bluuebunny/crossref_metadata_2025 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.
Multivalent S2-subunit Vaccines Provide Broad Protection Against Clade 1 Sarbecoviruses
Authors: Kane Ravi , Halfmann Peter , Patel Raj , Loeffler Kathryn , Yasuhara Atsuhiro , de Velde Lee-Ann Van , Yang Jie , Chervin Jordan , Troxell Chloe , Huang Min , Zheng Naiying , Wright Elizabeth , Thomas Paul , Wilson Patrick , Kawaoka Yoshihiro
Published: April 2024

The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak have accentuated the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2-subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection. Here, expanding on our previous work with S2-based vaccines, we developed a nanoparticle vaccine displaying multiple copies of the SARS-CoV-1 S2 subunit. This vaccine alone, or as a cocktail with a SARS-CoV-2 S2 subunit vaccine, protected transgenic K18-hACE2 mice from challenges with Omicron subvariant XBB as well as several sarbecoviruses identified as having pandemic potential including the bat sarbecovirus WIV1, BANAL-236, and a pangolin sarbecovirus. Challenge studies in Fc-g receptor knockout mice revealed that antibody-based cellular effector mechanisms played a role in protection elicited by these vaccines. These results demonstrate that our S2-based vaccines provide broad protection against clade 1 sarbecoviruses and offer insight into the mechanistic basis for protection.
Exploring extreme-rainfall forcings over Tucumán (Argentina) in the last 108 years and an extension to Subtropical South America
Authors: Medina Franco D. , Zossi Bruno S. , Elias Ana G.
Published: April 2024

In this work the maximum daily rainfall (Rx1) is analyzed based on the longest and highest-quality daily precipitation record available in Northwestern Argentina (NWA). Rx1 is a proxy of the daily-rainfall intensity and, thus, the analysis is useful due to their relation to the flood events. The selected series has a length of 108 years and corresponds to San Miguel de Tucumán (TUC, 26.8°S, 65.2°W), a city located in Subtropical South America (SSA). The methodology proposed was detecting the period of minimum p-value (PmPV) in the linear correlation coefficients to determine closer relationships between Rx1 and large-scale climate forcings. Results show a transition from a stronger Rx1-El Niño Southern Oscillation (ENSO) association in 1945–1974 to a tighter Rx1-Southern Annular Mode (SAM) relationship in 1974–2007. The PmPV of ENSO indices aligns with the cold PDO phase, while SAM's PmPV coincides with a warm PDO phase, highlighting their significant impact on Rx1 relationships. On the other hand, using HadEX3 and ERA5 data, it was shown that the results are consistent over part of SSA respecting Rx1 and atmospheric variables behavior. Analysis reveals a shifting Rx1-ENSO relationship over NWA in contrast with the observed in eastern Argentina. Also, a positive association Rx1-SAM over NWA, western Paraguay, eastern Bolivia and central Brazil during the PDO positive phase was found. We show that changes in Rx1 arise in response to changes in ENSO and SAM teleconnections driven by PDO. Thus, this study underscores the role of global variability in driving regional extreme precipitation.
Environmental Conditions in the Pre-jenkyns Event Times (Late Pliensbachian – Early Toarcian) in the Southiberian Palaeomargin (Betic External Zones, Southern Spain)
Authors: Nieto Luis M. , Ayadi Chaima , Fraguas Agela , Molina José Miguel , Reolid Matías
Published: April 2024

Three stratigraphic sections of the Betic External Zones have been studied, two from the Median Subbetic (PEL and PR) and one from the External Subbetic (CE). The upper Pliensbachian materials and the transition to the lower Toarcian have been dated with calcareous nannofossils in PEL and PR in this paper, while in the CE section, previous ammonite and nannofossil biostratigraphies have been considered. The dominant facies are alternance of marly limestone - marl, although in the CE section, the Toarcian is represented by marls, where the Jenkyns Event has been recorded. In terms of ichnofossils, in the PEL section Macaronichnus predominates. In the PR and CE sections, the ichnoassemblages are dominated by Planolites, Thalassinoides and Chondrites. Therefore, the facies and ichnofacies observed were generated in pelagic or hemipelagic marine environments. Analysis of the correlation between δ13C and δ18O and of each of them with Sr and Fe/Ca and Sr/Ca, as well as the Z-factor, indicate that the geochemical signal has not been modified by diagenesis. In the PEL and PR sections, the δ13C and δ18O ratios do not allow to clearly identify isotopic events, except in CE where the Jenkyns Event was recorded. The proxies used to study detritism (Zr/Rb, Sr/Cu, CIA and C-value) show trends opposite to those detected in other Tethys sections and even between them. These peculiarities in the geochemical data are interpreted as the result of the opening of the Hispanic Corridor, the mixing of Panthalassa and Tethys seawaters and extensional tectonics, which favoured the development of half grabens with significant differential subsidence, especially during the NJT5b Subzone (latest Pliensbachian). These half grabens could be affected by contourite currents according to the Macaronichnus assemblage in some of these sections.
An experimental test of environmental filtering in zooplankton pond communities
Authors: Parry Victor , Pawlak Julia , Tiedemann Ralph , Weithoff Guntram
Published: April 2024

Understanding the assembly of communities in separate patches with restricted connectivity is a central goal in spatial community ecology. In such meta-communities, several processes structure the local communities. Besides dispersal/drift and local processes, environmental filtering is often regarded as one important driver which refers to specific environmental characteristics of different patches that restrict the colonization and/or persistence of individual species. An aquatic example of a meta-community is a set of ponds scattered in the landscape. Many aquatic organisms disperse passively among ponds. As dispersal rates increase in a metacommunity, local environmental conditions primarily shape the zooplankton community structure. Local dynamics prevail and species generally exist in habitats where they are highly adapted to and in a few places where they are sub-optimally adapted (species sorting). Under high dispersal rates, spatial dynamics are more important to local densities than temporal, within-lake dynamics by frequently providing individual patches with immigrants (mass effects). We examine the influence of environmental filtering on the zooplankton community structure in a group of ponds within an agricultural landscape. We used an experimental approach to directly quantify environmental filtering and the potential local adaptation of individual species. We sampled four ponds in an agricultural matrix and measured the performance of the zooplankton community in their home and away environment. Common garden experiments revealed that the zooplankton communities developed differently in their home and away environment and there might have been some degree of local adaptation as some species were better adapted/had a higher fitness to their home habitat than away. However, the opposite case, lower abundance at home than away, was also found for some species. Thus, we found environmental filtering on the community level, but no consistent sign for local adaptation.
Venous excess ultrasonography (VExUS) captures dynamic changes in volume status surrounding hemodialysis: A multicenter prospective observational study
Authors: Leyba Katarina , Longino August , Ormesher Ryen , Krienke Mary , Ochten Natalie Van , Zimmerman Katherine , McCormack Luke , Martin Katharine , Thai Theresa , Furgeson Seth , Teitelbaum Isaac , Burke Joseph , Douglas Ivor , Gill Edward
Published: April 2024

Background: The evaluation of volume status is essential to clinical decision-making, yet multiple studies have shown that physical exam does not reliably estimate a patient’s intravascular volume. Venous excess ultrasound score (VExUS) is an emerging volume assessment tool that utilizes inferior vena cava (IVC) diameter and pulse-wave Doppler waveforms of the portal, hepatic and renal veins to evaluate venous congestion. A point-of-care ultrasound exam initially developed by Beaubein-Souligny et al., VExUS represents a reproducible, non-invasive and accurate means of assessing intravascular congestion. VExUS has recently been validated against RHC—the gold-standard of hemodynamic evaluation for volume assessment. While VExUS scores were shown to correlate with elevated cardiac filling pressures (i.e., right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP)) at a static point in time, the ability of VExUS to capture dynamic changes in volume status has yet to be elucidated. We hypothesized that paired VExUS examinations performed before and after hemodialysis (HD) would reflect changes in venous congestion in a diverse patient population.
Methods: Inpatients with end-stage renal disease undergoing intermittent HD were evaluated with transabdominal VExUS and lung ultrasonography before and following HD. Paired t-tests were conducted to assess differences between pre-HD and post-HD VExUS scores, B-line scores and dyspnea scores.
Results: Fifty-six patients were screened for inclusion in this study. Ten were excluded due to insufficient image quality or incomplete exams, and forty-six patients (ninety-two paired ultrasound exams) were included in the final analysis. Paired t-test analysis of pre-HD and post-HD VExUS scores revealed a mean VExUS grade change of 0.82 (p<0.001) on a VExUS scale ranging from 0 to 4. The mean difference in B-line score following HD was 0.8 (p=0.001). There was no statistically significant difference in subjective dyspnea score (p=0.41).
Conclusions: Large-volume fluid removal with HD was represented by changes in VExUS score, highlighting the utility of the VExUS exam to capture dynamic shifts in intravascular volume status. Future studies should evaluate change in VExUS grade with intravenous fluid or diuretic administration, with the ultimate goal of evaluating the capacity of a standardized bedside ultrasound protocol to guide inpatient volume optimization.
Strain evolution from ferroelectric to relaxor state in BiFeO3-BaTiO3 based ceramics
Authors: Wang Ke , Feng Jiaqing , Tao Hong , Ma Jian , Wu Bo
Published: April 2024

BiFeO3 (BF)-based lead-free piezoelectric ceramics have been already widely exploited. In order to reduce the leakage current and resolve the problem of difficult polarization, BaTiO3 (BT) has been added to form the BiFeO3-BaTiO3(BF-BT) solid solution. The piezoelectric and ferroelectric properties have been greatly improved with modified phase structure and relaxor characteristics of BF-BT ceramics by ions doping. The mechanism of strain response from the ferroelectric to relaxor state in BF-BT based ceramics has not been thoroughly investigated. This work emphasizes on the evolution of strain from ferroelectric-relaxor state in (0.67-x)BF-0.33BT-xBMZ ceramics. Three states of ferroelectric-relaxor with strengthening relaxor are constructed via increasing Pm3m and reducing R3m symmetry. A tendency of increasing first and then decreasing is obtained for Suni and Spos with enhanced relaxor behavior along with a maximum strain (Suni = 0.25%, Spos = 0.24%) for x = 0.04, due to the promoted domain switching and strong random field with appropriate polar nanoregions merged into long-range ordered matrix. And the strain gradually increases with elevating temperature due to the improved polarization and growing ferroelectric domain. This study reveals the contribution of structure modification to piezoelectric response, promoting the development of lead-free piezoelectrics.
CtMYB1 regulate flavonoid biosynthesis in safflower flower by binding the CAACCA elements
Authors: Zhou YanXun , Wang Jie , Peng YanNi , Chen Chao , Xian Bin , Xi ZiQing , Ren ChaoXiang , Pei Jin , Chen Jiang
Published: April 2024

Background
Safflower (Carthamus tinctorius L.) is a valuable crop known for its flowers, which are rich in flavonoids and are used for promoting blood circulation and preventing atherosclerosis. However, the molecular regulation of flavonoid biosynthesis in safflower is still poorly understood. In this study, we identified a AtMYB12 homologous gene, CtMYB1, in safflower and characterized its sequence. The flower protoplast transient expression system and virus-induced gene silence (VIGS) technique were established in safflower and we tested the role of CtMYB1 in the regulation of flavonoid biosynthesis.
Results
Flower protoplast transient expression showed that flavonoid biosynthesis genes CtC4H2, CtF3H4, and CtHCT12 were upregulated after transfection with CtMYB1. Meanwhile, VIGS showed that the transfected petals were lighter in color, and there was a decrease in the amount of the major component Hydroxysafflor yellow A (HSYA) compared to the control. Additionally, the interaction analysis by the use of Biacore system revealed that CtMYB1 can bind to the CAACCA element of flavonoid biosynthesis genes promoters.
Conclusions
CtMYB1 can regulate flavonoid biosynthesis in safflower flower by binding the CAACCA elements of flavonoid biosynthesis related genes promoters,which shed light on the molecular regulation of flavonoid biosynthesis in safflower.The establishment of the flower protoplast expression system and VIGS in safflower provide a valuable tool for studying gene function, particularly those involved in the regulation and biosynthesis of-active compounds of safflower.
Lessons from the COVID-19 pandemic to strengthen NCD care and policy in humanitarian settings: a mixed methods study exploring humanitarian actors’ experiences.
Authors: Ansbro Éimhín , Heller Olivia , Vijayasingham Lavanya , Caroline Favas , Rintjema Jacqueline , Chase-Vilchez Alyssa , Stein Claire , Rita Issa , Sanga Leah , Murphy Adrianna , Perel Pablo
Published: April 2024

Background
The COVID-19 pandemic and response severely impacted people living with non-communicable diseases (PLWNCDs) globally. It exacerbated pre-existing health inequalities, severely disrupted access to care, and worsened clinical outcomes for PLWNCDs, who were at higher risk of morbidity and mortality from the virus. The pandemic’s effects were likely magnified in humanitarian settings, where there were pre-existing gaps in continuity of care for non-communicable diseases (NCDs). We sought to explore factors affecting implementation of NCD care in crises settings during the COVID-19 pandemic and the adaptations made to support implementation.
Methods
Guided by the Consolidated Framework for Implementation Research, we undertook an online survey of 98 humanitarian actors from multiple regions and organization types (March-July 2021), followed by in-depth interviews with 13 purposively selected survey respondents (October-December, 2021). Survey data were analysed using descriptive statistics, while interview data were analysed both deductively and inductively.
Results
Initially, humanitarian actors faced challenges influenced by external actors’ priorities, such as deprioritisation of NCD care by governments, travel restrictions and supply chain interruptions. With each infection wave and lockdown, humanitarian actors were better able to adapt and maintain NCD services. The availability of COVID-19 vaccines was a positive turning point, especially for the risk management of people with NCDs and protection of health workers. Key findings include that, despite pre-existing challenges, humanitarian actors largely continued NCD services during the crisis. Enabling factors that supported continuity of NCD services included the ability to quickly pivot to remote means of communication with PLWNCDs, flexibility in medicine dispensing, and successful advocacy to prioritize NCD management within health systems. Key lessons learned included the importance of partnerships and cooperation with other health actors and the mobilisation or repurposing of community health workers/volunteer networks.
Conclusions
The COVID-19 experience should prompt national and global health stakeholders to strengthen inclusion of NCDs in emergency preparedness, response, and resilience planning, building on lessons learned around remote care provision adapted to PLWNCDs severity, integrating community health workers, providing context-adapted PLWNCDs information and combating misinformation and strengthening cross-sectoral partnerships.
Long noncoding RNA LINC01842 enhances disulfidptosis resistance and promotes glioma progression via IQGAP1
Authors: Zhang Fuguang , Wang Heng , Zheng Weiqian , Wang Dinghao , Yan Chuangnan , Chen Shuxin , Xu Hongwu
Published: April 2024

Background: Long non-coding RNA (lncRNA) is widely present in cells and is demonstrated to play vital roles in the development and progression of glioma. However, the biological roles and function mechanisms of LINC01842 in glioma are not yet clear. This study aims to elucidate the potential role of LINC01842 in glioma, specifically its association with disulfidptosis.
Methods: We obtained sequencing data from The Cancer Gene Atlas (TCGA). Correction analysis was applied to select disulfidptosis-related lncRNAs (DRLs). Prognosis-associated DRLs were identified by least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). Receiver operating characteristic (ROC) curve and multivariate Cox regression analyses were used to screen our target gene LINC01842. Subsequently, expression of LINC01842, IQGAP1and SLC7A11 in glioma cell lines was detected by real-time quantitative polymerase chain reaction (qPCR). Additionally, CCK8 experiments and wound healing assays were performed to assess cell viability, migration, and invasion. Finally, online database predictions were used to validate the drug sensitivity of glioma.
Results: LINC01842 was more highly expressed in high-grade gliomas, and glioma patients with high expression level of LINC01842 had poorer survival. Additionally, tumor cells with high expression of LINC01842 exhibited stronger tumor characteristics, such as migratory and invasive abilities, as well as tolerance to disulfidptosis. Furthermore, strong binding between LINC01842 and the disulfidptosis-related gene IQGAP1 could be predicted, and their expression levels were positively correlated. Ultimately, drug sensitivity analysis suggested glioma patients with high expression level of LINC01842 were sensitive to eight drugs.
Conclusion: High expression of LINC01842 is associated with poor prognosis in glioma patients. By interacting with IQGAP1, the resistance to disulfidptosis of LINC0182 was stronger in glioma, which promotes the progression of glioma. Eight discovered sensitive drugs provided important clues for personalized treatment of glioma.
A Nonlinear Acoustic--Flame Synchronization Model for Thermoacoustic Instability in a Bluffbody-Stabilized Combustor
Authors: kumar Swarnalatha Kathalagiri Vasantha , Rani Sarma L.
Published: April 2024

A nonlinear coupled-oscillator model is developed that can predict the various stages of synchronization between the acoustic and heat-release oscillations in the lead-up to thermoacoustic instability in a dump combustor with a bluffbody-anchored flame. The flame is perturbed by vortices shed from the shear layer formed at the combustor dump plane. The resulting heat-release-rate fluctuations generate acoustic waves that travel upstream and interact with the shear layer, thereby modulating the vortex shedding process and closing the feedback loop. Coupled nonlinear equations governing the temporal evolution of pressure and heat-release-rate fluctuations are derived and evolved along with an equation for the build-up of circulation at the dump plane, as well as an equation for vortex advection. The effects of vortex impingement on the flame are modeled as a localized, instantaneous source term in the flame oscillator equation. With the mean flow velocity $\Bar{u}$ as the control parameter, the nonlinear model is applied to investigate the acoustic--flame--vortex interactions. For smaller $\Bar{u}$, chaotic combustion noise is observed with essentially no synchronization between the pressure and heat-release-rate fluctuations, $p'$ and $\dot{q}'$, respectively. As $\Bar{u}$ is increased, intermittent bursts of periodic fluctuations are seen in $p'$ and $\dot{q}'$, which is followed by a weakly periodic state with only frequency synchronization. Eventually, when $\Bar{u}$ exceeds a critical value, limit-cycle oscillations are seen with both frequency and amplitude synchronization between $p'$ and $\dot{q}'$ (also known as generalized synchronization). Thus, the model qualitatively captures the successive stages of acoustic--flame coupling seen in the experiments of \citet{pawar2017}. Furthermore, the derived nonlinear equations accurately predict the natural frequencies of the pressure and heat-release oscillators, as well as the lock-on frequency of the two oscillators with vortex shedding.
Genomic Analysis of Circulating Influenza Virus from 2016 in Nepal
Authors: Jha Bimalesh Kumar , Katuwal Nishan , Manandhar Krishna Das
Published: April 2024

Background
Influenza constitutes a contagious viral infection primarily attributed to influenza viruses A or B, predominantly affecting the upper respiratory system. The rapid evolution of influenza viruses results in substantial variability. Type A encompasses 16 highly variable hemagglutinins (H1 to H16) and 9 distinct NAs (N1 to N9). Conversely, influenza type B lacks subtypes owing to fixed, albeit small, antigenic variabilities. Given the swift evolution and diversification, comprehendinggenomic epidemiology becomes imperative for discerning emerging strains and trackingtransmission.
Objectives
This study delves into the genomic analysis of various sequences of H1N1 and Influenza type B, isolated from Nepal and deposited in the Global Initiative on Sharing Avian Influenza Data (GISAID).
Methods
The viral genomic material, after extraction, were sent to National Institute of Infectious Disease, Japan for whole genome sequencing in 2016. The sequences were subsequently submitted to GISAID. The H1N1 virus genomes (n=18) in this study were investigated against the reference genome A/California/07/2009 (GenBank: CY121680). Similarly, Influenza Type B virus genomes (n=27) were examined against reference genome B/Brisbane/60/2008 (GenBank: KX058884) and B/Wisconsin/01/2010 (GenBank: JN993010). Mutational analyses were performed using Nextclade, followed by an investigation into the mutations present in the sequences. Finally, phylogenetic analysis was conducted using the Nextclade and CLUSTAL Omega.
Results
Out of the 18 HA genome segments of H1N1, all (n=12) except 6 isolates belonged to clade 6B, while the remainder were of clade 6B.1. For Influenza Type B, all 27 HA genome segments were classified under clade V1A when compared to B/Brisbane/60/2008. Similarly, in comparison to the reference genome B/Wisconsin/01/2010 (genbank: JN993010), all (n=23) except 4 isolates were of clade Y3, while the rest were of clade Y2.
Conclusion
The analysis of the HA1 (sub-segment of HA) proves valuable for strain identification based on mutations. The HA segment in influenza type A exhibits the fastest mutation rate, influencing virulence, while mutations in NA are associated with drug resistance. Given the heightened risk of influenza outbreaks due to emerging mutations, assortments, and drug resistance, vigilance in monitoring mutations in these segments are crucial.