Medical Cell Biology Commons^™

Electronic Nose Based On Independent Component Analysis Combined With Partial Least Squares And Artificial Neural Networks For Wine Prediction, Teodoro Aguilera, Jesús Lozano, José A. Paredes, Francisco J. Alvarez, José I. Suárez

Neuroscience, Cell Biology & Physiology Faculty Publications

The aim of this work is to propose an alternative way for wine classification and prediction based on an electronic nose (e-nose) combined with Independent Component Analysis (ICA) as a dimensionality reduction technique, Partial Least Squares (PLS) to predict sensorial descriptors and Artificial Neural Networks (ANNs) for classification purpose. A total of 26 wines from different regions, varieties and elaboration processes have been analyzed with an e-nose and tasted by a sensory panel. Successful results have been obtained in most cases for prediction and classification.

Electrophysiological Abnormalities In Sod1 Transgenic Models In Amyotrophic Lateral Sclerosis: The Commonalities And Differences, Sherif M. Elbasiouny, Katharina Quinlan, Tahra L. Eissa, Charles J. Heckman

Neuroscience, Cell Biology & Physiology Faculty Publications

Since its first description in 1874 by Charcot, the hallmark feature of ALS is the progressive degeneration of upper and lower motoneurons (Charcot, 1874). In the spinal cord, motoneuron degeneration starts long before symptom onset and advances in a size-related fashion, in which large-size alpha-motoneurons degenerate first followed by small-size alpha-motoneurons (Pun et al., 2006; Hegedus et al., 2007; Hegedus et al., 2008). There are conflicting reports regarding the survival of the smallest-sized spinal motoneurons, the gamma-motoneurons (Swash and Fox, 1974; Sobue et al., 1981). Despite its original description, the neuronal degeneration in ALS is not limited to motoneurons. Recent …

One-Pot Regioselective Synthesis Of Tetrahydroindazolones And Evaluation Of Their Anti-Proliferative And Src Kinase Inhibitory Activities, V. Kameshwara Rao, Bhupender S. Chhikara, Rakesh Tiwari, Amir Nasrolahi Shirazi, Keykavous Parang, Anil Kumar

Pharmacy Faculty Articles and Research

A number of 2-substituted tetrahydroindazolones were synthesized by three-component condensation reaction of 1,3- diketones, substituted hydrazines, benzaldehydes, and Yb(OTf)3 as a catalyst in [bmim][BF4] ionic liquid using a simple, efficient, and economical one-pot method. The synthesized tetrahydroindazolones were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. 3,4-Dichlorophenyl tetrahydroindazolone derivative (15) inhibited the cell proliferation of HT-29 and SK-OV-3 cells by 62% and 58%, respectively. 2,3-Diphenylsubstituted tetrahydroindazolone derivatives, 19, 25, and 33, inhibited the cell proliferation of HT-29 cells by 6572% at a concentration of 50 μM. In general, the …

Thomas Jefferson University, Department Of Pathology, Anatomy And Cell Biology, Oral Administration Of Apigenin Inhibits Metastasis Through Akt/P70s6k1/Mmp-9 Pathway In Orthotopic Ovarian Tumor Model., Jun He, Qing Xu, Min Wang, Chongyong Li, Xu Qian, Zhumei Shi, Ling-Zhi Liu, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Apigenin, a flavonoid commonly present in the daily diet, is known for its potential anti-tumor properties. However, the effect of apigenin via oral administration on tumor growth and metastasis remains unknown. In this study we developed an orthotopic ovarian tumor model in nude mice to test the effect of apigenin oral administration, and showed that apigenin inhibited the micrometastasis of cancer cells in the animal tumor model. To understand the mechanism of apigenin in inhibiting metastasis, we found that apigenin greatly inhibited MMP-9 expression and p-AKT and p-p70S6K1 levels in the tumor tissues compared to the control group. We further …

Treatment Choices Based On Oncotypedx In The Breast Oncology Care Setting, Teri L. Malo, Isaac Lipkus, Tobi Wilson, Hyo S. Han, Geza Acs, Susan T. Vadaparampil

Pathology and Cell Biology Faculty Publications

Introduction. This study aimed to evaluate whether OncotypeDx test results predict receipt of adjuvant chemotherapy in breast cancer patients who received an OncotypeDx recurrence score (RS). Materials and Methods. Pathology records were used to identify breast cancer patients who had OncotypeDx testing between December 2004 and January 2009 (𝑛 = 1 1 8). Patient sociodemographic information, tumor characteristics, RS, and treatment-specific data were collected via chart review. RS was classified as follows: low (R S ≤ 1 7), intermediate (RS = 18–30), or high (R S ≥ 3 1). Bivariate analyses were …

Seg1 Controls Eisosome Assembly And Shape, Karen E. Moreira, Sebastian Schuck, Bianca Schrul, Florian Fröhlich, James B. Moseley

Dartmouth Scholarship

Eisosomes are stable domains at the plasma membrane of the budding yeast Saccharomyces cerevisiae and have been proposed to function in endocytosis. Eisosomes are composed of two main cytoplasmic proteins, Pil1 and Lsp1, that form a scaffold around furrow-like plasma membrane invaginations. We show here that the poorly characterized eisosome protein Seg1/Ymr086w is important for eisosome biogenesis and architecture. Seg1 was required for efficient incorporation of Pil1 into eisosomes and the generation of normal plasma membrane furrows. Seg1 preceded Pil1 during eisosome formation and established a platform for the assembly of other eisosome components. This platform was further shaped and …

Role Of The Immune System And Bioactive Lipids In Trafficking Bone Marrow-Derived Stem Cells In Patients With Ischemic Heart Disease, Ahmed Abdel-Latif

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Acute myocardial infarction (AMI) triggers the mobilization of stem/progenitor cells from bone marrow (BMSPCs) into peripheral blood (PB). The underlying mechanisms orchestrating this mobilization and subsequent homing of BMSPCs to the myocardium are poorly understood. While the role of traditional chemokines in the mobilization and homing of hematopoietic stem cell (HSCs) to BM niches is undisputed, their role in directing BMSPCs to the highly proteolytic environment of the ischemic myocardium is debatable and other redundant mechanism may exist. Based on our observation that bioactive lipids, such as sphingosine-1 phosphate (S1P) and ceramide-1 phosphate (C1P), play an important role in regulating …

C-Abl And Arg Drive Cancer Chemoresistance Via Activation Of Multiple Signaling Pathways, Jonathan Thomas Sims

Theses and Dissertations--Pharmacology and Nutritional Sciences

Despite 35 years of clinical trials, there has been little improvement in one-year survival rates with any chemotherapeutic regimen for the treatment of metastatic melanoma due to resistance to all known agents. Regardless of advances in detection and prevention, diagnosis of metastatic disease remains a death sentence. Resistance mechanisms, including aberrant kinase signaling and drug transport pumps, indicate a need for identification of other therapeutic targets that impinge upon multiple signaling pathways. The Abl family of non-receptor tyrosine kinases (c-Abl, Arg) has been indicted as a causative force in leukemia for more than three decades; however, their role in solid …

Orphan Nuclear Receptor Nur77 Regulates Androgen Receptor Gene Expression In Mouse Ovary., Anyi Dai, Guijun Yan, Qinyuan He, Yue Jiang, Qun Zhang, Ting Fang, Lijun Ding, Jianxin Sun, Haixiang Sun, Yali Hu

Center for Translational Medicine Faculty Papers

The androgen receptor (AR) is a nuclear receptor that is expressed in growing follicles and involved in folliculogenesis and follicle growth. The orphan nuclear receptor, Nur77, also has an important role in steroid signaling and follicle maturation. We hypothesized that AR levels and androgen signaling through AR are regulated by Nur77 in the ovary. In the ovaries of Nur77 knockout mice (n = 5), real-time PCR results showed that the mRNA levels of AR and an androgen signaling target gene, Kitl, were decreased by 35% and 24%, respectively, relative to wild-type mice (n = 5), which suggested transcriptional regulation of …

Blood-Brain Barrier Abnormalities Caused By Hiv-1 Gp120: Mechanistic And Therapeutic Implications., Jean-Pierre Louboutin, David S Strayer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The blood-brain barrier (BBB) is compromised in many systemic and CNS diseases, including HIV-1 infection of the brain. We studied BBB disruption caused by HIV-1 envelope glycoprotein 120 (gp120) as a model. Exposure to gp120, whether acute [by direct intra-caudate-putamen (CP) injection] or chronic [using SV(gp120), an experimental model of ongoing production of gp120] disrupted the BBB, and led to leakage of vascular contents. Gp120 was directly toxic to brain endothelial cells. Abnormalities of the BBB reflect the activity of matrix metalloproteinases (MMPs). These target laminin and attack the tight junctions between endothelial cells and BBB basal laminae. MMP-2 and …

Graft Versus Host Disease Of The Brain Following Allogeneic Stem Cell Transplant For Myelodysplastic Syndrome, Janet Yoo, Lindsay Simon, Zi-Xuan Wang, Phd, Lawrence C. Kenyon

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Graft-versus-host disease (GVHD) is a frequent cause of morbidity and mortality following bone marrow transplantation (BMT). GVHD occurs when immune cells transplanted from a non-identical donor (the graft) recognize the transplant recipient (the host) as foreign, thereby initiating an immune reaction that causes disease in the transplant recipient. GVHD, which can present either acutely or chronically, typically involves the skin, gastrointestinal tract, and liver. In contrast, GVHD involving other organs such as the heart and kidney is highly uncommon and involvement of the central nervous system has only very rarely been described in the literature. We report an unusual case …

Integrative Gene Regulatory Network Analysis Reveals Light-Induced Regional Gene Expression Phase Shift Programs In The Mouse Suprachiasmatic Nucleus., Haisun Zhu, Rajanikanth Vadigepalli, Rachel Rafferty, Gregory E Gonye, David R Weaver, James S Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

We use the multigenic pattern of gene expression across suprachiasmatic nuclei (SCN) regions and time to understand the dynamics within the SCN in response to a circadian phase-resetting light pulse. Global gene expression studies of the SCN indicate that circadian functions like phase resetting are complex multigenic processes. While the molecular dynamics of phase resetting are not well understood, it is clear they involve a "functional gene expression program", e.g., the coordinated behavior of functionally related genes in space and time. In the present study we selected a set of 89 of these functionally related genes in order to further …

Lung Carcinoma In The Era Of Personalized Medicine: The Role Of Cytology., Maureen F Zakowski, Marluce Bibbo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In 2004, three groups working independently [1–3] , almost simultaneously, reported remarkable findings: that activating mutations in the epidermal growth factor receptor (EGFR) were common in certain lung carcinomas and that these mutations correlated with the response of those lung tumors to therapy with gefitinib and erlotinib, both EGFR tyrosine kinase inhibitors (TKIs). This was the first time driver mutations in lung cancer that responded to targeted therapy had been identified, marking the beginning of a new era of personalized medicine in lung cancer. Prior to the discovery of these mutations, patients had been treated with EGFR TKIs but predicting …

Knockdown Of Ki-67 By Dicer-Substrate Small Interfering Rna Sensitizes Bladder Cancer Cells To Curcumin-Induced Tumor Inhibition., Sivakamasundari Pichu, Swapna Krishnamoorthy, Andrei Shishkov, Bi Zhang, Peter Mccue, Biddanda C Ponnappa

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Transitional cell carcinoma (TCC) of the urinary bladder is the most common cancer of the urinary tract. Most of the TCC cases are of the superficial type and are treated with transurethral resection (TUR). However, the recurrence rate is high and the current treatments have the drawback of inducing strong systemic toxicity or cause painful cystitis. Therefore, it would be of therapeutic value to develop novel concepts and identify novel drugs for the treatment of bladder cancer. Ki-67 is a large nucleolar phosphoprotein whose expression is tightly linked to cell proliferation, and curcumin, a phytochemical derived from the rhizome Curcuma …

Decorin Protein Core Affects The Global Gene Expression Profile Of The Tumor Microenvironment In A Triple-Negative Orthotopic Breast Carcinoma Xenograft Model., Simone Buraschi, Thomas Neill, Rick T Owens, Leonardo A Iniguez, George Purkins, Rajanikanth Vadigepalli, Barry Evans, Liliana Schaefer, Stephen C Peiper, Zi-Xuan Wang, Renato V Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin, a member of the small leucine-rich proteoglycan gene family, exists and functions wholly within the tumor microenvironment to suppress tumorigenesis by directly targeting and antagonizing multiple receptor tyrosine kinases, such as the EGFR and Met. This leads to potent and sustained signal attenuation, growth arrest, and angiostasis. We thus sought to evaluate the tumoricidal benefits of systemic decorin on a triple-negative orthotopic breast carcinoma xenograft model. To this end, we employed a novel high-density mixed expression array capable of differentiating and simultaneously measuring gene signatures of both Mus musculus (stromal) and Homo sapiens (epithelial) tissue origins. We found that …

Kaempferol Nanoparticles Achieve Strong And Selective Inhibition Of Ovarian Cancer Cell Viability., Haitao Luo, Bingbing Jiang, Bingyun Li, Zhaoliang Li, Bing-Hua Jiang, Yi Charlie Chen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Ovarian cancer is one of the leading causes of cancer death for women throughout the Western world. Kaempferol, a natural flavonoid, has shown promise in the chemoprevention of ovarian cancer. A common concern about using dietary supplements for chemoprevention is their bioavailability. Nanoparticles have shown promise in increasing the bioavailability of some chemicals. Here we developed five different types of nanoparticles incorporating kaempferol and tested their efficacy in the inhibition of viability of cancerous and normal ovarian cells. We found that positively charged nanoparticle formulations did not lead to a significant reduction in cancer cell viability, whereas nonionic polymeric nanoparticles …

Temporal Changes In Innate Immune Signals In A Rat Model Of Alcohol Withdrawal In Emotional And Cardiorespiratory Homeostatic Nuclei., Kate Freeman, Anthony Brureau, Rajanikanth Vadigepalli, Mary M Staehle, Melanie M Brureau, Gregory E Gonye, Jan B Hoek, D Craig Hooper, James S Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Chronic alcohol use changes the brain's inflammatory state. However, there is little work examining the progression of the cytokine response during alcohol withdrawal, a period of profound autonomic and emotional upset. This study examines the inflammatory response in the central nucleus of the amygdala (CeA) and dorsal vagal complex (DVC), brain regions neuroanatomically associated with affective and cardiorespiratory regulation in an in vivo rat model of withdrawal following a single chronic exposure.

METHODS: For qRT-PCR studies, we measured the expression of TNF-α, NOS-2, Ccl2 (MCP-1), MHC II invariant chain CD74, and the TNF receptor Tnfrsf1a in CeA and DVC …

Emergence Of Bimodal Cell Population Responses From The Interplay Between Analog Single-Cell Signaling And Protein Expression Noise., Marc R Birtwistle, Jens Rauch, Anatoly Kiyatkin, Edita Aksamitiene, Maciej Dobrzyński, Jan B. Hoek, Walter Kolch, Babatunde A Ogunnaike, Boris N Kholodenko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Cell-to-cell variability in protein expression can be large, and its propagation through signaling networks affects biological outcomes. Here, we apply deterministic and probabilistic models and biochemical measurements to study how network topologies and cell-to-cell protein abundance variations interact to shape signaling responses.

RESULTS: We observe bimodal distributions of extracellular signal-regulated kinase (ERK) responses to epidermal growth factor (EGF) stimulation, which are generally thought to indicate bistable or ultrasensitive signaling behavior in single cells. Surprisingly, we find that a simple MAPK/ERK-cascade model with negative feedback that displays graded, analog ERK responses at a single cell level can explain the experimentally …

Mir-145 Directly Targets P70s6k1 In Cancer Cells To Inhibit Tumor Growth And Angiogenesis., Qing Xu, Ling-Zhi Liu, Xu Qian, Qi Chen, Yue Jiang, Dan Li, Lihui Lai, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

MiR-145 can regulate cell apoptosis, proliferation, neural development and stem cell differentiation. Previous studies indicate that miR-145 is downregulated in human colon cancer cells. However, the molecular mechanisms of miR-145 used to regulate colon carcinogenesis and angiogenesis remain to be clarified. Here, we show that the expression of miR-145 is downregulated in colon and ovarian cancer tissues and cell lines. MiR-145 inhibits p70S6K1 post-transcriptional expression by binding to its 3'-UTR. The angiogenic factors hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF), which are downstream molecules of p70S6K1, are decreased by miR-145 overexpression. P70S6K1 rescues miR-145-suppressed HIF-1 and VEGF …

Limitations Of The Rhesus Macaque Draft Genome Assembly And Annotation, Xiongfei Zhang, Joel Goodsell, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

Finished genome sequences and assemblies are available for only a few vertebrates. Thus, investigators studying many species must rely on draft genomes. Using the rhesus macaque as an example, we document the effects of sequencing errors, gaps in sequence and misassemblies on one automated gene model pipeline, Gnomon. The combination of draft genome with automated gene finding software can result in spurious sequences. We estimate that approximately 50% of the rhesus gene models are missing, incomplete or incorrect. The problems identified in this work likely apply to all draft vertebrate genomes annotated with any automated gene model pipeline and thus …