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Abstracts from the 3rd Conference on Aneuploidy and Cancer: Clinical and Experimental Aspects
Cornish-Bowden, Athel; Rasnick, David; Heng, Henry H.; Horne, Steven; Abdallah, Batoul; Liu, Guo; Ye, Christine J.; Bloomfield, Mathew; Vincent, Mark D.; Aldaz, C. M.; Karlsson, Jenny; Valind, Anders; Jansson, Caroline; Gisselsson, David; Graves, Jennifer A. M.; Stepanenko, Aleksei A.; Andreieva, Svitlana V.; Korets, Kateryna V.; Mykytenko, Dmytro O.; Huleyuk, Nataliya L.; Baklaushev, Vladimir P.; Kovaleva, Oksana A.; Chekhonin, Vladimir P.; Vassetzky, Yegor S.; Avdieiev, Stanislav S.; Bakker, Bjorn; Taudt, Aaron S.; Belderbos, Mirjam E.; Porubsky, David; Spierings, Diana C. J.; de Jong, Tristan V.; Halsema, Nancy; Kazemier, Hinke G.; Hoekstra-Wakker, Karina; Bradley, Allan; de Bont, Eveline S. J. M.; van den Berg, Anke; Guryev, Victor; Lansdorp, Peter M.; Tatché, Maria C.; Foijer, Floris; Liehr, Thomas; Baudoin, Nicolaas C.; Nicholson, Joshua M.; Soto, Kimberly; Quintanilla, Isabel; Camps, Jordi; Cimini, Daniela; Dürrbaum, M.; Donnelly, N.; Passerini, V.; Kruse, C.; Habermann, B.; Storchová, Z.; Mandrioli, Daniele; Belpoggi, Fiorella; Silbergeld, Ellen K.; Perry, Melissa J.; Skotheim, Rolf I.; Løvf, Marthe; Johannessen, Bjarne; Hoff, Andreas M.; Zhao, Sen; SveeStrømme, Jonas M.; Sveen, Anita; Lothe, Ragnhild A.; Hehlmann, R.; Voskanyan, A.; Fabarius, A.; Böcking, Alfred; Biesterfeld, Stefan; Berynskyy, Leonid; Börgermann, Christof; Engers, Rainer; Dietz, Josef; Fritz, A.; Sehgal, N.; Vecerova, J.; Stojkovicz, B.; Ding, H.; Page, N.; Tye, C.; Bhattacharya, S.; Xu, J.; Stein, G.; Stein, J.; Berezney, R.; Gong, Xue; Grasedieck, Sarah; Swoboda, Julian; Rücker, Frank G.; Bullinger, Lars; Pollack, Jonathan R.; Roumelioti, Fani-Marlen; Chiourea, Maria; Raftopoulou, Christina; Gagos, Sarantis; Duesberg, Peter; Bloomfield, Mathew; Hwang, Sunyoung; Gustafsson, Hans T.; O’Sullivan, Ciara; Acevedo-Colina, Aracelli; Huang, Xinhe; Klose, Christian; Schevchenko, Andrej; Dickson, Robert C.; Cavaliere, Paola; Dephoure, Noah; Torres, Eduardo M.; Stampfer, Martha R.; Vrba, Lukas; LaBarge, Mark A.; Futscher, Bernard; Garbe, James C.; Trinh, Andrew L.; Zhou, Yi-Hong; Digman, Michelle (2017-06-22)
An aeroponic culture system for the study of root herbivory on Arabidopsis thaliana
Vaughan, Martha M.; Tholl, Dorothea; Tokuhisa, James G. (Biomed Central, 2011-03-10)
Background Plant defense against herbivory has been studied primarily in aerial tissues. However, complex defense mechanisms have evolved in all parts of the plant to combat herbivore attack and these mechanisms are likely to differ in the aerial and subterranean environment. Research investigating defense responses belowground has been hindered by experimental difficulties associated with the accessibility and quality of root tissue and the lack of bioassays using model plants with altered defense profiles. Results We have developed an aeroponic culture system based on a calcined clay substrate that allows insect herbivores to feed on plant roots while providing easy recovery of the root tissue. The culture method was validated by a root-herbivore system developed for Arabidopsis thaliana and the herbivore Bradysia spp. (fungus gnat). Arabidopsis root mass obtained from aeroponically grown plants was comparable to that from other culture systems, and the plants were morphologically normal. Bradysia larvae caused considerable root damage resulting in reduced root biomass and water absorption. After feeding on the aeroponically grown root tissue, the larvae pupated and emerged as adults. Root damage of mature plants cultivated in aeroponic substrate was compared to that of Arabidopsis seedlings grown in potting mix. Seedlings were notably more susceptible to Bradysia feeding than mature plants and showed decreased overall growth and survival rates. Conclusions A root-herbivore system consisting of Arabidopsis thaliana and larvae of the opportunistic herbivore Bradysia spp. has been established that mimics herbivory in the rhizosphere. Bradysia infestation of Arabidopsis grown in this culture system significantly affects plant performance. The culture method will allow simple profiling and in vivo functional analysis of root defenses such as chemical defense metabolites that are released in response to belowground insect attack.
The Alternaria alternata Mycotoxin Alternariol Suppresses Lipopolysaccharide-Induced Inflammation
Grover, Shivani; Lawrence, Christopher B. (MDPI, 2017-07-20)
The Alternaria mycotoxins alternariol (AOH) and alternariol monomethyl ether (AME) have been shown to possess genotoxic and cytotoxic properties. In this study, the ability of AOH and AME to modulate innate immunity in the human bronchial epithelial cell line (BEAS-2B) and mouse macrophage cell line (RAW264.7) were investigated. During these studies, it was discovered that AOH and to a lesser extent AME potently suppressed lipopolysaccharide (LPS)-induced innate immune responses in a dose-dependent manner. Treatment of BEAS-2B cells with AOH resulted in morphological changes including a detached pattern of growth as well as elongated arms. AOH/AME-related immune suppression and morphological changes were linked to the ability of these mycotoxins to cause cell cycle arrest at the G2/M phase. This model was also used to investigate the AOH/AME mechanism of immune suppression in relation to aryl hydrocarbon receptor (AhR). AhR was not found to be important for the immunosuppressive properties of AOH/AME, but appeared important for the low levels of cell death observed in BEAS-2B cells.
The Alternaria genomes database: a comprehensive resource for a fungal genus comprised of saprophytes, plant pathogens, and allergenic species
Dang, Ha X.; Pryor, Barry M.; Peever, Tobin L.; Lawrence, Christopher B. (2015-03-25)
Background Alternaria is considered one of the most common saprophytic fungal genera on the planet. It is comprised of many species that exhibit a necrotrophic phytopathogenic lifestyle. Several species are clinically associated with allergic respiratory disorders although rarely found to cause invasive infections in humans. Finally, Alternaria spp. are among the most well known producers of diverse fungal secondary metabolites, especially toxins. Description We have recently sequenced and annotated the genomes of 25 Alternaria spp. including but not limited to many necrotrophic plant pathogens such as A. brassicicola (a pathogen of Brassicaceous crops like cabbage and canola) and A. solani (a major pathogen of Solanaceous plants like potato and tomato), and several saprophytes that cause allergy in human such as A. alternata isolates. These genomes were annotated and compared. Multiple genetic differences were found in the context of plant and human pathogenicity, notably the pro-inflammatory potential of A. alternata. The Alternaria genomes database was built to provide a public platform to access the whole genome sequences, genome annotations, and comparative genomics data of these species. Genome annotation and comparison were performed using a pipeline that integrated multiple computational and comparative genomics tools. Alternaria genome sequences together with their annotation and comparison data were ported to Ensembl database schemas using a self-developed tool (EnsImport). Collectively, data are currently hosted using a customized installation of the Ensembl genome browser platform. Conclusion Recent efforts in fungal genome sequencing have facilitated the studies of the molecular basis of fungal pathogenicity as a whole system. The Alternaria genomes database provides a comprehensive resource of genomics and comparative data of an important saprophytic and plant/human pathogenic fungal genus. The database will be updated regularly with new genomes when they become available. The Alternaria genomes database is freely available for non-profit use at http://alternaria.vbi.vt.edu .
Alternative translation initiation codons for the plastid maturase MatK: unraveling the pseudogene misconception in the Orchidaceae
Barthet, Michelle M.; Moukarzel, Keenan; Smith, Kayla N.; Patel, Jaimin; Hilu, Khidir W. (2015-09-29)
Background The plastid maturase MatK has been implicated as a possible model for the evolutionary “missing link” between prokaryotic and eukaryotic splicing machinery. This evolutionary implication has sparked investigations concerning the function of this unusual maturase. Intron targets of MatK activity suggest that this is an essential enzyme for plastid function. The matK gene, however, is described as a pseudogene in many photosynthetic orchid species due to presence of premature stop codons in translations, and its high rate of nucleotide and amino acid substitution. Results Sequence analysis of the matK gene from orchids identified an out-of-frame alternative AUG initiation codon upstream from the consensus initiation codon used for translation in other angiosperms. We demonstrate translation from the alternative initiation codon generates a conserved MatK reading frame. We confirm that MatK protein is expressed and functions in sample orchids currently described as having a matK pseudogene using immunodetection and reverse-transcription methods. We demonstrate using phylogenetic analysis that this alternative initiation codon emerged de novo within the Orchidaceae, with several reversal events at the basal lineage and deep in orchid history. Conclusion These findings suggest a novel evolutionary shift for expression of matK in the Orchidaceae and support the function of MatK as a group II intron maturase in the plastid genome of land plants including the orchids.
Analysis of rice glycosyl hydrolase family 1 and expression of Os4bglu12 beta-glucosidase
Opassiri, Rodjana; Pomthong, Busarakum; Onkoksoong, Tassanee; Akiyama, Takashi; Esen, Asim; Ketudat Cairns, James R. (2006-12-29)
Background Glycosyl hydrolase family 1 (GH1) β-glucosidases have been implicated in physiologically important processes in plants, such as response to biotic and abiotic stresses, defense against herbivores, activation of phytohormones, lignification, and cell wall remodeling. Plant GH1 β-glucosidases are encoded by a multigene family, so we predicted the structures of the genes and the properties of their protein products, and characterized their phylogenetic relationship to other plant GH1 members, their expression and the activity of one of them, to begin to decipher their roles in rice. Results Forty GH1 genes could be identified in rice databases, including 2 possible endophyte genes, 2 likely pseudogenes, 2 gene fragments, and 34 apparently competent rice glycosidase genes. Phylogenetic analysis revealed that GH1 members with closely related sequences have similar gene structures and are often clustered together on the same chromosome. Most of the genes appear to have been derived from duplications that occurred after the divergence of rice and Arabidopsis thaliana lineages from their common ancestor, and the two plants share only 8 common gene lineages. At least 31 GH1 genes are expressed in a range of organs and stages of rice, based on the cDNA and EST sequences in public databases. The cDNA of the Os4bglu12 gene, which encodes a protein identical at 40 of 44 amino acid residues with the N-terminal sequence of a cell wall-bound enzyme previously purified from germinating rice, was isolated by RT-PCR from rice seedlings. A thioredoxin-Os4bglu12 fusion protein expressed in Escherichia coli efficiently hydrolyzed β-(1,4)-linked oligosaccharides of 3-6 glucose residues and laminaribiose. Conclusion Careful analysis of the database sequences produced more reliable rice GH1 gene structure and protein product predictions. Since most of these genes diverged after the divergence of the ancestors of rice and Arabidopsis thaliana, only a few of their functions could be implied from those of GH1 enzymes from Arabidopsis and other dicots. This implies that analysis of GH1 enzymes in monocots is necessary to understand their function in the major grain crops. To begin this analysis, Os4bglu12 β-glucosidase was characterized and found to have high exoglucanase activity, consistent with a role in cell wall metabolism.
Analysis of T-DNA alleles of flavonoid biosynthesis genes in Arabidopsis ecotype Columbia
Bowerman, Peter A.; Ramirez, Melissa V.; Price, Michelle B.; Helm, Richard F.; Winkel, Brenda S. J. (2012-09-04)
BACKGROUND: The flavonoid pathway is a long-standing and important tool for plant genetics, biochemistry, and molecular biology. Numerous flavonoid mutants have been identified in Arabidopsis over the past several decades in a variety of ecotypes. Here we present an analysis of Arabidopsis lines of ecotype Columbia carrying T-DNA insertions in genes encoding enzymes of the central flavonoid pathway. We also provide a comprehensive summary of various mutant alleles for these structural genes that have been described in the literature to date in a wide variety of ecotypes. FINDINGS: The confirmed knockout lines present easily-scorable phenotypes due to altered pigmentation of the seed coat (or testa). Knockouts for seven alleles for six flavonoid biosynthetic genes were confirmed by PCR and characterized by UPLC for altered flavonol content. CONCLUSION: Seven mutant lines for six genes of the central flavonoid pathway were characterized in ecotype, Columbia. These lines represent a useful resource for integrating biochemical and physiological studies with genomic, transcriptomic, and proteomic data, much of which has been, and continues to be, generated in the Columbia background.
Another turn for p53
Tyson, John J. (Nature Publishing Group, 2006-01-01)
Assessment of Nutrient Limitation in Floodplain Forests with Two Different Techniques
Neatrour, Matthew A.; Jones, Robert H.; Golladay, Stephen W. (Hindawi, 2008-05-15)
We assessed nitrogen and phosphorus limitation in a floodplain forest in southern Georgia in USA using two commonly used methods: nitrogen to phosphorus (N:P) ratios in litterfall and fertilized ingrowth cores. We measured nitrogen (N) and phosphorus (P) concentrations in litterfall to determine N:P mass ratios. We also installed ingrowth cores within each site containing native soil amended with nitrogen (N), phosphorus (P), or nitrogen and phosphorus (N + P) fertilizers or without added fertilizer (C). Litter N:P ratios ranged from 16 to 22, suggesting P limitation. However, fertilized ingrowth cores indicated N limitation because fine-root length density was greater in cores fertilized with N or N + P than in those fertilized with P or without added fertilizer. We feel that these two methods of assessing nutrient limitation should be corroborated with fertilization trials prior to use on a wider basis.
Association of RERG Expression with Female Survival Advantage in Malignant Pleural Mesothelioma
De Rienzo, Assunta; Coleman, Melissa H.; Yeap, Beow Y.; Severson, David T.; Wadowski, Benjamin; Gustafson, Corinne E.; Jensen, Roderick V.; Chirieac, Lucian R.; Richards, William G.; Bueno, Raphael (MDPI, 2021-02-02)
Sex differences in incidence, prognosis, and treatment response have been described for many cancers. In malignant pleural mesothelioma (MPM), a lethal disease associated with asbestos exposure, men outnumber women 4 to 1, but women consistently live longer than men following surgery-based therapy. This study investigated whether tumor expression of genes associated with estrogen signaling could potentially explain observed survival differences. Two microarray datasets of MPM tumors were analyzed to discover estrogen-related genes associated with survival. A validation cohort of MPM tumors was selected to balance the numbers of men and women and control for competing prognostic influences. The RAS like estrogen regulated growth inhibitor (RERG) gene was identified as the most differentially-expressed estrogen-related gene in these tumors and predicted prognosis in discovery datasets. In the sex-matched validation cohort, low RERG expression was significantly associated with increased risk of death among women. No association between RERG expression and survival was found among men, and no relationship between estrogen receptor protein or gene expression and survival was found for either sex. Additional investigations are needed to elucidate the molecular mechanisms underlying this association and its sex specificity.
Attracting and Retaining Minorities in the Biomedical Sciences Including Genomics: a Community-based Approach
Smith, Edward J. (2014-08-21)
The balance of reproducibility, sensitivity, and specificity of lists of differentially expressed genes in microarray studies
Shi, Leming; Jones, Wendell D.; Jensen, Roderick V.; Harris, Stephen C.; Perkins, Roger G.; Goodsaid, Federico M.; Guo, Lei; Croner, Lisa J.; Boysen, Cecilie; Fang, Hong; Qian, Feng; Amur, Shashi; Bao, Wenjun; Barbacioru, Catalin C.; Bertholet, Vincent; Cao, Xiaoxi M.; Chu, Tzu-Ming; Collins, Patrick J.; Fan, Xiao-hui; Frueh, Felix W.; Fuscoe, James C.; Guo, Xu; Han, Jing; Herman, Damir; Hong, Huixiao; Kawasaki, Ernest S.; Li, Quan-Zhen; Luo, Yuling; Ma, Yunqing; Mei, Nan; Peterson, Ron L.; Puri, Raj K.; Shippy, Richard; Su, Zhenqiang; Sun, Yongming A.; Sun, Hongmei; Thorn, Brett; Turpaz, Yaron; Wang, Charles; Wang, Sue J.; Warrington, Janet A.; Willey, James C.; Wu, Jie; Xie, Qian; Zhang, Liang; Zhang, Lu; Zhong, Sheng; Wolfinger, Russell D.; Tong, Weida (2008-08-12)
Background Reproducibility is a fundamental requirement in scientific experiments. Some recent publications have claimed that microarrays are unreliable because lists of differentially expressed genes (DEGs) are not reproducible in similar experiments. Meanwhile, new statistical methods for identifying DEGs continue to appear in the scientific literature. The resultant variety of existing and emerging methods exacerbates confusion and continuing debate in the microarray community on the appropriate choice of methods for identifying reliable DEG lists. Results Using the data sets generated by the MicroArray Quality Control (MAQC) project, we investigated the impact on the reproducibility of DEG lists of a few widely used gene selection procedures. We present comprehensive results from inter-site comparisons using the same microarray platform, cross-platform comparisons using multiple microarray platforms, and comparisons between microarray results and those from TaqMan - the widely regarded "standard" gene expression platform. Our results demonstrate that (1) previously reported discordance between DEG lists could simply result from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion with a non-stringent P-value cutoff filtering, the DEG lists become much more reproducible, especially when fewer genes are selected as differentially expressed, as is the case in most microarray studies; and (3) the instability of short DEG lists solely based on P-value ranking is an expected mathematical consequence of the high variability of the t-values; the more stringent the P-value threshold, the less reproducible the DEG list is. These observations are also consistent with results from extensive simulation calculations. Conclusion We recommend the use of FC-ranking plus a non-stringent P cutoff as a straightforward and baseline practice in order to generate more reproducible DEG lists. Specifically, the P-value cutoff should not be stringent (too small) and FC should be as large as possible. Our results provide practical guidance to choose the appropriate FC and P-value cutoffs when selecting a given number of DEGs. The FC criterion enhances reproducibility, whereas the P criterion balances sensitivity and specificity.
Bifurcation analysis of a model of the budding yeast cell cycle
Battogtokh, D.; Tyson, John J. (American Institute of Physics, 2004-09-01)
We study the bifurcations of a set of nine nonlinear ordinary differential equations that describe regulation of the cyclin-dependent kinase that triggers DNA synthesis and mitosis in the budding yeast, Saccharomyces cerevisiae. We show that Clb2-dependent kinase exhibits bistability (stable steady states of high or low kinase activity). The transition from low to high Clb2-dependent kinase activity is driven by transient activation of Cln2-dependent kinase, and the reverse transition is driven by transient activation of the Clb2 degradation machinery. We show that a four-variable model retains the main features of the nine-variable model. In a three-variable model exhibiting birhythmicity (two stable oscillatory states), we explore possible effects of extrinsic fluctuations on cell cycle progression. (C) 2004 American Institute of Physics.
A Bistable Switch Mechanism for Stem Cell Domain Nucleation in the Shoot Apical Meristem
Battogtokh, D.; Tyson, John J. (Frontiers, 2016-05-23)
The Cannabis Proteome Draft Map Project
Jenkins, Conor; Orsburn, Benjamin (MDPI, 2020-01-31)
Recently we have seen a relaxation of the historic restrictions on the use and subsequent research on the Cannabis plants, generally classified as Cannabis sativa and Cannabis indica. What research has been performed to date has centered on chemical analysis of plant flower products, namely cannabinoids and various terpenes that directly contribute to phenotypic characteristics of the female flowers. In addition, we have seen many groups recently completing genetic profiles of various plants of commercial value. To date, no comprehensive attempt has been made to profile the proteomes of these plants. We report herein our progress on constructing a comprehensive draft map of the Cannabis proteome. To date we have identified over 17,000 potential protein sequences. Unfortunately, no annotated genome of Cannabis plants currently exists. We present a method by which “next generation” DNA sequencing output and shotgun proteomics data can be combined to produce annotated FASTA files, bypassing the need for annotated genetic information altogether in traditional proteomics workflows. The resulting material represents the first comprehensive annotated protein FASTA for any Cannabis plant. Using this annotated database as reference we can refine our protein identifications, resulting in the confident identification of 13,000 proteins with putative function. Furthermore, we demonstrate that post-translational modifications play an important role in the proteomes of Cannabis flower, particularly lysine acetylation and protein glycosylation. To facilitate the evolution of analytical investigations into these plant materials, we have created a portal to host resources developed from our proteomic and metabolomic analysis of Cannabis plant material as well as our results integrating these resources.
Cell cycle control and environmental response by second messengers in Caulobacter crescentus
Xu, Chunrui; Weston, Bronson R.; Tyson, John J.; Cao, Yang (2020-09-30)
Background Second messengers, c-di-GMP and (p)ppGpp, are vital regulatory molecules in bacteria, influencing cellular processes such as biofilm formation, transcription, virulence, quorum sensing, and proliferation. While c-di-GMP and (p)ppGpp are both synthesized from GTP molecules, they play antagonistic roles in regulating the cell cycle. In C. crescentus, c-di-GMP works as a major regulator of pole morphogenesis and cell development. It inhibits cell motility and promotes S-phase entry by inhibiting the activity of the master regulator, CtrA. Intracellular (p)ppGpp accumulates under starvation, which helps bacteria to survive under stressful conditions through regulating nucleotide levels and halting proliferation. (p)ppGpp responds to nitrogen levels through RelA-SpoT homolog enzymes, detecting glutamine concentration using a nitrogen phosphotransferase system (PTS Ntr). This work relates the guanine nucleotide-based second messenger regulatory network with the bacterial PTS Ntr system and investigates how bacteria respond to nutrient availability. Results We propose a mathematical model for the dynamics of c-di-GMP and (p)ppGpp in C. crescentus and analyze how the guanine nucleotide-based second messenger system responds to certain environmental changes communicated through the PTS Ntr system. Our mathematical model consists of seven ODEs describing the dynamics of nucleotides and PTS Ntr enzymes. Our simulations are consistent with experimental observations and suggest, among other predictions, that SpoT can effectively decrease c-di-GMP levels in response to nitrogen starvation just as well as it increases (p)ppGpp levels. Thus, the activity of SpoT (or its homologues in other bacterial species) can likely influence the cell cycle by influencing both c-di-GMP and (p)ppGpp. Conclusions In this work, we integrate current knowledge and experimental observations from the literature to formulate a novel mathematical model. We analyze the model and demonstrate how the PTS Ntr system influences (p)ppGpp, c-di-GMP, GMP and GTP concentrations. While this model does not consider all aspects of PTS Ntr signaling, such as cross-talk with the carbon PTS system, here we present our first effort to develop a model of nutrient signaling in C. crescentus.
Cell Cycle Control by a Minimal Cdk Network
Gerard, Claude; Tyson, John J.; Coudreuse, Damien; Novak, Bela (PLOS, 2015-02-01)
In present-day eukaryotes, the cell division cycle is controlled by a complex network of interacting proteins, including members of the cyclin and cyclin-dependent protein kinase (Cdk) families, and the Anaphase Promoting Complex (APC). Successful progression through the cell cycle depends on precise, temporally ordered regulation of the functions of these proteins. In light of this complexity, it is surprising that in fission yeast, a minimal Cdk network consisting of a single cyclin-Cdk fusion protein can control DNA synthesis and mitosis in a manner that is indistinguishable from wild type. To improve our understanding of the cell cycle regulatory network, we built and analysed a mathematical model of the molecular interactions controlling the G1/S and G2/M transitions in these minimal cells. The model accounts for all observed properties of yeast strains operating with the fusion protein. Importantly, coupling the model’s predictions with experimental analysis of alternative minimal cells, we uncover an explanation for the unexpected fact that elimination of inhibitory phosphorylation of Cdk is benign in these strains while it strongly affects normal cells. Furthermore, in the strain without inhibitory phosphorylation of the fusion protein, the distribution of cell size at division is unusually broad, an observation that is accounted for by stochastic simulations of the model. Our approach provides novel insights into the organization and quantitative regulation of wild type cell cycle progression. In particular, it leads us to propose a new mechanistic model for the phenomenon of mitotic catastrophe, relying on a combination of unregulated, multi-cyclin-dependent Cdk activities.
Cell cycle regulation by feed-forward loops coupling transcription and phosphorylation
Csikasz-Nagy, Attila; Kapuy, Orsolya; Toth, Attila; Pal, Csaba; Jensen, Lars Juhl; Uhlmann, Frank; Tyson, John J.; Novak, Bela (Nature Publishing Group, 2009-01-01)
The eukaryotic cell cycle requires precise temporal coordination of the activities of hundreds of ‘executor’ proteins (EPs) involved in cell growth and division. Cyclin-dependent protein kinases (Cdks) play central roles in regulating the production, activation, inactivation and destruction of these EPs. From genome-scale data sets of budding yeast, we identify 126 EPs that are regulated by Cdk1 both through direct phosphorylation of the EP and through phosphorylation of the transcription factors that control expression of the EP, so that each of these EPs is regulated by a feed-forward loop (FFL) from Cdk1. By mathematical modelling, we show that such FFLs can activate EPs at different phases of the cell cycle depending of the effective signs (+ or -) of the regulatory steps of the FFL.We provide several case studies of EPs that are controlled by FFLs exactly as our models predict. The signal-transduction properties of FFLs allow one (or a few) Cdk signal(s) to drive a host of cell cycle responses in correct temporal sequence.
Changes in the expression of genes encoding type IV pili-associated proteins are seen when Clostridium perfringens is grown in liquid or on surfaces
Soncini, Samantha R.; Hartman, Andrea H.; Gallagher, Tara M.; Camper, Gary J.; Jensen, Roderick V.; Melville, Stephen B. (2020-01-14)
Background Clostridium perfringens is a Gram-positive anaerobic pathogen that causes multiple diseases in humans and animals. C. perfringens lack flagella but have type IV pili (TFP) and can glide on agar surfaces. When C. perfringens bacteria are placed on surfaces, they become elongated, flexible and have TFP on their surface, traits not seen in liquid-grown cells. In addition, the main pilin in C. perfringens TFP, PilA2, undergoes differential post-translational modification when grown in liquid or on plates. To understand the mechanisms underlying these phenotypes, bacteria were grown in three types of liquid media and on agar plates with the same medium to compare gene expression using RNA-Seq. Results Hundreds of genes were differentially expressed, including transcriptional regulatory protein-encoding genes and genes associated with TFP functions, which were higher on plates than in liquid. Transcript levels of TFP genes reflected the proportion of each protein predicted to reside in a TFP assembly complex. To measure differences in rates of translation, the Escherichia coli reporter gene gusA gene (encoding β-glucuronidase) was inserted into the chromosome downstream of TFP promoters and in-frame with the first gene of the operon. β-glucuronidase expression was then measured in cells grown in liquid or on plates. β-glucuronidase activity was proportional to mRNA levels in liquid-grown cells, but not plate-grown cells, suggesting significant levels of post-transcriptional regulation of these TFP-associated genes occurs when cells are grown on surfaces. Conclusions This study reveals insights into how a non-flagellated pathogenic rod-shaped bacterium senses and responds to growth on surfaces, including inducing transcriptional regulators and activating multiple post-transcriptional regulatory mechanisms associated with TFP functions.
The Changing Pattern of Nontuberculous Mycobacterial Disease
Falkinham, Joseph O. III (Hindawi, 2003-01-01)
Nontuberculous mycobacteria are human opportunistic pathogens whose source of infection is the environment. These include both slow-growing (eg, Mycobacterium kansasii and Mycobacterium avium) and rapid-growing (eg, Mycobacterium abscessus and Mycobacterium fortuitum) species. Transmission is through ingestion or inhalation of water, particulate matter or aerosols, or through trauma. The historic presentation of pulmonary disease in older individuals with predisposing lung conditions and in children has been changing. Pulmonary disease in elderly individuals who lack the classic predisposing lung conditions is increasing. Pulmonary disease and hypersensitivity pneumonitis have been linked with occupational or home exposures to nontuberculous mycobacteria. There has been a shift from Mycobacterium scrofulaceum to M avium in children with cervical lymphadenitis. Further, individuals who are immunosuppressed due to therapy or HIV-infection are at a greatly increased risk for nontuberculous mycobacterial infection. The changing pattern of nontuberculous mycobacterial disease is due in part to the ability of these pathogens to survive and proliferate in habitats that they share with humans, such as drinking water. The advent of an aging population and an increase in the proportion of immunosuppressed individuals suggest that the prevalence of nontuberculous mycobacterial disease will increase.

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