bluuebunny/crossref_metadata_2025_split huggingface dataset:
Full-length RNA-Seq of RHOH gene in human B-cells reveals new exons and splicing patterns
Authors: Leprêtre Frédéric , Meneboo Jean-Pascal , Villenet Céline , Delestré Laure , Quesnel Bruno , Shelley Carl Simon , Figeac Martin , Galiègue-Zouitina Sylvie 
Published: April 2024

Abstract

The RhoH protein is a member of the Ras superfamily of guanosine triphosphate-binding proteins. RhoH is an atypical Rho family member that is always GTP-bound and thus always activated. It is restrictively expressed in normal hematopoietic cells, where it is a negative regulator of cell growth and survival. We previously analyzed the RHOH gene structure and demonstrated that this gene is composed of 7 exons, one single encoding exon located at the 3’ extremity of the gene, preceded by 6 noncoding exons. To further understand the transcription events associated with this gene, we performed full-length RNA-Seq on 12 B-cell lines. We identified new exons, new splice events and new splice sites, leading to the discovery of 38 RHOH mRNA molecules, 27 of which have never been described before. Here, we also describe new fusion transcripts. Moreover, our method allowed quantitative measurements of the different mRNA species relative to each other in relation to B-cell differentiation.
Brain activities in the auditory area and insula represent stimuli evoking emotional response
Authors: Tsushima Yoshiaki , Nakayama Koharu , Okuya Teruhisa , Koiwa Hiroko , Ando Hiroshi , Watanabe Yoshiaki 
Published: April 2024

Abstract

Cinema, a modern titan of entertainment, holds power to move people with the artful manipulation of auditory and visual stimuli. Despite this, the mechanisms behind how sensory stimuli elicit emotional responses are unknown. Thus, this study evaluated which brain regions were involved when sensory stimuli evoke auditory- or visual-driven emotions during film viewing. Using functional magnetic resonance imaging (fMRI) decoding techniques, we found that brain activities in the auditory area and insula represent the stimuli that evoke emotional response. The observation of brain activities in these regions could provide further insights to these mechanisms for the improvement of film-making, as well as the development of novel neural techniques in neuroscience. In near feature, such a “neuro-designed” products/ applications might gain in popularity.
Agrobacterium-mediated transformation of B. juncea reveal BjuLKP2 functions in plant yellowing
Authors: zeng jing , zhao liang , lu yuanqing , zuo tonghong , wang diandong , zhou yawen , lei zongxin , liu yihua , gao jian , Mo Yanling 
Published: April 2024

Abstract

A stable and efficient transform system was necessary to verification gene functions in plant. To construct an agrobacterium-mediated transform system in B. juncea, explants, as well as the combination and concentration of hormones, the concentration and timing of infection were optimized. Eventually, a stable transgenic system was established and two BjuLKP2 OE lines were obtained. Phenotypic observation found that both two BjuLKP2 OE lines displayed yellowing cotyledon, shoot tips, leaves, flower buds and reduction total Chl content. qRT-PCR assays indicated that five Chl synthesis genes were significantly up-regulated and one gene was down-regulated in BjuLKP2 OE line. Additionally, antioxidant capacity assays revealed decreased activities of APX, CAT and SOD, while POD activity was up-regulated in BjuLKP2 OE line. Further chlorophyll fluorescence induction kinetic determination results indicated a reduction in photosynthetic ability in BjuLKP2 OE line. GUS assays results showed that BjuLKP2 was expressed in various tissues, including root, hypocotyl, cotyledon and vascular tissues of leaves. It was also expressed in trichome, sepals, petals, filaments, styles and the stigma base, but did not detect in seeds. Scanning electron microscope observed found that chloroplasts ultra-structure in both sponge and palisade tissues were changed. All the results demonstrated that BjuLKP2 functions in plant yellowing by reduction in Chl content and changing chloroplasts structure.
An Analytical Surveillance of Land Utilization and Expansion of Urban Areas Employing Remote Sensing Algorithms
Authors: Al-Ansari Nadhir , Dibs Hayder , Al-Janabi Ahmed 
Published: April 2024

Abstract

In recent years, the city of AL-Hilla in Babylon, Iraq has suffered from the illegal fragmentation of agricultural and orchard lands, leading to their conversion into residential areas. This transformation has had a negative impact on the economic viability of plantation and vegetation lands, affecting the climate and causing an increase in temperatures, winds, and dust storms. This study aims to examine the spatio-temporal dynamics of changes in land-use/land-cover (LU/LC) using different spatial resolutions of satellite images to detect urban sprawl. The present study utilizes a supervised imagery classifier, employing the Mahalanobis distance (MD) technique to produce three distinct LU/LC maps for 2002, 2011, and 2022. The accuracy of the outcomes is assessed using a confusion matrix, and a comparison was made to compute the changes in land categories. The research reveals that the expansion of the urban region in AL-Hilla has significantly increased from 33.40 km² in 2002 to 89.16 km² in 2022, with an Annual Growth Rate of (6.74%) between 2002 and 2011 and 6.14% between 2011 and 2022. The growth in urban area now constitutes 38.45% of the entire city area and has resulted in a decline in other land categories such as water bodies, soil, and vegetation. The study highlights the necessity for effective management and planning strategies to address the adverse impact of urban expansion on the environment and agriculture
Estimating the risk of gastrointestinal illness associated with drinking water in Norway: a prospective cohort study
Authors: Hyllestad Susanne , Lyngstad Trude Marie , Lindstrøm Jonas Christoffer , White Richard Aubrey , Andreassen Monica , Svendsen Camilla 
Published: April 2024

Abstract

Background: The delivery of safe drinking water has high public health relevance, as reflected in the Sustainable Development Goals (SDG6). Several precautionary actions have resulted in a minimum burden associated with infectious diseases in high-income countries; however, there is increased awareness that the distribution system represents a risk factor for gastrointestinal illness. Sporadic cases of waterborne infections are expected to be underreported since a sick person is less likely to seek healthcare for a self-limiting gastrointestinal infection. Hence, knowledge on the true burden of waterborne diseases is scarce.
Methods: We conducted a cohort study of self-reported gastrointestinal infections and water consumption to estimate the risk of acute gastrointestinal infection (AGI) associated with drinking water in Norway.
Results: In total, 9,946 persons participated in this cohort study, accounting for 11.5% of all invited participants. Overall, we found a relatively low number of AGI per 100 person-months (5.5) and a very low number of severe AGI per 100 person-months (0.8). There were no clinically significant associations between the consumption of tap water and AGI or severe AGI in the models adjusted for possible confounders, with the expectation of a small effect of age on AGI. The risk of AGI was higher among small children (0-5 years; 5 percent points higher risk of AGI than among those 19-49 years old). AGI varied by season, but other possible confounding variables (sex, education level and size of water supply) were not statistically or clinically significant.
Conclusions: This is the largest cohort study in Norway estimating the burden of self-reported gastrointestinal infections linked to the consumption of drinking-based water in Norway. Overall, the results from the adjusted model show either no or very small associations of AGI or severe AGI with water consumption (glasses of water consumed). There was a small association with age. The data indicate that water-related AGI is not currently a major burden in Norway, but the findings need to be used with caution. The importance of continued efforts and investments in the maintenance of drinking water supplies in Norway to address the low burden of sporadic waterborne cases and to prevent future outbreaks needs to be emphasised.
Identification of bioactive natural products as potential inhibitors of cyclin-dependent kinase-8: A virtual screening study for anticancer therapeutics
Authors: Zehra . , Hussain Afzal , AlAjmi Mohamed F. , Ishrat Romana , Shamsi Anas , Hassan Md. Imtaiyaz 
Published: April 2024

Abstract
Cyclin-dependent kinase 8 (CDK8) is one of the members of the cyclin-dependent kinase family. It is highly expressed in various diseases and is a potent therapeutic target for developing anticancer drugs. We performed a virtual screening using the ZINC library to elucidate its potential inhibitors. We initiated our study by performing virtual screening using the ZINC library, which comprises approximately 90,000 compounds and applied Lipinski's rule of five, ADMET properties and PAINS filter to eliminate promiscuous binders. Subsequently, the filtered compounds underwent molecular docking to predict their binding affinity and interactions with the CDK8 protein. Interaction analysis was carried out to elucidate the interaction mechanism of the screened hits with binding pockets of the CDK8. Finally, ZINC02152165, ZINC04236005, and ZINC02134595 were selected with appreciable specificity and affinity with CDK8. To explore the conformational dynamics of CDK8 with the elucidated compounds, an all-atom molecular dynamic (MD) simulation followed by essential dynamics was performed for 200 ns. Overall, the result indicated that ZINC02152165, ZINC04236005, and ZINC02134595 could be exploited as potential leads in therapeutic development. The comprehensive computational approach provides valuable insights into the molecular mechanisms underlying CDK8 inhibition and paves the way for further experimental validation and drug development efforts.
Development of a First-in-Class RIPK1 Degrader to Enhance Antitumor Immunity
Authors: Wang Jin , Lu Dong , Yu Xin , Qi Xiaoli , Lin Hanfeng , Holloman Bryan L. , Jin Feng , Xu Longyong , Ding Lang , Peng Weiyi , Wang Meng , Chen Xi 
Published: April 2024

Abstract

The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and has emerged as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain, we harnessed proteolysis targeting chimera (PROTAC) technology to develop a first-in-class RIPK1 degrader, LD4172. LD4172 exhibited potent and selective RIPK1 degradation both in vitro and in vivo. Degradation of RIPK1 by LD4172 triggered immunogenic cell death (ICD) and enriched tumor-infiltrating lymphocytes and substantially sensitized the tumors to anti-PD1 therapy. This work reports the first RIPK1 degrader that serves as a chemical probe for investigating the scaffolding functions of RIPK1 and as a potential therapeutic agent to enhance tumor responses to immune checkpoint blockade therapy.
Evening inulin treatment alleviate anxiety and depression via gut-brain axis: A crucial role for microbiota and amino acids metabolism
Authors: Chen Ping , Chen Fanyang , Hou Tao , Hu Xueqin , Xia Chenxing , Zhang Jiaming , Shen Shanshan , Li Chenmei , Li Kaikai 
Published: April 2024

Abstract
Background
Increasing evidence has demonstrated that an imbalance in the microbiota-gut-brain axis exerts an essential effect on the pathophysiology of depressive and anxiety disorders. Our previous research revealed that the timing of inulin administration altered its influence on CUMS-induced anxiety and depression; however, it is still unclear if the gut-brain axis is primarily responsible for these effects.
Results
Serum metabolomics analysis showed that inulin treatment can alleviate the inflammatory response in CUMS-treated mice and that amino acid metabolic pathways were crucial for its anxiolytic and antidepressant effects. The time of administration seemed to modify the anxiolytic and antidepressant effects of inulin, and inulin intervention in the evening was more pronounced in improving amino acid metabolism and inhibiting the inflammatory response than that of morning inulin treatment. In addition, inulin treatment in the evening significantly reduced serum glucose and insulin levels. The main differential metabolites, including fenofibric acid, 4’-Hydroxyfenoprofen glucuronide and 5-(4-Hydroxybenzyl)thiazolidine-2,4-dione may play important roles for the anxiolytic and antidepressant ability of inulin. Fecal microbiota transplantation confirmed that inulin treatment alleviated CUMS-induced anxiety- and depression-like behaviors via gut-brain axis.
Conclusions
Our results suggest that inulin administration in the evening is more effective in alleviating the inflammatory response and improving amino acid metabolism. This study provides a new potential link between the microbiota-gut-brain axis and chrono-nutrition, which indicates that a more appropriate administration time results in a better intervention effect.
Analysis of NHL-1 gene family based on full-length transcriptome in Neocaridina denticulata sinensis
Authors: Xing Kefan , Li Huimin , Wang Xiongfei , Sun Yuying , Zhang Jiquan 
Published: April 2024

Abstract
Neocaridina denticulata sinensis has emerged as a promising model organism for basic studies in Decapod. However, the current transcriptome information in this species is based on next generation sequencing (NGS) technologies, which is limited by the short read length. Therefore, the present study aims to generate a full-length transcriptome assembly of N. denticulata sinensis utilizing the PacBio Sequel Ⅱ platform. The resulting transcriptome assembly comprised 5831 transcripts, with an N50 of 3697 bp. Remarkably, 90.5% of these transcripts represented novel isoforms of known genes. The transcripts were further searched against NR, SwissProt, KEGG, KOG, GO, NT and Pfam databases. 24.8% of the transcripts can be annotated across all seven databases. Additionally, 1236 alternative splicing (AS) events, 344 transcription factors (TFs), and 124 long non-coding RNAs (lncRNAs) were predicted. Based on the AS annotation results, a RING finger protein NHL-1 gene from N. denticulata sinensis (NdNHL-1) was identified. There are 15 transcripts in NdNHL-1. The longest transcript is 4995 bp in length and encodes a putative protein of 1665 amino acids. Phylogenetic analysis showed its close relationship with NHL-1 from other crustacean species. This report represents the full-length transcriptome of N. denticulata sinensis, and will facilitate the research of functional genomics and environmental adaptation in this species.
Natural pest regulation along a tropical agricultural landscape gradient: complexity counts
Authors: Samajpati Indranil , Basu Parthiba 
Published: April 2024

Abstract
Agricultural intensification is a threat to arthropod natural enemies of crop pests in agricultural landscapes due to multiple reasons. This may disrupt the biological pest regulation in the agro-ecosystems and thereby affect their sustainability. Natural enemies are reliant on natural and semi natural vegetation in the landscape which serves as alternative resources and provide refuge, decline of which may affect pest regulation through both direct and indirect mechanisms. We examined how landscape complexity affects natural arthropod enemies, pest, intraguild predators (Insectivorous birds), predation rate and pest damage at different spatial scales. We modeled the interrelationship between different farm scale parameters through Structural equational models (SEM) at 1000m and 2000m. There was significant positive association between landscape complexity and coccinellidae and parasitic hymenoptera abundance. Arthropod predation rate on artificial plascticine caterpillar also increased significantly with landscape complexity at different spatial scale. Structural equational models revealed latent relationships between different farm level components which were not directly found through simple correlative models. Comprehensive studies incorporating direct and indirect effect of landscape complexity on farm level biodiversity elements is necessary for ecologically intensive farms in the future.
A massive acute tubulointerstitial nephritis as an expression of a kappa light chain multiple myeloma: a case study
Authors: Angioi Andrea , Lepori Nicola , Floris Matteo , Cheungpasitporn Wisit , Bianco Paola , Cabiddu Gianfranca , Pani Antonello 
Published: April 2024

Abstract

Interstitial nephritis associated with multiple myeloma (LCTIN) is a rare histological finding defined as an abundant inflammatory infiltrate of polyclonal lymphocytes and plasma cells in the interstitium, not related to secondary causes other than a coexistent malignant plasma cell dyscrasia. The present case report illustrates an LCTIN associated with a light chain proximal tubulopathy, secondary to a kappa light chain MM, previously addressed as steroid-resistant drug-induced interstitial nephritis.
Three Novel Neuroblastoma Biomarkers Revealed by Integrative Analysis of GEO data
Authors: Xiong Zijun , Xu Mingjun , Yuan Ping , Yu Kefei , Xing Huanhuan , Yang Ruofan , Zhang Pu , Li Qiang , Zhang Jun , Wang Zihan , Zhao Liang , Gu Jiaowei , Liu Wenting 
Published: April 2024

Abstract

Comprehensive bioinformatics analysis was used to identify the differentially expressed genes (DEGs) between neuroblastoma samples and normal samples in GSE54720 and GSE78061 datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on common DEGs. The protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape software. The top 15 hub genes were screened out. TAGLN3, KIF5C and SNAP91 were identified by alignment in the PubMed, OMIM, DisGeNET and GeneCards databases and validated by quantitative real-time polymerase chain reaction (qPCR). These three are have never been previously reported in the literature and experimentally validated. We identified a total of 37 commom DEGs from the two microarray databases. The KEGG pathway analysis showed that these DEGs were primarily involved in pathway related to dopaminergic synapses, motor proteins and phenylalanine metabolism related pathways. GO enrichment analysis showed that TAGLN3, KIF5C, and SNAP91 related pathway were mainly concentrated in axon guidance, axon genesis, axon development, distal axon, neuronal cell body, and synaptic vesicle transport, suggesting that they may be involved in biological functions such as protein binding, plasma membrane, membrane composition and nucleus. OMIM, DisGeNET, GeneCards databases, and PubMed have identified that TAGLN3, KIF5C, and SNAP91 were linked to proliferation, migration, and invasion of other tumors. Finally, the expression levels of TAGLN3, KIF5C and SNAP91 were significantly increased in SH-SY5Y cells compared with ARPE-19 cells as verified by qPCR, consistent with our bioinformatics analysis, suggesting that TAGLN3, KIF5C and SNAP91 may be involved in the occurrence and development of neuroblastoma. In this study, some key genes and molecules were identified by bioinformatics methods, revealing the potential pathogenic mechanism of neuroblastoma. These genes can serve as diagnostic indicators and therapeutic biomarkers for neuroblastoma, thereby enhancing our understanding of the molecular mechanisms underlying this disease.
Small molecule-induced ERBB4 activation to treat heart failure
Authors: Segers Vincent , Cools Julie , Feyen Eline , Bogaert Siel Van den , Goovaerts Bo , Fu Yile , Civati Celine , fraeyenhove Jens Van , Tubeeckx Michiel , Haver Jasper Van , Nguyen Long , Wülfers Eike , Berlo Benji Van , De Vries Antoine , Vandersickel Nele , Pijnappels Daniël , Audenaert Dominique , Roderick Llew , De Winter Hans , De Keulenaer Gilles W. 
Published: April 2024

Abstract

Heart failure is a common and deadly disease, requiring new therapeutic approaches. The neuregulin-1 (NRG1)/erythroblastic leukemia viral oncogene homolog 4 (ERBB4) pathway is an interesting target because of its cardioprotective effects. The therapeutic use of recombinant NRG1 has been difficult, because it requires intravenous administration and is non-selective for the ERBB4 receptor. Moreover, development of small-molecule agonists of receptor dimers is generally considered to be challenging. Here, we hypothesized that small-molecule-induced activation of ERBB4 is feasible and can protect against myocardial cell death and fibrosis. To this end, we screened 10,240 compounds for their ability to induce homodimerization of ERBB4. We identified a series of 8 structurally similar compounds (named EF-1 – EF-8) that concentration-dependently induced ERBB4 dimerization, with EF-1 being the most potent. EF-1 decreased in an ERBB4-dependent manner cell death and hypertrophy in cultured atrial cardiomyocytes and collagen production in cultured human cardiac fibroblasts. EF-1 also inhibited angiotensin-II (AngII)-induced myocardial fibrosis in wild-type mice, but not in Erbb4-null mice. Additionally, EF-1 decreased troponin release in wild-type mice treated with doxorubicin (DOX), but not in Erbb4-null mice. Finally, EF-1 improved cardiac function in a mouse model of myocardial infarction (MI). In conclusion, we show that small-molecule-induced ERBB4 activation is possible, displaying anti-fibrotic and cardiomyocyte protective effects in the heart. This study can be the start for the development of small-molecule ERBB4 agonists as a novel class of drugs to treat heart failure.
Solving a Real-World Package Delivery Routing Problem Using Quantum Annealers
Authors: Osaba Eneko , Villar-Rodriguez Esther , Asla Antón 
Published: April 2024

Abstract

Research focused on the conjunction between quantum computing and routing problems has been very prolific in recent years. Most of the works revolve around classical problems such as the Traveling Salesman Problem or the Vehicle Routing Problem. Even though working on these problems is valuable, it is also undeniable that their academic-oriented nature falls short of real-world requirements. The main objective of this research is to present a solving method for realistic instances, avoiding problem relaxations or technical shortcuts. Instead, a quantum-classical hybrid solver has been developed, coined Q4RPD, that considers a set of real constraints such as a heterogeneous fleet of vehicles, priority deliveries, and capacities characterized by two values: weight and dimensions of the packages. \Q4RPD resorts to the Leap Constrained Quadratic Model Hybrid Solver of D-Wave. To demonstrate the application of Q4RPD, an experimentation composed of six different instances has been conducted, aiming to serve as illustrative examples.