Cell and Developmental Biology Commons^™

Yeast Help Identify Cytopathic Factors Of Zika Virus, Michael I. Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Accumulating evidence implicates Zika virus (ZIKV) in pathogenesis of microcephaly in newborns and Guillain-Barré syndrome in adults. However, it remains unclear which viral proteins are responsible for these effects and what are the underlying mechanisms of their pathogenic activity. A recent paper by Drs. Zhao and Gallo, and their colleagues at University of Maryland in Baltimore used fission yeast for genome-wide analysis of ZIKV proteins. They demonstrated cytopathogenic activity for seven ZIKV proteins, anaC, C, prM, M, E, NS2B and NS4A. This activity was shown to be dependent on oxidative stress, and for NS4A they demonstrated involvement of the TOR …

Biophysical Tools To Study Cellular Mechanotransduction, Ismeel Muhamed, Farhan Chowdhury, Venkat Maruthamuthu

Mechanical & Aerospace Engineering Faculty Publications

The cell membrane is the interface that volumetrically isolates cellular components from the cell's environment. Proteins embedded within and on the membrane have varied biological functions: reception of external biochemical signals, as membrane channels, amplification and regulation of chemical signals through secondary messenger molecules, controlled exocytosis, endocytosis, phagocytosis, organized recruitment and sequestration of cytosolic complex proteins, cell division processes, organization of the cytoskeleton and more. The membrane's bioelectrical role is enabled by the physiologically controlled release and accumulation of electrochemical potential modulating molecules across the membrane through specialized ion channels (e.g., Na^⁺, Ca²⁺, K^⁺ channels). …

Lipid Sensing By Mammalian Target Of Rapamycin, Deepak Menon

Dissertations, Theses, and Capstone Projects

Mammalian target of Rapamycin (mTOR) is a protein kinase that integrates nutrient and growth factor signals to promote cellular growth and proliferation. mTOR exists in two complexes - mTORC1 and mTORC2 that are distinguished by their binding partners and signaling inputs. mTORC1 is responsive to growth factors, amino acids and glucose and is associated with Raptor; whereas, mTORC2 is responsive primarily to growth factors and is associated with Rictor. Raptor and Rictor confer substrate specificity to mTORC1 and mTORC2 respectively. Phosphatidic acid (PA), a lipid second messenger and a central metabolite for membrane phospholipid biosynthesis, is required for the stability …

Inducible Nitric Oxide Synthase (Inos) Is A Novel Negative Regulator Of Hematopoietic Stem/Progenitor Cell Trafficking, Mateusz Adamiak, Ahmed Abdelbaset-Ismail, Joseph B. Moore Iv, J. Zhao, Ahmed Abdel-Latif, Marcin Wysoczynski, Mariusz Z. Ratajczak

Internal Medicine Faculty Publications

Nitric oxide (NO) is a gaseous free radical molecule involved in several biological processes related to inflammation, tissue damage, and infections. Based on reports that NO inhibits migration of granulocytes and monocytes, we became interested in the role of inducible NO synthetase (iNOS) in pharmacological mobilization of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM) into peripheral blood (PB). To address the role of NO in HSPC trafficking, we upregulated or downregulated iNOS expression in hematopoietic cell lines. Next, we performed mobilization studies in iNOS^−/− mice and evaluated engraftment of iNOS^−/− HSPCs in wild type (control) animals. Our …

Post-Transcriptional Regulation Of The Drosophila Anterior Determinant, Bicoid, John Mclaughlin

Dissertations, Theses, and Capstone Projects

In a wide variety of biological contexts, messenger RNA (mRNA) is known to have a complex and dynamic life cycle. In particular, the localization and translational control of mRNA are essential for proper development in eukaryotes. The fly Drosophila melanogaster is an excellent model for studying these processes. During D. melanogaster oogenesis, several mRNAs are trafficked and localized within the developing egg chamber, and regulated at the translational level to enable embryo patterning. One such mRNA, bicoid, is localized at the anterior of the oocyte and translated in the early embryo, where its encoded protein directs formation of the fly's …

Environmental Changes Turn On The Sinorhizobium Melitloti Exor-Exos/Chvi (Rsi) Host Invasion Switch, Shari N. Walcott

Dissertations, Theses, and Capstone Projects

The free-living Gram-negative soil bacterium, Sinorhizobium meliloti, must switch into its host-invading form in order to infect the root hairs of the host plant, alfalfa (Medicago sativa), and establish a nitrogen-fixing symbiosis. The activation of the switch is believed to occur inside the infection chamber that is formed by curling of the root hairs. It is not fully understood what signals in the environment of the root hairs trigger and infection chamber S. meliloti to switch into a host-invading form since these signals were not extensively examined until now. This switch can be observed directly, due to …

Transcriptional And Post-Transcriptional Regulation Of Histone Variant H2a.Z During Sea Urchin Development, Mihai Hajdu

Dissertations, Theses, and Capstone Projects

Histone variant H2A.Z promotes chromatin accessibility at transcriptional regulatory elements and is developmentally regulated in metazoans. We characterize the transcriptional and post-transcriptional regulation of H2A.Z in the purple sea urchin Strongylocentrotus purpuratus. H2A.Z depletion by antisense translation-blocking morpholino oligonucleotides during early development causes developmental collapse, in agreement with its previously demonstrated general role in transcriptional multipotency. During H2A.Z peak expression in 24-h embryos, endogenous H2A.Z 3’ UTR sequences stabilize GFP mRNAs relative to those with SV40 3’ UTR sequences, although the 3’UTR of H2A.Z does not determine the spatial distribution of H2A.Z transcripts during embryonic and postembryonic development. We …

Adaptor Protein 2 (Ap-2) Complex Is Essential For Functional Axogenesis In Hippocampal Neurons, Jae Won Kyung, In Ha Cho, Sukmook Lee, Woo Keun Song, Timothy A. Ryan, Michael B. Hoppa, Sung Hyun Kim

Dartmouth Scholarship

The complexity and diversity of a neural network requires regulated elongation and branching of axons, as well as the formation of synapses between neurons. In the present study we explore the role of AP-2, a key endocytic adaptor protein complex, in the development of rat hippocampal neurons. We found that the loss of AP-2 during the early stage of development resulted in impaired axon extension and failed maturation of the axon initial segment (AIS). Normally the AIS performs two tasks in

concert, stabilizing neural polarity and generating action potentials. In AP-2 silenced axons polarity is established, however there is a …

Analysis For Science Librarians Of The 2016 Nobel Prize In Physiology Or Medicine: The Life And Work Of Yoshinori Ohsumi, Neyda Gilman

Library Scholarship

Autophagy is a cellular process of destruction and recycling. Cellular materials are broken down and recycled as needed, providing the body a way to remove unwanted material while also providing the means to create new needed items. The importance of this process and its possible role in numerous diseases is why Yoshinori Ohsumi has been awarded a 2016 Noble Prize. Ohsumi has been awarded the 2016 Nobel in Physiology or Medicine for his “discoveries of mechanisms for autophagy and thus paving the way for the exciting field of autophagy research” (Nobelprize.org “Press release: The 2016 Nobel Prize in Physiology or …

Evolution Of Complex Target Selex To Identify Aptamers Against Mammalian Cell-Surface Antigens, Prabodhika R. Mallikaratchy

Publications and Research

The demand has increased for sophisticated molecular tools with improved detection limits. Such molecules should be simple in structure, yet stable enough for clinical applications. Nucleic acid aptamers (NAAs) represent a class of molecules able to meet this demand. In particular, aptamers, a class of small nucleic acid ligands that are composed of single-stranded modified/unmodified RNA/DNA molecules, can be evolved from a complex library using Systematic Evolution of Ligands by EXponential enrichment (SELEX) against almost any molecule. Since its introduction in 1990, in stages, SELEX technology has itself undergone several modifications, improving selection and broadening the repertoire of targets. This …

Sleep Spindles And Intellectual Ability: Epiphenomenon Or Directly Related?, Zhuo Fang, Valya Sergeeva, Laura B. Ray, Adrian M. Owen, Stuart M. Fogel

Anatomy and Cell Biology Publications

Sleep spindlesshort, phasic, oscillatory bursts of activity that characterize non-rapid eye movement sleepare one of the only electrophysiological oscillations identified as a biological marker of human intelligence (e.g., cognitive abilities commonly assessed using intelligence quotient tests). However, spindles are also important for sleep maintenance and are modulated by circadian factors. Thus, the possibility remains that the relationship between spindles and intelligence quotient may be an epiphenomenon of a putative relationship between good quality sleep and cognitive ability or perhaps modulated by circadian factors such as morningness-eveningness tendencies. We sought to ascertain whether spindles are directly or indirectly related to cognitive …

Mechanisms Of Ikbke Activation In Cancer, Sridevi Challa

USF Tampa Graduate Theses and Dissertations

Cancer is the second leading cause of death in the USA and it is expected to surpass heart diseases making it important to understand the underlying mechanisms of cancer. The efforts to target single signaling molecule showed little success in increasing the patient survival and it can be due to increased compensation for cell survival by alternative pathway activations. Hence comprehensive understanding of the alternative signaling pathways may help us treat cancer better. Chronic inflammation is attributed to increased risk of cancer and emerging studies show the growing importance of both canonical and non-canonical IκB kinases such as IKKα, IKKβ, …

Bioethics In The Work Of Ernest Everett Just: + Missing - Some 400 Pages, Theodore Walker

Perkins Faculty Research and Special Events

Biology + ethics = bioethics. Here we see that Howard University biologist Ernest Everett Just (born 1883, died 1941) connected biology to ethics.

According to Just, various forms of specific biology (including especially cell biology) plus “general biology” are necessary for explaining adequately the origin of ethical behaviors. Social ethical behaviors, especially mutual aid and cooperative interactions with others and the environment, are essential to evolutionary advances among living creatures, ranging from humans to cells. Accordingly, theory of ethics (moral theory) should have roots in biology.

Also, Just wrote an unpublished book-length manuscript—“some 400 typed pages” (Just 1940)—on seeking the …

The Subject Librarian Newsletter, Biology, Spring 2017, Sandy Avila

Libraries' Newsletters

No abstract provided.

Evolutionary Adaptations Of Biofilms Infecting Cystic Fibrosis Lungs Promote Mechanical Toughness By Adjusting Polysaccharide Production, Kristin Kovach, Megan Davis-Fields, Yasuhiko Irie, Kanishk Jain, Shashvat Doorwar, Katherine Vuong, Numa Dhamani, Kishore Mohanty, Ahmed Touhami, Vernita D. Gordon

Biology Faculty Publications

Biofilms are communities of microbes embedded in a matrix of extracellular polymeric substances, largely polysaccharides. Multiple types of extracellular polymeric substances can be produced by a single bacterial strain. The distinct polymer components of biofilms are known to provide chemical protection, but little is known about how distinct extracellular polysaccharides may also protect biofilms against mechanical stresses such as shear or phagocytic engulfment. Decades-long infections of Pseudomonas. aeruginosa biofilms in the lungs of cystic fibrosis patients are natural models for studies of biofilm fitness under pressure from antibiotics and the immune system. In cystic fibrosis infections, production of the extracellular …

Phlpp Regulates Hexokinase 2-Dependent Glucose Metabolism In Colon Cancer Cells, Xiaopeng Xiong, Yang-An Wen, Mihail I. Mitov, Mary C. Oaks, Shigeki Miyamoto, Tianyan Gao

Markey Cancer Center Faculty Publications

Increased glucose metabolism is considered as one of the most important metabolic alterations adapted by cancer cells in order to generate energy as well as high levels of glycolytic intermediates to support rapid proliferation. PH domain leucine-rich repeat protein phosphatase (PHLPP) belongs to a novel family of Ser/Thr protein phosphatases that function as tumor suppressors in various types of human cancer. Here we determined the role of PHLPP in regulating glucose metabolism in colon cancer cells. Knockdown of PHLPP increased the rate of glucose consumption and lactate production, whereas overexpression of PHLPP had the opposite effect. Bioenergetic analysis using Seahorse …

Identification, Validation, And Targeting Of The Mutant P53- Parp-Mcm Chromatin Axis In Triple Negative Breast Cancer, Wei-Gang Qiu, Alla Polotskaia, Gu Xiao, Lia Di, Yuhan Zhao, Wenwei Hu, John Philip, Ronald C. Hendrickson, Jill Bargonetti

Publications and Research

Over 80% of triple negative breast cancers express mutant p53. Mutant p53 often gains oncogenic function suggesting that triple negative breast cancers may be driven by p53 protein type. To determine the chromatin targets of this gain-of-function mutant p53 we used inducible knockdown of endogenous gain-of-function mtp53 in MDA-MB-468 cells in conjunction with stable isotope labeling with amino acids in cell culture and subcellular fractionation. We sequenced over 70,000 total peptides for each corresponding reciprocal data set and were able to identify 3010 unique cytoplasmic fraction proteins and 3403 unique chromatin fraction proteins. The present proteomics experiment corroborated our previous …

Crispr-Cas9 Mediated Nox4 Knockout Inhibits Cell Proliferation And Invasion In Hela Cells, Naser Jafari, Hyunju Kim, Rackhyun Park, Liqing Li, Minsu Jang, Andrew J. Morris, Junsoo Park, Cai Huang

Markey Cancer Center Faculty Publications

Increased expression of NOX4 protein is associated with cancer progression and metastasis but the role of NOX4 in cell proliferation and invasion is not fully understood. We generated NOX4 knockout HeLa cell lines using the CRISPR-Cas9 gene editing system to explore the cellular functions of NOX4. After transfection of CRISPR-Cas9 construct, we performed T7 endonuclease 1 assays and DNA sequencing to generate and identify insertion and deletion of the NOX4 locus. We confirmed the knockout of NOX4 by Western blotting. NOX4 knockout cell lines showed reduced cell proliferation with an increase of sub-G1 cell population and the decrease of S/G2/M …

Effects Of Pentachlorophenol And Dichlorodiphenyltrichloroethane On Secretion Of Interferon Gamma (Ifnγ) And Tumor Necrosis Factor Alpha (Tnfα) From Human Immune Cells, Reda Massawe, Leon Drabo, Margaret Whalen

Chemistry Faculty Research

Pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) are pesticides that have been widely used and significantly contaminate the environment. Both are found in human blood and have been shown to alter the lytic and binding function of human natural killer (NK) cells. Interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) are pro-inflammatory cytokines, which regulate immune responsiveness to pathogens and tumors. Their levels require very tight control to prevent loss of immune competence or excessive inflammation. Here, we examined the capacity of PCP and DDT to alter the secretion of these critical pro-inflammatory cytokines from increasingly reconstituted (more complex) preparations of …

A Cascade Of Multiple Proteins And Lipids Catalyzes Membrane Fusion, William Wickner, Josep Rizo

Dartmouth Scholarship

Recent studies suggest revisions to the SNARE paradigm of membrane fusion. Membrane tethers and/or SNAREs recruit proteins of the Sec 1/Munc18 family to catalyze SNARE assembly into trans-complexes. SNARE-domain zippering draws the bilayers into immediate apposition and provides a platform to position fusion triggers such as Sec 17/α-SNAP and/or synaptotagmin, which insert their apolar "wedge" domains into the bilayers, initiating the lipid rearrangements of fusion.