Leveraging computer vision for predicting collision risks: a cross-sectional analysis of 2019-2021 fatal collisions in the USA.

OBJECTIVE: The USA has higher rates of fatal motor vehicle collisions than most high-income countries. Previous studies examining the role of the built environment were generally limited to small geographic areas or single cities. This study aims to quantify associations between built environment characteristics and traffic collisions in the USA. METHODS: Built environment characteristics were derived from Google Street View images and summarised at the census tract level. Fatal traffic collisions were obtained from the 2019-2021 Fatality Analysis Reporting System. Fatal and non-fatal traffic collisions in Washington DC were obtained from the District Department of Transportation. Adjusted Poisson regression models examined whether built environment characteristics are related to motor vehicle collisions in the USA, controlling for census tract sociodemographic characteristics. RESULTS: Census tracts in the highest tertile of sidewalks, single-lane roads, streetlights and street greenness had 70%, 50%, 30% and 26% fewer fatal vehicle collisions compared with those in the lowest tertile. Street greenness and single-lane roads were associated with 37% and 38% fewer pedestrian-involved and cyclist-involved fatal collisions. Analyses with fatal and non-fatal collisions in Washington DC found streetlights and stop signs were associated with fewer pedestrians and cyclists-involved vehicle collisions while road construction had an adverse association. CONCLUSION: This study demonstrates the utility of using data algorithms that can automatically analyse street segments to create indicators of the built environment to enhance understanding of large-scale patterns and inform interventions to decrease road traffic injuries and fatalities.

Self-Supervised Medical Image Denoising Based on WISTA-Net for Human Healthcare in Metaverse.

Medical image processing plays an important role in the interaction of real world and metaverse for healthcare. Self-supervised denoising based on sparse coding methods, without any prerequisite on large-scale training samples, has been attracting extensive attention for medical image processing. Whereas, existing self-supervised methods suffer from poor performance and low efficiency. In this paper, to achieve state-of-the-art denoising performance on the one hand, we present a self-supervised sparse coding method, named the weighted iterative shrinkage thresholding algorithm (WISTA). It does not rely on noisy-clean ground-truth image pairs to learn from only a single noisy image. On the other hand, to further improve denoising efficiency, we unfold the WISTA to construct a deep neural network (DNN) structured WISTA, named WISTA-Net. Specifically, in WISTA, motivated by the merit of the lp-norm, WISTA-Net has better denoising performance than the classical orthogonal matching pursuit (OMP) algorithm and the ISTA. Moreover, leveraging the high-efficiency of DNN structure in parameter updating, WISTA-Net outperforms the compared methods in denoising efficiency. In detail, for a 256 by 256 noisy image, the running time of WISTA-Net is 4.72 s on the CPU, which is much faster than WISTA, OMP, and ISTA by 32.88 s, 13.06 s, and 6.17 s, respectively.

RNA-seq identifies differentially expressed genes involved in csal1 overexpression in granulosa cells of prehierarchical follicles in Chinese Dagu hens.

The transcription factor csal1 is an important molecule that plays a critical regulatory function in ovarian follicle development, as confirmed by our previous data. However, the candidate genes of csal1 and its regulatory mechanism remain poorly understood in the granulosa cells (GCs) of chicken prehierarchical follicles (PFs). Six transcriptomes of csal1 and empty vector were analyzed in Chinese Dagu hens by RNA sequencing. Six cDNA libraries were constructed, with more than 42 million clean reads and 16,779 unigenes. Of these 16,779 unigenes, 2,762 differentially expressed genes (DEGs) were found in GCs, including 1,605 upregulated and 1,157 downregulated unigenes. Fourteen genes, including BMP5, TACR2, AMH, PLAG1, MYOD1, BOP1, SIPA1, NOTCH1, BCL2L1, SOX9, ADGRA2, WNT5A, SLC7A11, and GATAD2B, were related to GC proliferation and differentiation, hormone production, ovarian follicular development, regulation of reproductive processes, and signaling pathways in the PFs. Further analysis demonstrated the DEGs in GCs of ovarian follicles were enriched in neuroactive ligand-receptor interaction, cell adhesion molecules, and pathways related to cytochrome P450, indicating a critical function for csal1 in the generation of egg-laying features by controlling ovarian follicle development. For the first time, the current study represents the transcriptome analysis with ectopic csal1 expression. These findings provide significant evidence for investigating the molecular mechanism by which csal1 controls PF development in the hen ovary.

Mechanisms underlying impaired spermatogenic function in orchitis induced by busulfan.

Busulfan is an alkylating agent commonly used in cancer chemotherapy. It is also an ideal agent for preparing transplant recipients of spermatogonial stem cells because of its high efficiency in destroying endogenous germ cells in the testis. However, its toxicity mechanism remains unclear, affecting its clinical use and applications. Based on reports of busulfan causing orchitis and a previous study by our team, this article summarizes the relationship between busulfan and orchitis, cytokines, the blood-testis barrier, and the cytoskeleton, unravels the regulatory pathways and mechanism behind busulfan-induced orchitis, and reveals the molecular mechanism underlying impaired spermatogenic function in orchitis, providing new ideas for the clinical application of busulfan while reducing its testicular toxicity.

The Age-Accompanied and Diet-Associated Remodeling of the Phospholipid, Amino Acid, and SCFA Metabolism of Healthy Centenarians from a Chinese Longevous Region: A Window into Exceptional Longevity.

As centenarians provide a paradigm of healthy aging, investigating the comprehensive metabolic profiles of healthy centenarians is of utmost importance for the pursuit of health and longevity. However, relevant reports, especially studies considering the dietary influence on metabolism, are still limited, mostly lacking the guidance of a model of healthy aging. Therefore, exploring the signatures of the integrative metabolic profiles of the healthy centenarians from a famous longevous region, Bama County, China, should be an effective way. The global metabolome in urine and the short-chain fatty acids (SCFAs) in the feces of 30 healthy centenarians and 31 elderly people aged 60−70 from the longevous region were analyzed by non-targeted metabolomics combined with metabolic target analysis. The results showed that the characteristic metabolites related to longevity were mostly summarized into phosphatidylserine, lyso-phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, bile acids, and amino acids (p < 0.05). Six metabolic pathways were found significant relevant to longevity. Furthermore, acetic acid, propionic acid, butyric acid, valeric acid, and total SCFA were significantly increased in the centenarian group (p < 0.05) and were also positively associated with the dietary fiber intake (p < 0.01). It was age-accompanied and diet-associated remodeling of phospholipid, amino acid, and SCFA metabolism that expressed the unique metabolic signatures related to exceptional longevity. This metabolic remodeling is suggestive of cognitive benefits, better antioxidant capacity, the attenuation of local inflammation, and health-span-promoting processes, which play a critical and positive role in shaping healthy aging.

Deep Ladder-Suppression Network for Unsupervised Domain Adaptation.

Unsupervised domain adaptation (UDA) aims at learning a classifier for an unlabeled target domain by transferring knowledge from a labeled source domain with a related but different distribution. Most existing approaches learn domain-invariant features by adapting the entire information of the images. However, forcing adaptation of domain-specific variations undermines the effectiveness of the learned features. To address this problem, we propose a novel, yet elegant module, called the deep ladder-suppression network (DLSN), which is designed to better learn the cross-domain shared content by suppressing domain-specific variations. Our proposed DLSN is an autoencoder with lateral connections from the encoder to the decoder. By this design, the domain-specific details, which are only necessary for reconstructing the unlabeled target data, are directly fed to the decoder to complete the reconstruction task, relieving the pressure of learning domain-specific variations at the later layers of the shared encoder. As a result, DLSN allows the shared encoder to focus on learning cross-domain shared content and ignores the domain-specific variations. Notably, the proposed DLSN can be used as a standard module to be integrated with various existing UDA frameworks to further boost performance. Without whistles and bells, extensive experimental results on four gold-standard domain adaptation datasets, for example: 1) Digits; 2) Office31; 3) Office-Home; and 4) VisDA-C, demonstrate that the proposed DLSN can consistently and significantly improve the performance of various popular UDA frameworks.

Joint Clustering and Discriminative Feature Alignment for Unsupervised Domain Adaptation.

Unsupervised Domain Adaptation (UDA) aims to learn a classifier for the unlabeled target domain by leveraging knowledge from a labeled source domain with a different but related distribution. Many existing approaches typically learn a domain-invariant representation space by directly matching the marginal distributions of the two domains. However, they ignore exploring the underlying discriminative features of the target data and align the cross-domain discriminative features, which may lead to suboptimal performance. To tackle these two issues simultaneously, this paper presents a Joint Clustering and Discriminative Feature Alignment (JCDFA) approach for UDA, which is capable of naturally unifying the mining of discriminative features and the alignment of class-discriminative features into one single framework. Specifically, in order to mine the intrinsic discriminative information of the unlabeled target data, JCDFA jointly learns a shared encoding representation for two tasks: supervised classification of labeled source data, and discriminative clustering of unlabeled target data, where the classification of the source domain can guide the clustering learning of the target domain to locate the object category. We then conduct the cross-domain discriminative feature alignment by separately optimizing two new metrics: 1) an extended supervised contrastive learning, i.e., semi-supervised contrastive learning 2) an extended Maximum Mean Discrepancy (MMD), i.e., conditional MMD, explicitly minimizing the intra-class dispersion and maximizing the inter-class compactness. When these two procedures, i.e., discriminative features mining and alignment are integrated into one framework, they tend to benefit from each other to enhance the final performance from a cooperative learning perspective. Experiments are conducted on four real-world benchmarks (e.g., Office-31, ImageCLEF-DA, Office-Home and VisDA-C). All the results demonstrate that our JCDFA can obtain remarkable margins over state-of-the-art domain adaptation methods. Comprehensive ablation studies also verify the importance of each key component of our proposed algorithm and the effectiveness of combining two learning strategies into a framework.

miR-92a promotes cervical cancer cell proliferation, invasion, and migration by directly targeting PIK3R1.

OBJECTIVE: To clarify the role of miR-92a in regulating the malignant progression of cervical cancer and its specific molecular mechanism. METHODS: qRT-PCR was used to detect the differential expression of miR-92a in cervical cancer and adjacent tissues. The effects of overexpression of miR-92a on the proliferation, migration, and invasion of HeLa and SiHa cells were tested. Luciferase assays and rescue experiments were used to investigate the regulatory mechanism of miR-92a on its downstream gene PIK3R1 and their interaction in the progression of cervical cancer. RESULTS: miR-92a was significantly up-regulated in cervical cancer tissues. Overexpression of miR-92a significantly increased the ability of cervical cancer cells to proliferate, migrate, and invade. PIK3R1 was identified as a downstream gene of miR-92a. In cervical cancer tissues, PIK3R1 was found to be down-regulated and negatively correlated with the level of miR-92a. Overexpression of PIK3R1 reversed the promotional effect of overexpressed miR-92a on the proliferation, migration, and invasion of cervical cancer. CONCLUSION: miR-92a is up-regulated in cervical cancer tissues. miR-92a promotes the malignant development of cervical cancer by negatively regulating PIK3R1.

LncRNA HOXA-AS2 Activates the Notch Pathway to Promote Cervical Cancer Cell Proliferation and Migration.

Long non-coding RNAs (lncRNAs) are crucial participants in cancer development. HOXA cluster antisense RNA 2 (HOXA-AS2) plays a tumor promoter role in bladder cancer. However, the functional role of HOXA-AS2 in cervical cancer remains unclear. Our study first found that HOXA-AS2 expression was up-regulated in cervical cancer cells. Then functional analysis including cell counting kit-8 (CCK-8), colony formation, transwell, and wound healing uncovered that reduction of HOXA-AS2 remarkably impeded cell proliferation and migration in cervical cancer. Additionally, luciferase reporter assays were performed to confirm that HOXA-AS2 activated Notch signaling pathway via the mediation of independent recombination signal binding protein for JK (RBP-JK) activity. As we know, Notch intracellular domain (NICD) is associated with RBP-JK in the nucleus to promote target genes in the Notch pathway. Through RNA immunoprecipitation (RIP), RNA pull down, and fluorescent in situ hybridization (FISH) assays, we observed that HOXA-AS2 combined with NICD. Moreover, the data from Co-IP assays indicated that HOXA-AS2 reduction weakened the interaction of NICD and RBP-JK. Collectively, HOXA-AS2 played a cancer-promoting role in cervical cancer development by modulating the Notch pathway, which might become a novel target for cervical cancer treatment.

Clinical Efficacy of Combined Hysteroscopic and Laparoscopic Surgery and Reversible Ligation of the Uterine Artery for Excision and Repair of Uterine Scar in Patients with Type II and III Cesarean Scar Pregnancy.

BACKGROUND With the changes in China's family planning policy, the incidence of cesarean scar pregnancy (CSP) significantly increased in recent years. The present study aimed to investigate the clinical efficacy of combined hysteroscopic and laparoscopic surgery and reversible ligation of the uterine artery for cesarean scar excision and repair in patients with type II and III CSP. MATERIAL AND METHODS This was a retrospective study of 173 patients with type II and III CSP. They were assigned to the hysteroscopy and laparoscopy group (group A), hysteroscopy group (group B), and curettage group (group C) according to the surgery they underwent. The surgical indicators (intraoperative bleeding volume and hospital stay), postoperative recovery (time of serum ß-hCG returning to the normal, postoperative residual lesion, the thickness of the uterine scar, and recovery time of menstruation), and the postoperative complications were compared among the 3 groups. RESULTS In patients with type II and III CSP, significant differences (P<0.05) were observed between group A vs. groups B and C in terms of the time of serum ß-HCG returning to normal, postoperative residual lesions, the thickness of the uterine scar, and recovery time of menstruation, while there were no significant differences in intraoperative bleeding volume and postoperative hospital stay (P>0.05). CONCLUSIONS For patients with type II and III CSP, hysteroscopy and laparoscopy surgery and reversible ligation of the uterine artery achieved better clinical outcomes than hysteroscopy or curettage with respect to postoperative recovery. This could be suitable for patients with CSP and desire for fertility.

Inactivation of Pseudomonas aeruginosa Biofilms by 405-Nanometer-Light-Emitting Diode Illumination.

Biofilm formation by Pseudomonas aeruginosa contributes to its survival on surfaces and represents a major clinical threat because of the increased tolerance of biofilms to disinfecting agents. This study aimed to investigate the efficacy of 405-nm light-emitting diode (LED) illumination in eliminating P. aeruginosa biofilms formed on stainless steel coupons under different temperatures. Time-dependent killing assays using planktonic and biofilm cells were used to determine the antimicrobial and antibiofilm activities of LED illumination. We also evaluated the effects of LED illumination on the disinfectant susceptibility, biofilm structure, extracellular polymeric substance (EPS) structure and composition, and biofilm-related gene expression of P. aeruginosa biofilm cells. Results showed that the abundance of planktonic P. aeruginosa cells was reduced by 0.88, 0.53, and 0.85 log CFU/ml following LED treatment for 2 h compared with untreated controls at 4, 10, and 25°C, respectively. For cells in biofilms, significant reductions (1.73, 1.59, and 1.68 log CFU/cm2) were observed following LED illumination for 2 h at 4, 10, and 25°C, respectively. Moreover, illuminated P. aeruginosa biofilm cells were more sensitive to benzalkonium chloride or chlorhexidine than untreated cells. Scanning electron microscopy and confocal laser scanning microscopic observation indicated that both the biofilm structure and EPS structure were disrupted by LED illumination. Further, reverse transcription-quantitative PCR revealed that LED illumination downregulated the transcription of several genes associated with biofilm formation. These findings suggest that LED illumination has the potential to be developed as an alternative method for prevention and control of P. aeruginosa biofilm contamination.IMPORTANCEPseudomonas aeruginosa can form biofilms on medical implants, industrial equipment, and domestic surfaces, contributing to high morbidity and mortality rates. This study examined the antibiofilm activity of 405-nm light-emitting diode (LED) illumination against mature biofilms formed on stainless steel coupons. We found that the disinfectant susceptibility, biofilm structure, and extracellular polymeric substance structure and composition were disrupted by LED illumination. We then investigated the transcription of several critical P. aeruginosa biofilm-related genes and analyzed the effect of illumination temperature on the above characteristics. Our results confirmed that LED illumination could be developed into an effective and safe method to counter P. aeruginosa biofilm contamination. Further research will be focused on the efficacy and application of LED illumination for elimination of complicated biofilms in the environment.

Programmed cell death factor 4 enhances the chemosensitivity of colorectal cancer cells to Taxol.

Drug resistance and disease relapse are still challenging problems in the chemotherapy of colorectal cancer (CRC). Programmed cell death factor 4 (PDCD4) has previously been reported to act as a tumor suppressor and was implicated in the chemosensitivity of numerous types of human malignancy. In this study, the effect of PDCD4 in the sensitivity of CRC to the chemotherapy drug Taxol was investigated. The results confirmed that lower PDCD4 expression was present in CRC tumor tissues, when compared with in normal adjacent tissues (p) and closely associated with the prognosis of patients with CRC. Upregulation of PDCD4 significantly enhanced the sensitivity of CRC cells to Taxol, by partially contributing to pro-apoptosis and anti-invasion pathways, both through upregulation of the apoptosis-associated protein Bax, and downregulation of the anti-apoptosis protein Bcl-2 and invasion-associated proteins MMP-9. These findings might present a novel strategy for sensitizing tumor cells to apoptosis and, thus, overcoming chemotherapy resistance in CRC.

Identification of a panel of MYC and Tip60 co-regulated genes functioning primarily in cell cycle and DNA replication.

We recently reported that adenovirus E1A enhances MYC association with the NuA4/Tip60 histone acetyltransferase (HAT) complex to activate a panel of genes enriched for DNA replication and cell cycle. Genes from this panel are highly expressed in examined cancer cell lines when compared to normal fibroblasts. To further understand gene regulation in cancer by MYC and the NuA4 complex, we performed RNA-seq analysis of MD-MB231 breast cancer cells following knockdown of MYC or Tip60 - the HAT enzyme of the NuA4 complex. We identify here a panel of 424 genes, referred to as MYC-Tip60 co-regulated panel (MTcoR), that are dependent on both MYC and Tip60 for expression and likely co-regulated by MYC and the NuA4 complex. The MTcoR panel is most significantly enriched in genes involved in cell cycle and/or DNA replication. In contrast, genes repressed by shMYC but not by shTip60 (224 genes) have a low significance of enrichment in identifiable biological processes other than cell cycle and DNA replication. Genes repressed by shTip60 but not by shMYC (102 genes) have no significant identifiable gene enrichment. We propose that MYC cooperates with the NuA4 complex to activate the MTcoR panel of genes to promote DNA replication and cell cycle.

Synchronous occurrence of primary right ovarian endometrioid adenocarcinoma and primary left ovarian clear cell adenocarcinoma: A case report.

RATIONALE: Ovarian malignancy is associated with one of the highest rates of death among gynecological reproductive system malignancies. While progress has been made in surgical and postoperative adjuvant treatment approaches, the early atypical clinical manifestations, quick progression, and lack of the effective early screening means imply that the prognosis remains poor. Bilateral ovarian cancers are common, but different types of primary bilateral ovarian carcinomas are extremely rare. PATIENT CONCERNS: According to clinical pathologic, immunohistochemistry, and medical imaging data, a 51-year-old Chinese woman with abdominal pain was diagnosed as having right ovarian well-differentiated endometrioid adenocarcinoma with mucinous adenocarcinoma and left ovarian clear cell adenocarcinoma. DIAGNOSES: Immunohistochemistry confirmed the diagnosis of primary bilateral ovarian cancers. INTERVENTIONS: She received multimodal treatment including surgery and chemotherapy. OUTCOMES: The patient's recovery was uneventful, and she responded well to the chemotherapy. LESSONS: We speculate that the different types of primary bilateral ovarian carcinomas presented in this case may be due to different malignant transformations of the endometriotic lesions. Therefore, clinicians should pay special attention to the possible malignant transformation of endometriosis.

A Case of Psoas Muscle Endometriosis: A Distinct Approach to Diagnosis and Management.

Endometriosis is a common disease in women of childbearing age. Here, we report a case of psoas muscle endometriosis and our approach to treatment. A 28-year-old woman presented with an 8-month history of lower left abdominal and back pain. She was incorrectly diagnosed and treated for a psoas abscess at a previous hospital. Based on imaging results and previous history of severe dysmenorrhea, a diagnosis of psoas muscle endometriosis was considered. The patient underwent treatment with gonadotropin-releasing hormones and laparoscopic surgery and currently reports alleviation of symptoms. Psoas muscle endometriosis is rare, and the diagnosis can be difficult. It is important to recognize signs and symptoms to determine adequate treatment.

Primary leiomyosarcoma of the fallopian tube: A case report and literature review.

RATIONALE: Primary leiomyosarcoma (LMS) of the fallopian tube is extremely uncommon. To the best of our knowledge, so far only 21 cases of primary fallopian tube LMS have been reported in English-language literature. No new case has been reported in the past 7 years. PATIENT CONCERNS: A 44-year-old premenopausal patient presented with a 5-day history of lower abdominal pain. DIAGNOSES: Pelvic ultrasonography detected an 8.8 × 7.8 × 6.5 cm solid and cystic mass in the left side of the pelvic cavity. The tumor was diagnosed as a primary fallopian tube LMS on paraffin section. INTERVENTIONS: The patient treated surgically followed by 4 cycles of postoperative chemotherapy with dacarbazine and DDP. OUTCOMES: The patient succumbed to the disease 27 months after the initial therapy. LESSONS: Tube LMS is a rare malignant tumor with unknown etiology, difficult early diagnosis, highly invasiveness, high local recurrence and distant metastasis rate, rapid progress, and poor prognosis. It is extremely rare so we can only summarize limited experience from limited data. Every case of tubal LMS is worth being reported.

[Effects of Thalidomide on the Ratio of Th17 to Treg Cells in Peripheral Blood and Expression of IL-17 and IL-35 in Patients with Multiple Myeloma].

OBJECTIVE: To explore the effects of thalidomide on the ratio of Th17 to Treg cells in peripheral blood and expression of IL-17 and IL-35 in patients with multiple myeloma(MM), so as to provide reference for the clinical treatment of patients with MM. METHODS: A total of 82 MM patients treated with thalidomide from January 2014 to December 2016 were enrolled in MM group, 30 healthy subjects were selected as control (control group). The ratio of T cell subsets and Treg cells accounted for CD4+T cell were detected by flow cytometer. The levels of IL-17 and IL-35 in serum were measured by ELISA, and the differences of various indexes were compared between 2 groups. RESULTS: Compared with the control group, the ratio of Th17 cells in peripheral blood and serum levels of IL-17 of MM patients were significantly increased, the ratio of Treg cells and the level of IL-35 were significantly decreased and the ratio of Th17/Treg cells was significantly increased in the patients with multiple myeloma before treatment (P<0.05). The ratio of Th17 cells in peripheral blood and serum levels of IL-17 in patients with multiple myeloma after treatment with thalidomide were significantly lower than those before treatment, and the ratio of Treg cells and levels of IL-35 were significantly higher than those before treatment, and the ratio of Th17 / Treg cells was higher than that before treatment (P<0.05). The indexes in ineffective treatment were not significantly changed (P> 0.05). CONCLUSION: The unbanlace of Th17/Treg cell ratio and abnormality of IL-17, IL-35 levels play an important role in the progression of multiple myeloma. The anti-MM mechanism of thalidomide may relate with the regulation of Th17 / Treg cell ratio and expression levels of IL-17 and IL-35.

Clinical significance of BCL11A expression in ER-negative and PR-negative endometrial carcinoma.

OBJECTIVE: To study the mechanism and clinical significance of B-cell lymphoma/leukemia 11A (BCL11A) gene in the development of endometrial carcinoma (EC). METHODS: 100 EC, 20 normal endometrium and 20 atypical hyperplasia endometrium specimens were collected from West China Second University Hospital from January 2005 to January 2015. The expression of BCL11A was detected by immunohistochemistry and its relationships with clinicopathological features and survival were analyzed. RESULTS: The expression of BCL11A in ER-/PR-EC was higher than that in normal endometrium, atypical hyperplasia endometrium, and ER+/PR+EC (P < 0.001). The expression of BCL11A in EC was associated with age, menopause, EC classification, para-aortic lymph node metastasis, tumor differentiation, histological type, ER/PR expression and p53 expression (P < 0.05). The expression of BCL11A in the deceased group was significantly higher than that in the survival group (P = 0.011). Survival analysis indicated that the high expression of BCL11A was associated with low survival rate (P < 0.001). CONCLUSIONS: BCL11A may play an important role in the development of ER-/PR-EC. It may serve as a potential target for therapy and a predict factor for prognosis. It can also provide molecular basis for new EC classification.

Adenovirus E1A TRRAP-targeting domain-mediated enhancement of MYC association with the NuA4 complex activates a panel of MYC target genes enriched for gene expression and ribosome biogenesis.

Cellular transformation by adenovirus E1A requires targeting TRRAP, a scaffold protein which helps assemble histone acetyltransferase complexes, including the NuA4 complex. We recently reported that E1A and E1A 1-80 (N-terminal 80 aa) promote association of the proto-oncogene product MYC with the NuA4 complex. The E1A N-terminal TRRAP-targeting (ET) domain is required for E1A 1-80 to interact with the NuA4 complex. We demonstrate that an ET-MYC fusion associates with the NuA4 complex more efficiently than does MYC alone. Because MYC regulates genes for multiple cellular pathways, we performed global RNA-sequence analysis of cells expressing MYC or ET-MYC, and identified a panel of genes (262) preferentially activated by ET-MYC and significantly enriched in genes involved in gene expression and ribosome biogenesis, suggesting that E1A enhances MYC association with the NuA4 complex to activate a set of MYC target genes likely involved in cellular proliferation and cellular transformation by E1A and by MYC.