Recent publications
In bioarchaeology, funerary taphonomy and preservation become part of the biocultural narrative of the dead. We evaluate the role of these factors in reconstructing the identities of those buried in an emerging deathway, the ventrally placed legs flexed (VPLF) burial position, during the Terminal Classic (750–900/1000 CE) period at the Maya polity of Lower Dover in western Belize. The term “VPLF” describes a divergent burial practice which may have resulted from intentional binding prior to burial. In our analysis of VPLF burials (n = 12), we use a two-step process to reconstruct the social identities and potential meaning of the burial pattern: (1) interpretation of the archaeological context based on excavation observations and biogeochemistry and (2) osteological analysis of curated individuals to reconstruct their biological profiles and post-mortem/post-excavation histories. Osteological analyses included age and sex estimation, paleopathological assessment of frailty and trauma, and skeletal modifications from cultural and taphonomic forces. Radiocarbon dating and ceramic analyses were used to date the burials. Stable and radiogenic isotopic analyses were applied to reconstruct diet and mobility for a subset of the VPLF burials. Our results show that individuals were buried in the VPLF position irrespective of age, sex, or social status, consistent with patterns at other Terminal Classic and Postclassic Maya sites, although VPLF interment may have been practiced earlier at Lower Dover. We hypothesize that the appearance of VPLF burials in the Terminal Classic period signified an ideological shift in light of emerging social and environmental pressures in the region.
The native extracellular matrix is continuously remodeled to form complex interconnected network structures that reversibly regulate stem cell behaviors. Both regulation and understanding of its intricate dynamicity can help to modulate numerous cell behaviors. However, neither of these has yet been achieved due to the lack of designing and modeling such complex structures with dynamic controllability. Here we report modularity-based mathematical modeling of extracellular matrix-emulating ligand inter-cluster connectivity using the graph theory. Increasing anisotropy of magnetic nano-blockers proportionately disconnects arginine-glycine-aspartic acid ligand-to-ligand interconnections and decreases the number of ligand inter-cluster edges. This phenomenon deactivates stem cells, which can be partly activated by linearizing the nano-blockers. Remote cyclic elevation of high-anisotropy nano-blockers flexibly generates nano-gaps under the nano-blockers and augments the number of ligand inter-cluster edges. Subsequently, integrin-presenting stem cell infiltration is stimulated, which reversibly intensifies focal adhesion and mechanotransduction-driven differentiation both in vitro and in vivo. Designing and systemically modeling extracellular matrix-mimetic geometries opens avenues for unraveling dynamic cell-material interactions for tissue regeneration.
Michael J. Arena, Andras Vicsek, John Golden, and Scott Hines use a network lens to illuminate their preliminary research on cultivating culture across a physical environment, an entirely remote environment, and a hybrid work model.
Skin-on-a-chip models provide physiologically relevant platforms for studying diseases and drug evaluation, replicating the native skin structures and functions more accurately than traditional 2D or simple 3D cultures. However, challenges remain in creating models suitable for microneedling applications and monitoring, as well as developing skin cancer models for analysis and targeted therapy. Here, we developed a human skin/skin cancer-on-a-chip platform within a microfluidic device using bioprinting/bioengineering techniques. The fabricated skin models include vascular, dermal, and epidermal layers, demonstrating increased functionalities and maturation of dermal (Collagen I & Fibronectin for 7 days) as well as epidermal (Filaggrin & Keratin 10, 14, and 19 at the air-liquid interface (ALI) for 21 days) layers. Histological analysis confirmed the formation of a differentiated epidermis and ridges at the dermal-epidermal junction in our model, closely resembling native skin tissue. Melanoma cells were embedded approximately 400 μm beneath the epidermis to simulate tumor invasion into the dermis. The platform was further used to test doxorubicin (DOX)-loaded gelatin methacryloyl (GelMA) microneedles (MNs) for localized transdermal drug delivery targeting melanoma. The DOX-loaded MNs penetrated uniformly to a depth of approximately 600 μm, effectively reaching the melanoma cells. Drug delivery via MNs demonstrated significantly higher efficiency than diffusion through media flow, confirming the practicality and robustness of the proposed model for future therapeutic applications.
Tissue regeneration involves dynamic dialogue between and among different cells and their surrounding matrices. Bone regeneration is specifically governed by reciprocity between osteoblasts and osteoclasts within the bone microenvironment. Osteoclast‐directed resorption and osteoblast‐directed formation of bone are essential to bone remodeling, and the crosstalk between these cells is vital to curating a sequence of events that culminate in the creation of bone tissue. Among bone biomaterial strategies, many have investigated the use of different material cues to direct the development and activity of osteoblasts. However, less attention has been given to exploring features that similarly target osteoclast formation and activity, with even fewer strategies demonstrating or integrating biomaterial‐directed modulation of osteoblast‐osteoclast coupling. This review aims to describe various biomaterial cues demonstrated to influence osteoclastogenesis and osteoclast function, emphasizing those that enhance a material construct's ability to achieve bone healing and regeneration. Additionally discussed are approaches that influence the communication between osteoclasts and osteoblasts, particularly in a manner that takes advantage of their coupling. Deepening the understanding of how biomaterial cues may dictate osteoclast differentiation, function, and influence on the microenvironment may enable the realization of bone‐replacement interventions with enhanced integrative and regenerative capacities.
Background
Tissue-resident memory T cells (TRM) are a specialized subset of long-lived memory T cells that reside in peripheral tissues.¹⁻³ However, the impact of TRM-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated.⁴⁻⁶
Methods
Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique TRM signatures, through which we inferred the abundance of TRM in NSCLC. A machine learning model was developed to prognosticate survival, tested in multiple independent NSCLC cohorts. Model performance was corroborated through Kaplan-Meier survival plots, receiver operating characteristic (ROC) curves, principal component analysis, and t-SNE analyses.
Results
We discovered that TRM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. In addition, TRM signatures are strongly associated with immune checkpoint genes and the prognosis of NSCLC patients. A TRM-based machine learning model to predict patient survival was validated and an 18-gene risk score was further developed to effectively stratify patients into low-risk and high-risk categories, wherein patients with high-risk scores had significantly lower overall survival than patients with low-risk. The prognostic value of the risk score was independently validated by the TCGA dataset and multiple independent NSCLC patient datasets. Notably, low-risk NSCLC patients with higher TRM infiltration exhibited enhanced T-cell immunity, nature killer cell activation, and other TIME immune responses related pathways, indicating a more active immune profile benefitting from immunotherapy. However, the TRM signature revealed low TRM abundance and a lack of prognostic association among lung squamous cell carcinoma patients in contrast to adenocarcinoma, indicating that the two NSCLC subtypes are driven by distinct TIMEs.
Conclusions
Altogether, this study provides valuable insights into the complex interactions between TRM and TIME and their impact on NSCLC patient prognosis. The development of a simplified 18-gene risk score provides a practical prognostic marker for risk stratification.
Acknowledgements
This work is supported by the National Institutes of Health, United States (NIH) R01 DK119795 and R35 GM122465. We would like to thank to Dr. Xiling Shen and Dr. Chao Cheng for their valuable discussions and critical feedback. Thank Xiuying Li, Zhaohui Wang, Qian Chen and Sheng Chang for their useful suggestions.
References
• Mirhadi S, Tam S, Li Q, Moghal N, Pham N-A, Tong J, Golbourn BJ, Krieger JR, Taylor P, Li M, et al. Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes. Nat. Commun 2022;
13
:1811.
• Yang L, He Y-T, Dong S, Wei X-W, Chen Z-H, Zhang B, Chen W-D, Yang X-R, Wang F, Shang X-M, et al. Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma. J. Immunother. Cancer 2022;
10
.
• Oja AE, Piet B, van der Zwan D, Blaauwgeers H, Mensink M, de Kivit S, Borst J, Nolte MA, van Lier RAW, Stark R, et al. Functional heterogeneity of CD4+ tumor-infiltrating lymphocytes with a resident memory phenotype in NSCLC. Front. Immunol. 2018;
9
:2654. 10.3389/fimmu.2018.02654.
• Marceaux C, Weeden CE, Gordon CL, Asselin-Labat M-L. Holding our breath: the promise of tissue-resident memory T cells in lung cancer. Transl. Lung Cancer Res 2021;
10
:2819–2829.
• Amsen D, van Gisbergen KPJM, Hombrink P, van Lier RAW. Tissue-resident memory T cells at the center of immunity to solid tumors. Nat. Immunol 2018;
19
:538–546.
• Yang G, Cai S, Hu M, Li C, Yang L, Zhang W, Sun J, Sun F, Xing L, Sun X. Spatial features of specific CD103+CD8+ tissue-resident memory T cell subsets define the prognosis in patients with non-small cell lung cancer. J. Transl. Med 2024;
22
:27.
A longitudinal qualitative study was conducted to explore the experiences of church leaders (10 priests, pastors, and pastors’ wives) who provided disaster spiritual/emotional care (DSEC) to the island of Puerto Rico during a period of intense and repeated crises from 2017 to 2022. Utilizing a narrative inquiry approach, 18 in-depth interviews were conducted and analyzed. Findings indicated that the participants engaged in psychological, social, and religious coping strategies to actively cope with the stress and trauma of being first responder rescuer/victims. Regional, cultural and contextual factors are considered in an effort to understand and enhance services to populations where disaster is the new normal.
Research demonstrates that people draw on their religions in coping with difficult life circumstances, and that more religious people tend to cope better than less religious people. Lament is a religious prayer practice that constitutes a form of meaning-making coping. Here, we explicate this form of coping and, in a series of three studies with Christian participants, report on the development of a lament scale. In the first study, we develop items and test the items for clarity and for generalizability to diverse Christian groups using expert review and cognitive interviewing with participants representing five Christian groups. In the second study, we report results of exploratory factor analysis using data from primarily White and Protestant MTurk participants ( N = 303). In the third study, we report on factor stability and construct validity using data from largely White and African American Protestant and Catholic Prolific participants ( N = 346). The studies demonstrated generalizability to diverse Christian groups, a three-factor structure consistent with our theoretical formulation, good construct validity and relationships with well-being. Moderation analyses also indicated that when both Complaint and Praise are either high or low, the severity of the event is inversely related to flourishing. However, when either Complaint or Praise is high, the negative relationship between severity of the event and flourishing is ameliorated. The Lament Scale is a reliable and valid instrument for assessing lament in ways that are consistent with the conceptualization of lament as a meaning-making coping practice.
Most academic study of the Hebrew Bible/Old Testament in North America has been done from a White European or North American perspective. Post-graduate schools have predominantly required students to read works written by White authors, and the vast majority of professors are White. However, the Hebrew Bible/Old Testament also has a long history of interpretation by non-White and Majority World thinkers, and their contributions need to be more widely acknowledged and employed in studying the Hebrew Bible/Old Testament. This article surveys the contributions of Black Hebrew Bible/Old Testament scholars on the book of Exodus. Black scholars employ a variety of methods and approaches as they engage with the biblical text. We consider these approaches by category, beginning with textual criticism and translation before exploring works that focus on Africa in the Bible, those that draw on African or African American context, and those that highlight issues of gender or the perspectives of liberation theology. We conclude with those employing multi-faceted or integrative approaches.
This article explores the impact of Jesus’ “true vine” metaphor on discipleship and spirituality. The first part is a study of John 15:1-8, the passage where these teachings are recorded. The second part presents some theological developments, showing how Jesus’ lessons about abiding on Him have influenced the doctrine of unio mystica within the Reformed tradition. Finally, the third section features some implications from the exegetical and theological study for Christian ministries and discipleship.
Introduction
Large variations in fatty and amino acid natural ²H/¹H ratios in reference with solvent water point to the active involvement of compartmental, inter- and intramolecular deuterium disequilibrium in adaptive biology. Yet, the human deutenome is an untapped area of energy metabolism and health in humans.
Objectives
The purpose of this scoping review is to examine health effects through deuterium homeostasis using deuterium-depleted water and/or a deuterium-depleted diet. We also aim to reveal health effects of nutritional, metabolic and exercise ketosis, i.e. complete mitochondrial fatty acid oxidation with the production of deuterium depleted (deupleted) metabolic water.
Methods
A protocol process approach was used to retrieve current research in deuterium depletion according to the preferred reporting items protocol for systematic reviews and meta-analyses, extension for scoping reviews with checklist (PRISMA-ScR).
Results
Fifteen research articles were used. All retrieved articles were heterogenous in nature and additional themes did not evolve. Deuterium depletion was found to have beneficial health effects in the following conditions: cancer prevention, cancer treatment, depression, diabetes, long-term memory, anti-aging, and sports performance. Deutenomics is actively pursued in drug research and there are biomarker roles attributed to large natural variations with adaptive significance in biology.
Conclusion
Even with limited data, consistent deuterium depletion can be seen across all conditions reviewed. More randomized control trials are recommended to confirm cause and effect for translationally and clinically informed integrative nutrition-based medical interventions.
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