Read by QxMD icon Read

Molecular Systems Biology

Magali Richard, Florent Chuffart, Hélène Duplus-Bottin, Fanny Pouyet, Martin Spichty, Etienne Fulcrand, Marianne Entrevan, Audrey Barthelaix, Michael Springer, Daniel Jost, Gaël Yvert
More and more natural DNA variants are being linked to physiological traits. Yet, understanding what differences they make on molecular regulations remains challenging. Important properties of gene regulatory networks can be captured by computational models. If model parameters can be "personalized" according to the genotype, their variation may then reveal how DNA variants operate in the network. Here, we combined experiments and computations to visualize natural alleles of the yeast GAL3 gene in a space of model parameters describing the galactose response network...
January 15, 2018: Molecular Systems Biology
Adam James Waite, Nicholas W Frankel, Yann S Dufour, Jessica F Johnston, Junjiajia Long, Thierry Emonet
No abstract text is available yet for this article.
January 10, 2018: Molecular Systems Biology
Irina Pavelescu, Josep Vilarrasa-Blasi, Ainoa Planas-Riverola, Mary-Paz González-García, Ana I Caño-Delgado, Marta Ibañes
Plant roots grow due to cell division in the meristem and subsequent cell elongation and differentiation, a tightly coordinated process that ensures growth and adaptation to the changing environment. How the newly formed cells decide to stop elongating becoming fully differentiated is not yet understood. To address this question, we established a novel approach that combines the quantitative phenotypic variability of wild-type Arabidopsis roots with computational data from mathematical models. Our analyses reveal that primary root growth is consistent with a Sizer mechanism, in which cells sense their length and stop elongating when reaching a threshold value...
January 10, 2018: Molecular Systems Biology
Anisha M Perez, Marcella M Gomez, Prashant Kalvapalle, Erin O'Brien-Gilbert, Matthew R Bennett, Yousif Shamoo
The major facilitator superfamily (MFS) effluxers are prominent mediators of antimicrobial resistance. The biochemical characterization of MFS proteins is hindered by their complex membrane environment that makes in vitro biochemical analysis challenging. Since the physicochemical properties of proteins drive the fitness of an organism, we posed the question of whether we could reverse that relationship and derive meaningful biochemical parameters for a single protein simply from fitness changes it confers under varying strengths of selection...
December 22, 2017: Molecular Systems Biology
Maria Polychronidou, Thomas Lemberger
No abstract text is available yet for this article.
December 21, 2017: Molecular Systems Biology
Lisa Van den Broeck, Marieke Dubois, Mattias Vermeersch, Veronique Storme, Minami Matsui, Dirk Inzé
Plants have established different mechanisms to cope with environmental fluctuations and accordingly fine-tune their growth and development through the regulation of complex molecular networks. It is largely unknown how the network architectures change and what the key regulators in stress responses and plant growth are. Here, we investigated a complex, highly interconnected network of 20 Arabidopsis transcription factors (TFs) at the basis of leaf growth inhibition upon mild osmotic stress. We tracked the dynamic behavior of the stress-responsive TFs over time, showing the rapid induction following stress treatment, specifically in growing leaves...
December 21, 2017: Molecular Systems Biology
Jochen Weile, Song Sun, Atina G Cote, Jennifer Knapp, Marta Verby, Joseph C Mellor, Yingzhou Wu, Carles Pons, Cassandra Wong, Natascha van Lieshout, Fan Yang, Murat Tasan, Guihong Tan, Shan Yang, Douglas M Fowler, Robert Nussbaum, Jesse D Bloom, Marc Vidal, David E Hill, Patrick Aloy, Frederick P Roth
Although we now routinely sequence human genomes, we can confidently identify only a fraction of the sequence variants that have a functional impact. Here, we developed a deep mutational scanning framework that produces exhaustive maps for human missense variants by combining random codon mutagenesis and multiplexed functional variation assays with computational imputation and refinement. We applied this framework to four proteins corresponding to six human genes: UBE2I (encoding SUMO E2 conjugase), SUMO1 (small ubiquitin-like modifier), TPK1 (thiamin pyrophosphokinase), and CALM1/2/3 (three genes encoding the protein calmodulin)...
December 21, 2017: Molecular Systems Biology
Jian Wang, Keke Huo, Lixin Ma, Liujun Tang, Dong Li, Xiaobi Huang, Yanzhi Yuan, Chunhua Li, Wei Wang, Wei Guan, Hui Chen, Chaozhi Jin, Juncheng Wei, Wanqiao Zhang, Yongsheng Yang, Qiongming Liu, Ying Zhou, Cuili Zhang, Zhihao Wu, Wangxiang Xu, Ying Zhang, Tao Liu, Donghui Yu, Yaping Zhang, Liang Chen, Dewu Zhu, Xing Zhong, Lixin Kang, Xiang Gan, Xiaolan Yu, Qi Ma, Jing Yan, Li Zhou, Zhongyang Liu, Yunping Zhu, Tao Zhou, Fuchu He, Xiaoming Yang
No abstract text is available yet for this article.
December 18, 2017: Molecular Systems Biology
Marie-Therese Mackmull, Bernd Klaus, Ivonne Heinze, Manopriya Chokkalingam, Andreas Beyer, Robert B Russell, Alessandro Ori, Martin Beck
Nuclear transport receptors (NTRs) recognize localization signals of cargos to facilitate their passage across the central channel of nuclear pore complexes (NPCs). About 30 different NTRs constitute different transport pathways in humans and bind to a multitude of different cargos. The exact cargo spectrum of the majority of NTRs, their specificity and even the extent to which active nucleocytoplasmic transport contributes to protein localization remains understudied because of the transient nature of these interactions and the wide dynamic range of cargo concentrations...
December 18, 2017: Molecular Systems Biology
Rachel A Haggerty, Jeremy E Purvis
No abstract text is available yet for this article.
December 18, 2017: Molecular Systems Biology
Paul I Costea, Luis Pedro Coelho, Shinichi Sunagawa, Robin Munch, Jaime Huerta-Cepas, Kristoffer Forslund, Falk Hildebrand, Almagul Kushugulova, Georg Zeller, Peer Bork
Population genomics of prokaryotes has been studied in depth in only a small number of primarily pathogenic bacteria, as genome sequences of isolates of diverse origin are lacking for most species. Here, we conducted a large-scale survey of population structure in prevalent human gut microbial species, sampled from their natural environment, with a culture-independent metagenomic approach. We examined the variation landscape of 71 species in 2,144 human fecal metagenomes and found that in 44 of these, accounting for 72% of the total assigned microbial abundance, single-nucleotide variation clearly indicates the existence of sub-populations (here termed subspecies)...
December 14, 2017: Molecular Systems Biology
Klas Hatje, Raza-Ur Rahman, Ramon O Vidal, Dominic Simm, Björn Hammesfahr, Vikas Bansal, Ashish Rajput, Michel Edwar Mickael, Ting Sun, Stefan Bonn, Martin Kollmar
Mutually exclusive splicing of exons is a mechanism of functional gene and protein diversification with pivotal roles in organismal development and diseases such as Timothy syndrome, cardiomyopathy and cancer in humans. In order to obtain a first genomewide estimate of the extent and biological role of mutually exclusive splicing in humans, we predicted and subsequently validated mutually exclusive exons (MXEs) using 515 publically available RNA-Seq datasets. Here, we provide evidence for the expression of over 855 MXEs, 42% of which represent novel exons, increasing the annotated human mutually exclusive exome more than fivefold...
December 14, 2017: Molecular Systems Biology
Noam Auslander, Chelsea E Cunningham, Behzad M Toosi, Emily J McEwen, Keren Yizhak, Frederick S Vizeacoumar, Sreejit Parameswaran, Nir Gonen, Tanya Freywald, Kalpana K Bhanumathy, Andrew Freywald, Franco J Vizeacoumar, Eytan Ruppin
Metabolic alterations play an important role in cancer and yet, few metabolic cancer driver genes are known. Here we perform a combined genomic and metabolic modeling analysis searching for metabolic drivers of colorectal cancer. Our analysis predicts FUT9, which catalyzes the biosynthesis of Ley glycolipids, as a driver of advanced-stage colon cancer. Experimental testing reveals FUT9's complex dual role; while its knockdown enhances proliferation and migration in monolayers, it suppresses colon cancer cells expansion in tumorspheres and inhibits tumor development in a mouse xenograft models...
December 1, 2017: Molecular Systems Biology
Julia Jabs, Franziska M Zickgraf, Jeongbin Park, Steve Wagner, Xiaoqi Jiang, Katharina Jechow, Kortine Kleinheinz, Umut H Toprak, Marc A Schneider, Michael Meister, Saskia Spaich, Marc Sütterlin, Matthias Schlesner, Andreas Trumpp, Martin Sprick, Roland Eils, Christian Conrad
Cancer drug screening in patient-derived cells holds great promise for personalized oncology and drug discovery but lacks standardization. Whether cells are cultured as conventional monolayer or advanced, matrix-dependent organoid cultures influences drug effects and thereby drug selection and clinical success. To precisely compare drug profiles in differently cultured primary cells, we developed DeathPro, an automated microscopy-based assay to resolve drug-induced cell death and proliferation inhibition. Using DeathPro, we screened cells from ovarian cancer patients in monolayer or organoid culture with clinically relevant drugs...
November 27, 2017: Molecular Systems Biology
Benjamin M Gyori, John A Bachman, Kartik Subramanian, Jeremy L Muhlich, Lucian Galescu, Peter K Sorger
Word models (natural language descriptions of molecular mechanisms) are a common currency in spoken and written communication in biomedicine but are of limited use in predicting the behavior of complex biological networks. We present an approach to building computational models directly from natural language using automated assembly. Molecular mechanisms described in simple English are read by natural language processing algorithms, converted into an intermediate representation, and assembled into executable or network models...
November 24, 2017: Molecular Systems Biology
Thomas E Gorochowski, Amin Espah Borujeni, Yongjin Park, Alec Ak Nielsen, Jing Zhang, Bryan S Der, D Benjamin Gordon, Christopher A Voigt
Genetic circuits implement computational operations within a cell. Debugging them is difficult because their function is defined by multiple states (e.g., combinations of inputs) that vary in time. Here, we develop RNA-seq methods that enable the simultaneous measurement of: (i) the states of internal gates, (ii) part performance (promoters, insulators, terminators), and (iii) impact on host gene expression. This is applied to a three-input one-output circuit consisting of three sensors, five NOR/NOT gates, and 46 genetic parts...
November 9, 2017: Molecular Systems Biology
Eunyong Ahn, Praveen Kumar, Dzmitry Mukha, Amit Tzur, Tomer Shlomi
Cellular metabolic demands change throughout the cell cycle. Nevertheless, a characterization of how metabolic fluxes adapt to the changing demands throughout the cell cycle is lacking. Here, we developed a temporal-fluxomics approach to derive a comprehensive and quantitative view of alterations in metabolic fluxes throughout the mammalian cell cycle. This is achieved by combining pulse-chase LC-MS-based isotope tracing in synchronized cell populations with computational deconvolution and metabolic flux modeling...
November 6, 2017: Molecular Systems Biology
Martin Frejno, Riccardo Zenezini Chiozzi, Mathias Wilhelm, Heiner Koch, Runsheng Zheng, Susan Klaeger, Benjamin Ruprecht, Chen Meng, Karl Kramer, Anna Jarzab, Stephanie Heinzlmeir, Elaine Johnstone, Enric Domingo, David Kerr, Moritz Jesinghaus, Julia Slotta-Huspenina, Wilko Weichert, Stefan Knapp, Stephan M Feller, Bernhard Kuster
Most molecular cancer therapies act on protein targets but data on the proteome status of patients and cellular models for proteome-guided pre-clinical drug sensitivity studies are only beginning to emerge. Here, we profiled the proteomes of 65 colorectal cancer (CRC) cell lines to a depth of > 10,000 proteins using mass spectrometry. Integration with proteomes of 90 CRC patients and matched transcriptomics data defined integrated CRC subtypes, highlighting cell lines representative of each tumour subtype...
November 3, 2017: Molecular Systems Biology
Alvaro Rada-Iglesias
No abstract text is available yet for this article.
October 23, 2017: Molecular Systems Biology
Markus Hartl, Magdalena Füßl, Paul J Boersema, Jan-Oliver Jost, Katharina Kramer, Ahmet Bakirbas, Julia Sindlinger, Magdalena Plöchinger, Dario Leister, Glen Uhrig, Greg Bg Moorhead, Jürgen Cox, Michael E Salvucci, Dirk Schwarzer, Matthias Mann, Iris Finkemeier
Histone deacetylases have central functions in regulating stress defenses and development in plants. However, the knowledge about the deacetylase functions is largely limited to histones, although these enzymes were found in diverse subcellular compartments. In this study, we determined the proteome-wide signatures of the RPD3/HDA1 class of histone deacetylases in Arabidopsis Relative quantification of the changes in the lysine acetylation levels was determined on a proteome-wide scale after treatment of Arabidopsis leaves with deacetylase inhibitors apicidin and trichostatin A...
October 23, 2017: Molecular Systems Biology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"