Recognition Complex Research Articles

Genome-Wide Mapping of Autonomously Replicating Sequences in the Marine Diatom Phaeodactylum tricornutum.

Autonomously replicating sequences (ARSs) are important accessories in episomal vectors that allow them to be replicated and stably maintained within transformants. Despite their importance, no information on ARSs in diatoms has been reported. Therefore, we attempted to identify ARS candidates in the model diatom, Phaeodactylum tricornutum, via chromatin immunoprecipitation sequencing. In this study, subunits of the origin recognition complex (ORC), ORC2 and ORC4, were used to screen for ARS candidates. ORC2 and ORC4 bound to 355 sites on the P. tricornutum genome, of which 69 were constantly screened after multiple attempts. The screened ARS candidates had an AT-richness of approximately 50% (44.39-52.92%) and did not have conserved sequences. In addition, ARS candidates were distributed randomly but had a dense distribution pattern at several sites. Their positions tended to overlap with those of the genetic region (73.91%). Compared to the ARSs of several other eukaryotic organisms, the characteristics of the screened ARS candidates are complex. Thus, our findings suggest that the diatom has a distinct and unique native ARSs.

Multiple mechanisms for licensing human replication origins.

Loading of replicative helicases is obligatory for the assembly of DNA replication machineries. The eukaryotic MCM2-7 replicative helicase motor is deposited onto DNA by the origin recognition complex (ORC) and co-loader proteins as a head-to-head double hexamer to license replication origins. Although extensively studied in budding yeast1-4, the mechanisms of origin licensing in multicellular eukaryotes remain poorly defined. Here we use biochemical reconstitution and electron microscopy to reconstruct the human MCM loading pathway. We find that unlike in yeast, the ORC6 subunit of the ORC is not essential for-but enhances-human MCM loading. Electron microscopy analyses identify several intermediates en route to MCM double hexamer formation in the presence and absence of ORC6, including a DNA-loaded, closed-ring MCM single hexamer intermediate that can mature into a head-to-head double hexamer through multiple mechanisms. ORC6 and ORC3 facilitate the recruitment ofthe ORC to the dimerization interface of the first hexamer into MCM-ORC (MO)complexes that are distinct from the yeast MO complex5,6 and may orientthe ORC for second MCM hexamer loading. Additionally, MCM double hexamer formation can proceed through dimerization of independently loaded MCM single hexamers, promoted by a propensity of human MCM2-7 hexamers to self-dimerize. This flexibility in human MCM loading may provide resilience against cellular replication stress, and the reconstitution system will enable studies addressing outstanding questions regarding DNA replication initiation and replication-coupled events in the future.

REVIEW OF MODERN METHODS OF REDUCING THE COMPUTATIONAL COMPLEXITY OF IMAGE RECOGNITION IN COMPUTER-ASSISTED SURGERY

Abstract. The article is devoted to the review of modern methods of reducing the computational complexity of image recognition in computer-assisted surgery. The problem of computational complexity can adversely affect the image recognition process, slowing it down and reducing its accuracy. Given the relevance of existing image recognition technologies in surgery, a number of methods for reducing computational complexity are considered, based on existing scientific research. Calculations are presented, examples of the use of the proposed methods are considered. The research is the basis for further study of optimised methods and their integration into surgical practice.

A Review of Research on Handwritten Chinese Character Recognition with Multi-Feature Fusion

This paper analyzes the progress of handwritten Chinese character recognition technology, from two perspectives: traditional recognition methods and deep learning-based recognition methods. Firstly, the complexity of Chinese character recognition is pointed out, including its numerous categories, complex structure, and the problem of similar characters, especially the variability of handwritten Chinese characters. Subsequently, recognition methods based on feature optimization, model optimization, and fusion techniques are highlighted. The fusion studies between feature optimization and model improvement are further explored, and these studies further enhance the recognition effect through complementary advantages. Finally, the article summarizes the current challenges of Chinese character recognition technology, including accuracy improvement, model complexity, and real-time problems, and looks forward to future research directions.

Elevated origin recognition complex subunit 6 expression promotes non-small cell lung cancer cell growth

Exploring novel targets for non-small cell lung cancer (NSCLC) remains of utmost importance. This study focused on ORC6 (origin recognition complex subunit 6), investigating its expression and functional significance within NSCLC. Analysis of the TCGA-lung adenocarcinoma database revealed a notable increase in ORC6 expression in lung adenocarcinoma tissues, correlating with reduced overall survival, advanced disease stages, and other key clinical parameters. Additionally, in patients undergoing surgical resection of NSCLC at a local hospital, ORC6 mRNA and protein levels were elevated in NSCLC tissues while remaining low in adjacent normal tissues. Comprehensive bioinformatics analyses across various cancers suggested that ORC6 might play a significant role in crucial cellular processes, such as mitosis, DNA synthesis and repair, and cell cycle progression. Knocking down ORC6 using virus-delivered shRNA in different NSCLC cells, both primary and immortalized, resulted in a significant hindrance to cell proliferation, cell cycle progression, migration and invasion, accompanied by caspase-apoptosis activation. Similarly, employing CRISPR-sgRNA for ORC6 knockout (KO) exhibited significant anti-NSCLC cell activity. Conversely, increasing ORC6 levels using a viral construct augmented cell proliferation and migration. Silencing or knockout of ORC6 in primary NSCLC cells led to reduced expression of several key cyclins, including Cyclin A2, Cyclin B1, and Cyclin D1, whereas their levels increased in NSCLC cells overexpressing ORC6. In vivo experiments demonstrated that intratumoral injection of ORC6 shRNA adeno-associated virus markedly suppressed the growth of primary NSCLC cell xenografts. Reduced ORC6 levels, downregulated cyclins, and increased apoptosis were evident in ORC6-silenced NSCLC xenograft tissues. In summary, elevated ORC6 expression promotes NSCLC cell growth.

Replication licensing regulated by a short linear motif within an intrinsically disordered region of origin recognition complex

In eukaryotes, the origin recognition complex (ORC) faciliates the assembly of pre-replicative complex (pre-RC) at origin DNA for replication licensing. Here we show that the N-terminal intrinsically disordered region (IDR) of the yeast Orc2 subunit is crucial for this process. Removing a segment (residues 176-200) from Orc2-IDR or mutating a key isoleucine (194) significantly inhibits replication initiation across the genome. These Orc2-IDR mutants are capable of assembling the ORC-Cdc6-Cdt1-Mcm2-7 intermediate, which exhibits impaired ATP hydrolysis and fails to be convered into the subsequent Mcm2-7-ORC complex and pre-RC. These defects can be partially rescued by the Orc2-IDR peptide. Moreover, the phosphorylation of this Orc2-IDR region by S cyclin-dependent kinase blocks its binding to Mcm2-7 complex, causing a defective pre-RC assembly. Our findings provide important insights into the multifaceted roles of ORC in supporting origin licensing during the G1 phase and its regulation to restrict origin firing within the S phase.

Quantifying the Transition from Unconscious to Conscious Detection of Temporal Patterns in Vigilance Tasks: A Unique Adaptation of Mackworth's Clock Test.

This study investigates the cognitive mechanisms underlying vigilance and pattern recognition using a novel adaptation of Mackworth's Clock Test. We aimed to quantify the time it takes for temporal patterns detected unconsciously through implicit learning to surface in the conscious mind within a dynamic vigilance task environment. Forty-eight participants detected random and non-disclosed rhythmic anomalous clock hand movements in this setting. Our results indicate significant variability in detection accuracy, reaction times, and the ability to recognize the hidden pattern among participants. Notably, 23% of all participants and 56% of those who consciously reported the pattern exhibited statistically lower reaction times indicative of knowledge of the pattern 40 s before conscious identification. These findings provide valuable insights into the transition from unconscious to conscious detection, highlighting the complexity of sustained attention and pattern recognition. The study's implications extend to designing training programs and tasks for high-stakes professions requiring prolonged vigilance. Future research should further explore the cognitive and neural correlates of these processes and the impact of task complexity on performance.

MCM2-7 loading-dependent ORC release ensures genome-wide origin licensing

Origin recognition complex (ORC)-dependent loading of the replicative helicase MCM2-7 onto replication origins in G1-phase forms the basis of replication fork establishment in S-phase. However, how ORC and MCM2-7 facilitate genome-wide DNA licensing is not fully understood. Mapping the molecular footprints of budding yeast ORC and MCM2-7 genome-wide, we discovered that MCM2-7 loading is associated with ORC release from origins and redistribution to non-origin sites. Our bioinformatic analysis revealed that origins are compact units, where a single MCM2-7 double hexamer blocks repetitive loading through steric ORC binding site occlusion. Analyses of A-elements and an improved B2-element consensus motif uncovered that DNA shape, DNA flexibility, and the correct, face-to-face spacing of the two DNA elements are hallmarks of ORC-binding and efficient helicase loading sites. Thus, our work identified fundamental principles for MCM2-7 helicase loading that explain how origin licensing is realised across the genome.

A homobimetallic nickel(II) complex for discriminative chromogenic recognition of aqueous cyanide and silver(I) from medicinal products: Role of end-on thiocyanate bridging

Herein, a homobimetallic azomethine-functionalized nickel(II) complex, [Ni2L2(van)(μ1,1-NCS)] (AMR-1, where L = 2-[(2-Hydroxy-1,1-dimethyl-ethylimino)-methyl]-6-methoxyphenol, molecular weight = 788.20 (found)) has been judiciously synthesized with N-coordinated end-on thiocyanate. AMR-1 exhibited promising chromogenic variation from pale green to colourless with hypochromic shifting in the visible region in the presence of silver(I). Herein, the exposed sulfur site of the co-ligand acts as chemodosimetric recognition site for highly selective detection of a soft metal pollutant, silver ion (Ag+) with the limit of detection (LOD) of 0.37 ppm. Along with this, aqueous cyanide (CN−) recognition was accomplished in a mutually independent way with distinct chromogenic variation from pale green to yellowish color within ∼5 s. This led to the LOD of 0.46 ppm, which is much lower than the safe limit, set by the World Health Organization (WHO). The stability constant value for cyanide interaction with AMR-1 is obtained to be 1.49 × 103 M−1 as per 1:1 binding stoichiometry. Experimental findings, obtained from UV–Vis, HR-MS, FT-IR, and 1H NMR spectroscopic studies in conjugation with the decreased HOMO-LUMO energy gap from 3.40 eV to 2.07 eV, obtained from density functional theory studies, support the mechanistic pathway of interaction. Implementing molecular logic platforms benefits from fabricating three-input-two-output logic circuits by imitating variable spectroscopic outcomes. Real-time multifarious applications of AMR-1 have been accomplished with paper strip-based solid-state assay and recognition of the target-specific analytes from targeted medicinal specimens and from both cyanogenic as well as non-cyanogenic food sources. To the best of our knowledge, this is probably the first nickel(II) complex derived sensory receptor that is effectually implemented towards recognition of another metal ion, silver (I) along with CN− from aqueous as well as from real specimens.

Origin recognition complex subunit 6 (ORC6) is a key mediator of LPS-induced NFκB activation and the pro-inflammatory response

Lipopolysaccharide (LPS)-activated pro-inflammatory responses play a critical role in sepsis, a life-threatening condition. This study investigates the role of origin recognition complex subunit 6 (ORC6) in LPS responses in macrophages and monocytes. Silencing ORC6 using targeted shRNA significantly reduced LPS-induced expression and production of IL-1β (interleukin-1 beta), TNF-α (tumor necrosis factor alpha), and IL-6 (interleukin-6) in THP-1 human macrophages, peripheral blood mononuclear cells (PBMCs), and bone marrow-derived macrophages (BMDMs). Additionally, ORC6 knockout (KO) via the CRISPR/Cas9 method in THP-1 macrophages inhibited LPS-induced pro-inflammatory responses, while ectopic overexpression of ORC6 enhanced LPS-induced expression and production of pro-inflammatory cytokines. ORC6 is crucial for the activation of the nuclear factor kappa B (NFκB) signaling cascade in macrophages and monocytes. LPS-induced NFκB activation was largely inhibited by ORC6 silencing or KO, but potentiated following ORC6 overexpression. Mechanistically, ORC6 associated with nuclear p65 after LPS stimulation, an interaction necessary for NFκB activation. Overexpression of ORC6 did not recover the reduced pro-inflammatory response to LPS in THP-1 macrophages with silenced p65. Furthermore, the NFκB inhibitor BMS-345,541 nearly eliminated the pro-inflammatory response enhanced by ORC6 overexpression in response to LPS. Further studies revealed that ORC6 depletion inhibited NFκB activation induced by double-stranded RNA (dsRNA) and high mobility group box 1 (HMGB1) in THP-1 macrophages. In vivo experiments demonstrated that macrophage-specific knockdown of ORC6 protected mice from LPS-induced septic shock and inhibited LPS-stimulated production of IL-1β, TNF-α, and IL-6 in mouse serum. ORC6 silencing also inhibited LPS-induced NFκB activation in ex vivo cultured PBMCs following macrophage-specific knockdown of ORC6. These findings highlight ORC6 as a pivotal mediator in LPS-induced NFκB activation and the pro-inflammatory response in sepsis, suggesting that targeting ORC6 could be a novel therapeutic strategy for managing sepsis and related inflammatory conditions.

(Invited) Hypersectral Sensing of Biological Markers at the Point of Need

There is an urgent need for truly reagent free and agnostic sensing at the point of need for biological and chemical targets. Indeed, the COVID-19 pandemic has re-emphasized the significant need for truly agnostic diagnostics at the point of need. Whereas highly targeted and tailored diagnostics can help us address a known and anticipated threat, they do not prepare us against the next emerging outbreak. To address the significant challenge of developing truly agnostic diagnostics that can improve situational awareness and guide decision making, our team has looked to spectroscopy as an inspiration for the sensing modality; and innate immunity as an inspiration for the biological process and signatures. All biological molecules emanate spectral signatures along the electromagnetic spectrum, integral information from which can provide insights into processes or signatures more effectively. Therefore, we propose the use of hyperspectral sensing as a modality for accurate diagnosis and detection of signatures. With regards to the biology - innate immunity is a broad, agnostic pathogen sensing strategy that allows for the early recognition of all pathogens – known and unknown – with an associated response. Our team has developed strategies to mimic this response in the laboratory, culminating with the (ongoing) development of a data-science and machine learning enabled effort to unravel the complexity of the immune recognition (host cytokine and chemokine response), allowing for their ability to inform on categories of pathogens/disease. It is important to integrate this knowledge with a point of contact diagnostic approach in order to be able to translate the data into usable diagnostic information. To this end, we are working on developing a hyperspectral approach that measures these signatures without reagents from saliva samples in a few seconds. Charged by a back-end machine learning/artificial intelligence algorithm, our approach uses Pattern’s ProSpectral Sensor that measures signatures across various realms of the electromagnetic spectrum. Data on developing this sensing modality as a diagnostic in real time – challenges and advantages – will be presented.

The budding yeast Fkh1 Forkhead associated (FHA) domain promotes a G1-chromatin state and the activity of chromosomal DNA replication origins.

In Saccharomyces cerevisiae, the forkhead (Fkh) transcription factor Fkh1 (forkhead homolog) enhances the activity of many DNA replication origins that act in early S-phase (early origins). Current models posit that Fkh1 acts directly to promote these origins' activity by binding to origin-adjacent Fkh1 binding sites (FKH sites). However, the post-DNA binding functions that Fkh1 uses to promote early origin activity are poorly understood. Fkh1 contains a conserved FHA (forkhead associated) domain, a protein-binding module with specificity for phosphothreonine (pT)-containing partner proteins. At a small subset of yeast origins, the Fkh1-FHA domain enhances the ORC (origin recognition complex)-origin binding step, the G1-phase event that initiates the origin cycle. However, the importance of the Fkh1-FHA domain to either chromosomal replication or ORC-origin interactions at genome scale is unclear. Here, S-phase SortSeq experiments were used to compare genome replication in proliferating FKH1 and fkh1-R80A mutant cells. The Fkh1-FHA domain promoted the activity of ≈ 100 origins that act in early to mid- S-phase, including the majority of centromere-associated origins, while simultaneously inhibiting ≈ 100 late origins. Thus, in the absence of a functional Fkh1-FHA domain, the temporal landscape of the yeast genome was flattened. Origins are associated with a positioned nucleosome array that frames a nucleosome depleted region (NDR) over the origin, and ORC-origin binding is necessary but not sufficient for this chromatin organization. To ask whether the Fkh1-FHA domain had an impact on this chromatin architecture at origins, ORC ChIPSeq data generated from proliferating cells and MNaseSeq data generated from G1-arrested and proliferating cell populations were assessed. Origin groups that were differentially regulated by the Fkh1-FHA domain were characterized by distinct effects of this domain on ORC-origin binding and G1-phase chromatin. Thus, the Fkh1-FHA domain controlled the distinct chromatin architecture at early origins in G1-phase and regulated origin activity in S-phase.

Hand Trajectory Recognition by Radar with a Finite-State Machine and a Bi-LSTM

Gesture plays an important role in human–machine interaction. However, the insufficient accuracy and high complexity of gesture recognition have blocked its widespread application. A gesture recognition method that combines state machine and bidirectional long short-term memory (Bi-LSTM) fusion neural network is proposed to improve the accuracy and efficiency. Firstly, gestures with large movements are categorized into simple trajectory gestures and complex trajectory gestures in advance. Afterwards, different recognition methods are applied for the two categories of gestures, and the final result of gesture recognition is obtained by combining the outputs of the two methods. The specific method used is a state machine that recognizes six simple trajectory gestures and a bidirectional LSTM fusion neural network that recognizes four complex trajectory gestures. Finally, the experimental results show that the proposed simple trajectory gesture recognition method has an average accuracy of 99.58%, and the bidirectional LSTM fusion neural network has an average accuracy of 99.47%, which can efficiently and accurately recognize 10 gestures with large movements. In addition, by collecting more gesture data from untrained participants, it was verified that the proposed neural network has good generalization performance and can adapt to the various operating habits of different users.

F-norm based low-power motion recognition on wearable devices in the presence of outlier motions

Motion recognition refers to the intelligent recognition of human motion using data collected from wearable sensors, which exceedingly has gained significant interest from both academic and industrial fields. However, temporary-sudden activities caused by accidental behavior pose a major challenge to motion recognition and have been largely overlooked in existing works. To address this problem, the multi-dimensional time series of motion data is modeled as a Time-Frequency (TF) tensor, and the original challenge is transformed into a problem of outlier-corrupted tensor pattern recognition, where transient sudden activity data are considered as outliers. Since the TF tensor can capture the latent spatio-temporal correlations of the motion data, the tensor MPCA is used to derive the principle spatio-temporal pattern of the motion data. However, traditional MPCA uses the squared F-norm as the projection distance measure, which makes it sensitive to the presence of outlier motion data. Therefore, in the proposed outlier-robust MPCA scheme, the F-norm with the desirable geometric properties is used as the distance measure to simultaneously mitigate the interference of outlier motion data while preserving rotational invariance. Moreover, to reduce the complexity of outlier-robust motion recognition, we impose the proposed outlier-robust MPCA scheme on the traditional MPCANet which is a low-complexity deep learning network. The experimental results show that our proposed outlier-robust MPCANet can simultaneously improve motion recognition performance and reduce the complexity, especially in practical scenarios where the real-time data is corrupted by temporary-sudden activities.

Improved FasterViT model for citrus disease diagnosis

Despite advances in deep learning for plant leaf disease recognition, accurately distinguishing morphological features under varying environmental conditions continues to pose significant challenges. Traditional deep learning models often fail to effectively merge local and global information, especially in small-scale datasets, impairing performance and elevating training costs. Focusing on citrus diseases, we propose an improved FasterViT Model, an advanced hybrid CNN-ViT framework that builds upon the FasterViT model. The proposed model seamlessly integrates CNN's rapid local learning capabilities with ViT's global information processing strength, thereby effectively extracting complex textures and morphological features from images. Cross-stage alternating Mixup and Cutout methods are strategically employed to enhance model robustness and generalization capabilities, particularly valuable for fast learning on small-scale datasets by simulating a more diverse training environment. Triplet Attention and AdaptiveAvgPool mechanisms are utilized to reduce training costs and optimize training performance. The proposed model is tested on both our specially constructed small-scale citrus disease dataset called in-field small dataset and the comprehensive PlantVillage dataset. The experimental results demonstrated that the model exhibits the capability of fast learning and adaptation to small sample training in plant disease detection tasks, and demonstrates the effectiveness of our improvement approach in improving model accuracy and reducing training costs. Additionally, its exemplary performance in transfer learning scenarios underscores its adaptability and broad applicability. This study not only highlights the efficacy of the improved FasterViT model in addressing the complexities of plant disease image recognition but also pioneers a new paradigm for developing efficient, scalable, and robust classification systems.

ORC1 enhances repressive epigenetic modifications on HIV-1 LTR to promote HIV-1 latency.

Identifying host factors involved in maintaining human immunodeficiency virus type 1 (HIV-1) latency and understanding their mechanisms prepares the groundwork to discover novel targets for HIV-1 latent infection and provides further options for the selection of latency-reversing agents in the "shock" strategy. In this study, we identified a novel role of the DNA replication factor origin recognition complex 1 (ORC1) in maintaining repressive chromatin structures surrounding the HIV-1 promoter region, thereby contributing to HIV-1 latency. This discovery expands our understanding of the non-replicative functions of the ORC complex and provides a potential therapeutic strategy for HIV-1 cure.

Dynamics of Replication-Associated Protein Levels through the Cell Cycle.

The measurement of dynamic changes in protein level and localization throughout the cell cycle is of major relevance to studies of cellular processes tightly coordinated with the cycle, such as replication, transcription, DNA repair, and checkpoint control. Currently available methods include biochemical assays of cells in bulk following synchronization, which determine protein levels with poor temporal and no spatial resolution. Taking advantage of genetic engineering and live-cell microscopy, we performed time-lapse imaging of cells expressing fluorescently tagged proteins under the control of their endogenous regulatory elements in order to follow their levels throughout the cell cycle. We effectively discern between cell cycle phases and S subphases based on fluorescence intensity and distribution of co-expressed proliferating cell nuclear antigen (PCNA)-mCherry. This allowed us to precisely determine and compare the levels and distribution of multiple replication-associated factors, including Rap1-interacting factor 1 (RIF1), minichromosome maintenance complex component 6 (MCM6), origin recognition complex subunit 1 (ORC1, and Claspin, with high spatiotemporal resolution in HeLa Kyoto cells. Combining these data with available mass spectrometry-based measurements of protein concentrations reveals the changes in the concentration of these proteins throughout the cell cycle. Our approach provides a practical basis for a detailed interrogation of protein dynamics in the context of the cell cycle.

Cdt1 Self-associates via the Winged-Helix Domain of the Central Region during the Licensing Reaction, Which Is Inhibited by Geminin.

The initiation of DNA replication is tightly controlled by the licensing system that loads replicative DNA helicases onto replication origins to form pre-replicative complexes (pre-RCs) once per cell cycle. Cdc10-dependent transcript 1 (Cdt1) plays an essential role in the licensing reaction by recruiting mini-chromosome maintenance (MCM) complexes, which are eukaryotic replicative DNA helicases, to their origins via direct protein-protein interactions. Cdt1 interacts with other pre-RC components, the origin recognition complex, and the cell division cycle 6 (Cdc6) protein; however, the molecular mechanism by which Cdt1 functions in the MCM complex loading process has not been fully elucidated. Here, we analyzed the protein-protein interactions of recombinant Cdt1 and observed that Cdt1 self-associates via the central region of the molecule, which is inhibited by the endogenous licensing inhibitor, geminin. Mutation of two β-strands of the winged-helix domain in the central region of Cdt1 attenuated its self-association but could still interact with other pre-RC components and DNA similarly to wild-type Cdt1. Moreover, the Cdt1 mutant showed decreased licensing activity in Xenopus egg extracts. Together, these results suggest that the self-association of Cdt1 is crucial for licensing.

Origin recognition complex 6 overexpression promotes growth of glioma cells

The discovery of novel oncotargets for glioma is of immense significance. We here explored the expression patterns, biological functions, and underlying mechanisms associated with ORC6 (origin recognition complex 6) in glioma. Through the bioinformatics analyses, we found a significant increase in ORC6 expression within human glioma tissues, correlating with poorer overall survival, higher tumor grade, and wild-type isocitrate dehydrogenase status. Additionally, ORC6 overexpression is detected in glioma tissues obtained from locally-treated patients and across various primary/established glioma cells. Further bioinformatics scrutiny revealed that genes co-expressed with ORC6 are enriched in multiple signaling cascades linked to cancer. In primary and immortalized (A172) glioma cells, depleting ORC6 using specific shRNA or Cas9-sgRNA knockout (KO) significantly decreased cell viability and proliferation, disrupted cell cycle progression and mobility, and triggered apoptosis. Conversely, enhancing ORC6 expression via a lentiviral construct augmented malignant behaviors in human glioma cells. ORC6 emerged as a crucial regulator for the expression of key oncogenic genes, including Cyclin A2, Cyclin B2, and DNA topoisomerase II (TOP2A), within glioma cells. Silencing or KO of ORC6 reduced the mRNA and protein levels of these genes, while overexpression of ORC6 increased their expression in primary glioma cells. Bioinformatics analyses further identified RBPJ as a potential transcription factor of ORC6. RBPJ shRNA decreased ORC6 expression in primary glioma cells, while its overexpression increased it. Additionally, significantly enhanced binding between the RBPJ protein and the proposed ORC6 promoter region was detected in glioma tissues and cells. In vivo experiments demonstrated a significant reduction in the growth of patient-derived glioma xenografts in the mouse brain subsequent to ORC6 KO. ORC6 depletion, inhibited proliferation, decreased expression of Cyclin A2/B2/TOP2A, and increased apoptosis were detected within these ORC6 KO intracranial glioma xenografts. Altogether, RBPJ-driven ORC6 overexpression promotes glioma cell growth, underscoring its significance as a promising therapeutic target.

Women’s health at work: a qualitative study on women’s health issues in relation to work participation. Experiences and perspectives from female teachers and managers in Norwegian high schools

BackgroundPublic health and working life are closely related. Even though Norway is one of the world’s most equality-oriented countries, working life is still divided by gender. Women have a lower rate of participation in working life than men, they work more part-time and they have a higher sickness absence. Research has mostly focused on structural and cultural reasons for gender differences, rather than on the fact that women and men have different biology and face different health challenges. The aim of this project was to explore experienced associations between women’s health and female participation in working life.MethodsQualitative methods were chosen for investigating women’s experiences. We carried out in-depth interviews with 11 female high school teachers and supplemented the material with a focus group with five managers from the same organisation. The interviews were recorded and transcribed verbatim. We used the six steps of reflexive thematic analysis for consistency in the analysis process.ResultsThe teachers shared a variety of experienced health issues within the field of women’s health and perceived barriers in the work environment. Four main themes were identified: (1) invisibility of women’s health at work, (2) complexity and lack of recognition of women’s health at work, (3) women’s health in work environment and (4) women’s health and role conflicts. There were few contradictions between the two informant groups. We found that health, work and total life intertwine and that complexity, lack of recognition and invisibility of women’s health appear at different levels in a mutual influence: for the women themselves, in the organisation and in society.ConclusionLack of recognition and invisibility of women’s health in the work environment is suggested to influence women’s work participation. The complexity of female health is not captured by gender-neutral structures in the work environment meant to protect and promote employees’ occupational health. Recognition of women’s health in the work context can therefore contribute to a gender-equal, health-promoting and sustainable working life.