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The competition for nursing faculty has reached a crisis point, with over 2000 schools of nursing vying for a shrinking pool of qualified candidates. This shortage hits research-intensive institutions hardest because nurses may delay entry into academic research careers following extended clinical practice. Although strategic faculty recruitment and development in research-intensive institutions is critical for advancing science, little is known about successful organizational strategies implemented within research-intensive schools of nursing. This article presents organizational strategies for recruiting and developing research-intensive nursing faculty through a mission-driven, human-centered approach at the Nell Hodgson Woodruff School of Nursing at Emory University. The authors highlight three key approaches: mission-aligned recruitment practices, human-centered approaches to creating supportive environments, and the integration of individual- and organization-centered approaches to faculty development. Success requires recruiting faculty with diverse disciplinary expertise, implementing transparent processes, and achieving a balance between individual career aspirations and institutional research, education, and service priorities. As federal research priorities rapidly evolve and the shortage of research-intensive nursing faculty deepens, institutions must invest in adaptive recruitment strategies, robust mentoring programs, and equitable resource allocation to build sustainable research capacity and leadership pipelines.

Understanding how the spliceosome integrates regulatory cues to generate RNA diversity remains a central question in gene expression control. Emerging evidence reveals a multilayered framework in which splicing is governed by nuclear architecture and the physical state of nuclear speckles. These condensates function as phosphorylation-sensitive hubs that concentrate splicing machinery and couple signaling pathways to RNA processing. Chromatin organization, transcript architecture, and condensate properties are tightly coordinated, adding spatial constraints to spliceosome function. Recent findings further uncover temporal regulation through cell cycle and ultradian dynamics of speckle assembly. In this review, we synthesize these advances and propose a unified model in which charge-dependent phosphorylation of splicing factors drives condensate remodeling, linking nuclear organization to regulated splicing outcomes across space and time.

In this work, the effects of two UV filters - avobenzone and oxybenzone - on the membranes of fibroblasts and keratinocytes in ex vivo model systems (Langmuir monolayers) and cell line experiments were examined. The goal of these studies was to analyze the significance of lipid structures in the mechanism of UV filter-induced toxicity to skin cells. Monolayers composed of lipids characteristic of mammalian cell membranes - namely phosphatidylcholine (SOPC), sphingomyelin (SM), cholesterol (Chol) and ceramides (Ceramide 22 and Ceramide 17) - were used as model systems. Both mixed monolayers mimicking fibroblast and keratinocyte membranes and one-component lipid films were investigated. The surface pressure/area measurements and penetration studies were done, and Brewster angle microscopy was applied to verify the morphology of the studied systems. It was found that avobenzone has a stronger impact on molecular organization of skin cell model membranes than oxybenzone; however, its effect is concentration-limited. Both UV filters exhibited stronger affinity to Chol, SM and SOPC monolayers than to ceramides, which are the lipids characteristic for skin cells. Therefore, it can be suggested that ceramides may hinder the penetration of UV filter molecules into the interior of skin cells. Cell line model studied with SEM microscopy suggested that UV filters alter the skin cell membrane. Finally, it was summarized that the mechanism of UV filter toxicity is complex, but one of its important elements is the impact on the organization of lipid structures.

Although poly (ADP-ribose) polymerase inhibitors (PARPi) have been established to enhance ovarian cancer outcomes, the emergence of drug resistance poses considerable clinical challenges. In this study, we constructed a Hi-C atlas to systematically characterize the effect of olaparib on chromatin organization at multiple hierarchical scales, namely, chromosomes, A/B compartments, topologically associating domains, and chromatin loops. To investigate the effects of PARPi on expression of the cohesion subunit RAD21, we established olaparib-resistant ovarian cancer cell line. Furthermore, we examined the effects of RAD21 on the functions of ovarian cancer cells and spheroids based on cell proliferation, apoptosis, and comet assays. In addition, by performing integrated analyses using ChIP-seq datasets, ChIP-qPCR, and chromosome conformation capture assays, we assessed the influence of RAD21 on the enhancer-promoter interactions of a homologous recombination repair gene. Moreover, on the basis of our findings in previous studies using clinical samples, we further evaluated the clinical value of RAD21 in multiple databases. Genome-wide Hi-C heatmap analysis revealed that olaparib led to a reduction in the genome-wide contact frequency for long distance interactions, altered the degree of chromatin compartmentalization, and promoted compartment switching in ovarian cancer. Differences between the olaparib-treated and control cells with respect to topologically associating domain boundaries and chromatin loops were found to be associated with key cellular functions, such as DNA repair and transcriptional mis-regulation in cancer. Furthermore, PARPi treatment was observed to induce the expression of RAD21, whereas an upregulation of RAD21 promoted proliferation and inhibited apoptosis in ovarian cancer spheroids. Mechanistically, we obtained evidence to indicate that by maintaining enhancer-promoter interactions within chromatin conformation, RAD21 regulates the transcription of RAD51, thereby mediating olaparib resistance in ovarian cancer. The high expression of RAD21 was found to show a significant association with poor overall and progression-free survival in patients with ovarian cancer. Our findings in this study indicate that RAD21 could serve as a potential therapeutic target for overcoming olaparib resistance in ovarian cancer, and provide new insights into the mechanisms underlying the resistance to PARPi from the perspective of chromatin organization.

Insect's body barriers rely on specialized extracellular matrices that protect against harmful environmental influences. The outer barrier is the cuticle, which is composed of chitin, cuticle proteins and lipids. The peritrophic matrix (PM) serves as an inner barrier lining the midgut epithelium. It is composed of chitin fibers that are organized by PM proteins. While cuticle and PM proteins have received considerable attention in the past, supramolecular organization and physicochemical properties of the chitin component - particularly of the PM - remain poorly understood. Here, we combine synchrotron-based X-ray diffraction data from the PMs of Manduca sexta and Zophobas morio with RNA interference (RNAi), mass spectrometric and histochemical analyses of the PM from Tribolium castaneum to determine chitin's allomorphic state and degree of acetylation. The chitin of the PM exhibits signatures characteristic of dihydrate β-chitin along the entire midgut. In contrast, the cuticle is made of tightly packed α-chitin nanofibrils. Mass spectrometry revealed that the PM's chitin is highly acetylated (>95%). RNAi silencing of gut-specific genes encoding chitin deacetylasesTcCDA6-9 further increases the degree of acetylation. Histochemical analyses staining chitin with different degrees of acetylation confirm the predominance of highly acetylated chitin in the PM. Notably, the larval cuticle has a layered organization with deacetylated chitin present in exo- and highly acetylated chitin in endocuticles. Depletion of both TcCDA1 or TcCDA2 impairs chitin deacetylation, which indicates that both proteins cooperate in their activity in the integument. These results establish fundamental principles of polysaccharide-based extracellular matrices, with broad implications for insect biology.

The mechanical responses and properties of breast epithelial cells are known to change during malignant transformation and progression due to the dynamics of their actin cytoskeleton network organization and the resulting viscoelastic deformability. Studying the viscoelastic creep behavior of breast cells may reveal new avenues for developing novel cancer diagnostic and therapeutic biomarkers and improving fundamental biophysical understanding of the disease. Here we present an approach that uses functional principal component analysis (fPCA) to distinguish between the viscoelastic responses of malignant and non-malignant live breast cells that are subjected to shear flow in microfluidic channels under in-situ observation with optical, fluorescence, and confocal microscopy. The fPCA method extracts critical features of cell viscoelasticity from the in-situ measured creep responses of non-tumorigenic breast cells (MCF-10A), less metastatic triple-negative breast cancer (TNBC) cells (MDA-MB-468), and highly metastatic breast cancer cells (MDA-MB-231). The results demonstrate distinguishable clustering patterns for the three types of cells in the first principal component (PC) and the second PC space. The first PC, indicative of the overall level of creep compliance, accounts for more than 98% of the total variance in the observed creep responses. The scores of the cells examined on the first PC axis increase with increasing cancer malignancy. They also correlate highly with the average moduli and viscosities extracted from viscoelastic models (-83% correlation with moduli and -85% correlation with viscosities). This suggests a direct link between the malignancy of cancer and the overall creep compliance level that is governed by cell viscoelastic properties. The implications of the results are discussed for the detection of non-tumorigenic and tumorigenic breast cells at different stages of cancer progression.

Achilles tendinopathy is a common musculoskeletal disorder with limited self-repair capacity. Although extracorporeal shock wave therapy (ESWT) and platelet-rich plasma (PRP) are widely used, their therapeutic mechanisms remain unclear. A rat model of overuse Achilles tendinopathy was established by uphill treadmill running. Tendon morphology and structure were assessed by ultrasound and histology, and proteomic profiling was performed to identify differentially expressed proteins (DEPs) and enriched pathways. Ultrasound revealed subcutaneous edematous infiltration after overuse, and histology showed disorganized collagen fibers and altered cellular density. Compared with the normal group, the injury group showed 429 DEPs, which were enriched in pathways related to actin cytoskeleton and complement and coagulation cascades. Both ESWT and PRP treatments ameliorated these overuse-induced pathological changes. Compared with the rest group, the ESWT group showed 30 DEPs, while the PRP group showed 244, with 17 DEPs overlapping between the two comparisons. In the ESWT group, enriched pathways included actin cytoskeleton organization, protein stabilization, and sulfur metabolism. In the PRP group, enriched pathways included FcγR-mediated phagocytosis, lysosome, and endoplasmic reticulum protein processing. Compared with the normal group, the ESWT group showed 32 DEPs, whereas the PRP group showed only one (Serpina6), which was the only protein shared between the two comparisons. ESWT and PRP improve tendon healing in overuse Achilles tendinopathy through different molecular mechanisms. The PRP group showed a proteomic profile more similar to the normal group than the ESWT group. These findings provide a molecular basis for optimizing clinical treatment strategies.

Intermediate Respiratory Care Units (IRCUs) play an increasingly important role in the management of patients with acute or acute-on-chronic respiratory failure who require more advanced monitoring and respiratory support than can be provided on conventional hospital wards but do not require admission to an Intensive Care Unit (ICU). Their development has been driven by the widespread adoption of noninvasive ventilation, high-flow nasal cannula (HFNC) therapy, and continuous respiratory monitoring, and their strategic value was clearly demonstrated during the COVID-19 pandemic. This position paper from the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) provides evidence-informed recommendations regarding the infrastructure, technology, staffing, organization, and quality standards necessary for the optimal functioning of IRCUs in Spain. A multidisciplinary panel of experts developed consensus-based guidance drawing on available scientific evidence and clinical experience, addressing architectural design, technological resources, professional roles, training pathways, clinical care models, and quality indicators. IRCUs have emerged as a key component in the management of acute and chronic respiratory failure, contributing to improved clinical outcomes and more efficient use of critical care resources. This document highlights the importance of standardized admission criteria, structured care processes, multidisciplinary coordination, and continuous performance evaluation using validated indicators to support the consolidation of IRCUs as high-value, sustainable components of modern respiratory care systems.

In the non-small cell lung cancer (NSCLC) tumor microenvironment (TME), tumor cells mediate inhibitory signals to key immune cells, promoting an immunosuppressive environment that facilitates tumor immune evasion. CD8 + cytotoxic T lymphocytes are central mediators of antitumor immunity, and tumors can be classified by immunohistochemistry (IHC) as immune-hot or immune-cold based on the abundance of tumor-infiltrating lymphocytes (TILs). Although cancer immunotherapy can boost lymphocyte functions and improve progression-free survival in patients with advanced NSCLC, only a minority of patients experience a durable clinical benefit. Tumor-associated macrophages (TAMs) are key immunoregulatory cells in the NSCLC microenvironment and capable of generating potent immunosuppressive signals. However, their functional roles in immune-hot versus immune-cold tumors remain poorly understood. In this study, we compared the transcriptional programs of TAMs from NSCLC patients with immune-hot or immune-cold tumors. We classified 11 surgically resected NSCLC tumors as immune‑hot or immune‑cold based on quantitative immunohistochemistry of CD4⁺ and CD8⁺ tumor‑infiltrating lymphocytes. TAMs were isolated from tumor and adjacent healthy tissue by fluorescence-activated cell sorting (FACS), followed by bulk RNA sequencing and differential gene expression analysis. TAMs from immune‑cold tumors exhibited a striking upregulation of genes involved in immunoglobulin-mediated immune responses. Additionally, these TAMs demonstrated increased expression of genes involved in extracellular matrix organization, including matrix metalloproteinases and collagen‑associated genes, suggesting enhanced matrix remodeling activity. These findings highlight TAMs' potential contribution to immunosuppression, stromal remodeling, and impaired lymphocyte infiltration. The TAM-mediated pathways identified here may represent actionable targets for future immunotherapeutic strategies aimed at reshaping the tumor microenvironment.

Adolescent aggression is influenced by multiple interacting cognitive and behavioral processes. Previous research has primarily used mediation and moderation models to examine directional mechanisms such as hostile attribution bias and anger rumination. However, these approaches provide limited insight into how these factors operate as an interconnected system. To this end, we employed cross-sectional network analysis to exploratorily examine the structural organization of the aggression-related network in Chinese adolescents, identify nodes with the highest centrality and bridge centrality, and explore differences in network structure between males and females. We recruited 927 Chinese adolescents (Mage = 16.20 ± 1.21 SD; 55.88% female), who completed measures of aggression, peer victimization, hostile attribution bias, anger rumination, and self-control. Network analysis was conducted to identify core and bridge nodes within the network and to compare network structures across gender groups. Our findings revealed that angry afterthoughts (AR1) and angry memories (AR3) showed the highest expected influence, highlighting their central role in the aggression network. Hostile attribution bias (HAB), hostility (A4), and relational victimization (PV2) acted as bridge nodes connecting cognitive and behavioral clusters. Although gender-specific networks displayed similar centrality patterns, the overall network structures differed significantly between males and females. These findings suggest that interventions targeting the most central elements of anger rumination may be particularly effective. Addressing these core and bridge nodes, which connect cognitive and behavioral components, could enhance the efficacy of strategies aimed at reducing aggression in Chinese adolescents.

Sustaining evidence-based HIV prevention interventions remains a challenge, particularly among at-risk youth in Africa. The 4 Youth by Youth (4YBY) sustainment study is a hybrid type 2 cluster randomized controlled trial that evaluates the sustainability and cost-effectiveness of a crowdsourced approach to sustaining a package of evidence-based HIV prevention services. The study will be conducted across 40 community sites, supported by 18 community-based organizations (CBOs) providing HIV prevention services in Nigeria. Given their longstanding engagement with young people, CBOs serve as key partners in assessing long-term sustainability strategies for the 4YBY intervention, which has proven effective in increasing HIV prevention service uptake among youth. This protocol describes a cluster randomized controlled trial that will be conducted across 40 sites, all randomized into two arms. Half of the sites (20) will be assigned to receive the standard 4YBY intervention (4YBY-S), while the other 20 sites will receive the standard 4YBY intervention plus an enhanced sustainability strategy (4YBY-S + 4YBY-E). While the 4YBY-S group will continue implementing core intervention activities, the 4YBY-E group will receive additional sustainability-focused support. The Enhanced Sustainability Strategy in the 4YBY-E arm consists of four key components. First, "People" involves identifying and training sustainability teams within CBOs to champion intervention longevity. Second, "Learning", where bi-weekly collaborative sessions will be established to foster knowledge-sharing and problem-solving among stakeholders. Third, "Adaptation Monitoring" will focus on continuously tracking and modifying intervention strategies to better align with local needs. Finally, "Nurturing Coaches" includes dedicated coaches who will provide technical assistance, conduct audits, and offer feedback to strengthen sustainability efforts. Evaluation will be guided by Youth Participatory Action Research (YPAR), the PEN-3 Cultural Model, Proctor's Implementation Outcomes Framework, and the Consolidated Framework for Implementation Research (CFIR). The study hypothesizes that sites receiving the enhanced sustainability strategy (4YBY-S + 4YBY-E) will exhibit greater sustainability of core intervention components, defined as the continued delivery, adaptation, and integration of the intervention within community-based organizations-compared to sites receiving only the standard 4YBY intervention (4YBY-S). Additionally, the 4YBY-S + 4YBY-E arm is expected to achieve a higher uptake of HIV prevention services at 24 months, reflecting both the intervention's effectiveness and its long-term viability within community settings. This protocol represents one of the first cluster randomized controlled trials evaluating intervention sustainment strategies for a youth-led, evidence-based HIV prevention program in Africa. Findings will advance implementation science by establishing a threshold for sustainable strategies and identifying the key factors that support the long-term integration and continuation of HIV prevention services for at-risk youth. The results critically impact scaling up community-led interventions and shaping policy frameworks to strengthen the global HIV response. The protocol was registered with clinicaltrials.gov under registration NCT07072481.

The potential re-emergence of Mpox poses an increasing public health concern in the Horn of Africa, particularly in Ethiopia. This study examined perceptions of preparedness among surveyed surveillance professionals in Ethiopia regarding the disease surveillance system's ability to detect and respond to a potential Mpox outbreak. A descriptive cross-sectional survey design was employed, utilizing a structured 58-item questionnaire that assessed preparedness across five domains: general awareness and understanding, surveillance infrastructure and resources, coordination and communication, preparedness and response, and policy, training, and equity. The survey was distributed to disease surveillance professionals at both federal and regional levels through purposive sampling. The data were analyzed using descriptive statistics, Mann-Whitney U tests, Cramér's V, and content analysis. Among the 42 surveyed surveillance professionals, 45.3% believed that the surveillance system could effectively respond to an Mpox outbreak, while 54.7% disagreed, reflecting divided perceptions within the sample. Respondents identified several perceived gaps, including limited awareness of Mpox-specific protocols, insufficient training, inadequate diagnostic capacity, and fragmented coordination across sectors. A substantial proportion of respondents reported system-related challenges, with 83.3% perceiving laboratory facilities as inadequate and 78.6% noting the absence of contingency plans. In addition, 57.1% indicated that their organizations lacked staff trained on Mpox, and 59.5% reported no stockpiles of personal protective equipment. Overall, the surveyed professionals expressed mixed perceptions of preparedness, with notable concerns regarding resource allocation, infrastructure, and policy implementation. The study identifies perceived gaps among the 42 surveyed surveillance professionals regarding Mpox preparedness in Ethiopia, highlighting the need for enhanced training, strengthened infrastructure, improved coordination, and more equitable resource distribution. Addressing these gaps through targeted interventions may help strengthen disease surveillance capacity and improve the ability to detect, respond to, and manage emerging health threats such as Mpox.

Intra-hospital transfers (IHT) of hospitalized children are unavoidable practices often performed with emergency patients and postoperative patients. Standardizing IHT processes to minimize adverse events might improve children's outcomes. We developed an evidence-based clinical practice IHT guideline for hospitalized children. The aim of this study was to evaluate the implementation process and the effectiveness of the implementation of this guideline on patient outcomes, healthcare professionals' knowledge and behavior, and hospital organizational context. A type III hybrid effectiveness-implementation design was adopted, using a pre-post intervention trial (January-December 2024). Data of patient demographics, transport-related outcomes, and healthcare providers' knowledge and compliance were collected. We used the RE-AIM framework to assess effectiveness across four dimensions: Reach, Effectiveness, Adoption, and Implementation. Totally, 110 healthcare professionals conducted 213 IHTs of eligible children (109 children in the pre-intervention group and 104 in post-intervention group). The Reach outcomes demonstrated that participation among hospitalized children (n&#x2009;=&#x2009;312) was suboptimal at 33% (104/312). No differences were observed between the pre- and post-intervention group regarding gender, disease distribution, or pediatric early warning scores. The implementation showed favorable outcomes in the dimensions Effectiveness, Adoption, and Implementation. Healthcare professionals engagement was 95%, with 86% (19/22) of the implementation strategies successfully completed. Healthcare professionals' knowledge in the pre-intervention group (n&#x2009;=&#x2009;109) improved from median 40 (IQR 28;52) to median 76 (IQR 64;84) in the post-intervention group (n&#x2009;=&#x2009;104; p&#x2009;<&#x2009;0.001). Clinically, the new guideline reduced adverse events (12 vs 4; p&#x2009;=&#x2009;0.047), reduced the median minutes of bedside handover time from 5 (IQR 3;7) to 4 (IQR 3;5; p&#x2009;<&#x2009;0.001), and improved handover information completeness from median score of 5 (IQR 4;6) to 20 (IQR 12;23, p&#x2009;<&#x2009;0.001). The total transport time increased from 14 to 19&#x2009;minutes in the post-intervention group (p&#x2009;<&#x2009;0.05), while no significant changes were observed in handover interruptions or post-transfer vital sign stability (p&#x2009;>&#x2009;0.05). The RE-AIM-based evaluation confirmed that the implementation strategies effectively enhanced healthcare professionals' knowledge and compliance while reducing adverse events and optimizing handover efficiency. However, the limited patient participation rate and increased transport duration highlight areas requiring further refinement to maximize the guideline's impact. ClinicalTrials.gov, NCT06512805. Registered 27 June 2024.

Frailty is defined by the World Health Organization as a state of increased vulnerability in older adults, characterized by a decline in physiological functions across multiple systems and heightened sensitivity to external stressors. The global prevalence of frailty is expected to rise due to population ageing, highlighting the need for effective preventive strategies. However, while diet can play a crucial role in this context, their relationship is complex and potentially bidirectional: unhealthy dietary patterns may contribute to the onset of frailty, whereas early stages of frailty may influence food choices through limitations in meal preparation, and appetite. Hence, identifying biomarkers associated with frailty phenotypes may help clarify these mechanisms and improve prevention strategies. This systematic review aims to summarize current evidence on metabolomics-derived biomarkers potentially involved in the relationship between dietary patterns and frailty. A comprehensive literature search was conducted across three electronic databases (PubMed, Web of Science, Scopus) in accordance with the PRISMA guidelines, yielding 1661 studies, of which five met the inclusion criteria. Three dietary exposures were identified and analyzed: fruit and vegetable, plant/animal protein intake, and adherence to the Mediterranean diet. The findings suggest that specific metabolites, such as hippuric acid, different amino acids, and lipid derived compounds may represent potential candidates for establishing a metabolic signature of frailty. Nevertheless, current evidence remains limited and unclear about the direction of associations. Further research is needed, particularly in healthy populations, to validate the effectiveness of these biomarkers, and tailor guidelines specific for older adults.

Anxiety disorders and insomnia are common modifiable conditions in older adults, but their independent and combined effects on the risk of incident Alzheimer's disease and related dementias (ADRD) remain unclear. To estimate the independent and combined associations of anxiety disorders and insomnia with the risk of incident ADRD. Retrospective cohort study using an intention-to-treat approach with a 10-year follow-up period (2014-2023). De-identified electronic health record (EHR) data from 70 participating healthcare organizations within the TriNetX Research Network. Adults aged &#x2265;50 years without prior dementia who had regular ambulatory care during a three-year baseline period (n = 1,868,790). Anxiety and insomnia were identified using ICD-based algorithms and categorized into four exposure groups: neither condition, anxiety only, insomnia only, and both. Incident ADRD was defined by two or more diagnostic codes within 12 months. Entropy balancing controlled for confounding, and weighted Cox proportional hazards models estimated hazard ratios (HRs). At baseline, 4.1% had anxiety only, 3.8% had insomnia only, and 1.1% had both. Over follow-up, 2.3% developed ADRD. In weighted models, insomnia alone (HR: 1.12; 95% CI: 1.06-1.19), anxiety alone (HR: 1.49; 95% CI: 1.39-1.60), and co-occurring anxiety and insomnia (HR: 1.31; 95% CI: 1.06-1.62) were each associated with higher ADRD risk compared with neither condition. No significant effect modification by age, sex, or race was observed. Anxiety and insomnia independently increase ADRD risk, though insomnia's contribution is very modest compared to the primary association demonstrated by anxiety. Co-occurrence does not confer additional risk beyond anxiety alone. Clinically, routine screening and treatment of anxiety and sleep disturbances represent actionable, broadly applicable strategies for ADRD prevention and healthy cognitive aging.

UNC-89 is a giant modular protein located at the sarcomeric M-line of C. elegans striated muscle and is required for sarcomere organization and function. UNC-89 contains two protein kinase domains, PK1 and PK2, separated by 850 residues, that includes a 645-residue long intrinsically disordered sequence that acts like an elastic spring. Bioinformatic analysis suggests that PK2 is an active kinase whereas PK1 is a pseudokinase. We recently reported that a genome-edited worm, unc-89(sf22), that expresses UNC-89 carrying a kinase-inactivating point mutation in PK2 has an unusual phenotype with normally organized sarcomeres and SR, normal muscle function and yet fragmented mitochondria, increased ATP levels, increased glycolysis and alterations in electron transport chain complexes and respiration. Here, we show that a genome-edited worm unc-89(sf23), that expresses UNC-89 with an in-frame deletion of the C-lobe of PK1 has approximately the same phenotype as the PK2 catalytically dead mutant. The fact that mutations in two different regions of UNC-89 result in a mitochondrial phenotype is further evidence of communication between the sarcomere and mitochondria. We further demonstrate that in vitro PK2 interacts with full length PK1 and the C-lobe of PK1. The protein kinase domains of giant sarcomeric proteins are autoinhibited by parts of their own sequence, and this is also likely for PK2, but the mechanism by which PK2 would be activated is unknown. Our data is compatible with a model in which PK1 interacts with PK2 and thereby stimulates PK2 kinase activity.

Spatial ATAC-seq enables simultaneous profiling of cellular locations and chromatin accessibility in intact tissues but faces challenges from high dimensionality, noise, and sparsity. Moreover, existing methods often overlook DNA sequence information, which contains critical regulatory motifs. To address these limitations, we introduce SpaDC, a graph-regularized convolutional neural network that integrates spatial location, chromatin accessibility, and DNA sequence. SpaDC employs a triplet loss function to integrate multiple spatial ATAC-seq datasets and remove batch effects. Benchmark analyses on real datasets demonstrate state-of-the-art performance in spatial domain identification, data denoising, and gene regulatory network (GRN) inference. Applied to mouse embryonic brain spatial ATAC-seq data, SpaDC accurately identified known brain structures and recovered chromatin accessibility signals. On P22 mouse brain spatial multi-omics data, SpaDC revealed spatial domain-specific cis-regulatory elements and GRNs. Collectively, SpaDC provides a powerful, sequence-based solution for spatial ATAC-seq analysis, enabling more accurate and robust investigation of tissue architecture and chromatin organization.

A central goal in developmental biology is to understand how cell fates are specified during development. Advances in stem cell-derived embryoid models, such as gastruloids, have enabled the use of powerful single-cell lineage tracing approaches that are difficult to apply in whole organisms due to the complexities of genetic engineering. Here, we highlight four recent studies that use these techniques to examine fate decisions and spatial organization in gastruloids, uncovering the interplay between cell lineage and signaling in cell fate decisions.