Plasma and CSF biomarkers of aging and cognitive decline in Caribbean vervets.

INTRODUCTION: Vervets are non-human primates that share high genetic homology with humans and develop amyloid beta (Aß) pathology with aging. We expand current knowledge by examining Aß pathology, aging, cognition, and biomarker proteomics. METHODS: Amyloid immunoreactivity in the frontal cortex and temporal cortex/hippocampal regions from archived vervet brain samples ranging from young adulthood to old age was quantified. We also obtained cognitive scores, plasma samples, and cerebrospinal fluid (CSF) samples in additional animals. Plasma and CSF proteins were quantified with platforms utilizing human antibodies. RESULTS: We found age-related increases in Aß deposition in both brain regions. Bioinformatic analyses assessed associations between biomarkers and age, sex, cognition, and CSF Aß levels, revealing changes in proteins related to immune-related inflammation, metabolism, and cellular processes. DISCUSSION: Vervets are an effective model of aging and early-stage Alzheimer's disease, and we provide translational biomarker data that both align with previous results in humans and provide a basis for future investigations. HIGHLIGHTS: We found changes in immune and metabolic plasma biomarkers associated with age and cognition. Cerebrospinal fluid (CSF) biomarkers revealed changes in cell signaling indicative of adaptative processes. TNFRSF19 (TROY) and Artemin co-localize with Alzheimer's disease pathology. Vervets are a relevant model for translational studies of early-stage Alzheimer's disease.

mRNA-lncRNA gene expression signature in HPV-associated neoplasia and cervical cancer.

Cervical cancer is one of the most frequent cancers in women and is associated with human papillomavirus (HPV) in 70 % of cases. Cervical cancer occurs because of progression of low-differentiated cervical intraepithelial neoplasia through grade 2 and 3 lesions. Along with the protein-coding genes, long noncoding RNAs (lncRNAs) play an important role in the development of malignant cell transformation. Although human papillomavirus is widespread, there is currently no well-characterized transcriptomic signature to predict whether this tumor will develop in the presence of HPV-associated neoplastic changes in the cervical epithelium. Changes in gene activity in tumors reflect the biological diversity of cellular phenotype and physiological functions and can be an important diagnostic marker. We performed comparative transcriptome analysis using open RNA sequencing data to assess differentially expressed genes between normal tissue, neoplastic epithelium, and cervical cancer. Raw data were preprocessed using the Galaxy platform. Batch effect correction, identification of differentially expressed genes, and gene set enrichment analysis (GSEA) were performed using R programming language packages. Subcellular localization of lncRNA was analyzed using Locate-R and iLoc-LncRNA 2.0 web services. 1,572 differentially expressed genes (DEGs) were recorded in the "cancer vs. control" comparison, and 1,260 DEGs were recorded in the "cancer vs. neoplasia" comparison. Only two genes were observed to be differentially expressed in the "neoplasia vs. control" comparison. The search for common genes among the most strongly differentially expressed genes among all comparison groups resulted in the identification of an expression signature consisting of the CCL20, CDKN2A, CTCFL, piR-55219, TRH, SLC27A6 and EPHA5 genes. The transcription level of the CCL20 and CDKN2A genes becomes increased at the stage of neoplastic epithelial changes and stays so in cervical cancer. Validation on an independent microarray dataset showed that the differential expression patterns of the CDKN2A and SLC27A6 genes were conserved in the respective gene expression comparisons between groups.

The making of the Homo Polaris: human acclimatization to the Arctic environment and Soviet ideologies in Northern Medical Institutions.

This paper examines the history of the Soviet human acclimatization project in the North and Siberia, which spanned from medical experiments in Stalin's forced labor camps to the subsequent wave of industrialization in the region. The author argues that human acclimatization in the North was a settler colonial science project aimed at facilitating Russian administrators and engineers in asserting control over the territory and its resources, while creating a new homogeneous 'indigenous population' in Siberia and the North. This envisioned population, referred to as Homo Polaris by the author, was intended to emerge through a two-way transformation: the adaptation of Indigenous peoples into Soviet ideologies and practices, and the acclimatization of settlers coming from the European part of the country to the Arctic environment. Although the administrators and medical doctors were unable to achieve this biopolitical objective, the complexities and dialogues surrounding these transformations shed light on the late Soviet settler-colonial ideologies and their impact on social life in Siberia from the 1950s to the 1980s. The research is based on a comprehensive analysis of both published and archival works by scholars involved in the project.

Comparative efficacy of tocotrienol and tocopherol (vitamin E) on atherosclerotic cardiovascular diseases in humans.

Objective: To compare the efficacy of tocotrienol and tocopherol in the management of patients with atherosclerotic cardiovascular diseases. METHODS: The systematic review was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines 2020, and comprised literature search from 2002 till January 5, 2023, on PubMed, Google Scholar, Cochrane Library, Google, Wiley-Inter Science Library, Medline, SpringerLink, Taylor and Francis databases. The search was conducted using key words, such as: "tocopherol", "tocotrienol", "vitamin E", "dyslipidaemia", "cardiovascular diseases" "cardioprotective", "hypercholesterolemia" and "atherosclerosis" along with Boolean operators. Human clinical studies regarding the use of tocotrienol or tocopherol or comparison of its efficacy in patients having atherosclerosis, dyslipidaemia leading to cardiovascular diseases, and studies including details of efficacy of any of the four alpha, beta, gamma, delta isomers of tocopherol or tocotrienol were included. Pertinent data from the eligible studies was retrieved and reviewed. RESULTS: Of the 516 articles identified, 26 (5%) articles met eligibility criteria. Of them 5(19%) were subjected to detailed analysis. Tocotrienol showed significant anti-oxidant efficacy at (250 mg/d) by decreasing cholesterol and serum inflammatory biomarkers i.e C-reactive protein (40%), malondialdehyde (34%), gamma-glutamyl transferase (22%) (p<0.001). Total anti-oxidant status (TAS) levels raised 22% (p<0.001) and Inflammatory cytokines i.e resistin, interleukin (IL)-1, IL-12, Interferon-gamma were decreased 15-17% (p<0.05-0.01) respectively by tocotrienol. Several microRNA (miRNA-133a, miRNA-223, miRNA-214, miRNA-155) were modulated by δ-tocotrienol. Whereas, tocopherol showed heterogeneity of results by either decreasing or increasing the risk of mortality in atherosclerotic cardiovascular diseases. Conclusion: Compared to tocopherol, tocotrienol was found to be safe and potential candidate for improving cardiovascular health in the management of atherosclerotic cardiovascular diseases.

The place for people in rewilding.

Rewilding, although controversial, is increasingly presented as humanity's best hope of addressing the global biodiversity crisis, but it remains unclear how restoring nonhuman autonomy affects people's relationships with nature. We conceptualized 3 human-nature relationships (HNRs) that could occur when restoring nonhuman autonomy: human-nature dichotomy, human-nature compromise, and human-nature mutualism. Through 51 interviews, we then empirically tested the occurrence of these HNRs across diverse actors living and working in 2 longstanding British rewilding initiatives to better understand the place for people in rewilding. Actors' HNRs aligned with the 3 conceptual framings, but these relationships were complex. Individuals often demonstrated multiple perspectives that transcended conventional actor categorization. The tripartite framing also revealed conflicting values across and within individuals, resulting in pluralistic HNRs. Our work adds to the theory and practice surrounding the place for people in rewilding by cautioning against a single preferred HNR when restoring nonhuman autonomy and advocating that a diversity of human interactions with nature should be integrated into the global rewilding movement.

El lugar de las personas en la renaturalización Resumen Aunque la renaturalización es controversial, se presenta cada vez más como la mejor esperanza para que la humanidad aborde la crisis mundial de biodiversidad, aunque todavía no está claro el efecto de la restauración de la autonomía no humana sobre las relaciones entre las personas y la naturaleza. Conceptualizamos tres relaciones humanidad­naturaleza (RHN) que podrían ocurrir al restaurar la autonomía no humana: dicotomía, equilibrio y mutualismo, todas entre los humanos y la naturaleza. Realizamos 51 entrevistas para probar de forma empírica la ocurrencia de estas RHN con varios actores que viven y trabajan dentro de las dos iniciativas británicas de renaturalización más antiguas y así entender mejor el lugar de las personas en la renaturalización. Las HNR de los actores se alinearon con los tres marcos conceptuales, aunque estas relaciones fueron complejas. Los individuos frecuentemente mostraron tener varias perspectivas que trascendían la categoría de los actores. El marco tripartito también reveló valores conflictivos entre y en los individuos, lo que resultó en RHN pluralistas. Nuestro trabajo suma a la teoría y práctica en torno al lugar de la gente en la renaturalización con la prevención de una sola relación humanidad­naturaleza preferida cuando se restaura la autonomía no humana y con la recomendación de que la diversidad de interacciones humanas con la naturaleza debería integrarse al movimiento mundial de renaturalización.

Decoding dysregulated genes, molecular pathways and microRNAs involved in cervical cancer.

BACKGROUND: The present study aimed to identify dysregulated genes, molecular pathways, and regulatory mechanisms in human papillomavirus (HPV)-associated cervical cancers. We have investigated the disease-associated genes along with the Gene Ontology, survival prognosis, transcription factors and the microRNA (miRNA) that are involved in cervical carcinogenesis, enabling a deeper comprehension of cervical cancer linked to HPV. METHODS: We used 10 publicly accessible Gene Expression Omnibus (GEO) datasets to examine the patterns of gene expression in cervical cancer. Differentially expressed genes (DEGs), which showed a clear distinction between cervical cancer and healthy tissue samples, were analyzed using the GEO2R tool. Additional bioinformatic techniques were used to carry out pathway analysis and functional enrichment, as well as to analyze the connection between altered gene expression and HPV infection. RESULTS: In total, 48 DEGs were identified to be differentially expressed in cervical cancer tissues in comparison to healthy tissues. Among DEGs, CCND1, CCNA2 and SPP1 were the key dysregulated genes involved in HPV-associated cervical cancer. The five common miRNAs that were identified against these genes are miR-7-5p, miR-16-5p, miR-124-3p, miR-10b-5p and miR-27a-3p. The hub-DEGs targeted by miRNA hsa-miR-27a-3p are controlled by the common transcription factor SP1. CONCLUSIONS: The present study has identified DEGs involved in HPV-associated cervical cancer progression and the various molecular pathways and transcription factors regulating them. These findings have led to a better understanding of cervical cancer resulting in the development and identification of possible therapeutic and intervention targets, respectively.

Leveraging human-mouse studies to advance the genetics of hearing impairment in Africa.

Mouse models are used extensively to understand human pathobiology and mechanistic functions of disease-associated loci. However, in this review, we investigate the potential of using genetic mouse models to identify genetic markers that can disrupt hearing thresholds in mice and then target the hearing-enriched orthologues and loci in humans. Currently, little is known about the real prevalence of genes that cause hearing impairment (HI) in Africa. Pre-screening mouse cell lines to identify orthologues of interest has the potential to improve the genetic diagnosis for HI in Africa to a significant percentage, for example, 10-20%. Furthermore, the functionality of a candidate gene derived from mouse screening with heterogeneous genetic backgrounds and multi-omic approaches can shed light on the molecular, genetic heterogeneity and plausible mode of inheritance of a gene in hearing-impaired individuals especially in the absence of large families to investigate.

Bidirectional transfer of human cytomegalovirus strains in donor and recipient seropositive lung transplant patients.

Donor and recipient human cytomegalovirus (HCMV) seropositive (D+R+) lung transplant recipients (LTRs) often harbor multiple strains of HCMV, likely due to transmitted donor (D) strains and reactivated recipient (R) strains. To date, the extent and timely occurrence of each likely source in shaping the post-transplantation (post-Tx) strain population is unknown. Here, we deciphered the D and R origin of the post-Tx HCMV strain composition in blood, bronchoalveolar lavage (BAL), and CD45+ BAL cell subsets. We investigated either D and/or R formalin-fixed paraffin-embedded blocks or fresh D lung tissue from four D+R+ LTRs obtained before transplantation. HCMV strains were characterized by short amplicon deep sequencing. In two LTRs, we show that the transplanted lung is reseeded by R strains within the first 6 months after transplantation, likely by infiltrating CD14+ CD163+/- alveolar macrophages. In three LTRs, we demonstrate both rapid D-strain dissemination and persistence in the transplanted lung for >1 year post-Tx. Broad inter-host diversity contrasts with intra-host genotype sequence stability upon transmission, during follow-up and across compartments. In D+R+ LTRs, HCMV strains of both, D and R origin can emerge first and dominate long-term in subsequent episodes of infection, indicating replication of both sources despite pre-existing immunity.

The Human-Animal Bond and Older Adults: The Role of a Community-Based Organization's "Heart to Heart" Program.

In the field of gerontological social work, there is growing interest in further exploring and understanding human-animal bonds and relationships, a trend that accelerated significantly during the early years of the COVID-19 pandemic. Community-based organizations are promising partners as they provide acknowledgment and support for older adults' relationships with their pets and the strengthening of the human-animal bond. This brief report discusses the history, impact, and potential of one community-based organization's annual Valentine's Day event, Heart to Heart. Initiated at the height of the COVID-19 pandemic by Animal Advocates of Greater Lafayette (AAGL), an Indiana-based community organization, Heart to Heart recognizes, celebrates, and supports older adults' bonds with their pets through delivering pet presents directly to older adults' homes. Despite the mounting evidence that pets provide support and comfort for people of all ages, but particularly older adults, social service agencies and programs that serve older adults are often reluctant to recognize the power of the human-animal bond. Heart to Heart allows our community to see and appreciate the strength of these relationships, contributing to new conversations and possibilities for keeping pets and people together through the lifespan.

Dynamics of peripheral T cell exhaustion and monocyte subpopulations in neurocognitive impairment and brain atrophy in chronic HIV infection.

BACKGROUND: HIV-associated neurocognitive disorders (HAND) is hypothesized to be a result of myeloid cell-induced neuro-inflammation in the central nervous system that may be initiated in the periphery, but the contribution of peripheral T cells in HAND pathogenesis remains poorly understood. METHODS: We assessed markers of T cell activation (HLA-DR + CD38+), immunosenescence (CD57 + CD28-), and immune-exhaustion (TIM-3, PD-1 and TIGIT) as well as monocyte subsets (classical, intermediate, and non-classical) by flow cytometry in peripheral blood derived from individuals with HIV on long-term stable anti-retroviral therapy (ART). Additionally, normalized neuropsychological (NP) composite test z-scores were obtained and regional brain volumes were assessed by magnetic resonance imaging (MRI). Relationships between proportions of immune phenotypes (of T-cells and monocytes), NP z-scores, and brain volumes were analyzed using Pearson correlations and multiple linear regression models. RESULTS: Of N = 51 participants, 84.3% were male, 86.3% had undetectable HIV RNA < 50 copies/ml, median age was 52 [47, 57] years and median CD4 T cell count was 479 [376, 717] cells/uL. Higher CD4 T cells expressing PD-1 + and/or TIM-3 + were associated with lower executive function and working memory and higher CD8 T cells expressing PD-1+ and/or TIM-3+ were associated with reduced brain volumes in multiple regions (putamen, nucleus accumbens, cerebellar cortex, and subcortical gray matter). Furthermore, higher single or dual frequencies of PD-1 + and TIM-3 + expressing CD4 and CD8 T-cells correlated with higher CD16 + monocyte numbers. CONCLUSIONS: This study reinforces evidence that T cells, particularly those with immune exhaustion phenotypes, are associated with neurocognitive impairment and brain atrophy in people living with HIV on ART. Relationships revealed between T-cell immune exhaustion and inflammatory in CD16+ monocytes uncover interrelated cellular processes likely involved in the immunopathogenesis of HAND.

Heparan sulfate-dependent phase separation of CCL5 and its chemotactic activity.

Secreted chemokines form concentration gradients in target tissues to control migratory directions and patterns of immune cells in response to inflammatory stimulation; however, how the gradients are formed is much debated. Heparan sulfate (HS) binds to chemokines and modulates their activities. In this study, we investigated the roles of HS in the gradient formation and chemoattractant activity of CCL5 that is known to bind to HS. CCL5 and heparin underwent liquid-liquid phase separation and formed gradient, which was confirmed using CCL5 immobilized on heparin-beads. The biological implication of HS in CCL5 gradient formation was established in CHO-K1 (wild-type) and CHO-677 (lacking HS) cells by Transwell assay. The effect of HS on CCL5 chemoattractant activity was further proved by Transwell assay of human peripheral blood cells. Finally, peritoneal injection of the chemokines into mice showed reduced recruitment of inflammatory cells either by mutant CCL5 (lacking heparin-binding sequence) or by addition of heparin to wild-type CCL5. Our experimental data propose that co-phase separation of CCL5 with HS establishes a specific chemokine concentration gradient to trigger directional cell migration. The results warrant further investigation on other heparin-binding chemokines and allows for a more elaborate insight into disease process and new treatment strategies.

Comparison of joint kinematics between upright front squat exercise and horizontal squat exercise performed on a short arm human centrifugation.

This study compared the joint kinematics between the front squat (FS) conducted in the upright (natural gravity) position and in the supine position on a short arm human centrifuge (SAHC). Male participants (N = 12) with no prior experience exercising on a centrifuge completed a FS in the upright position before (PRE) and after (POST) a FS exercise conducted on the SAHC while exposed to artificial gravity (AG). Participants completed, in randomized order, three sets of six repetitions with a load equal to body weight or 1.25 × body weight for upright squats, and 1 g and 1.25 g at the center of gravity (COG) for AG. During the terrestrial squats, the load was applied with a barbell. Knee (left/right) and hip (left/right) flexion angles were recorded with a set of inertial measurement units. AG decreased the maximum flexion angle (MAX) of knees and hips as well as the range of motion (ROM), both at 1 and 1.25 g. Minor adaptation was observed between the first and the last repetition performed in AG. AG affects the ability to FS in naïve participants by reducing MAX, MIN and ROM of the knees and hip.

Variant analysis of human papillomavirus type 52 in Iranian women during 2018-2020: A case-control study.

Background and Aims: Knowing the regional variants of distinct human papillomavirus (HPV) types is valuable as it can be beneficial for studying their epidemiology, pathogenicity, and evolution. For this reason, the sequence variations of the E6 gene of HPV 52 were investigated among women with normal cervical cytology and premalignant/malignant cervical samples. Methods: Sixty-four HPV 52-positive samples were analyzed using semi-nested PCR and sequencing. Results: Our findings showed that all samples belonged to lineage A (61%) or B (39%). Among samples that were infected with the A lineage, sublineages A1 and A2 were detected and sublineage A1 was dominant. No association was found between lineages and stage of disease (p > 0.05). Conclusion: Our results revealed that the A lineage, sublineage A1, and B lineage were common in Iranian women. Nevertheless, more studies with larger sample sizes are required to estimate the pathogenicity risk of HPV 52 lineages in Iranian women with cervical cancer.

Contextual emotion detection in images using deep learning.

Introduction: Computerized sentiment detection, based on artificial intelligence and computer vision, has become essential in recent years. Thanks to developments in deep neural networks, this technology can now account for environmental, social, and cultural factors, as well as facial expressions. We aim to create more empathetic systems for various purposes, from medicine to interpreting emotional interactions on social media. Methods: To develop this technology, we combined authentic images from various databases, including EMOTIC (ADE20K, MSCOCO), EMODB_SMALL, and FRAMESDB, to train our models. We developed two sophisticated algorithms based on deep learning techniques, DCNN and VGG19. By optimizing the hyperparameters of our models, we analyze context and body language to improve our understanding of human emotions in images. We merge the 26 discrete emotional categories with the three continuous emotional dimensions to identify emotions in context. The proposed pipeline is completed by fusing our models. Results: We adjusted the parameters to outperform previous methods in capturing various emotions in different contexts. Our study showed that the Sentiment_recognition_model and VGG19_contexte increased mAP by 42.81% and 44.12%, respectively, surpassing the results of previous studies. Discussion: This groundbreaking research could significantly improve contextual emotion recognition in images. The implications of these promising results are far-reaching, extending to diverse fields such as social robotics, affective computing, human-machine interaction, and human-robot communication.

A pan-cancer analysis of EphA family gene expression and its association with prognosis, tumor microenvironment, and therapeutic targets.

Background: Erythropoietin-producing human hepatocellular (Eph) receptors stand out as the most expansive group of receptor tyrosine kinases (RTKs). Accumulating evidence suggests that within this expansive family, the EphA subset is implicated in driving cancer cell progression, proliferation, invasion, and metastasis, making it a promising target for anticancer treatment. Nonetheless, the extent of EphA family involvement across diverse cancers, along with its intricate interplay with immunity and the tumor microenvironment (TME), remains to be fully illuminated. Methods: The relationships between EphA gene expression and patient survival, immunological subtypes, and TME characteristics were investigated based on The Cancer Genome Atlas (TCGA) database. The analyses employed various R packages. Results: A significant difference in expression was identified for most EphA genes when comparing cancer tissues and non-cancer tissues. These genes independently functioned as prognostic factors spanning multiple cancer types. Moreover, a significant correlation surfaced between EphA gene expression and immune subtypes, except for EphA5, EphA6, and EphA8. EphA3 independently influenced the prognosis of papillary renal cell carcinoma (KIRP). This particular gene exhibited links with immune infiltration subtypes and clinicopathologic parameters, holding promise as a valuable biomarker for predicting prognosis and responsiveness to immunotherapy in patients with KIRP. Conclusion: By meticulously scrutinizing the panorama of EphA genes in a spectrum of cancers, this study supplemented a complete map of the effect of EphA family in Pan-cancer and suggested that EphA family may be a potential target for cancer therapy.

Identification of osteoblastic autophagy-related genes for predicting diagnostic markers in osteoarthritis.

The development of osteoarthritis (OA) involves subchondral bone lesions, but the role of osteoblastic autophagy-related genes (ARGs) in osteoarthritis is unclear. Through integrated analysis of single-cell dataset, Bulk RNA dataset, and 367 ARGs extracted from GeneCards, 40 ARGs were found. By employing multiple machine learning algorithms and PPI networks, three key genes (DDIT3, JUN, and VEGFA) were identified. Then the RF model constructed from these genes indicated great potential as a diagnostic tool. Furthermore, the model's effectiveness in predicting OA has been confirmed through external validation datasets. Moreover, the expression of ARGs was examined in osteoblasts subject to excessive mechanical stress, human and mouse tissues. Finally, the role of ARGs in OA was confirmed through co-culturing explants and osteoblasts. Thus, osteoblastic ARGs could be crucial in OA development, providing potential diagnostic and treatment strategies.

JointTracker: Real-time inertial kinematic chain tracking with joint position estimation.

In-field human motion capture (HMC) is drawing increasing attention due to the multitude of application areas. Plenty of research is currently invested in camera-based (markerless) HMC, with the advantage of no infrastructure being required on the body, and additional context information being available from the surroundings. However, the inherent drawbacks of camera-based approaches are the limited field of view and occlusions. In contrast, inertial HMC (IHMC) does not suffer from occlusions, thus being a promising approach for capturing human motion outside the laboratory. However, one major challenge of such methods is the necessity of spatial registration. Typically, during a predefined calibration sequence, the orientation and location of each inertial sensor are registered with respect to the underlying skeleton model. This work contributes to calibration-free IHMC, as it proposes a recursive estimator for the simultaneous online estimation of all sensor poses and joint positions of a kinematic chain model like the human skeleton. The full derivation from an optimization objective is provided. The approach can directly be applied to a synchronized data stream from a body-mounted inertial sensor network. Successful evaluations are demonstrated on noisy simulated data from a three-link chain, real lower-body walking data from 25 young, healthy persons, and walking data captured from a humanoid robot. The estimated and derived quantities, global and relative sensor orientations, joint positions, and segment lengths can be exploited for human motion analysis and anthropometric measurements, as well as in the context of hybrid markerless visual-inertial HMC.

The HHV-6B U20 glycoprotein binds ULBP1, masking it from recognition by NKG2D and interfering with natural killer cell activation.

Introduction: Human Herpesvirus 6B (HHV-6B) impedes host immune responses by downregulating class I MHC molecules (MHC-I), hindering antigen presentation to CD8+ T cells. Downregulation of MHC-I disengages inhibitory receptors on natural killer (NK) cells, resulting in activation and killing of the target cell if NK cell activating receptors such as NKG2D have engaged stress ligands upregulated on the target cells. Previous work has shown that HHV-6B downregulates three MHC-like stress ligands MICB, ULBP1, and ULBP3, which are recognized by NKG2D. The U20 glycoprotein of the related virus HHV-6A has been implicated in the downregulation of ULBP1, but the precise mechanism remains undetermined. Methods: We set out to investigate the role of HHV-6B U20 in modulating NK cell activity. We used HHV-6B U20 expressed as a recombinant protein or transduced into target cells, as well as HHV-6B infection, to investigate binding interactions with NK cell ligands and receptors and to assess effects on NK cell activation. Small-angle X-ray scattering was used to align molecular models derived from machine-learning approaches. Results: We demonstrate that U20 binds directly to ULBP1 with sub-micromolar affinity. Transduction of U20 decreases NKG2D binding to ULBP1 at the cell surface but does not decrease ULBP1 protein levels, either at the cell surface or in toto. HHV-6B infection and soluble U20 have the same effect. Transduction of U20 blocks NK cell activation in response to cell-surface ULBP1. Structural modeling of the U20 - ULBP1 complex indicates some similarities to the m152-RAE1γ complex.