted both feed efficiency (FE) (P = 0.0076) and feed intake (FI) (P = 0.0076). Temperature did not significantly affect WG (P = 0.1231), FE (P = 0.0634), FI (P = 0.0879), CF (P = 0.8277), or SGR (P = 0.1232). The diet × temperature interaction did not significantly affect WG (P = 0.7203), FE (P = 0.4799), FI (P = 0.2783), CF (P = 0.5071), or SGR (P = 0.7429). Furthermore, temperature did not influence protein efficiency ratio (P = 0.0633), lipid efficiency ratio (P = 0.0630), protein productive value (P = 0.0756), energy productive value (P = 0.1048), and lipid productive value (P = 0.1386); however, diet had significant main effects on PER (P = 0.0076), LPV (P = 0.0075), and PPV (P = 0.0138). Temperature regimens induced increased activities of mitochondrial complexes I (P = 0.0120), II (P = 0.0008), III (P = 0.0010), IV (P &lt; 0.0001), V (P &lt; 0.0001), and citrate synthase (CS) (P &lt; 0.0001) in the intestine; complexes I (P &lt; 0.0001), II (P &lt; 0.0001), and CS (P = 0.0122) in the muscle; and complexes I (P &lt; 0.0001), II (P &lt; 0.0001), and III (P &lt; 0.0001) in the liver. Similarly, dietary composition significantly affected complexes I (P &lt; 0.0001), II (P &lt; 0.0001), IV (P &lt; 0.0001), V (P &lt; 0.0001), and CS (P &lt; 0.0001) in the intestine; complexes I (P &lt; 0.0001), II (P &lt; 0.0001), III (P = 0.0002), IV (P &lt; 0.0001), V (P = 0.0060), and CS (P &lt; 0.0001) in the muscle; and complexes I (P &lt; 0.0001), II (P &lt; 0.0001), IV (P &lt; 0.0001), V (P &lt; 0.0001), and CS (P &lt; 0.0001) in the liver activities except complex III activities in intestine (P = 0.0817) and liver (P = 0.4662). The diet × temperature interaction impacted CS activity in the intestine (P = 0.0010), complex II in the muscle (P = 0.0079), and complexes I (P = 0.0009) and II (P = 0.0348) in the liver. Overall, comparing partial to full dietary substitution of FO with CO, partial dietary replacement showed similar effects on complex activities.
Baseline characteristics may impact treatment duration of cabazitaxel in patients with mCRPC: a subanalysis of data from a post-marketing surveillance
Authors: Matsubara Nobuaki , Matsuyama Hideyasu , Kazama Hirotaka , Seto Takeshi , Sunaga Yoshinori , Suzuki Kazuhiro 
Published: October 2023

Abstract

Objective
Cabazitaxel has demonstrated improvements in overall survival among patients with metastatic castration-resistant prostate cancer (mCRPC) in the pivotal comparison clinical trials TROPIC, PROSELICA and CARD. However, these trials include mCRPC patients with similar characteristics, and there are limited data on how baseline characteristics affect treatment discontinuation in the patient population.

Methods
To assess individual factors that may impact the discontinuation rate of cabazitaxel treatment, we conducted a post hoc analysis of data from a nationwide all-case, post-marketing surveillance of cabazitaxel in Japan. Patients were grouped according to the number of cabazitaxel treatment cycles received (1–2 and ≥3 cycles). Predictive factors were identified through multivariate logistic regression analysis.

Results
Across 660 patients with metastatic castration-resistant prostate cancer, 70.2% received ≥3 cycles of cabazitaxel treatment. Those receiving 1–2 cycles of cabazitaxel had a greater proportion of patients with poorer Eastern Cooperative Oncology Group Performance Status, presence of lung and liver metastases, higher prostate-specific antigen level and prior radiation therapy at baseline. Regardless of the number of cabazitaxel cycles received, the primary reason for discontinuation was progression of disease rather than adverse events. Compared with those receiving 1–2 cycles, a lower proportion of patients receiving 3–10 and ≥11 cycles of cabazitaxel treatment experienced adverse events. Multivariate analysis showed a significant association between early discontinuation and presence of liver lesions, poorer Eastern Cooperative Oncology Group Performance Status and higher prostate-specific antigen level at baseline.

Conclusions
Post-marketing surveillance data suggest physicians should individualize cabazitaxel treatment based on certain patient characteristics at baseline.
Transforming Lost Time into Migration Capital: Hazara Refugee Social and Cultural Capital Development in Indonesia
Authors: Fiske Lucy 
Published: October 2023

Abstract
Refugees spend an average of 17 years living in limbo. This time is usually seen by refugees and scholars as ‘lost’ or ‘wasted’ time. Pierre Bourdieu theorized time as critical in accumulating social and cultural capital; foundations of socio-economic status. Families with greater economic capital can provide their offspring with more ‘time free from economic necessity’, enabling activities that will enhance their status. Time and economic capital are often de-linked by refugee journeys, stripping refugees of economic capital, but leaving an over-abundance of time. This paper uses Bourdieu’s work on time and capital to examine how refugees in one community use time during multi-year transit. Based on fieldwork with a single community, this paper argues that, rather than ‘wasting’ time, members of this community are using refugee time to accumulate social and cultural capital, which some then convert to migration capital and hasten their refugee journeys.
An interaction between eIF4A3 and eIF3g drives the internal initiation of translation
Authors: Chang Jeeyoon , Shin Min-Kyung , Park Joori , Hwang Hyun Jung , Locker Nicolas , Ahn Junhak , Kim Doyeon , Baek Daehyun , Park Yeonkyoung , Lee Yujin , Boo Sung Ho , Kim Hyeong-In , Kim Yoon Ki 
Published: October 2023

Abstract
An RNA structure or modified RNA sequences can provide a platform for ribosome loading and internal translation initiation. The functional significance of internal translation has recently been highlighted by the discovery that a subset of circular RNAs (circRNAs) is internally translated. However, the molecular mechanisms underlying the internal initiation of translation in circRNAs remain unclear. Here, we identify eIF3g (a subunit of eIF3 complex) as a binding partner of eIF4A3, a core component of the exon-junction complex (EJC) that is deposited onto spliced mRNAs and plays multiple roles in the regulation of gene expression. The direct interaction between eIF4A3-eIF3g serves as a molecular linker between the eIF4A3 and eIF3 complex, thereby facilitating internal ribosomal entry. Protein synthesis from in vitro-synthesized circRNA demonstrates eIF4A3-driven internal translation, which relies on the eIF4A3-eIF3g interaction. Furthermore, our transcriptome-wide analysis shows that efficient polysomal association of endogenous circRNAs requires eIF4A3. Notably, a subset of endogenous circRNAs can express a full-length intact protein, such as β-catenin, in an eIF4A3-dependent manner. Collectively, our results expand the understanding of the protein-coding potential of the human transcriptome, including circRNAs.
m7GHub V2.0: an updated database for decoding the N7-methylguanosine (m7G) epitranscriptome
Authors: Wang Xuan , Zhang Yuxin , Chen Kunqi , Liang Zhanmin , Ma Jiongming , Xia Rong , de Magalhães João Pedro , Rigden Daniel J , Meng Jia , Song Bowen 
Published: October 2023

Abstract
With recent progress in mapping N7-methylguanosine (m7G) RNA methylation sites, tens of thousands of experimentally validated m7G sites have been discovered in various species, shedding light on the significant role of m7G modification in regulating numerous biological processes including disease pathogenesis. An integrated resource that enables the sharing, annotation and customized analysis of m7G data will greatly facilitate m7G studies under various physiological contexts. We previously developed the m7GHub database to host mRNA m7G sites identified in the human transcriptome. Here, we present m7GHub v.2.0, an updated resource for a comprehensive collection of m7G modifications in various types of RNA across multiple species: an m7GDB database containing 430 898 putative m7G sites identified in 23 species, collected from both widely applied next-generation sequencing (NGS) and the emerging Oxford Nanopore direct RNA sequencing (ONT) techniques; an m7GDiseaseDB hosting 156 206 m7G-associated variants (involving addition or removal of an m7G site), including 3238 disease-relevant m7G-SNPs that may function through epitranscriptome disturbance; and two enhanced analysis modules to perform interactive analyses on the collections of m7G sites (m7GFinder) and functional variants (m7GSNPer). We expect that m7Ghub v.2.0 should serve as a valuable centralized resource for studying m7G modification. It is freely accessible at: www.rnamd.org/m7GHub2.
Inhibition of CDK12 elevates cancer cell dependence on P-TEFb by stimulation of RNA polymerase II pause release
Authors: Wang Zhijia , Himanen Samu V , Haikala Heidi M , Friedel Caroline C , Vihervaara Anniina , Barborič Matjaž 
Published: October 2023

AbstractP-TEFb and CDK12 facilitate transcriptional elongation by RNA polymerase II. Given the prominence of both kinases in cancer, gaining a better understanding of their interplay could inform the design of novel anti-cancer strategies. While down-regulation of DNA repair genes in CDK12-targeted cancer cells is being explored therapeutically, little is known about mechanisms and significance of transcriptional induction upon inhibition of CDK12. We show that selective targeting of CDK12 in colon cancer-derived cells activates P-TEFb via its release from the inhibitory 7SK snRNP. In turn, P-TEFb stimulates Pol II pause release at thousands of genes, most of which become newly dependent on P-TEFb. Amongst the induced genes are those stimulated by hallmark pathways in cancer, including p53 and NF-κB. Consequently, CDK12-inhibited cancer cells exhibit hypersensitivity to inhibitors of P-TEFb. While blocking P-TEFb triggers their apoptosis in a p53-dependent manner, it impedes cell proliferation irrespective of p53 by preventing induction of genes downstream of the DNA damage-induced NF-κB signaling. In summary, stimulation of Pol II pause release at the signal-responsive genes underlies the functional dependence of CDK12-inhibited cancer cells on P-TEFb. Our study establishes the mechanistic underpinning for combinatorial targeting of CDK12 with either P-TEFb or the induced oncogenic pathways in cancer.
Lineage specific 3D genome structure in the adult human brain and neurodevelopmental changes in the chromatin interactome
Authors: Rahman Samir , Dong Pengfei , Apontes Pasha , Fernando Michael B , Kosoy Roman , Townsley Kayla G , Girdhar Kiran , Bendl Jaroslav , Shao Zhiping , Misir Ruth , Tsankova Nadia , Kleopoulos Steven P , Brennand Kristen J , Fullard John F , Roussos Panos 
Published: October 2023

Abstract
The human brain is a complex organ comprised of distinct cell types, and the contribution of the 3D genome to lineage specific gene expression remains poorly understood. To decipher cell type specific genome architecture, and characterize fine scale changes in the chromatin interactome across neural development, we compared the 3D genome of the human fetal cortical plate to that of neurons and glia isolated from the adult prefrontal cortex. We found that neurons have weaker genome compartmentalization compared to glia, but stronger TADs, which emerge during fetal development. Furthermore, relative to glia, the neuronal genome shifts more strongly towards repressive compartments. Neurons have differential TAD boundaries that are proximal to active promoters involved in neurodevelopmental processes. CRISPRi on CNTNAP2 in hIPSC-derived neurons reveals that transcriptional inactivation correlates with loss of insulation at the differential boundary. Finally, re-wiring of chromatin loops during neural development is associated with transcriptional and functional changes. Importantly, differential loops in the fetal cortex are associated with autism GWAS loci, suggesting a neuropsychiatric disease mechanism affecting the chromatin interactome. Furthermore, neural development involves gaining enhancer-promoter loops that upregulate genes that control synaptic activity. Altogether, our study provides multi-scale insights on the 3D genome in the human brain.
STAMarker: determining spatial domain-specific variable genes with saliency maps in deep learning
Authors: Zhang Chihao , Dong Kangning , Aihara Kazuyuki , Chen Luonan , Zhang Shihua 
Published: October 2023

Abstract
Spatial transcriptomics characterizes gene expression profiles while retaining the information of the spatial context, providing an unprecedented opportunity to understand cellular systems. One of the essential tasks in such data analysis is to determine spatially variable genes (SVGs), which demonstrate spatial expression patterns. Existing methods only consider genes individually and fail to model the inter-dependence of genes. To this end, we present an analytic tool STAMarker for robustly determining spatial domain-specific SVGs with saliency maps in deep learning. STAMarker is a three-stage ensemble framework consisting of graph-attention autoencoders, multilayer perceptron (MLP) classifiers, and saliency map computation by the backpropagated gradient. We illustrate the effectiveness of STAMarker and compare it with serveral commonly used competing methods on various spatial transcriptomic data generated by different platforms. STAMarker considers all genes at once and is more robust when the dataset is very sparse. STAMarker could identify spatial domain-specific SVGs for characterizing spatial domains and enable in-depth analysis of the region of interest in the tissue section.
Resolving altered base-pairing of RNA modifications with DNA nanoswitches
Authors: Todkari Iranna Annappa , Chandrasekaran Arun Richard , Punnoose Jibin Abraham , Mao Song , Haruehanroengra Phensinee , Beckles Camryn , Sheng Jia , Halvorsen Ken 
Published: October 2023

Abstract
There are &gt;170 naturally occurring RNA chemical modifications, with both known and unknown biological functions. Analytical methods for detecting chemical modifications and for analyzing their effects are relatively limited and have had difficulty keeping pace with the demand for RNA chemical biology and biochemistry research. Some modifications can affect the ability of RNA to hybridize with its complementary sequence or change the selectivity of base pairing. Here, we investigate the use of affinity-based DNA nanoswitches to resolve energetic differences in hybridization. We found that a single m3C modification can sufficiently destabilize hybridization to abolish a detection signal, while an s4U modification can selectively hybridize with G over A. These results establish proof of concept for using DNA nanoswitches to detect certain RNA modifications and analyzing their effects in base pairing stability and specificity.
Detection of queuosine and queuosine precursors in tRNAs by direct RNA sequencing
Authors: Sun Yu , Piechotta Michael , Naarmann-de Vries Isabel , Dieterich Christoph , Ehrenhofer-Murray Ann E 
Published: October 2023

Abstract
Queuosine (Q) is a complex tRNA modification found in bacteria and eukaryotes at position 34 of four tRNAs with a GUN anticodon, and it regulates the translational efficiency and fidelity of the respective codons that differ at the Wobble position. In bacteria, the biosynthesis of Q involves two precursors, preQ0 and preQ1, whereas eukaryotes directly obtain Q from bacterial sources. The study of queuosine has been challenging due to the limited availability of high-throughput methods for its detection and analysis. Here, we have employed direct RNA sequencing using nanopore technology to detect the modification of tRNAs with Q and Q precursors. These modifications were detected with high accuracy on synthetic tRNAs as well as on tRNAs extracted from Schizosaccharomyces pombe and Escherichia coli by comparing unmodified to modified tRNAs using the tool JACUSA2. Furthermore, we present an improved protocol for the alignment of raw sequence reads that gives high specificity and recall for tRNAs ex cellulo that, by nature, carry multiple modifications. Altogether, our results show that 7-deazaguanine-derivatives such as queuosine are readily detectable using direct RNA sequencing. This advancement opens up new possibilities for investigating these modifications in native tRNAs, furthering our understanding of their biological function.
ClinicalOmicsDB: exploring molecular associations of oncology drug responses in clinical trials
Authors: Moon Chang In , Elizarraras John Michael , Lei Jonathan Thomas , Jia Byron , Zhang Bing 
Published: October 2023

AbstractMatching patients to optimal treatment is challenging, in part due to the limited availability of real-world clinical datasets for predictive biomarker identification. The growing integration of omics profiling into clinical trials presents a new opportunity to tackle this challenge. Here, we introduce ClinicalOmicsDB, a web application for exploring molecular associations of oncology drug responses in clinical trials. This database includes transcriptomic data from 40 clinical trial studies, with 5913 patients spanning 11 cancer types. These studies include 67 treatment arms with a variety of chemotherapy, targeted therapy and immunotherapy drugs, and their combinations, which we organize based on an established ontology for easier navigation. The web application provides users with three options to explore molecular associations of oncology drug responses, focusing on studies, treatments or genes, respectively. Gene set analysis further connects treatment response to pathway activity and tumor microenvironment attributes. The user-friendly web interface of ClinicalOmicsDB streamlines interactive analysis. A Rust-based backend speeds up response time, and application programming interfaces and an R package enable programmatic access. We use three case studies to demonstrate the utility of this resource in human cancer studies. ClinicalOmicsDB is freely available at http://trials.linkedomics.org/.
The cytokinin receptor OHK4/OsHK4 regulates inflorescence architecture in rice via an IDEAL PLANT ARCHITECTURE1/WEALTHY FARMER’S PANICLE-mediated positive feedback circuit
Authors: Chun Yan , Fang Jingjing , Savelieva Ekaterina M , Lomin Sergey N , Shang Jiangyuan , Sun Yinglu , Zhao Jinfeng , Kumar Ashmit , Yuan Shoujiang , Yao Xuefeng , Liu Chun-Ming , Arkhipov Dmitry V , Romanov Georgy A , Li Xueyong 
Published: October 2023

Abstract
Inflorescence architecture is important for rice (Oryza sativa) grain yield. The phytohormone cytokinin (CK) has been shown to regulate rice inflorescence development; however, the underlying mechanism mediated by CK perception is still unclear. Employing a forward genetic approach, we isolated an inactive variant of the CK receptor OHK4/OsHK4 gene named panicle length1, which shows decreased panicle size due to reduced inflorescence meristem (IM) activity. A 2-amino acid deletion in the long α-helix stalk of the sensory module of OHK4 impairs the homodimerization and ligand-binding capacity of the receptor, even though the residues do not touch the ligand-binding domain or the dimerization interface. This deletion impairs CK signaling that occurs through the type-B response regulator OsRR21, which acts downstream of OHK4 in controlling inflorescence size. Meanwhile, we found that IDEAL PLANT ARCHITECTURE1(IPA1)/WEALTHY FARMER'S PANICLE (WFP), encoding a positive regulator of IM development, acts downstream of CK signaling and is directly activated by OsRR21. Additionally, we revealed that IPA1/WFP directly binds to the OHK4 promoter and upregulates its expression through interactions with 2 TCP transcription factors, forming a positive feedback circuit. Altogether, we identified the OHK4-OsRR21-IPA1 regulatory module, providing important insights into the role of CK signaling in regulating rice inflorescence architecture.