Publications by authors named "Dongyu Jia"

28 Publications

  • Page 1 of 1

Doubling Time of the COVID-19 Epidemic by Chinese Province.

medRxiv 2020 Apr 24. Epub 2020 Apr 24.

Georgia Southern University, Statesboro, GA, USA (K. Muniz-Rodriguez, D. Jia, M. Liu, S. K. Ofori, I. C.-H. Fung); Georgia State University, Atlanta, GA, USA (G. Chowell, Y. Lee, K. M. Roosa); Independent researcher (C.-H. Cheung); Boston University, Boston, MA, USA (P.-Y. Lai); Roskilde University, Roskilde, Denmark (L. Simonsen); The National Institutes of Health, Bethesda, MD, USA (G. Chowell, C. Viboud).

COVID-19 epidemic doubling time by Chinese province was increasing from January 20 through February 9, 2020. The harmonic mean of the arithmetic mean doubling time estimates ranged from 1.4 (Hunan, 95% CI, 1.2-2.0) to 3.1 (Xinjiang, 95% CI, 2.1-4.8), with an estimate of 2.5 days (95% CI, 2.4-2.6) for Hubei.
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http://dx.doi.org/10.1101/2020.02.05.20020750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216847PMC
April 2020

Very Short-Term Surface Solar Irradiance Forecasting Based On FengYun-4 Geostationary Satellite.

Sensors (Basel) 2020 May 3;20(9). Epub 2020 May 3.

College of Geography and Environmental Engineering, Lanzhou City University, Lanzhou 730070, China.

An algorithm to forecast very short-term (30-180 min) surface solar irradiance using visible and near infrared channels (AGRI) onboard the FengYun-4A (FY-4A) geostationary satellite was constructed and evaluated in this study. The forecasting products include global horizontal irradiance (GHI) and direct normal irradiance (DNI). The forecast results were validated using data from Chengde Meteorological Observatory for four typical months (October 2018, and January, April, and July 2019), representing the four seasons. Particle Image Velocimetry (PIV) was employed to calculate the cloud motion vector (CMV) field from the satellite images. The forecast results were compared with the smart persistence (SP) model. A seasonal study showed that July and April forecasting is more difficult than during October and January. For GHI forecasting, the algorithm outperformed the SP model for all forecasting horizons and all seasons, with the best result being produced in October; the skill score was greater than 20%. For DNI, the algorithm outperformed the SP model in July and October, with skill scores of about 12% and 11%, respectively. Annual performances were evaluated; the results show that the normalized root mean square error (nRMSE) value of GHI for 30-180 min horizon ranged from 26.78% to 36.84%, the skill score reached a maximum of 20.44% at the 30-min horizon, and the skill scores were all above 0 for all time horizons. For DNI, the maximum skill score was 6.62% at the 180-min horizon. Overall, compared with the SP model, the proposed algorithm is more accurate and reliable for GHI forecasting and slightly better for DNI forecasting.
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http://dx.doi.org/10.3390/s20092606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248847PMC
May 2020

Analysis of the Temporal Patterning of Notch Downstream Targets during Drosophila melanogaster Egg Chamber Development.

Sci Rep 2020 04 30;10(1):7370. Epub 2020 Apr 30.

Department of Biology, Georgia Southern University, Statesboro, GA, 30460, USA.

Living organisms require complex signaling interactions and proper regulation of these interactions to influence biological processes. Of these complex networks, one of the most distinguished is the Notch pathway. Dysregulation of this pathway often results in defects during organismal development and can be a causative mechanism for initiation and progression of cancer. Despite previous research entailing the importance of this signaling pathway and the organismal processes that it is involved in, less is known concerning the major Notch downstream targets, especially the onset and sequence in which they are modulated during normal development. As timing of regulation may be linked to many biological processes, we investigated and established a model of temporal patterning of major Notch downstream targets including broad, cut, and hindsight during Drosophila melanogaster egg chamber development. We confirmed the sequential order of Broad upregulation, Hindsight upregulation, and Cut downregulation. In addition, we showed that Notch signaling could be activated at stage 4, one stage earlier than the stage 5, a previously long-held belief. However, our further mitotic marker analysis re-stated that mitotic cycle continues until stage 5. Through our study, we once again validated the effectiveness and reliability of our MATLAB toolbox designed to systematically identify egg chamber stages based on area size, ratio, and additional morphological characteristics.
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http://dx.doi.org/10.1038/s41598-020-64247-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193588PMC
April 2020

Doubling Time of the COVID-19 Epidemic by Province, China.

Emerg Infect Dis 2020 08 24;26(8):1912-1914. Epub 2020 Apr 24.

In China, the doubling time of the coronavirus disease epidemic by province increased during January 20-February 9, 2020. Doubling time estimates ranged from 1.4 (95% CI 1.2-2.0) days for Hunan Province to 3.1 (95% CI 2.1-4.8) days for Xinjiang Province. The estimate for Hubei Province was 2.5 (95% CI 2.4-2.6) days.
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http://dx.doi.org/10.3201/eid2608.200219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392464PMC
August 2020

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer.

J Vis Exp 2020 01 12(155). Epub 2020 Jan 12.

Department of Biology, Georgia Southern University;

Notch signaling is a highly conserved regulatory pathway involved in many cellular processes. Dysregulation of this signaling pathway often leads to interference with proper development and may even result in initiation or progression of cancers in certain cases. Because this pathway serves complex and versatile functions, it can be studied extensively through many different approaches. Of these, bioinformatics provides an undeniably cost-efficient, approachable, and user-friendly method of study. Bioinformatics is a useful way to extract smaller pieces of information from large-scale datasets. Through the implementation of various bioinformatics approaches, researchers can quickly, reliably, and efficiently interpret these large datasets, yielding insightful applications and scientific discoveries. Here, a protocol is presented for integration of bioinformatics approaches to investigate the role of Notch signaling in ovarian cancer. Furthermore, bioinformatics findings are validated through experimentation.
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http://dx.doi.org/10.3791/60502DOI Listing
January 2020

A rare case of stent-assisted coil embolization of coronary artery aneurysm in the left main trigeminal position: Case report.

Medicine (Baltimore) 2019 Dec;98(50):e18173

Department of Biology, Georgia Southern University, Statesboro, GA.

Rationale: Coronary artery aneurysms (CAAs) are uncommon in patients with acute coronary syndrome (ACS). We describe the clinical features and outcomes of stent-assisted coil embolization of a CAA in the trigeminal position.

Patient Concerns: We present a 73-year-old woman with a history of paroxysmal episodes of precordial pain since 1 year. Coronary computed tomography angiography (CTA) revealed an aneurysm (diameter: 9 mm) at the junction of the distal left main coronary artery and the anterior descending branch. Troponin I, CK-MB, creatinine and routine blood investigations were within the normal range.

Diagnosis: Coronary artery aneurysm in the left main trigeminal position.

Interventions: The patient was treated with stent-assisted coil embolization.

Outcomes: After complete filling of the aneurysm with coil, the microcatheter was withdrawn and the stent released in the descending branch. Two stents were successfully implanted.

Lessons: There is no clear consensus on the optimal therapy for patients with CAAs. Clinicians should be aware of the possible complications of stent-assisted coil embolization of CAA in the main trunk of the coronary artery.
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http://dx.doi.org/10.1097/MD.0000000000018173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6922376PMC
December 2019

DNA topoisomerase IIα and RAD21 cohesin complex component are predicted as potential therapeutic targets in bladder cancer.

Oncol Lett 2019 Jul 17;18(1):518-528. Epub 2019 May 17.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400044, P.R. China.

Cancer is essentially a genetic disease. Accumulated gene mutations accelerate genome instability, which eventually leads to uncontrollable growth of the tumor. Bladder cancer is the most common form of urinary tract cancer. This form of cancer has a poor prognosis due to its clinical heterogeneity and molecular diversity. Despite recent scientific advances, the knowledge and treatment of bladder cancer still lags behind that of other types of solid tumor. In the present study, available large data portals and other studies were used to obtain clinically relevant information, and the data were systematically processed to decipher the genes associated with bladder cancer. Genes associated with the survival time of patients with bladder cancer were successfully identified. The genes were enriched in common biological processes and pathways, and upregulated in tumor samples from patients. Among the top genes identified as associated with good or poor survival in bladder cancer, DNA topoisomerase IIα (TOP2α) and RAD21 cohesin complex component (RAD21) were also increased in bladder cancer tissues and cell lines. Therefore, TOP2α and RAD21 could be used as potential therapeutic targets in bladder cancer.
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http://dx.doi.org/10.3892/ol.2019.10365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539755PMC
July 2019

Polyamine Oxidases Play Various Roles in Plant Development and Abiotic Stress Tolerance.

Plants (Basel) 2019 Jun 21;8(6). Epub 2019 Jun 21.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou 510642, China.

Polyamines not only play roles in plant growth and development, but also adapt to environmental stresses. Polyamines can be oxidized by copper-containing diamine oxidases (CuAOs) and flavin-containing polyamine oxidases (PAOs). Two types of PAOs exist in the plant kingdom; one type catalyzes the back conversion (BC-type) pathway and the other catalyzes the terminal catabolism (TC-type) pathway. The catabolic features and biological functions of plant PAOs have been investigated in various plants in the past years. In this review, we focus on the advance of PAO studies in rice, Arabidopsis, and tomato, and other plant species.
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http://dx.doi.org/10.3390/plants8060184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6632040PMC
June 2019

NOTCH2/NOTCH3/DLL3/MAML1/ADAM17 signaling network is associated with ovarian cancer.

Oncol Lett 2019 Jun 19;17(6):4914-4920. Epub 2019 Mar 19.

Morphism Institute, Seattle, WA 98117, USA.

Notch signaling is well-known for its role in regulating cell self-renewal and differentiation. Within the cancer research field, it has been identified that dysregulated Notch signaling is involved directly with various types of cancer. Although Notch signaling is generally considered as oncogenic, it sometimes acts as a tumor suppressor, highlighting the complexity of the role of Notch in cancer. A number of studies have associated Notch signaling components with ovarian cancer, but the underlying molecular mechanisms are not well-elucidated. In the present study, the roles of main components of Notch signaling in ovarian cancer were systematically analyzed through large data portals, including Prediction of Clinical Outcomes from Genomic Profiles, Gene Expression across Normal and Tumor tissue, CSIOVDB, Broad Institute Cancer Cell Line Encyclopedia and cBioPortal. Upregulated expression of proteins in the Notch signaling pathway components in ovarian cancer was identified to be generally associated with poor overall and disease-free survival time, and more advanced cancer stages. In addition, Notch components were enriched in ovarian cancer tissues and cell lines. These results led to a proposed neurogenic locus notch homolog protein (NOTCH)2/NOTCH3/Delta-like protein 3/Mastermind-like protein 1/a disintegrin and metalloproteinase domain-containing protein 17 network. Anticancer drugs, developed to target this network, may have high specificity in treating Notch-associated ovarian cancer.
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http://dx.doi.org/10.3892/ol.2019.10170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507302PMC
June 2019

The expansion process of a Stellera chamaejasme population in a degraded alpine meadow of Northwest China.

Environ Sci Pollut Res Int 2019 Jul 17;26(20):20469-20474. Epub 2019 May 17.

Lanzhou City University, Lanzhou, 730070, China.

The expansion of poisonous plants can change vegetation community structures and affect grassland ecosystem service values. Stellera chamaejasme is one of the most important poisonous plants and has rapidly expanded in the arid areas of Northwest China in recent decades. The objective of this study was to elucidate the expansion process and model of an S. chamaejasme population. Therefore, we classified the S. chamaejasme population into five classes based on coverage: 31-40%, 41-50%, 51-60%, 61-70% and 71-80%. We investigated the spatial distribution patterns and the size compositions of S. chamaejasme under different coverages. The results show that the spatial distribution pattern of S. chamaejasme under low coverage (31-40%) at all study scales (0-100 cm) was random; the spatial distribution pattern translated to a clumped distribution from a random distribution at some scales, and the clumped distributions gradually became obvious, with coverage increasing from 41-50% to 61-70%; the spatial distribution tended to be random at all study scales when coverage was increased further (71-80%). However, the spatial distribution patterns were closely related to the size composition of the S. chamaejasme population. In particular, the quantity of older individuals had a significant impact on the variation of the spatial distribution patterns of S. chamaejasme. The spatial distribution pattern varied from a random distribution to a clumped distribution and then returned to a random distribution with increasing coverage (from 31-40% to 71-80%), and this may indicate that the S. chamaejasme patches experienced patch formation and extension and merged with each other.
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http://dx.doi.org/10.1007/s11356-019-05421-6DOI Listing
July 2019

Effect of simulated microgravity induced PI3K-nos2b signalling on zebrafish cardiovascular plexus network formation.

J Biomech 2019 04 28;87:83-92. Epub 2019 Feb 28.

Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China. Electronic address:

Local abnormal angiogenesis and cardiovascular system reorganization have been observed in embryos exposed to a simulated microgravity (SM) environment. In this study, changes in key molecular signals and pathways in cardiovascular development have been investigated under microgravity conditions. In particular, the caudal vein plexus (CVP) network, formed by sprouting angiogenesis has been chosen. Zebrafish embryos were exposed to SM using a ground-based microgravity bioreactor for 24 and 36 h. The SM was observed to have no effect on the zebrafish length, tail width and incubation time whereas it was observed to significantly reduce the heart rate frequency and to promote abnormal development of the CVP network in the embryos. Nitric oxide (NO) content demonstrated that the total proteins in zebrafish embryos were significantly higher in SM than in the control group grown under normal conditions. It was then preliminarily determined how NO signals were involved in SM regulated zebrafish CVP network formation. nos2b MO was injected and CVP network evolution was observed in 36 h post fertilization (hpf) under SM condition. The results showed that the CVP network formation was considerably decreased in the nos2b MO treated group. However, this inhibition of the CVP network development was not observed in control MO group, indicating that nos2b is involved in the SM-regulated vascular development process in zebrafish. Moreover, specific phosphoinositide 3-kinase (PI3K) inhibitors such as LY294002 were also tested on zebrafish embryos under SM condition. This treatment significantly inhibited the formation of zebrafish CVP network. Furthermore, overexpression of nos2b partly rescued the LY294002-caused CVP network failure. Therefore, it can be concluded that SM affects zebrafish CVP network remodeling by enhancing angiogenesis. Additionally, the PI3K-nos2b signaling pathway is involved in this process.
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http://dx.doi.org/10.1016/j.jbiomech.2019.02.019DOI Listing
April 2019

Inflammation is a key contributor to ovarian cancer cell seeding.

Sci Rep 2018 08 17;8(1):12394. Epub 2018 Aug 17.

Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

The incidence of ovarian cancer dramatically increases in early menopause but the factors contributing to cancer onset are unclear. Most ovarian cancers originate in the fallopian tube with subsequent implantation of malignant cells into the ovary. However, the events and conditions that lead to cancer cell implantation are unknown. To quantify which conditions are conducive to the seeding of cancer cells in an immunocompetent mouse model, we surgically implanted mouse ovarian cancer cells into the oviducts of syngeneic mice and simulated conditions associated with ovulatory wound repair, incessant ovulation, ovarian surface scarring, and aging. We found that the dominant site of cancer cell seeding was not the ovary but the nearby surgical wound site, which was associated with a strong and persistent inflammatory reaction. Conditions in the ovary associated with inflammation, such as acute ovulatory wound repair, active healing of the scarred ovarian surface, and mouse aging, contributed to increased seeding of the cancer cells to the surgical wound site and tissues surrounding the ovary. Changes in the ovary not accompanied by inflammation, such as completed ovulatory cycles and fully-healed scars on the ovarian surface, did not contribute to increased cancer cell seeding. We conclude that inflammation is the most likely mechanism by which ovulation and postmenopausal events contribute to the increased risk of ovarian cancer.
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http://dx.doi.org/10.1038/s41598-018-30261-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098104PMC
August 2018

Endovascular stent-induced alterations in host artery mechanical environments and their roles in stent restenosis and late thrombosis.

Regen Biomater 2018 Jun 2;5(3):177-187. Epub 2018 May 2.

Key Laboratory of Biorheological Science and Technology, Ministry of Education; State and Local Joint Engineering Laboratory for Vascular Implants; Bioengineering College of Chongqing University, Chongqing, China.

Cardiovascular stent restenosis remains a major challenge in interventional treatment of cardiovascular occlusive disease. Although the changes in arterial mechanical environment due to stent implantation are the main causes of the initiation of restenosis and thrombosis, the mechanisms that cause this initiation are still not fully understood. In this article, we reviewed the studies on the issue of stent-induced alterations in arterial mechanical environment and discussed their roles in stent restenosis and late thrombosis from three aspects: (i) the interaction of the stent with host blood vessel, involve the response of vascular wall, the mechanism of mechanical signal transmission, the process of re-endothelialization and late thrombosis; (ii) the changes of hemodynamics in the lumen of the vascular segment and (iii) the changes of mechanical microenvironment within the vascular segment wall due to stent implantation. This review has summarized and analyzed current work in order to better solve the two main problems after stent implantation, namely in stent restenosis and late thrombosis, meanwhile propose the deficiencies of current work for future reference.
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http://dx.doi.org/10.1093/rb/rby006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007795PMC
June 2018

Identification of seven polyamine oxidase genes in tomato (Solanum lycopersicum L.) and their expression profiles under physiological and various stress conditions.

J Plant Physiol 2018 Sep 15;228:1-11. Epub 2018 May 15.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Polyamines (PAs) are implicated in developmental processes and stress responses of plants. Polyamine oxidases (PAOs), flavin adenine dinucleotide-dependent enzymes that function in PA catabolism, play a critical role. Even though PAO gene families of Arabidopsis and rice have been intensely characterized and their expression in response to developmental and environmental changes has been investigated, little is known about PAOs in tomato (Solanum lycopersicum). We found seven PAO genes in S. lycopersicum and named them SlPAO1∼7. Plant PAOs form four clades in phylogenetic analysis, of which SlPAO1 belongs to clade-I, SlPAO6 and SlPAO7 to clade-III, and the residual four (SlPAO2∼5) to clade-IV, while none belongs to clade-II. All the clade-IV members in tomato also retain the putative peroxisomal-targeting signals in their carboxy termini, suggesting their peroxisome localization. SlPAO1 to SlPAO5 genes consist of 10 exons and 9 introns, while SlPAO6 and SlPAO7 are intronless genes. To address the individual roles of SlPAOs, we analyzed their expression in various tissues and during flowering and fruit development. The expression of SlPAO2∼4 was constitutively high, while that of the other SlPAO members was relatively lower. We further analyzed the expressional changes of SlPAOs upon abiotic stresses, oxidative stresses, phytohormone application, and PA application. Based on the data obtained, we discuss the distinctive roles of SlPAOs.
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http://dx.doi.org/10.1016/j.jplph.2018.05.004DOI Listing
September 2018

Germline silencing of UASt depends on the piRNA pathway.

J Genet Genomics 2018 05 9;45(5):273-276. Epub 2018 May 9.

Department of Biological Science, Florida State University, Tallahassee, FL 32306-4295, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jgg.2018.04.005DOI Listing
May 2018

Elevated serum level of pancreatic stone protein/regenerating protein (PSP/reg) is observed in diabetic kidney disease.

Oncotarget 2017 Jun;8(24):38145-38151

Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Dingjiaqiao, Nanjing, PR China.

Diabetic kidney disease (DKD) is a major complication of diabetes, and serves as an important cause of end-stage renal disease (ESRD). The role of chronic inflammation in DKD is becoming widely accepted. Pancreatic stone protein/regenerating protein (PSP/reg) is a secretory protein, which is elevated in blood during infected conditions and organ failure. The aim of this study was to investigate the relationship between serum PSP/reg and DKD in patients with type 2 diabetes (T2DM). A total of 120 subjects which includes newly diagnosed T2DM patients, diabetes patients without DKD, DKD patients, as well as healthy controls were enrolled in this study. Serum PSP/reg levels were significantly higher in DKD subjects compared with those of healthy controls (p < 0.001), newly diagnosed T2DM (p < 0.001) and diabetes patients without DKD (p < 0.001). PSP/reg levels correlated positively with glycated hemoglobin (HbA1c) (p < 0.001) and serum creatinine (p < 0.001). Meanwhile, serum PSP level was negatively correlated with estimated glomerular filtration rate (eGFR) (p < 0.001). The area under the curve (AUC) for presence of DKD was 0.854.

In Conclusion: PSP/reg levels are significantly up-regulated in DKD patients and might be related to renal injury. A follow-up study with a large cohort is needed.
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http://dx.doi.org/10.18632/oncotarget.16369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503521PMC
June 2017

Smart mechanosensing machineries enable migration of vascular smooth muscle cells in atherosclerosis-relevant 3D matrices.

Cell Biol Int 2017 Jun 11;41(6):586-598. Epub 2017 Apr 11.

Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), State and Local Joint Engineering Laboratory for Vascular Implants (Chongqing), Bioengineering College of Chongqing University, Chongqing, China.

At the early stage of atherosclerosis, neointima is formed due to the migration of vascular smooth muscle cells (VSMCs) from the media to the intima. VSMCs are surrounded by highly adhesive 3D matrices. They take specific strategies to cross various 3D matrices in the media, including heterogeneous collagen and mechanically strong basement membrane. Migration of VSMCs is potentially caused by biomechanical mechanism. Most in vitro studies focus on cell migration on 2D substrates in response to biochemical factors. How the cells move through 3D matrices under the action of mechanosensing machineries remains unexplored. In this review, we propose that several interesting tension-dependent machineries act as "tractor"-posterior myosin II accumulation, and "wrecker"-anterior podosome maintaining, to power VSMCs ahead. VSMCs embedded in 3D matrices may accumulate a minor myosin II isoform, myosin IIB, at the cell rear. Anisotropic myosin IIB distribution creates cell rear, polarizes cell body, pushes the nucleus and reshapes the cell body, and cooperates with a uniformly distributed myosin IIA to propel the cell forward. On the other hand, matrix digestion by podosome further promote the migration when the matrix becomes denser. Actomyosin tension activates Src to induce podosome in soft 3D matrices and retain the podosome integrity to steadily digest the matrix.
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http://dx.doi.org/10.1002/cbin.10764DOI Listing
June 2017

The SWI/SNF Complex Protein Snr1 Is a Tumor Suppressor in Imaginal Tissues.

Cancer Res 2017 02 6;77(4):862-873. Epub 2016 Dec 6.

Department of Biological Science, Florida State University, Tallahassee, Florida.

Components of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in various human cancers, yet only SMARCB1/hSNF5, a core member of the SWI/SNF complex, is mutated in malignant rhabdoid tumors (MRT). How SMARCB1/hSNF5 functions differently from other members of the SWI/SNF complex remains unclear. Here, we use imaginal epithelial tissues to demonstrate that Snr1, the conserved homolog of human SMARCB1/hSNF5, prevents tumorigenesis by maintaining normal endosomal trafficking-mediated signaling cascades. Removal of Snr1 resulted in neoplastic tumorigenic overgrowth in imaginal epithelial tissues, whereas depletion of any other members of the SWI/SNF complex did not induce similar phenotypes. Unlike other components of the SWI/SNF complex that were detected only in the nucleus, Snr1 was observed in both the nucleus and the cytoplasm. Aberrant regulation of multiple signaling pathways, including Notch, JNK, and JAK/STAT, was responsible for tumor progression upon -depletion. Our results suggest that the cytoplasmic Snr1 may play a tumor suppressive role in imaginal tissues, offering a foundation for understanding the pivotal role of SMARCB1/hSNF5 in suppressing MRT during early childhood. .
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http://dx.doi.org/10.1158/0008-5472.CAN-16-0963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885033PMC
February 2017

A COL11A1-correlated pan-cancer gene signature of activated fibroblasts for the prioritization of therapeutic targets.

Cancer Lett 2016 11 5;382(2):203-214. Epub 2016 Sep 5.

Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. Electronic address:

Although cancer-associated fibroblasts (CAFs) are viewed as a promising therapeutic target, the design of rational therapy has been hampered by two key obstacles. First, attempts to ablate CAFs have resulted in significant toxicity because currently used biomarkers cannot effectively distinguish activated CAFs from non-cancer associated fibroblasts and mesenchymal progenitor cells. Second, it is unclear whether CAFs in different organs have different molecular and functional properties that necessitate organ-specific therapeutic designs. Our analyses uncovered COL11A1 as a highly specific biomarker of activated CAFs. Using COL11A1 as a 'seed', we identified co-expressed genes in 13 types of primary carcinoma in The Cancer Genome Atlas. We demonstrated that a molecular signature of activated CAFs is conserved in epithelial cancers regardless of organ site and transforming events within cancer cells, suggesting that targeting fibroblast activation should be effective in multiple cancers. We prioritized several potential pan-cancer therapeutic targets that are likely to have high specificity for activated CAFs and minimal toxicity in normal tissues.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5077659PMC
http://dx.doi.org/10.1016/j.canlet.2016.09.001DOI Listing
November 2016

FOXC2 augments tumor propagation and metastasis in osteosarcoma.

Oncotarget 2016 Oct;7(42):68792-68802

Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Osteosarcoma is a highly malignant tumor that contains a small subpopulation of tumor-propagating cells (also known as tumor-initiating cells) characterized by drug resistance and high metastatic potential. The molecular mechanism by which tumor-propagating cells promote tumor growth is poorly understood. Here, we report that the transcription factor forkhead box C2 (FOXC2) is frequently expressed in human osteosarcomas and is important in maintaining osteosarcoma cells in a stem-like state. In osteosarcoma cell lines, we show that anoikis conditions stimulate FOXC2 expression. Downregulation of FOXC2 decreases anchorage-independent growth and invasion in vitro and lung metastasis in vivo, while overexpression of FOXC2 increases tumor propagation in vivo. In osteosarcoma cell lines, we demonstrate that high levels of FOXC2 are associated with and required for the expression of osteosarcoma tumor-propagating cell markers. In FOXC2 knockdown cell lines, we show that CXCR4, a downstream target of FOXC2, can restore osteosarcoma cell invasiveness and metastasis to the lung.
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http://dx.doi.org/10.18632/oncotarget.11990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356590PMC
October 2016

The Ecdysone and Notch Pathways Synergistically Regulate Cut at the Dorsal-Ventral Boundary in Drosophila Wing Discs.

J Genet Genomics 2016 04 17;43(4):179-86. Epub 2016 Mar 17.

Department of Biological Science, Florida State University, Tallahassee, FL 32306-4295, USA. Electronic address:

Metazoan development requires coordination of signaling pathways to regulate patterns of gene expression. In Drosophila, the wing imaginal disc provides an excellent model for the study of how signaling pathways interact to regulate pattern formation. The determination of the dorsal-ventral (DV) boundary of the wing disc depends on the Notch pathway, which is activated along the DV boundary and induces the expression of the homeobox transcription factor, Cut. Here, we show that Broad (Br), a zinc-finger transcription factor, is also involved in regulating Cut expression in the DV boundary region. However, Br expression is not regulated by Notch signaling in wing discs, while ecdysone signaling is the upstream signal that induces Br for Cut upregulation. Also, we find that the ecdysone-Br cascade upregulates cut-lacZ expression, a reporter containing a 2.7 kb cut enhancer region, implying that ecdysone signaling, similar to Notch, regulates cut at the transcriptional level. Collectively, our findings reveal that the Notch and ecdysone signaling pathways synergistically regulate Cut expression for proper DV boundary formation in the wing disc. Additionally, we show br promotes Delta, a Notch ligand, near the DV boundary to suppress aberrant high Notch activity, indicating further interaction between the two pathways for DV patterning of the wing disc.
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http://dx.doi.org/10.1016/j.jgg.2016.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391978PMC
April 2016

Automatic stage identification of Drosophila egg chamber based on DAPI images.

Sci Rep 2016 Jan 6;6:18850. Epub 2016 Jan 6.

Department of Biological Science, Florida State University, Tallahassee, FL 32306-4370, USA.

The Drosophila egg chamber, whose development is divided into 14 stages, is a well-established model for developmental biology. However, visual stage determination can be a tedious, subjective and time-consuming task prone to errors. Our study presents an objective, reliable and repeatable automated method for quantifying cell features and classifying egg chamber stages based on DAPI images. The proposed approach is composed of two steps: 1) a feature extraction step and 2) a statistical modeling step. The egg chamber features used are egg chamber size, oocyte size, egg chamber ratio and distribution of follicle cells. Methods for determining the on-site of the polytene stage and centripetal migration are also discussed. The statistical model uses linear and ordinal regression to explore the stage-feature relationships and classify egg chamber stages. Combined with machine learning, our method has great potential to enable discovery of hidden developmental mechanisms.
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http://dx.doi.org/10.1038/srep18850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702167PMC
January 2016

Suboptimal cytoreduction in ovarian carcinoma is associated with molecular pathways characteristic of increased stromal activation.

Gynecol Oncol 2015 Dec 6;139(3):394-400. Epub 2015 Sep 6.

Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. Electronic address:

Objective: Suboptimal cytoreductive surgery in advanced epithelial ovarian cancer (EOC) is associated with poor survival but it is unknown if poor outcome is due to the intrinsic biology of unresectable tumors or insufficient surgical effort resulting in residual tumor-sustaining clones. Our objective was to identify the potential molecular pathway(s) and cell type(s) that may be responsible for suboptimal surgical resection.

Methods: By comparing gene expression in optimally and suboptimally cytoreduced patients, we identified a gene network associated with suboptimal cytoreduction and explored the biological processes and cell types associated with this gene network.

Results: We show that primary tumors from suboptimally cytoreduced patients express molecular signatures that are typically present in a distinct molecular subtype of EOC characterized by increased stromal activation and lymphovascular invasion. Similar molecular pathways are present in EOC metastases, suggesting that primary tumors in suboptimally cytoreduced patients are biologically similar to metastatic tumors. We demonstrate that the suboptimal cytoreduction network genes are enriched in reactive tumor stroma cells rather than malignant tumor cells.

Conclusion: Our data suggest that the success of cytoreductive surgery is dictated by tumor biology, such as extensive stromal reaction and increased invasiveness, which may hinder surgical resection and ultimately lead to poor survival.
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http://dx.doi.org/10.1016/j.ygyno.2015.08.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4679504PMC
December 2015

Analysis of Cell Cycle Switches in Drosophila Oogenesis.

Methods Mol Biol 2015 ;1328:207-16

Department of Biological Science, Florida State University, Tallahassee, FL, USA.

The study of Drosophila oogenesis provides invaluable information about signaling pathway regulation and cell cycle programming. During Drosophila oogenesis, a string of egg chambers in each ovariole progressively develops toward maturity. Egg chamber development consists of 14 stages. From stage 1 to stage 6 (mitotic cycle), main-body follicle cells undergo mitotic divisions. From stage 7 to stage 10a (endocycle), follicle cells cease mitosis but continue three rounds of endoreduplication. From stage 10b to stage 13 (gene amplification), instead of whole genome duplication, follicle cells selectively amplify specific genomic regions, mostly for chorion production. So far, Drosophila oogenesis is one of the most well studied model systems used to understand cell cycle switches, which furthers our knowledge about cell cycle control machinery and sheds new light on potential cancer treatments. Here, we give a brief summary of cell cycle switches, the associated signaling pathways and factors, and the detailed experimental procedures used to study the cell cycle switches.
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http://dx.doi.org/10.1007/978-1-4939-2851-4_15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455776PMC
May 2016

A large-scale in vivo RNAi screen to identify genes involved in Notch-mediated follicle cell differentiation and cell cycle switches.

Sci Rep 2015 Jul 24;5:12328. Epub 2015 Jul 24.

Department of Biological Science, Florida State University, Tallahassee, FL 32306-4370, USA.

During Drosophila oogenesis, follicle cells sequentially undergo three distinct cell-cycle programs: the mitotic cycle, endocycle, and gene amplification. Notch signaling plays a central role in regulating follicle-cell differentiation and cell-cycle switches; its activation is essential for the mitotic cycle/endocycle (M/E) switch. Cut, a linker between Notch signaling and cell-cycle regulators, is specifically downregulated by Notch during the endocycle stage. To determine how signaling pathways coordinate during the M/E switch and to identify novel genes involved in follicle cell differentiation, we performed an in vivo RNAi screen through induced knockdown of gene expression and examination of Cut expression in follicle cells. We screened 2205 RNAi lines and found 33 genes regulating Cut expression during the M/E switch. These genes were confirmed with the staining of two other Notch signaling downstream factors, Hindsight and Broad, and validated with multiple independent RNAi lines. We applied gene ontology software to find enriched biological meaning and compared our results with other publications to find conserved genes across tissues. Specifically, we found earlier endocycle entry in anterior follicle cells than those in the posterior, identified that the insulin-PI3K pathway participates in the precise M/E switch, and suggested Nejire as a cofactor of Notch signaling during oogenesis.
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http://dx.doi.org/10.1038/srep12328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513280PMC
July 2015

Cis-interactions between Notch and its ligands block ligand-independent Notch activity.

Elife 2014 Dec 8;3. Epub 2014 Dec 8.

Department of Biological Science, Florida State University, Tallahassee, United States.

The Notch pathway is integrated into numerous developmental processes and therefore is fine-tuned on many levels, including receptor production, endocytosis, and degradation. Notch is further characterized by a twofold relationship with its Delta-Serrate (DSL) ligands, as ligands from opposing cells (trans-ligands) activate Notch, whereas ligands expressed in the same cell (cis-ligands) inhibit signaling. We show that cells without both cis- and trans-ligands can mediate Notch-dependent developmental events during Drosophila oogenesis, indicating ligand-independent Notch activity occurs when the receptor is free of cis- and trans-ligands. Furthermore, cis-ligands can reduce Notch activity in endogenous and genetically induced situations of elevated trans-ligand-independent Notch signaling. We conclude that cis-expressed ligands exert their repressive effect on Notch signaling in cases of trans-ligand-independent activation, and propose a new function of cis-inhibition which buffers cells against accidental Notch activity.
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http://dx.doi.org/10.7554/eLife.04415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286723PMC
December 2014

E(y)1/TAF9 mediates the transcriptional output of Notch signaling in Drosophila.

J Cell Sci 2014 Sep 11;127(Pt 17):3830-9. Epub 2014 Jul 11.

Department of Biological Science, Florida State University, Tallahassee, FL 32304-4295, USA

Transcriptional activation of Notch signaling targets requires the formation of a ternary complex that involves the intracellular domain of the Notch receptor (NICD), DNA-binding protein Suppressor of Hairless [Su(H), RPBJ in mammals] and coactivator Mastermind (Mam). Here, we report that E(y)1/TAF9, a component of the transcription factor TFIID complex, interacts specifically with the NICD-Su(H)-Mam complex to facilitate the transcriptional output of Notch signaling. We identified E(y)1/TAF9 in a large-scale in vivo RNA interference (RNAi) screen for genes that are involved in a Notch-dependent mitotic-to-endocycle transition in Drosophila follicle cells. Knockdown of e(y)1/TAF9 displayed Notch-mutant-like phenotypes and defects in target gene and activity reporter expression in both the follicle cells and wing imaginal discs. Epistatic analyses in these two tissues indicated that E(y)1/TAF9 functions downstream of Notch cleavage. Biochemical studies in S2 cells demonstrated that E(y)1/TAF9 physically interacts with the transcriptional effectors of Notch signaling Su(H) and NICD. Taken together, our data suggest that the association of the NICD-Su(H)-Mastermind complex with E(y)1/TAF9 in response to Notch activation recruits the transcription initiation complex to induce Notch target genes, coupling Notch signaling with the transcription machinery.
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http://dx.doi.org/10.1242/jcs.154583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150066PMC
September 2014

Regulation of broad by the Notch pathway affects timing of follicle cell development.

Dev Biol 2014 Aug 9;392(1):52-61. Epub 2014 May 9.

Department of Biological Science, Florida State University, Tallahassee, FL 32306-4370, USA. Electronic address:

During Drosophila oogenesis, activation of Notch signaling in the follicular epithelium (FE) around stage 6 of oogenesis is essential for entry into the endocycle and a series of other changes such as cell differentiation and migration of subsets of the follicle cells. Notch induces the expression of zinc finger protein Hindsight and suppresses homeodomain protein Cut to regulate the mitotic/endocycle (ME) switch. Here we report that broad (br), encoding a small group of zinc-finger transcription factors resulting from alternative splicing, is a transcriptional target of Notch nuclear effector Suppressor of Hairless (Su(H)). The early pattern of Br in the FE, uniformly expressed except in the polar cells, is established by Notch signaling around stage 6, through the binding of Su(H) to the br early enhancer (brE) region. Mutation of the Su(H) binding site leads to a significant reduction of brE reporter expression in follicle cells undergoing the endocycle. Chromatin immunoprecipitation results further confirm Su(H) binding to the br early enhancer. Consistent with its expression in follicle cells during midoogenesis, loss of br function results in a delayed entry into the endocycle. Our findings suggest an important role of br in the timing of follicle cell development, and its transcriptional regulation by the Notch pathway.
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http://dx.doi.org/10.1016/j.ydbio.2014.04.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296560PMC
August 2014
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