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2020

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Articles 271 - 300 of 457

Full-Text Articles in Cell and Developmental Biology

Pthr1/Sox9 And Idh1/Idh2 Relative Expression In Primary Chondrocyte And Chondrosarcoma Cells Under The Synergistic Influence Of Inducible Hypoxia And Extracellular Acidosis, Kostika Vangjeli Apr 2020

Pthr1/Sox9 And Idh1/Idh2 Relative Expression In Primary Chondrocyte And Chondrosarcoma Cells Under The Synergistic Influence Of Inducible Hypoxia And Extracellular Acidosis, Kostika Vangjeli

Biological Sciences Theses & Dissertations

Cartilage cells (Chondrocytes) grow in rather unique environmental conditions in the human body. Cartilage is avascular tissue and lacks innervation. Its main source of nutrients is derived from the synovial fluid and/or perichondrium. Consequently, these cells must survive and thrive under hypoxic and acidic stressors. Published data suggests that there are a multitude of genes affected from either one of these two stressors or both. However, these factors are frequently overlooked in cartilage research, and results are reported in either normoxia/pH=7.0 conditions, or they only account for one of the conditions. The scope of this study is to examine how …


A High Glucose Concentration Is Well Tolerated By Colorectal Adenocarcinoma And Melanoma Cells But Toxic To Normal Human Gingival Fibroblast: Results Of An In Vitro Investigation, Muhammad Alif Mazlan, Afzan Mat Yusof, Muhammad Lokman Md Isa Apr 2020

A High Glucose Concentration Is Well Tolerated By Colorectal Adenocarcinoma And Melanoma Cells But Toxic To Normal Human Gingival Fibroblast: Results Of An In Vitro Investigation, Muhammad Alif Mazlan, Afzan Mat Yusof, Muhammad Lokman Md Isa

Makara Journal of Health Research

Background: Glucose is associated with weight gain, which increases the risk of cancer. There is insufficient information on the effects of high glucose concentrations on cell lines. This study evaluated the viability patterns of human cancer and normal cell lines treated with glucose.

Methods: Human gingival fibroblast (hGF), colorectal adenocarcinoma (HT29), and skin malignant melanoma (A375) cell lines were cultured and treated with additional glucose in three respective concentrations: 1 mg/ml, 5 mg/ml, and 10 mg/ml. Then, cell viability was measured using an MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide)-assay. The data were analyzed using the Statistical Package for the Social Sciences …


Tip60 Regulation Of Δnp63Α Is Associated With Cisplatin Resistance, Akshay Hira, Andrew Stacy, Jin Zhang, Michael P. Craig, Madhavi Kadakia Apr 2020

Tip60 Regulation Of Δnp63Α Is Associated With Cisplatin Resistance, Akshay Hira, Andrew Stacy, Jin Zhang, Michael P. Craig, Madhavi Kadakia

Celebration of Undergraduate & Graduate Research, Scholarship, and Creative Activities Materials

About 5.4 million basal and squamous cell skin cancers are diagnosed every year in the US. ΔNp63a, a member of the p53 transcription factor family, is overexpressed in non-melanoma skin cancer and regulates cell survival, migration and invasion. TIP60 is histone acetyltransferase (HAT) which mediates cellular processes such as transcription and the DNA damage response (DDR). Previous studies in our lab have shown that overexpression of TIP60 induces ΔNp63a protein stabilization in a catalytic-dependent manner. Since ΔNp63a is known to transcriptionally regulate several DDR genes and promote cisplatin resistance, its stabilization by TIP60 may contribute to the failure of platinum-based …


Embryonic Development Of The Pharyngeal Arch Arteries In Mammals, Megan E. Zierold Apr 2020

Embryonic Development Of The Pharyngeal Arch Arteries In Mammals, Megan E. Zierold

Student Publications

The pharyngeal arch arteries (PAAs) in mammals undergo asymmetric remodeling to give rise to the major blood vessels. The first and second PAAs form rudimentarily in mammalian embryos and eventually regress as the third, fourth, and sixth PAAs predominate. Cell migration, proliferation, and apoptosis drive the remodeling process, stimulated by a number of underlying molecular mechanisms. Sonic hedgehog, Hox genes, Tgfβ2, Tbx1, and a number of transcription regulators all influence PAA morphogenesis. Tbx1, which is found in the deleted region of Chromosome 22 in DiGeorge Syndrome patients, forms anterior-to-posterior and medial-tolateral gradients in the developing PAA system to promote remodeling. …


Assessing Seed Handling Processes To Facilitate A Community-Engaged Approach To Regional Forest Restoration, Meredith Cobb, Michaela J. Woods, Ryan Mcewan Apr 2020

Assessing Seed Handling Processes To Facilitate A Community-Engaged Approach To Regional Forest Restoration, Meredith Cobb, Michaela J. Woods, Ryan Mcewan

Biology Faculty Publications

In the Midwestern United States, there is a strong management impetus toward reforestation to replace trees lost to due to tree mortality and to establish forests on previously cleared properties. Here, we describe a public outreach and volunteer effort that aimed to generate positive, community-engaged restoration outcomes and report on a practical experiment involving seed handling. We obtained tree seeds that were donated by members of the community to local land managers. We evaluated the size of the seeds collected and tested the influence of common stratification media (none, sand and vermiculite) and seed size on germination success of three …


Elucidating The Regulon Of A Fur-Like Protein In Mycobacterium Avium Subsp. Paratuberculosis (Map), Fernanda Miyagaki Shoyama, Taveesak Janetanakit, John P. Bannantine, Raul G. Barletta, Srinand Sreevatsan Apr 2020

Elucidating The Regulon Of A Fur-Like Protein In Mycobacterium Avium Subsp. Paratuberculosis (Map), Fernanda Miyagaki Shoyama, Taveesak Janetanakit, John P. Bannantine, Raul G. Barletta, Srinand Sreevatsan

Nebraska Center for Virology: Faculty Publications

Intracellular iron concentration is tightly regulated to maintain cell viability. Iron plays important roles in electron transport, nucleic acid synthesis, and oxidative stress. A Mycobacterium avium subsp. paratuberculosis (MAP)-specific genomic island carries a putative metal transport operon that includes MAP3773c, which encodes a Fur-like protein. Although well characterized as a global regulator of iron homeostasis in multiple bacteria, the function of Fur (ferric uptake regulator) in MAP is unknown as this organism also carries IdeR (iron dependent regulator), a native iron regulatory protein specific to mycobacteria. Computational analysis using PRODORIC identified 23 different pathways involved in respiration, metabolism, and virulence …


Evaluation Of Autoreactivity In Vh4-34-Containing Antibodies From Human B-1 Vs B-2 Cells, Michelle E. Ray Apr 2020

Evaluation Of Autoreactivity In Vh4-34-Containing Antibodies From Human B-1 Vs B-2 Cells, Michelle E. Ray

Masters Theses

B-1 cells are a unique population of lymphocytes, with distinct phenotypic and functional characteristics in comparison to conventional B-2 cells. B-1 cells are thought to be more closely related to the innate immune system than the adaptive, and B-1 cells constitutively secrete antibody that is recognized as broadly reactive with low levels of autoreactivity. The antibody heavy chain segment, VH4-34, is overutilized by the human B-1 cell population. VH4-34 antibodies are associated with autoreactivity, although not all VH4-34 antibodies are autoreactive. The primary objective of this study was to determine whether autoreactive forms of VH4-34 antibodies are localized only to …


Dgts Production As A Phosphate Starvation Response In The Human Fungal Pathogen Candida Albicans, Caleb J. Wehling Apr 2020

Dgts Production As A Phosphate Starvation Response In The Human Fungal Pathogen Candida Albicans, Caleb J. Wehling

School of Biological Sciences: Dissertations, Theses, and Student Research

Betaine lipids are a class of membrane lipids with betaine head groups. Three betaine lipids are known: diacylglyceryltrimethylhomoserine (DGTS), diacylglycerylhydroxymethylalanine (DGTA), and diacylglycerylcarboxymethylcholine (DGCC). Betaine lipids are most common in algae, although DGTS, the most common betaine lipid, is also found in many bacteria and fungi. Organisms which produce betaine lipids (especially DGTS) often don’t produce phosphatidylcholine (PtdCho), and DGTS structure resembles PtdCho structure without any phosphorous, leading to the hypothesis that betaine lipids may substitute for phospholipids in some organisms. This has been confirmed by discoveries that some organisms are capable of switching their membrane composition from PtdCho to …


A Micro-Optic Stalk (Muos) System To Model The Collective Migration Of Retinal Neuroblasts, Stephanie Zhang, Miles Markey, Caroline D. Pena, Tadmiri Venkatesh, Maribel Vasquez Mar 2020

A Micro-Optic Stalk (Muos) System To Model The Collective Migration Of Retinal Neuroblasts, Stephanie Zhang, Miles Markey, Caroline D. Pena, Tadmiri Venkatesh, Maribel Vasquez

Publications and Research

Contemporary regenerative therapies have introduced stem-like cells to replace damaged neurons in the visual system by recapitulating critical processes of eye development. The collective migration of neural stem cells is fundamental to retinogenesis and has been exceptionally well-studied using the fruit fly model of Drosophila Melanogaster. However, the migratory behavior of its retinal neuroblasts (RNBs) has been surprisingly understudied, despite being critical to retinal development in this invertebrate model. The current project developed a new microfluidic system to examine the collective migration of RNBs extracted from the developing visual system of Drosophila as a model for the collective motile processes …


Inferring Tunicate Relationships And The Evolution Of The Tunicate Hox Cluster With The Genome Of Corella Inflata, M. B. Debiasse, William N. Colgan , '19, Lincoln J. Harris , '17, Bradley Justin Davidson , '91, J. F. Ryan Mar 2020

Inferring Tunicate Relationships And The Evolution Of The Tunicate Hox Cluster With The Genome Of Corella Inflata, M. B. Debiasse, William N. Colgan , '19, Lincoln J. Harris , '17, Bradley Justin Davidson , '91, J. F. Ryan

Biology Faculty Works

Tunicates, the closest living relatives of vertebrates, have served as a foundational model of early embryonic development for decades. Comparative studies of tunicate phylogeny and genome evolution provide a critical framework for analyzing chordate diversification and the emergence of vertebrates. Towards this goal, we sequenced the genome of Corella inflata (Ascidiacea, Phlebobranchia), so named for the capacity to brood self-fertilized embryos in a modified, “inflated” atrial chamber. Combining the new genome sequence for Co. inflata with publicly available tunicate data, we estimated a tunicate species phylogeny, reconstructed the ancestral Hox gene cluster at important nodes in the tunicate tree, and …


Role Of Bet Inhibitors In Triple Negative Breast Cancers, Durga Khandekar, Venkataswarup Tiriveedhi Mar 2020

Role Of Bet Inhibitors In Triple Negative Breast Cancers, Durga Khandekar, Venkataswarup Tiriveedhi

Biology Faculty Research

Bromodomain and extraterminal domain (BET) proteins have evolved as key multifunctional super-regulators that control gene expression. These proteins have been shown to upregulate transcriptional machinery leading to over expression of genes involved in cell proliferation and carcinogenesis. Based on favorable preclinical evidence of BET inhibitors in various cancer models; currently, 26 clinical trials are underway in various stages of study on various hematological and solid organ cancers. Unfortunately, preliminary evidence for these clinical studies does not support the application of BET inhibitors as monotherapy in cancer treatment. Furthermore, the combinatorial efficiency of BET inhibitors with other chemo-and immunotherapeutic agents remain …


To Mid-Cell And Beyond: Characterizing The Roles Of Gpsb And Ypsa In Cell Division Regulation In Gram-Positive Bacteria, Robert S. Brzozowski Mar 2020

To Mid-Cell And Beyond: Characterizing The Roles Of Gpsb And Ypsa In Cell Division Regulation In Gram-Positive Bacteria, Robert S. Brzozowski

USF Tampa Graduate Theses and Dissertations

The bacterial cell division protein FtsZ is a tubulin homolog that forms a ring-like structure at the site of cell division in most bacterial species. There it acts as a scaffold, aiding in the recruitment of other divisome proteins to the site of cell division. Furthermore, studies focusing on the role of FtsZ treadmilling and septal peptidoglycan synthesis implicates that FtsZ plays a direct role in the ultimate closure of the division septum. Thus, many studies in the field of bacterial cell division have focused on FtsZ in terms of its spatial and temporal regulation as well as its ability …


Metabolic Reprogramming By C-Met Inhibition As A Targetable Vulnerability In Glioblastoma, Trang Thi Thu Nguyen, Enyuan Shang, Georg Karpel-Massler, Markus D. Siegelin Mar 2020

Metabolic Reprogramming By C-Met Inhibition As A Targetable Vulnerability In Glioblastoma, Trang Thi Thu Nguyen, Enyuan Shang, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

The elucidation of better treatments for solid tumors and especially malignant glial tumors is a priority. Better understanding of the molecular underpinnings of treatment response and resistance are critical determinants in the success for this endeavor. Recently, a battery of novel tools have surfaced that allow to interrogate tumor cell metabolism to more precise extent than this was possible in the earlier days. At the forefront of these developments are the extracellular flux and carbon tracing analyses. Through utilization of these techniques our group made the recent observation that acute and chronic c-MET inhibition drives fatty acid oxidation that in …


Functional Blockade Of E-Selectin In Tumor-Associated Vessels Enhances Anti-Tumor Effect Of Doxorubicin In Breast Cancer, Yoshihiro Morita, Macall Leslie, Hiroyasu Kameyama, Ganesh L R Lokesh, Norihisa Ichimura, Rachel Davis, Natalie Hills, Nafis Hasan, Roy Zhang, Yuji Kondo, David G Gorenstein, David E Volk, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka Mar 2020

Functional Blockade Of E-Selectin In Tumor-Associated Vessels Enhances Anti-Tumor Effect Of Doxorubicin In Breast Cancer, Yoshihiro Morita, Macall Leslie, Hiroyasu Kameyama, Ganesh L R Lokesh, Norihisa Ichimura, Rachel Davis, Natalie Hills, Nafis Hasan, Roy Zhang, Yuji Kondo, David G Gorenstein, David E Volk, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Chemotherapy is a mainstay of treatment for solid tumors. However, little is known about how therapy-induced immune cell infiltration may affect therapy response. We found substantial CD45+ immune cell density adjacent to E-selectin expressing inflamed vessels in doxorubicin (DOX)-treated residual human breast tumors. While CD45 level was significantly elevated in DOX-treated wildtype mice, it remained unchanged in DOX-treated tumors from E-selectin null mice. Similarly, intravenous administration of anti-E-selectin aptamer (ESTA) resulted in a significant reduction in CD45+ immune cell density in DOX-treated residual tumors, which coincided with a delay in tumor growth and lung metastasis in MMTV-pyMT mice. Additionally, both …


Mob Family Proteins: Regulatory Partners In Hippo And Hippo-Like Intracellular Signaling Pathways, Juan Carlos Duhart, Laurel A. Raftery Mar 2020

Mob Family Proteins: Regulatory Partners In Hippo And Hippo-Like Intracellular Signaling Pathways, Juan Carlos Duhart, Laurel A. Raftery

Life Sciences Faculty Research

Studies in yeast first delineated the function of Mob proteins in kinase pathways that regulate cell division and shape; in multicellular eukaryotes Mobs regulate tissue growth and morphogenesis. In animals, Mobs are adaptors in Hippo signaling, an intracellular signal-transduction pathway that restricts growth, impacting the development and homeostasis of animal organs. Central to Hippo signaling are the Nuclear Dbf2-Related (NDR) kinases, Warts and LATS1 and LATS2, in flies and mammals, respectively. A second Hippo-like signaling pathway has been uncovered in animals, which regulates cell and tissue morphogenesis. Central to this emergent pathway are the NDR kinases, Tricornered, STK38, and STK38L. …


Investigating The Role Of Torc1 And The Transcription Factor Sfp1p In The Regulation Of Hmo1 Gene In Saccharomyces Cerevisiae, Mathew Damien Smith Mar 2020

Investigating The Role Of Torc1 And The Transcription Factor Sfp1p In The Regulation Of Hmo1 Gene In Saccharomyces Cerevisiae, Mathew Damien Smith

LSU Master's Theses

HMGB proteins are eukaryotic, chromatin-associated proteins that play roles in both DNA dynamics and transcription regulation. Hmo1p is an HMGB protein in Saccharomyces cerevisiae that behaves somewhat like a hybrid between mammalian HMGB proteins and the metazoan linker histone H1. mTORC1, a protein complex containing the Tor1p kinase and a major regulator of cellular growth, is inhibited by both rapamycin and stress. It has also been shown to not only associate with Hmo1p at various gene promoters, but also regulate the HMO1 gene itself through direct binding. In this study, the Hmo1p-mTORC1 relationship was further investigated through two questions: 1) …


Characterization Of Extracellular Vesicles Isolated From Human Milk Using A Precipitation-Based Method, Diana C. Bickmore, John Miklavcic Mar 2020

Characterization Of Extracellular Vesicles Isolated From Human Milk Using A Precipitation-Based Method, Diana C. Bickmore, John Miklavcic

Food Science Faculty Articles and Research

Extracellular vesicles (EV) function in intercellular communication, and those in human milk may confer immunologic benefits to infants. Methods of EV isolation such as ultracentrifugation (UC) may not be feasible for the study of EVs in human milk due to the need for large sample volume. A technique to isolate EVs from a small volume of human milk using a precipitation reagent is described herein. Electron microscopy, nanoparticle tracking analysis, and semi-quantitative antibody array were conducted to confirm isolation of human milk EVs. Count, size, protein content, and fatty acid quantification of EVs were determined. This isolation technique yielded 8.9 …


The Role Of Apkcs And Apkc Inhibitors In Cell Proliferation And Invasion In Breast And Ovarian Cancer, Tracess B. Smalley Mar 2020

The Role Of Apkcs And Apkc Inhibitors In Cell Proliferation And Invasion In Breast And Ovarian Cancer, Tracess B. Smalley

USF Tampa Graduate Theses and Dissertations

Research has demonstrated that the atypical protein kinase C-zeta (PKC-ζ) is a component of many dysregulated pathways in breast and ovarian cancer, including cellular proliferation, survival, and cell cycle upregulation. Breast and ovarian cancers affect women every day and are second and fifth leading cause of cancer death. Women who seek treatments are commonly met with invasive surgeries or chemotherapy. Protein kinase C (PKC) is a family of serine and threonine phosphorylating kinases that have been shown to modulate and transduce signaling cascades that play roles in the development and survival of cancers. Atypical PKC (aPKC), have been heavily suggested …


Functions Of Cdk/Cyclin Complexes In Endoreplication Regulation By The Cdk Inhibitor Siamese, Kai Wang Mar 2020

Functions Of Cdk/Cyclin Complexes In Endoreplication Regulation By The Cdk Inhibitor Siamese, Kai Wang

LSU Doctoral Dissertations

Arabidopsis trichome (leaf hair) is a specialized single cell extended from epidermal cell on the leaves, which is a typical endoreplication and is also known as endoreduplication. Several D-type cyclins were tested to check the cell division in trichome, and the trichome expressing either CYCB1;2 or CDKB2;2 cannot trigger cell division, even if simultaneous expression of CYCB1;2 and CDKB2;2 failed to produce mitosis in trichome. Only CYCD3;1 specifically promotes multicellular trichome. cdkb1;1cdbk1;2 double mutants and sim cdkb1;1cdkb1;2 triple mutants exhibit the phenotype similar to the wild type and very limited cell division respectively. Overexpression of a CDKB1;1 dominant-negative construct that …


Editorial: The Role Of Breast Cancer Stem Cells In Clinical Outcomes, Dayanidhi Raman, Amit K. Tiwari, Venkataswarup Tiriveedhi, Julie A. Rhoades Mar 2020

Editorial: The Role Of Breast Cancer Stem Cells In Clinical Outcomes, Dayanidhi Raman, Amit K. Tiwari, Venkataswarup Tiriveedhi, Julie A. Rhoades

Biology Faculty Research

No abstract provided.


Variation In Brown Rat Cranial Shape Shows Directional Selection Over 120 Years In New York City, Emily E. Puckett, Emma Sherratt, Matthew Combs, Elizabeth J. Carlen, William Harcourt-Smith, Jason Munshi-South Mar 2020

Variation In Brown Rat Cranial Shape Shows Directional Selection Over 120 Years In New York City, Emily E. Puckett, Emma Sherratt, Matthew Combs, Elizabeth J. Carlen, William Harcourt-Smith, Jason Munshi-South

Publications and Research

Urbanization exposes species to novel environments and selection pressures that may change morphological traits within a population. We investigated how the shape and size of crania and mandibles changed over time within a population of brown rats (Rattus norvegicus) living in Manhattan, New York, USA, a highly urbanized environment. We measured 3D landmarks on the cranium and mandible of 62 adult individuals sampled in the 1890s and 2010s. Static allometry explained approximately 22% of shape variation in crania and mandible datasets, while time accounted for approximately 14% of variation. We did not observe significant changes in skull size through time …


Dibutyltin Alters Immune Cell Production Of The Pro-Inflammatory Cytokines Interleukin (Il) 1Β And Il-6: Role Of Mitogen-Activated Protein Kinases And Changes In Mrna, Linda B Sushak, Sahra Gabure, Jaquel Maise, Jessica Arnett, Margaret Whalen Mar 2020

Dibutyltin Alters Immune Cell Production Of The Pro-Inflammatory Cytokines Interleukin (Il) 1Β And Il-6: Role Of Mitogen-Activated Protein Kinases And Changes In Mrna, Linda B Sushak, Sahra Gabure, Jaquel Maise, Jessica Arnett, Margaret Whalen

Chemistry Faculty Research

Dibutyltin (DBT) is used to stabilize plastics and as a deworming agent in some poultry. It is found in human blood (levels as high as 0.3 μM). Interleukin (IL) 1β (IL-1β) and IL-6 are pro-inflammatory cytokines produced by lymphocytes, monocytes, and other cells. Elevated levels of IL-1β and IL-6 have been associated with pathologies including rheumatoid arthritis and cancers. DBT was shown to decrease IL-1β and IL-6 secretion from immune cells at higher concentrations while causing increases at lower concentrations. However, it was not clear if these changes were due to DBT's alteration of the secretory process or due its …


Perplexing Role Of P-Glycoprotein In Tumor Microenvironment, Kianna Robinson, Venkataswarup Tiriveedhi Mar 2020

Perplexing Role Of P-Glycoprotein In Tumor Microenvironment, Kianna Robinson, Venkataswarup Tiriveedhi

Biology Faculty Research

Development of multidrug resistance (MDR) still remains a major obstacle to the long-term success of cancer therapy. P-glycoprotein (P-gp) is a well-identified membrane transporter with capability to efflux drug molecules out of the cancer cell leading to reduced efficiency of chemotherapy. Cancer cells upregulate P-gp expression as an adaptive response to evade chemotherapy mediated cell death. While several P-gp inhibitors have been discovered by in silico and pre-clinical studies, very few have successfully passed all phases of the clinical trials. Studies show that application of P-gp inhibitors in cancer therapy regimen following development of MDR achieved limited beneficial outcomes. While, …


Modulation Of The Pol Ii Ctd Phosphorylation Code By Rac1 And Cdc42 Small Gtpases In Cultured Human Cancer Cells And Its Implication For Developing A Synthetic-Lethal Cancer Therapy, Bo Zhang, Xuelin Zhong, Moira Sauane, Yihong Zhao, Zhi-Liang Zheng Mar 2020

Modulation Of The Pol Ii Ctd Phosphorylation Code By Rac1 And Cdc42 Small Gtpases In Cultured Human Cancer Cells And Its Implication For Developing A Synthetic-Lethal Cancer Therapy, Bo Zhang, Xuelin Zhong, Moira Sauane, Yihong Zhao, Zhi-Liang Zheng

Publications and Research

Rho GTPases, including Rho, Cdc42, Rac and ROP subfamilies, are key signaling molecules in RNA polymerase II (Pol II) transcriptional control. Our prior work has shown that plant ROP and yeast Cdc42 GTPases similarly modulate Ser2 and Ser5 phosphorylation status of the C-terminal domain (CTD) of the Pol II largest subunit by regulating CTD phosphatase degradation. Here, we present genetic and pharmacological evidence showing that Cdc42 and Rac1 GTPase signaling modulates a similar CTD Ser2 and Ser5 phosphorylation code in cultured human cancer cells. While siRNA knockdown of Cdc42 and Rac1, respectively, in HeLa cells increased the level of CTD …


A Positive Feedback Loop Of Hippo- And C-Jun-Amino-Terminal Kinase Signaling Pathways Regulates Amyloid-Beta-Mediated Neurodegeneration, Madison Irwin, Meghana Tare, Aditi Singh, Oorvashi Roy Puli, Neha Gogia, Matthew Riccetti, Prajakta Deshpande, Madhuri Kango-Singh, Amit Singh Mar 2020

A Positive Feedback Loop Of Hippo- And C-Jun-Amino-Terminal Kinase Signaling Pathways Regulates Amyloid-Beta-Mediated Neurodegeneration, Madison Irwin, Meghana Tare, Aditi Singh, Oorvashi Roy Puli, Neha Gogia, Matthew Riccetti, Prajakta Deshpande, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

Alzheimer's disease (AD, OMIM: 104300) is an age-related disorder that affects millions of people. One of the underlying causes of AD is generation of hydrophobic amyloid-beta 42 (Aβ42) peptides that accumulate to form amyloid plaques. These plaques induce oxidative stress and aberrant signaling, which result in the death of neurons and other pathologies linked to neurodegeneration. We have developed a Drosophila eye model of AD by targeted misexpression of human Aβ42 in the differentiating retinal neurons, where an accumulation of Aβ42 triggers a characteristic neurodegenerative phenotype. In a forward deficiency screen to look for genetic modifiers, we identified a molecularly …


Pan-Cancer Analysis Reveals Cooperativity Of Both Strands Of Microrna That Regulate Tumorigenesis And Patient Survival, Ramkrishna Mitra, Clare M. Adams, Wei Jiang, Evan J. Greenawalt, Christine M. Eischen Feb 2020

Pan-Cancer Analysis Reveals Cooperativity Of Both Strands Of Microrna That Regulate Tumorigenesis And Patient Survival, Ramkrishna Mitra, Clare M. Adams, Wei Jiang, Evan J. Greenawalt, Christine M. Eischen

Department of Cancer Biology Faculty Papers

Recently, both 5p and 3p miRNA strands are being recognized as functional instead of only one, leaving many miRNA strands uninvestigated. To determine whether both miRNA strands, which have different mRNA-targeting sequences, cooperate to regulate pathways/functions across cancer types, we evaluate genomic, epigenetic, and molecular profiles of >5200 patient samples from 14 different cancers, and RNA interference and CRISPR screens in 290 cancer cell lines. We identify concordantly dysregulated miRNA 5p/3p pairs that coordinately modulate oncogenic pathways and/or cell survival/growth across cancers. Down-regulation of both strands of miR-30a and miR-145 recurrently increased cell cycle pathway genes and significantly reduced patient …


Comparative Proteomics Of Root Apex And Root Elongation Zones Provides Insights Into Molecular Mechanisms For Drought Stress And Recovery Adjustment In Switchgrass, Zhujia Ye, Sasikiran Reddy Sangireddy, Chih-Li Yu, Dafeng Hui, Kevin Howe, Tara Fish, Theodore W. Thannhauser, Suping Zhou Feb 2020

Comparative Proteomics Of Root Apex And Root Elongation Zones Provides Insights Into Molecular Mechanisms For Drought Stress And Recovery Adjustment In Switchgrass, Zhujia Ye, Sasikiran Reddy Sangireddy, Chih-Li Yu, Dafeng Hui, Kevin Howe, Tara Fish, Theodore W. Thannhauser, Suping Zhou

Agricultural and Environmental Sciences Faculty Research

Switchgrass plants were grown in a Sandwich tube system to induce gradual drought stress by withholding watering. After 29 days, the leaf photosynthetic rate decreased significantly, compared to the control plants which were watered regularly. The drought-treated plants recovered to the same leaf water content after three days of re-watering. The root tip (1cm basal fragment, designated as RT1 hereafter) and the elongation/maturation zone (the next upper 1 cm tissue, designated as RT2 hereafter) tissues were collected at the 29th day of drought stress treatment, (named SDT for severe drought treated), after one (D1W) and three days (D3W) of re-watering. …


A Native Function For Ran Translation And Cgg Repeats In Regulating Fragile X Protein Synthesis, Caitlin M. Rodriguez, Shannon E. Wright, Michael G. Kearse, Jill M. Haenfler, Brittany N. Flores, Yu Liu, Marius F. Ifrim, M. Rebecca Glineburg, Amy Krans, Paymaan Jafar-Nejad, Michael A. Sutton, Gary J. Bassell, Jack M. Parent, Frank Rigo, Sami J. Barmada, Peter K. Todd Feb 2020

A Native Function For Ran Translation And Cgg Repeats In Regulating Fragile X Protein Synthesis, Caitlin M. Rodriguez, Shannon E. Wright, Michael G. Kearse, Jill M. Haenfler, Brittany N. Flores, Yu Liu, Marius F. Ifrim, M. Rebecca Glineburg, Amy Krans, Paymaan Jafar-Nejad, Michael A. Sutton, Gary J. Bassell, Jack M. Parent, Frank Rigo, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Repeat-associated non-AUG-initiated translation of expanded CGG repeats (CGG RAN) from the FMR1 5′-leader produces toxic proteins that contribute to neurodegeneration in fragile X-associated tremor/ataxia syndrome. Here we describe how unexpanded CGG repeats and their translation play conserved roles in regulating fragile X protein (FMRP) synthesis. In neurons, CGG RAN acts as an inhibitory upstream open reading frame to suppress basal FMRP production. Activation of mGluR5 receptors enhances FMRP synthesis. This enhancement requires both the CGG repeat and CGG RAN initiation sites. Using non-cleaving antisense oligonucleotides (ASOs), we selectively blocked CGG RAN. This ASO blockade enhanced endogenous FMRP expression in human …


Cysteine Dioxygenase Enzyme Activity And Gene Expression In The Dimorphic Pathogenic Fungus Histoplasma Capsulatum Is In Both The Mold And Yeast Morphotypes And Exhibits Substantial Strain Variation, Melissa Adams, Glen Shearer Feb 2020

Cysteine Dioxygenase Enzyme Activity And Gene Expression In The Dimorphic Pathogenic Fungus Histoplasma Capsulatum Is In Both The Mold And Yeast Morphotypes And Exhibits Substantial Strain Variation, Melissa Adams, Glen Shearer

Faculty Publications

In the dimorphism (mold/yeast) Histoplasma capsulatum (Hc) literature are reports that yeast (the so-called pathogenic form) uniquely expresses a cysteine dioxygenase (CDO, approx. 10,500 dal) activity which the mold morphotype (the so-called saprophytic soil form) does not express (C.F., Kumar et al., Biochem 22, 762, 1983). This yeast-specific CDO activity is postulated to play a critical role in the mold-to-yeast shift. A number of years ago, our lab isolated the gene encoding the Hc cysteine dioxygenase (CDO1, Genbank accession AY804144) and noted significant expression in the mold morphotype of several Histoplasma strains and also determined that the predicted protein would …


Prostate Field Cancerization And Exosomes: Association Between Cd9, Early Growth Response 1 And Fatty Acid Synthase, Farideh Amirrad, Philip A. Pytak, Neda Sadeghiani-Pelar, Julie P. T. Nguyen, Emily L. Cauble, Anna C. Jones Feb 2020

Prostate Field Cancerization And Exosomes: Association Between Cd9, Early Growth Response 1 And Fatty Acid Synthase, Farideh Amirrad, Philip A. Pytak, Neda Sadeghiani-Pelar, Julie P. T. Nguyen, Emily L. Cauble, Anna C. Jones

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Intracapsular and well‑defined adenocarcinomas of the prostate are often surrounded by tissue areas that harbor molecular aberrations, including those of genetic, epigenetic and biochemical nature. This is known as field cancerization, or a field effect and denotes a state of pre‑malignancy. Such alterations in histologically normal tumor‑adjacent prostatic tissues have been recognized as clinically important and are potentially exploitable as biomarkers of disease and/or targets for preventative/therapeutic intervention. The authors have previously identified and validated two protein markers of field cancerization: The expressional upregulation of the transcription factor early growth response 1 (EGR‑1) and the lipogenic enzyme fatty acid synthase …