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"Análise do conhecimento de conteúdos fundamentais de Genética e Biologia Celular apresentado por graduandos em Ciências Biológicas".; Analysis of the knowledge o fundamental contents of Genetics and Cellular Biology presented by graduating students in Biological Sciences.

Primon, Catia Sueli Fernandes
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 19/12/2005 PT
Relevância na Pesquisa
459.15043%
A Biologia hoje é a mais comentada ciência e a que ocupa maior espaço na mídia. No entanto, isso não significa que os conceitos biológicos sejam de conhecimento público, nem tampouco dos estudantes de Biologia. Para analisar o conhecimento de conceitos fundamentais de Genética, Biologia Molecular e Biologia celular apresentado por graduandos do último ano de Cursos Superiores de Ciências Biológicas é que realizamos esse trabalho de pesquisa. Iniciamos o trabalho com a seleção das questões do Exame Nacional de Cursos de Biologia (Provão) do ano de 2002 que abordavam conceitos de Genética e disciplinas correlatas, analisamos o relatório do ENC-BIO/2002 expedido pelo MEC, aplicamos questionários com as questões analisadas do ENC-BIO/2002 em 72 estudantes do último ano dos cursos de Ciências Biológicas, realizamos 33 entrevistas semi-estruturadas com estudantes do último ano dos cursos de Ciências Biológicas e, por fim, analisamos os resultados apresentados pelo relatório do MEC e das entrevistas realizadas. Concluímos que os estudantes não chegam a alcançar os objetivos que a ele são atribuídos pelo MEC, no que diz respeito à Genética e disciplinas correlatas e a maioria apresenta aprendizagem mecânica.; Biology today is the most talked about science and also the one which gets the largest media coverage. However...

Review of "System Modeling in Cellular Biology: From Concepts to Nuts and Bolts" by Szallasi, Stelling and Periwal

McSharry, Patrick E
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 30/01/2007 EN
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"System Modeling in Cellular Biology: From Concepts to Nuts and Bolts" by Szallasi, Stelling and Periwal introduces the relevant concepts, terminology, and techniques of this field of science. It emphasises the modelling and computational challenges of taking a multidisciplinary approach to biology. This book provides a comprehensive introduction to systems biology and will form a valuable resource for students, teachers and researchers from both experimental and theoretical disciplines.

Myosin II Tailpiece Determines Its Paracrystal Structure, Filament Assembly Properties, and Cellular Localization

Ronen, Daniel; Ravid, Shoshana
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
EN
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458.9503%
Non muscle myosin II (NMII) is a major motor protein present in all cell types. The three known vertebrate NMII isoforms share high sequence homology but play different cellular roles. The main difference in sequence resides in the C-terminal non-helical tailpiece (tailpiece). In this study we demonstrate that the tailpiece is crucial for proper filament size, overcoming the intrinsic properties of the coiled-coil rod. Furthermore, we show that the tailpiece by itself determines the NMII filament structure in an isoform-specific manner, thus providing a possible mechanism by which each NMII isoform carries out its unique cellular functions. We further show that the tailpiece determines the cellular localization of NMII-A and NMII-B and is important for NMII-C role in focal adhesion complexes. We mapped NMII-C sites phosphorylated by protein kinase C and casein kinase II and showed that these phosphorylations affect its solubility properties and cellular localization. Thus phosphorylation fine-tunes the tailpiece effects on the coiled-coil rod, enabling dynamic regulation of NMII-C assembly. We thus show that the small tailpiece of NMII is a distinct domain playing a role in isoform-specific filament assembly and cellular functions.

The Cellular Biology of Flexor Tendon Adhesion Formation : An Old Problem in a New Paradigm

Wong, Jason K.F.; Lui, Yin H.; Kapacee, Zoher; Kadler, Karl E.; Ferguson, Mark W. J.; McGrouther, Duncan A.
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /11/2009 EN
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Intrasynovial flexor tendon injuries of the hand can frequently be complicated by tendon adhesions to the surrounding sheath, limiting finger function. We have developed a new tendon injury model in the mouse to investigate the three-dimensional cellular biology of intrasynovial flexor tendon healing and adhesion formation. We investigated the cell biology using markers for inflammation, proliferation, collagen synthesis, apoptosis, and vascularization/myofibroblasts. Quantitative immunohistochemical image analysis and three-dimensional reconstruction with cell mapping was performed on labeled serial sections. Flexor tendon adhesions were also assessed 21 days after wounding using transmission electron microscopy to examine the cell phenotypes in the wound. When the tendon has been immobilized, the mouse can form tendon adhesions in the flexor tendon sheath. The cell biology of tendon healing follows the classic wound healing response of inflammation, proliferation, synthesis, and apoptosis, but the greater activity occurs in the surrounding tissue. Cells that have multiple “fibripositors” and cells with cytoplasmic protrusions that contain multiple large and small diameter fibrils can be found in the wound during collagen synthesis. In conclusion...

c-Jun Induces Mammary Epithelial Cellular Invasion and Breast Cancer Stem Cell Expansion*

Jiao, Xuanmao; Katiyar, Sanjay; Willmarth, Nicole E.; Liu, Manran; Ma, Xiaojing; Flomenberg, Neal; Lisanti, Michael P.; Pestell, Richard G.
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
EN
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The molecular mechanisms governing breast tumor cellular self-renewal contribute to breast cancer progression and therapeutic resistance. The ErbB2 oncogene is overexpressed in ∼30% of human breast cancers. c-Jun, the first cellular proto-oncogene, is overexpressed in human breast cancer. However, the role of endogenous c-Jun in mammary tumor progression is unknown. Herein, transgenic mice expressing the mammary gland-targeted ErbB2 oncogene were crossed with c-junf/f transgenic mice to determine the role of endogenous c-Jun in mammary tumor invasion and stem cell function. The excision of c-jun by Cre recombinase reduced cellular migration, invasion, and mammosphere formation of ErbB2-induced mammary tumors. Proteomic analysis identified a subset of secreted proteins (stem cell factor (SCF) and CCL5) induced by ErbB2 expression that were dependent upon endogenous c-Jun expression. SCF and CCL5 were identified as transcriptionally induced by c-Jun. CCL5 rescued the c-Jun-deficient breast tumor cellular invasion phenotype. SCF rescued the c-Jun-deficient mammosphere production. Endogenous c-Jun thus contributes to ErbB2-induced mammary tumor cell invasion and self-renewal.

TopBP1 Deficiency Causes an Early Embryonic Lethality and Induces Cellular Senescence in Primary Cells

Jeon, Yoon; Ko, Eun; Lee, Kyung Yong; Ko, Min Ji; Park, Seo Young; Kang, Jeeheon; Jeon, Chang Hwan; Lee, Ho; Hwang, Deog Su
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
EN
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TopBP1 plays important roles in chromosome replication, DNA damage response, and other cellular regulatory functions in vertebrates. Although the roles of TopBP1 have been studied mostly in cancer cell lines, its physiological function remains unclear in mice and untransformed cells. We generated conditional knock-out mice in which exons 5 and 6 of the TopBP1 gene are flanked by loxP sequences. Although TopBP1-deficient embryos developed to the blastocyst stage, no homozygous mutant embryos were recovered at E8.5 or beyond, and completely resorbed embryos were frequent at E7.5, indicating that mutant embryos tend to die at the peri-implantation stage. This finding indicated that TopBP1 is essential for cell proliferation during early embryogenesis. Ablation of TopBP1 in TopBP1flox/flox mouse embryonic fibroblasts and 3T3 cells using Cre recombinase-expressing retrovirus arrests cell cycle progression at the G1, S, and G2/M phases. The TopBP1-ablated mouse cells exhibit phosphorylation of H2AX and Chk2, indicating that the cells contain DNA breaks. The TopBP1-ablated mouse cells enter cellular senescence. Although RNA interference-mediated knockdown of TopBP1 induced cellular senescence in human primary cells, it induced apoptosis in cancer cells. Therefore...

New Tools and New Biology: Recent Miniaturized Systems for Molecular and Cellular Biology

Hamon, Morgan; Hong, Jong Wook
Fonte: Korea Society for Molecular and Cellular Biology Publicador: Korea Society for Molecular and Cellular Biology
Tipo: Artigo de Revista Científica
EN
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Recent advances in applied physics and chemistry have led to the development of novel microfluidic systems. Microfluidic systems allow minute amounts of reagents to be processed using μm-scale channels and offer several advantages over conventional analytical devices for use in biological sciences: faster, more accurate and more reproducible analytical performance, reduced cell and reagent consumption, portability, and integration of functional components in a single chip. In this review, we introduce how microfluidics has been applied to biological sciences. We first present an overview of the fabrication of microfluidic systems and describe the distinct technologies available for biological research. We then present examples of microsystems used in biological sciences, focusing on applications in molecular and cellular biology.

Protocols for Implementing an Escherichia coli Based TX-TL Cell-Free Expression System for Synthetic Biology

Sun, Zachary Z.; Hayes, Clarmyra A.; Shin, Jonghyeon; Caschera, Filippo; Murray, Richard M.; Noireaux, Vincent
Fonte: MyJove Corporation Publicador: MyJove Corporation
Tipo: Artigo de Revista Científica
Publicado em 16/09/2013 EN
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Ideal cell-free expression systems can theoretically emulate an in vivo cellular environment in a controlled in vitro platform.1 This is useful for expressing proteins and genetic circuits in a controlled manner as well as for providing a prototyping environment for synthetic biology.2,3 To achieve the latter goal, cell-free expression systems that preserve endogenous Escherichia coli transcription-translation mechanisms are able to more accurately reflect in vivo cellular dynamics than those based on T7 RNA polymerase transcription. We describe the preparation and execution of an efficient endogenous E. coli based transcription-translation (TX-TL) cell-free expression system that can produce equivalent amounts of protein as T7-based systems at a 98% cost reduction to similar commercial systems.4,5 The preparation of buffers and crude cell extract are described, as well as the execution of a three tube TX-TL reaction. The entire protocol takes five days to prepare and yields enough material for up to 3000 single reactions in one preparation. Once prepared, each reaction takes under 8 hr from setup to data collection and analysis. Mechanisms of regulation and transcription exogenous to E. coli, such as lac/tet repressors and T7 RNA polymerase...

Empirical Multiscale Networks of Cellular Regulation

de Bivort, Benjamin; Bar-Yam, Yaneer; Huang, Sui
Fonte: Public Library of Science Publicador: Public Library of Science
EN_US
Relevância na Pesquisa
462.6085%
Grouping genes by similarity of expression across multiple cellular conditions enables the identification of cellular modules. The known functions of genes enable the characterization of the aggregate biological functions of these modules. In this paper, we use a high-throughput approach to identify the effective mutual regulatory interactions between modules composed of mouse genes from the Alliance for Cell Signaling (AfCS) murine B-lymphocyte database which tracks the response of ?15,000 genes following chemokine perturbation. This analysis reveals principles of cellular organization that we discuss along four conceptual axes. (1) Regulatory implications: the derived collection of influences between any two modules quantifies intuitive as well as unexpected regulatory interactions. (2) Behavior across scales: trends across global networks of varying resolution (composed of various numbers of modules) reveal principles of assembly of high-level behaviors from smaller components. (3) Temporal behavior: tracking the mutual module influences over different time intervals provides features of regulation dynamics such as duration, persistence, and periodicity. (4) Gene Ontology correspondence: the association of modules to known biological roles of individual genes describes the organization of functions within coexpressed modules of various sizes. We present key specific results in each of these four areas...

Network-Scale Engineering: Systems Approaches to Synthetic Biology

Boyle, Patrick M.
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation
EN_US
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461.15883%
The field of Synthetic Biology seeks to develop engineering principles for biological systems. Modular biological parts are repurposed and recombined to develop new synthetic biological devices with novel functions. The proper functioning of these devices is dependent on the cellular context provided by the host organism, and the interaction of these devices with host systems. The field of Systems Biology seeks to measure and model the properties of biological phenomena at the network scale. We present the application of systems biology approaches to synthetic biology, with particular emphasis on understanding and remodeling metabolic networks. Chapter 2 demonstrates the use of a Flux Balance Analysis model of the Saccharomyces cerevisiae metabolic network to identify and construct strains of S. cerevisiae that produced increased amounts of formic acid. Chapter 3 describes the development of synthetic metabolic pathways in Escherichia coli for the production of hydrogen, and a directed evolution strategy for hydrogenase enzyme improvement. Chapter 4 introduces the use of metabolomic profiling to investigate the role of circadian regulation in the metabolic network of the photoautotrophic cyanobacterium Synechococcus elongatus PCC 7942. Together...

Identification of TRPV4 as a Regulator of Adipose Oxidative Metabolism, Inflammation and Energy Homeostasis by a Chemical Biology Approach

Ye, Li
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation
EN_US
Relevância na Pesquisa
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(PGC1alpha) is a key transcriptional coregulator of mitochondrial biogenesis, oxidative metabolism and thermogenesis. We developed a quantitative high throughput screen to identify small molecules that can induce (PGC1alpha) expression in adipocytes. Small molecules antagonizing the TRPVs (Transient Receptor Potential Vanilloid), a family of ion channels, induced (PGC1alpha) expression in adipocytes. In particular, inhibition of TRPV4 increased expression of (PGC1alpha), UCP1 and cellular respiration; conversely, chemical activation of TRPV4 repressed this pathway. Blocking TRPV4 in cultured adipocytes also reduced the expression of multiple proinflammatory genes that are involved in the development of insulin resistance. These effects of TRPV4 were mediated by the activation of ERK1/2. Finally, mice with a null mutation for TRPV4 showed higher energy expenditure with no change in movement or food intake, and were protected from diet-induced obesity, adipose inflammation and insulin resistance. This study links TRPV4 to robust pathways that offer therapeutic potential in obesity and related metabolic diseases.

Programming and reprogramming cellular identity

Marson, Alexander
Fonte: Massachusetts Institute of Technology Publicador: Massachusetts Institute of Technology
Tipo: Tese de Doutorado Formato: 242 leaves
ENG
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Every cell in the human body contains the same genetic information, with few exceptions, yet each cell type enacts a distinct gene expression program to allow for highly specialized functions. These tightly controlled programs are the results of transcriptional regulation, by transcription factors and chromatin regulators, as well as post-transcriptional regulation, mediated in part by microRNAs (miRNAs). Additionally, cells must respond to external cues, and signal transduction pathways converge on gene regulatory machinery to shape cellular identity. The work presented here focuses on the mechanisms by which transcription factors, chromatin regulators, miRNAs and signal transduction pathways coordinately regulate two particular medically important gene expression programs: (1) the program that controls pluripotency in embryonic stem (ES) cells, giving these cells the capacity to differentiate into every adult cell type, and (2) the program that allows regulatory T (Treg) cells to prevent autoimmunity by suppressing the response of self-reactive conventional T cells. Genomic investigations of the core regulatory circuitry of each of these cells types presented here provide new insight into the genetics of pluripotency and autoimmunity...

Criação, aplicação e avaliação de aulas com jogos cooperativos do tipo RPG para o ensino de biologia celular; Creation, application and evaluation of RPG-based classes for cell biology teaching

Marco Antonio Ferreira Randi
Fonte: Biblioteca Digital da Unicamp Publicador: Biblioteca Digital da Unicamp
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 26/08/2011 PT
Relevância na Pesquisa
563.81992%
O aluno que se envolve com seu processo de aprendizagem aprende melhor. A partir dessa premissa, nosso objetivo no presente estudo foi desenvolver, aplicar e avaliar uma nova ferramenta didática em disciplinas de Biologia Celular, baseada em aulas com RPG (roleplaying game). O RPG é um sistema de jogo cooperativo onde os participantes têm objetivos comuns e precisam atuar em grupo para alcançá-los. Aplicado à educação, acreditamos que funciona como um facilitador da aprendizagem ativa, sendo o aluno o construtor de seu conhecimento enquanto participa da aula, orientado pelo professor. A criação e aplicação dessas aulas constitui desafio estimulante para professores, e a formação de professores também constituiu foco dentro desse estudo. A metodologia incluiu: pesquisas teóricas sobre o assunto a ser trabalhado na aula (um processo celular como síntese de ATP, por exemplo) e subsequente criação da aula na forma de uma aventura; testes das aulas criadas; aplicação das aulas a alunos de nível superior em diferentes cursos em três diferentes universidades; avaliação dos resultados através de notas em provas regulares das disciplinas, questionários, construção de mapas conceituais, depoimentos dos alunos e dos professores participantes...

The chaos within: exploring noise in cellular biology

Johnston, Iain G.
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 10/08/2012
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Cellular biology exists embedded in a world dominated by random dynamics and chance. Many vital molecules and pieces of cellular machinery diffuse within cells, moving along random trajectories as they collide with the other biomolecular inhabitants of the cell. Cellular components may block each other's progress, be produced or degraded at random times, and become unevenly separated as cells grow and divide. Cellular behaviour, including important features of stem cells, tumours and infectious bacteria, is profoundly influenced by the chaos which is the environment within the cell walls. Here we will look at some important causes and effects of randomness in cellular biology, and some ways in which researchers, helped by the vast amounts of data that are now flowing in, have made progress in describing the randomness of nature.; Comment: 5 pages, 4 figures

Modeling multi-cellular systems using sub-cellular elements

Newman, T. J.
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 20/04/2005
Relevância na Pesquisa
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We introduce a model for describing the dynamics of large numbers of interacting cells. The fundamental dynamical variables in the model are sub-cellular elements, which interact with each other through phenomenological intra- and inter-cellular potentials. Advantages of the model include i) adaptive cell-shape dynamics, ii) flexible accommodation of additional intra-cellular biology, and iii) the absence of an underlying grid. We present here a detailed description of the model, and use successive mean-field approximations to connect it to more coarse-grained approaches, such as discrete cell-based algorithms and coupled partial differential equations. We also discuss efficient algorithms for encoding the model, and give an example of a simulation of an epithelial sheet. Given the biological flexibility of the model, we propose that it can be used effectively for modeling a range of multi-cellular processes, such as tumor dynamics and embryogenesis.; Comment: 20 pages, 4 figures

ComPPI, a cellular compartment-specific database for protein-protein interaction network analysis

Veres, Daniel V.; Gyurko, David M.; Thaler, Benedek; Szalay, Kristof Z.; Fazekas, David; Korcsmaros, Tamas; Csermely, Peter
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
457.84527%
Here we present ComPPI, a cellular compartment specific database of proteins and their interactions enabling an extensive, compartmentalized protein-protein interaction network analysis (http://ComPPI.LinkGroup.hu). ComPPI enables the user to filter biologically unlikely interactions, where the two interacting proteins have no common subcellular localizations and to predict novel properties, such as compartment-specific biological functions. ComPPI is an integrated database covering four species (S. cerevisiae, C. elegans, D. melanogaster and H. sapiens). The compilation of nine protein-protein interaction and eight subcellular localization data sets had four curation steps including a manually built, comprehensive hierarchical structure of more than 1600 subcellular localizations. ComPPI provides confidence scores for protein subcellular localizations and protein-protein interactions. ComPPI has user-friendly search options for individual proteins giving their subcellular localization, their interactions and the likelihood of their interactions considering the subcellular localization of their interacting partners. Download options of search results, whole proteomes, organelle-specific interactomes and subcellular localization data are available on its website. Due to its novel features...

First Passage processes in cellular biology

Iyer-Biswas, Srividya; Zilman, Anton
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 01/03/2015
Relevância na Pesquisa
457.84527%
Often sharp changes in cellular behavior are triggered by thresholded events, i.e., by the attainment of a threshold value of a relevant cellular or molecular dynamical variable. Since the governing variable itself typically undergoes noisy or stochastic dynamics, there is a corresponding variability in the times when the same change occurs in each cell of a population. This time is called the "first passage" time and the corresponding process is a "first passage" (FP) process, referring to the event when a random variable first passes the threshold value. In this review we first present and elucidate fundamentals of the FP formalism within a unified conceptual framework, which naturally integrates the existing techniques. We then discuss applications thereof, with emphasis on the practical use of FP techniques in biophysical systems. Our focus here is on covering a diverse set of analytical techniques; the number of reviewed biological applications is thus limited, out of necessity. We focus on three specific areas: channel transport; receptor binding and adhesion; and single-cell growth and division.

Closed-form stochastic solutions for non-equilibrium dynamics and inheritance of cellular components over many cell divisions

Johnston, Iain G.; Jones, Nick S.
Fonte: Universidade Cornell Publicador: Universidade Cornell
Tipo: Artigo de Revista Científica
Publicado em 25/01/2015
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460.04367%
Stochastic dynamics govern many important processes in cellular biology, and an underlying theoretical approach describing these dynamics is desirable to address a wealth of questions in biology and medicine. Mathematical tools exist for treating several important examples of these stochastic processes, most notably gene expression, and random partitioning at single cell divisions or after a steady state has been reached. Comparatively little work exists exploring different and specific ways that repeated cell divisions can lead to stochastic inheritance of unequilibrated cellular populations. Here we introduce a mathematical formalism to describe cellular agents that are subject to random creation, replication, and/or degradation, and are inherited according to a range of random dynamics at cell divisions. We obtain closed-form generating functions describing systems at any time after any number of cell divisions for binomial partitioning and divisions provoking a deterministic or random, subtractive or additive change in copy number, and show that these solutions agree exactly with stochastic simulation. We apply this general formalism to several example problems involving the dynamics of mitochondrial DNA (mtDNA) during development and organismal lifetimes.

Mechanisms of Chlamydia manipulation of host cell biology revealed through genetic approaches

Kokes, Marcela
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2015
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457.84527%

Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen and is the leading cause of preventable blindness worldwide. Chlamydia is particularly intriguing from the perspective of cell biology because it is an obligate intracellular pathogen that manipulates host cellular pathways to ensure its proliferation and survival. This is achieved through a significant remodeling of the host cell’s internal architecture from within a membrane-bound vacuole, termed the inclusion. However, given a previous lack of tools to perform genetic analysis, the mechanisms by which Chlamydia induces host cellular changes remained unclear. Here I present genetic and molecular mechanisms of chlamydial manipulation of the host cytoskeleton and organelles. Using a forward genetics screen, InaC was identified as a necessary factor for the assembly of an F-actin structure surrounding the inclusion. InaC associated with the vacuolar membrane where it recruited Golgi-specific ARF-family GTPases. Actin dynamics and ARF GTPases regulate Golgi morphology and positioning within cells, and InaC acted to redistribute the Golgi to surround the Chlamydia inclusion. These findings suggest that Chlamydia places InaC at the inclusion-cytosolic interface to recruit host ARF GTPases and F-actin to form a platform for rearranging intracellular organelles around the inclusion. The inclusion is also surrounded by the intermediate filament vimentin and the chlamydial protease CPAF cleaves vimentin in vitro. CPAF-dependent remodeling of vimentin occurred selectively in late stages of the infection. In living cells...

MicroRNA Function in Cellular Stress Response

Sangokoya, Carolyn Olufunmilayo
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2012
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460.91168%

MicroRNAs are key post-transcriptional regulators that have been found to play critical roles in the regulation of cellular functions. There is an emerging concept that microRNAs may be just as essential for fine-tuning physiological functions and responding to changing environments and stress conditions as for viability or development. In this dissertation, two studies are presented: The first study demonstrates a role for microRNA in the regulation of oxidative stress response in erythroid cells and the functional consequences of dysregulated microRNA expression in Sickle Cell Disease (SCD) pathobiology. The second study examines a functional role for microRNA in the cellular response to changes in cellular iron concentration. Together these studies illustrate the scope of importance of microRNAs in the coordination of cellular responses to diverse stresses.

Homozygous Sickle Cell (HbSS) erythrocytes are known to have reduced tolerance for oxidative stress, yet the basis for this phenotype has remained unknown. Here we use erythrocyte microRNA expression profiles to identify a subset of HbSS patients with higher miR-144 expression and more severe anemia. We reveal that in K562 erythroid cells and primary erythroid progenitor cells...