Browse Articles
Discover research articles across all indexed journals
Herpesviruses mimic zygotic genome activation to promote viral replication
Abstract Zygotic genome activation (ZGA) is crucial for maternal to zygotic transition at the 2-8-cell stage in order to overcome silencing of genes and enable transcription from the zygotic genome. In humans, ZGA is induced by DUX4, a pioneer factor that drives expression of downstream germline-specific genes and retroelements. Here we show that herpesviruses from all subfamilies, papillomaviruses and Merkel cell polyomavirus actively induce DUX4 expression to promote viral transcription and replication. Analysis of single-cell sequencing data sets from patients shows that viral DUX4 activation is of relevance in vivo. Herpes-simplex virus 1 (HSV-1) immediate early proteins directly induce expression of DUX4 and its target genes, which mimics zygotic genome activation. Upon HSV-1 infection, DUX4 directly binds to the viral genome and promotes viral transcription. DUX4 is functionally required for infection, since genetic depletion by CRISPR/Cas9 as well as degradation of DUX4 by nanobody constructs abrogates HSV-1 replication. Our results show that DNA viruses including herpesviruses mimic an embryonic-like transcriptional program that prevents epigenetic silencing of the viral genome and facilitates herpesviral gene expression.
Cellular senescence-associated genes in rheumatoid arthritis: Identification and functional analysis
Rheumatoid arthritis (RA), a long-term autoinflammatory condition causing joint damage and deformities, involves a multifaceted pathogenesis with genetic, epigenetic, and immune factors, including early immune aging. However, its precise cause remains elusive. Cellular senescence, a hallmark of aging marked by a permanent halt in cell division due to damage and stress, is crucial in aging and related diseases. In our study, we analyzed RA microarray data from the Gene Expression Omnibus (GEO) and focused on cellular senescence genes from the CellAge database. We started by selecting five RA datasets from GEO. Next, we pinpointed 29 differentially expressed genes (DEGs) linked to cellular senescence in RA, aligning them with genes from CellAge. We explored the roles of these DEGs in cellular senescence through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. We then pinpointed three key genes (DHX9, CYR61, and ITGB) using random forest and LASSO Cox regression machine learning techniques. An integrated diagnostic model was created using these genes. We also examined the variance in immune cell infiltration and immune checkpoint gene expression between RA and normal samples. Our methodology’s predictive accuracy was confirmed in external validation cohorts. Subsequently, RA samples were classified into three distinct subgroups based on the cellular senescence-associated DEGs, and we compared their immune landscapes. Our findings reveal a significant impact of cellular senescence-related DEGs on immune cell infiltration in RA samples. Hence, a deeper understanding of cellular senescence in RA could offer new perspectives for diagnosis and treatment.
Changes in event soil moisture-temperature coupling can intensify very extreme heat beyond expectations
The gender gap in STEM: (Female) teenagers’ ICT skills and subsequent career paths
Skills shortage in the fields of Sciences, Technology, Engineering, and Mathematics (STEM) poses a significant challenge for industries globally. To overcome shortage of STEM talent, the selection into STEM fields must be fully understood. We contribute to existing research on the selection of STEM careers by analysing the interplay between teenagers’ proficiency in Information and Communication Technology (ICT) and their career preferences in the STEM domain. Based on representative data for German teenagers, our study shows that female teenagers are less likely to choose a career in STEM unless they have strong ICT skills in secondary school. The relationship does not hold for male students. An increase in girls’ ICT skills by 10 percentage points in ninth grade is associated with an increase in the probability to choose a STEM career by 2.95 percentage points. Our findings can be explained with evidence that teenagers sort into occupations they believe to be good at and that female teenagers rather underestimate their true potential. Using different empirical approaches, we also show that ICT skills act as a moderator and not as a mediator in the gender-specific choice of training upon graduating from secondary school. By addressing the interplay between gender, ICT skills, and educational choices, the present study uncovers an additional lever of how to mitigate skills shortage in STEM.
Electrochromism via reversible electrodeposition of solid iodine
Single-cell and bulk RNA sequencing analysis reveals CENPA as a potential biomarker and therapeutic target in cancers
Background Cancer remains one of the most significant public health challenges worldwide. A widely recognized hallmark of cancer is the ability to sustain proliferative signaling, which is closely tied to various cell cycle processes. Centromere Protein A (CENPA), a variant of the standard histone H3, is crucial for selective chromosome segregation during the cell cycle. Despite its importance, a comprehensive pan-cancer bioinformatic analysis of CENPA has not yet been conducted. Methods Data on genomes, transcriptomes, and clinical information were retrieved from publicly accessible databases. We analyzed CENPA’s genetic alterations, mRNA expression, functional enrichment, association with stemness, mutations, expression across cell populations and cellular locations, link to the cell cycle, impact on survival, and its relationship with the immune microenvironment. Additionally, a prognostic model for glioma patients was developed to demonstrate CENPA’s potential as a biomarker. Furthermore, drugs targeting CENPA in cancer cells were identified and predicted using drug sensitivity correlations and protein-ligand docking. Results CENPA exhibited low levels of gene mutation across various cancers. It was found to be overexpressed in nearly all cancer types analyzed in TCGA, relative to normal controls, and was predominantly located in the nucleus of malignant cells. CENPA showed a strong association with the cancer cell cycle, particularly as a biomarker for the G2 phase. It also emerged as a valuable diagnostic and prognostic biomarker across multiple cancer types. In glioma, CENPA demonstrated reliable prognostic potential when used alongside other prognostic factors. Additionally, CENPA was linked to the immune microenvironment. Drugs such as CD-437, 3-Cl-AHPC, Trametinib, BI-2536, and GSK461364 were predicted to target CENPA in cancer cells. Conclusion CENPA serves as a crucial biomarker for the cell cycle in cancers, offering both diagnostic and prognostic value.
Striving for open-source and equitable speech-to-speech translation
Gypsum heterogenous nucleation pathways regulated by surface functional groups and hydrophobicity
Abstract Gypsum (CaSO4·2H2O) plays a critical role in numerous natural and industrial processes. Nevertheless, the underlying mechanisms governing the formation of gypsum crystals on surfaces with diverse chemical properties remain poorly understood due to a lack of sufficient temporal-spatial resolution. Herein, we use in situ microscopy to investigate the real-time gypsum nucleation on self-assembled monolayers (SAMs) terminated with −CH3, −hybrid (a combination of NH2 and COOH), −COOH, −SO3, −NH3, and −OH functional groups. We report that the rate of gypsum formation is regulated by the surface functional groups and hydrophobicity, in the order of −CH3 > −hybrid > −COOH > −SO3 ≈ − NH3 > − OH. Results based on classical nucleation theory and molecular dynamics simulations reveal that nucleation pathways for hydrophilic surfaces involve surface-induced nucleation, with ion adsorption sites (i.e., functional groups) serving as anchors to facilitate the growth of vertically oriented clusters. Conversely, hydrophobic surfaces involve bulk nucleation with ions near the surface that coalesce into larger horizontal clusters. These findings provide new insights into the spatial and temporal characteristics of gypsum formation on various surfaces and highlight the significance of surface functional groups and hydrophobicity in governing gypsum formation mechanisms, while also acknowledging the possibility of alternative nucleation pathways due to the limitations of experimental techniques.
The diagnostic accuracy of umbilical cord procalcitonin in predicting early-onset neonatal infection
Introduction To determine the threshold of umbilical cord blood procalcitonin for early-onset neonatal infection diagnosis. Method This prospective study was conducted on 126 neonates in the neonatal care unit of Hue University of Medicine and Pharmacy Hospital, Vietnam, from June 01, 2023 to August 31, 2024. All neonates showed signs at birth or risk factors for early-onset infection (EOI) and were divided into two groups: EOI group and non-EOI group. Umbilical cord blood samples were collected for procalcitonin analysis immediately after birth. Results The median procalcitonin (PCT) levels in umbilical cord blood were significantly higher in the EOI group (0.154 ng/ml [0.092–0.197]) compared to the non-EOI group (0.097 ng/ml [0.082–0.134]; p < 0.001). Receiver operating characteristic (ROC) curve determined the optimal threshold value of PCT of 0.142 ng/ml with an AUC 0.751 (95% CI: 0.661–0.841, p<0.001) in the total population. At this cut-off, the Se, Sp, PPV, and NPV were 68.2%, 76.8%, 61.2%, and 81.8%, respectively. The optimal cut-off value for preterm neonates was 0.122 ng/ml (AUC: 0.785, 95% CI: 0.658–0.911, p<0.001) corresponding a Se of 79.2%, Sp of 74.1%, PPV of 73.1%, and NPV of 80.0%. In term group, the optimal cut-off value was 0.150 ng/ml (AUC: 0.726, 95% CI: 0.583–0.860, p<0.01), with a Se of 60.0%, Sp of 80.4%, PPV of 52.2%, and NPV of 84.9%. Conclusions Umbilical cord blood PCT concentration were elevated in neonates with EOI. PCT could be a valuable marker for the early diagnosis of EOI.
Transport and inhibition of the sphingosine-1-phosphate exporter SPNS2
Abstract Sphingosine-1-phosphate (S1P) is a signaling lysolipid critical to heart development, immunity, and hearing. Accordingly, mutations in the S1P transporter SPNS2 are associated with reduced white cell count and hearing defects. SPNS2 also exports the S1P-mimicking FTY720-P (Fingolimod) and thereby is central to the pharmacokinetics of this drug when treating multiple sclerosis. Here, we use a combination of cryo-electron microscopy, immunofluorescence, in vitro binding and in vivo S1P export assays, and molecular dynamics simulations to probe SPNS2’s substrate binding and transport. These results reveal the transporter’s binding mode to its native substrate S1P, the therapeutic FTY720-P, and the reported SPNS2-targeting inhibitor 33p. Further capturing an inward-facing apo state, our structures illuminate the protein’s mechanism for exchange between inward-facing and outward-facing conformations. Finally, using these structural, localization, and S1P transport results, we identify how pathogenic mutations ablate the protein’s export activity and thereby lead to hearing loss.
A facial expression recognition network using hybrid feature extraction
Facial expression recognition faces great challenges due to factors such as face similarity, image quality, and age variation. Although various existing end-to-end Convolutional Neural Network (CNN) architectures have achieved good classification results in facial expression recognition tasks, these network architectures share a common drawback that the convolutional kernel can only compute the correlation between elements of a localized region when extracting expression features from an image. This leads to difficulties for the network to explore the relationship between all the elements that make up a complete expression. In response to this issue, this article proposes a facial expression recognition network called HFE-Net. In order to capture the subtle changes of expression features and the whole facial expression information at the same time, HFE-Net proposed a Hybrid Feature Extraction Block. Specifically, Hybrid Feature Extraction Block consists of parallel Feature Fusion Device and Multi-head Self-attention. Among them, Feature Fusion Device not only extracts the local information in expression features, but also measures the correlation between distant elements in expression features, which helps the network to focus more on the target region while realizing the information interaction between distant features. And Multi-head Self-attention can calculate the correlation between the overall elements in the feature map, which helps the network to extract the overall information of the expression features. We conducted a lot of experiments on four publicly available facial expression datasets and verified that the Hybrid Feature Extraction Block constructed in this paper can improve the network’s recognition ability for facial expressions.
Hydroclimatic extremes threaten groundwater quality and stability
Abstract Heavy precipitation, drought, and other hydroclimatic extremes occur more frequently than in the past climate reference period (1961–1990). Given their strong effect on groundwater recharge dynamics, these phenomena increase the vulnerability of groundwater quantity and quality. Over the course of the past decade, we have documented changes in the composition of dissolved organic matter in groundwater. We show that fractions of ingressing surface-derived organic molecules increased significantly as groundwater levels declined, whereas concentrations of dissolved organic carbon remained constant. Molecular composition changeover was accelerated following 2018’s extreme summer drought. These findings demonstrate that hydroclimatic extremes promote rapid transport between surface ecosystems and groundwaters, thereby enabling xenobiotic substances to evade microbial processing, accrue in greater abundance in groundwater, and potentially compromise the safe nature of these potable water sources. Groundwater quality is far more vulnerable to the impact of recent climate anomalies than is currently recognized, and the molecular composition of dissolved organic matter can be used as a comprehensive indicator for groundwater quality deterioration.
Beyond burnout: A comprehensive investigation of burnout, resilience, and career continuity among Palestinian lawyers in a complex socio-political environment
This article investigates burnout among lawyers and proposes systemic changes to reduce pressure and stress in the legal profession while enhancing resilience among lawyers. The article focuses on factors influencing career continuity among Palestinian lawyers within a socio-politically complex environment. It discusses elements contributing to resilience, including a positive mindset, a strong support system, training, and social support. The study reveals exceptional resilience among Palestinian lawyers. A quantitative cross-sectional study was used; the goals of the study involved 323 participants from different places in Palestine. Data analysis employed Smart PLS4 to build a regression model. Challenging conventional notions, the study provides valuable insights for state strategies, legal firms, educational institutions, and policymakers to address challenges and improve lawyer retention and job satisfaction in an environment marked by unstable economic and political conditions. Additionally, it examines gender-specific career intentions, notably women lawyers displaying a stronger inclination to stay, potentially linked to socio-economic responsibilities. This study contributes significantly to existing literature by providing a unique case study on career continuance determinants within economic and political instability. It sets a precedent for further study and strategic improvements in lawyer retention and job satisfaction within high-stress professions in an economically and politically complex environment.
Anti-proteolytic regulation of KRAS by USP9X/NDRG3 in KRAS-driven cancer development
Parental experience of change following VIPP-SD in families with preschool children with externalizing behavior: A qualitative interview study
Background Insensitive parenting and ineffective disciplinary strategies are known risk factors for child externalizing behavior. The Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) has documented effect in promoting sensitive parenting, but little is known on how VIPP-SD is experienced by parents. This study explores how parents of preschool children with externalizing behaviors experience change following VIPP-SD delivered by trained childcare providers. Methods Individual qualitative semi-structured interviews were conducted with 9 mothers and 2 fathers to explore the parents’ experiences of change following the intervention. Data were analyzed using Braun and Clarke’s reflexive thematic analysis. Results Four themes were generated: 1) “All of her behavior is actually just a result of how she feels, right?”—Enhanced parental understanding, 2) Meeting the child’s needs in comfort and in play, 3) Learning to prevent and manage conflicts is essential–diverse experiences of gains and progress, 4) “I’m actually not a bad parent”–new positive perspectives. Conclusion Parents experienced an enhanced capacity to understand their child and positive development in their parenting behavior, skills and confidence as well as improvements in the parent-child relationship after receiving VIPP-SD. Findings also suggest potential areas for adaptation of VIPP-SD when intervening in families with a child exhibiting externalizing behaviors, as parental experiences of gains related to conflict management varied. Further research on this matter is recommended.
Time-resolved spectroscopy uncovers deprotonation-induced reconstruction in oxygen-evolution NiFe-based (oxy)hydroxides
Non-linear dose-response relationship between uterine artery pulsatility index and risk of preeclampsia in early pregnancy: A secondary analysis based on a nested cohort study
Background Previous studies have shown that higher uterine artery pulsatility index (UtA-PI) values in early pregnancy have predictive value for the risk of preeclampsia (PE). However, the sensitivity and specificity of this marker remain controversial. This study aims to explore further the association between UtA-PI in early pregnancy and the incidence of preeclampsia. Methods A total of 5000 pregnant women who underwent prenatal examination and delivery at the same hospital were included in this nested cohort study. And the PI values of left and right uterine arteries of the subjects were obtained by transabdominal ultrasound using GE color doppler diagnostic device in early pregnancy (11–13 + 6 weeks), and finally the mean value of both was calculated and recorded as UtA-PI. Among them, 60 pregnant women developed preeclampsia and were randomly divided into a screening group (n = 12) and control group (n = 48) and matched with pregnant women who did not develop preeclampsia during the same period to form a subset for subsequent statistical analysis. A weighted multivariate logistic regression model was used to analyze the association between UtA-PI and PE. Additionally, the non-linear relationship between UtA-PI and the incidence of PE was examined using smooth curve fitting and a generalized additive model. Results After adjusting for other variables, UtA-PI values were positively correlated with the incidence of PE, and the relationship showed a non-linear U-shaped relationship (inflection point 1.83). Conclusion Our study showed a significantly increased risk of PE when UtA-PI exceeded 1.83. This provides a basis for clinicians to identify high-risk pregnant women early and implement timely intervention, which helps to reduce maternal and fetal complications and improve health outcomes.
An unusual chiral-at-metal mechanism for BINOL-metal asymmetric catalysis
Difference-Cum-Exponential-type estimators for estimation of finite population mean in survey sampling
Extensive research work has been done for the estimation of population mean using bivariate auxiliary information based on conventional measures. Conventional measures of the auxiliary variables provide suspicious results in the presence of outliers/extreme values. However, non-conventional measures of the auxiliary variables include quartile deviation, mid-range, inter-quartile range, quartile average, tri-mean, Hodge-Lehmann estimator etc. give efficient results in case of extreme values. Unfortunately, non-conventional measures are not used by survey practitioners to enhance the estimation of unknown population parameters using bivariate auxiliary information. In this article, difference-cum-exponential-type estimators for population mean utilizing bivariate auxiliary information based on non-conventional measures under simple and stratified random sampling schemes have been suggested. Mathematical properties such as bias and mean squared error are derived. To support theoretical findings, various real-life applications are used to confirm the superiority of the suggested estimators as compared to the competing estimators under study.