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630 Publications visible to you, out of a total of 630
Modeling the cell division cycle: cdc2 and cyclin interactions

Abstract (Expand)

The proteins cdc2 and cyclin form a heterodimer (maturation promoting factor) that controls the major events of the cell cycle. A mathematical model for the interactions of cdc2 and cyclin is constructed. … Simulation and analysis of the model show that the control system can operate in three modes: as a steady state with high maturation promoting factor activity, as a spontaneous oscillator, or as an excitable switch. We associate the steady state with metaphase arrest in unfertilized eggs, the spontaneous oscillations with rapid division cycles in early embryos, and the excitable switch with growth-controlled division cycles typical of nonembryonic cells.

Author: J. J. Tyson

Date Published: 15th Aug 1991

Publication Type: Not specified

Positive cooperative binding of calcium to bovine brain calmodulin

Abstract

Not specified

Authors: Thomas H. Crouch, Claude B. Klee

Date Published: 1st Aug 1980

Publication Type: Not specified

Digitoxin metabolism by rat liver microsomes.

Abstract

Not specified

Authors: A. Schmoldt, H. F. Benthe, G. Haberland

Date Published: 1st Sep 1975

Publication Type: Journal

Digitoxin metabolism by rat liver microsomes.

Abstract

Not specified

Authors: A. Schmoldt, H. F. Benthe, G. Haberland

Date Published: 1st Sep 1975

Publication Type: Journal

Digitoxin metabolism by rat liver microsomes.

Abstract

Not specified

Authors: A. Schmoldt, H. F. Benthe, G. Haberland

Date Published: 1st Sep 1975

Publication Type: Journal

Nested autoinhibitory feedbacks alter the resistance of homeostatic adaptive biochemical networks

Abstract (Expand)

Negative feedback control is a ubiquitous feature of biochemical systems, as is time delay between a signal and its response. Negative feedback in conjunction with time delay can lead to oscillations. … In a cellular context, it might be beneficial to mitigate oscillatory behaviour to avoid recurring stress situations. This can be achieved by increasing the distance between the parameters of the system and certain thresholds, beyond which oscillations occur. This distance has been termed resistance. Here, we prove that in a generic three-dimensional negative feedback system the resistance of the system is modified by nested autoinhibitory feedbacks. Our system features negative feedbacks through both input-inhibition as well as output-activation, a signalling component with mass conservation and perfect adaptation. We show that these features render the system applicable to biological data, exemplified by the high osmolarity glycerol system in yeast and the mammalian p53 system. Output-activation is better supported by data than input-inhibition and also shows distinguished properties with respect to the system's stimulus. Our general approach might be useful in designing synthetic systems in which oscillations can be tuned by synthetic autoinhibitory feedbacks.

Authors: J. Schaber, A. Lapytsko, D. Flockerzi

Date Published: No date defined

Publication Type: Not specified

Photoperiodic control of the Arabidopsis proteome reveals a translational coincidence mechanism

Abstract (Expand)

bioRxiv preprint 2017 Plants respond to seasonal cues such as the photoperiod, to adapt to current conditions and to prepare for environmental changes in the season to come. To assess photoperiodic … responses at the protein level, we quantified the proteome of the model plant Arabidopsis thaliana by mass spectrometry across four photoperiods. This revealed coordinated changes of abundance in proteins of photosynthesis, primary and secondary metabolism, including pigment biosynthesis, consistent with higher metabolic activity in long photoperiods. Higher translation rates in the day time than the night likely contribute to these changes via rhythmic changes in RNA abundance. Photoperiodic control of protein levels might be greatest only if high translation rates coincide with high transcript levels in some photoperiods. We term this proposed mechanism ‘translational coincidence’, mathematically model its components, and demonstrate its effect on the Arabidopsis proteome. Datasets from a green alga and a cyanobacterium suggest that translational coincidence contributes to seasonal control of the proteome in many phototrophic organisms. This may explain why many transcripts but not their cognate proteins exhibit diurnal rhythms.

Authors: Daniel Seaton, Alexander Graf, Katja Baerenfaller, Mark Stitt, Andrew Millar, Wilhelm Gruissem

Date Published: No date defined

Publication Type: Not specified

Photoperiod-dependent changes in the phase of core clock transcripts and global transcriptional outputs at dawn and dusk in Arabidopsis.

Abstract (Expand)

Plants use the circadian clock to sense photoperiod length. Seasonal responses like flowering are triggered at a critical photoperiod when a light-sensitive clock output coincides with light or darkness. … However, many metabolic processes, like starch turnover, and growth respond progressively to photoperiod duration. We first tested the photoperiod response of 10 core clock genes and two output genes. qRT-PCR analyses of transcript abundance under 6, 8, 12 and 18 h photoperiods revealed 1-4 h earlier peak times under short photoperiods and detailed changes like rising PRR7 expression before dawn. Clock models recapitulated most of these changes. We explored the consequences for global gene expression by performing transcript profiling in 4, 6, 8, 12 and 18 h photoperiods. There were major changes in transcript abundance at dawn, which were as large as those between dawn and dusk in a given photoperiod. Contributing factors included altered timing of the clock relative to dawn, light signalling and changes in carbon availability at night as a result of clock-dependent regulation of starch degradation. Their interaction facilitates coordinated transcriptional regulation of key processes like starch turnover, anthocyanin, flavonoid and glucosinolate biosynthesis and protein synthesis and underpins the response of metabolism and growth to photoperiod.

Authors: A. Flis, R. Sulpice, D. D. Seaton, A. A. Ivakov, M. Liput, C. Abel, A. J. Millar, M. Stitt

Date Published: No date defined

Publication Type: Not specified

Global transcript levels respond to small changes of the carbon status during progressive exhaustion of carbohydrates in Arabidopsis rosettes.

Abstract (Expand)

The balance between the supply and utilization of carbon (C) changes continually. It has been proposed that plants respond in an acclimatory manner, modifying C utilization to minimize harmful periods … of C depletion. This hypothesis predicts that signaling events are initiated by small changes in C status. We analyzed the global transcriptional response to a gradual depletion of C during the night and an extension of the night, where C becomes severely limiting from 4 h onward. The response was interpreted using published datasets for sugar, light, and circadian responses. Hundreds of C-responsive genes respond during the night and others very early in the extended night. Pathway analysis reveals that biosynthesis and cellular growth genes are repressed during the night and genes involved in catabolism are induced during the first hours of the extended night. The C response is amplified by an antagonistic interaction with the clock. Light signaling is attenuated during the 24-h light/dark cycle. A model was developed that uses the response of 22K genes during a circadian cycle and their responses to C and light to predict global transcriptional responses during diurnal cycles of wild-type and starchless pgm mutant plants and an extended night in wild-type plants. By identifying sets of genes that respond at different speeds and times during C depletion, our extended dataset and model aid the analysis of candidates for C signaling. This is illustrated for AKIN10 and four bZIP transcription factors, and sets of genes involved in trehalose signaling, protein turnover, and starch breakdown.

Authors: B. Usadel, O. E. Blasing, Y. Gibon, K. Retzlaff, M. Hohne, M. Gunther, M. Stitt

Date Published: No date defined

Publication Type: Not specified

Sugars and circadian regulation make major contributions to the global regulation of diurnal gene expression in Arabidopsis.

Abstract (Expand)

The diurnal cycle strongly influences many plant metabolic and physiological processes. Arabidopsis thaliana rosettes were harvested six times during 12-h-light/12-h-dark treatments to investigate … changes in gene expression using ATH1 arrays. Diagnostic gene sets were identified from published or in-house expression profiles of the response to light, sugar, nitrogen, and water deficit in seedlings and 4 h of darkness or illumination at ambient or compensation point [CO(2)]. Many sugar-responsive genes showed large diurnal expression changes, whose timing matched that of the diurnal changes of sugars. A set of circadian-regulated genes also showed large diurnal changes in expression. Comparison of published results from a free-running cycle with the diurnal changes in Columbia-0 (Col-0) and the starchless phosphoglucomutase (pgm) mutant indicated that sugars modify the expression of up to half of the clock-regulated genes. Principle component analysis identified genes that make large contributions to diurnal changes and confirmed that sugar and circadian regulation are the major inputs in Col-0 but that sugars dominate the response in pgm. Most of the changes in pgm are triggered by low sugar levels during the night rather than high levels in the light, highlighting the importance of responses to low sugar in diurnal gene regulation. We identified a set of candidate regulatory genes that show robust responses to alterations in sugar levels and change markedly during the diurnal cycle.

Authors: O. E. Blasing, Y. Gibon, M. Gunther, M. Hohne, R. Morcuende, D. Osuna, O. Thimm, B. Usadel, W. R. Scheible, M. Stitt

Date Published: No date defined

Publication Type: Not specified

Dynamic proteomic profiling of a unicellular cyanobacterium Cyanothece ATCC51142 across light-dark diurnal cycles.

Abstract (Expand)

BACKGROUND: Unicellular cyanobacteria of the genus Cyanothece are recognized for their ability to execute nitrogen (N2)-fixation in the dark and photosynthesis in the light. An understanding of these … mechanistic processes in an integrated systems context should provide insights into how Cyanothece might be optimized for specialized environments and/or industrial purposes. Systems-wide dynamic proteomic profiling with mass spectrometry (MS) analysis should reveal fundamental insights into the control and regulation of these functions. RESULTS: To expand upon the current knowledge of protein expression patterns in Cyanothece ATCC51142, we performed quantitative proteomic analysis using partial ("unsaturated") metabolic labeling and high mass accuracy LC-MS analysis. This dynamic proteomic profiling identified 721 actively synthesized proteins with significant temporal changes in expression throughout the light-dark cycles, of which 425 proteins matched with previously characterized cycling transcripts. The remaining 296 proteins contained a cluster of proteins uniquely involved in DNA replication and repair, protein degradation, tRNA synthesis and modification, transport and binding, and regulatory functions. Functional classification of labeled proteins suggested that proteins involved in respiration and glycogen metabolism showed increased expression in the dark cycle together with nitrogenase, suggesting that N2-fixation is mediated by higher respiration and glycogen metabolism. Results indicated that Cyanothece ATCC51142 might utilize alternative pathways for carbon (C) and nitrogen (N) acquisition, particularly, aspartic acid and glutamate as substrates of C and N, respectively. Utilization of phosphoketolase (PHK) pathway for the conversion of xylulose-5P to pyruvate and acetyl-P likely constitutes an alternative strategy to compensate higher ATP and NADPH demand. CONCLUSION: This study provides a deeper systems level insight into how Cyanothece ATCC51142 modulates cellular functions to accommodate photosynthesis and N2-fixation within the single cell.

Authors: U. K. Aryal, J. Stockel, R. K. Krovvidi, M. A. Gritsenko, M. E. Monroe, R. J. Moore, D. W. Koppenaal, R. D. Smith, H. B. Pakrasi, J. M. Jacobs

Date Published: No date defined

Publication Type: Not specified

Proteome turnover in the green alga Ostreococcus tauri by time course 15N metabolic labeling mass spectrometry.

Abstract (Expand)

Protein synthesis and degradation determine the cellular levels of proteins, and their control hence enables organisms to respond to environmental change. Experimentally, these are little known proteome … parameters; however, recently, SILAC-based mass spectrometry studies have begun to quantify turnover in the proteomes of cell lines, yeast, and animals. Here, we present a proteome-scale method to quantify turnover and calculate synthesis and degradation rate constants of individual proteins in autotrophic organisms such as algae and plants. The workflow is based on the automated analysis of partial stable isotope incorporation with (15)N. We applied it in a study of the unicellular pico-alga Ostreococcus tauri and observed high relative turnover in chloroplast-encoded ATPases (0.42-0.58% h(-1)), core photosystem II proteins (0.34-0.51% h(-1)), and RbcL (0.47% h(-1)), while nuclear-encoded RbcS2 is more stable (0.23% h(-1)). Mitochondrial targeted ATPases (0.14-0.16% h(-1)), photosystem antennae (0.09-0.14% h(-1)), and histones (0.07-0.1% h(-1)) were comparatively stable. The calculation of degradation and synthesis rate constants k(deg) and k(syn) confirms RbcL as the bulk contributor to overall protein turnover. This study performed over 144 h of incorporation reveals dynamics of protein complex subunits as well as isoforms targeted to different organelles.

Authors: S. F. Martin, V. S. Munagapati, E. Salvo-Chirnside, L. E. Kerr, T. Le Bihan

Date Published: No date defined

Publication Type: Not specified

Life-stage associated remodeling of lipid metabolism regulation in Atlantic salmon.

Abstract (Expand)

Atlantic salmon migrates from rivers to sea to feed, grow and develop gonads before returning to spawn in freshwater. The transition to marine habitats is associated with dramatic changes in the … environment, including water salinity, exposure to pathogens, and shift in dietary lipid availability. Many changes in physiology and metabolism occur across this life-stage transition, but little is known about the molecular nature of these changes. Here we use a long term feeding experiment to study transcriptional regulation of lipid metabolism in Atlantic salmon gut and liver in both fresh- and saltwater. We find that lipid metabolism becomes significantly less plastic to differences in dietary lipid composition when salmon transitions to saltwater and experiences increased dietary lipid availability. Expression of genes in liver relating to lipogenesis and lipid transport decrease overall and become less responsive to diet, while genes for lipid uptake in gut become more highly expressed. Finally, analyses of evolutionary consequences of the salmonid specific whole-genome duplication on lipid metabolism reveals several pathways with significantly different (p<0.05) duplicate retention or duplicate regulatory conservation. We also find a limited number of cases where the whole genome duplication has resulted in an increased gene dosage. In conclusion, we find variable and pathway-specific effects of the salmonid genome duplication on lipid metabolism genes. A clear life-stage associated shift in lipid metabolism regulation is evident, and we hypothesize this to be, at least partly, driven by non-dietary factors such as the preparatory remodeling of gene regulation and physiology prior to sea migration. This article is protected by copyright. All rights reserved.

Authors: G. Gillard, T. N. Harvey, A. Gjuvsland, Y. Jin, M. Thomassen, S. Lien, M. Leaver, J. S. Torgersen, T. R. Hvidsten, J. O. Vik, S. R. Sandve

Date Published: No date defined

Publication Type: Not specified

Suppression of indoleamine-2,3-dioxygenase 1 expression by promoter hypermethylation in ER-positive breast cancer.

Abstract (Expand)

Kynurenine formation by tryptophan-catabolic indoleamine-2,3-dioxygenase 1 (IDO1) plays a key role in tumor immune evasion and inhibition of IDO1 is efficacious in preclinical models of breast cancer. … As the response of breast cancer to immune checkpoint inhibitors may be limited, a better understanding of the expression of additional targetable immunomodulatory pathways is of importance. We therefore investigated the regulation of IDO1 expression in different breast cancer subtypes. We identified estrogen receptor alpha (ER) as a negative regulator of IDO1 expression. Serum kynurenine levels as well as tumoral IDO1 expression were lower in patients with ER-positive than ER-negative tumors and an inverse relationship between IDO1 and estrogen receptor mRNA was observed across 14 breast cancer data sets. Analysis of whole genome bisulfite sequencing, 450k, MassARRAY and pyrosequencing data revealed that the IDO1 promoter is hypermethylated in ER-positive compared with ER-negative breast cancer. Reduced induction of IDO1 was also observed in human ER-positive breast cancer cell lines. IDO1 induction was enhanced upon DNA demethylation in ER-positive but not in ER-negative cells and methylation of an IDO1 promoter construct reduced IDO1 expression, suggesting that enhanced methylation of the IDO1 promoter suppresses IDO1 in ER-positive breast cancer. The association of ER overexpression with epigenetic downregulation of IDO1 appears to be a particular feature of breast cancer as IDO1 was not suppressed by IDO1 promoter hypermethylation in the presence of high ER expression in cervical or endometrial cancer.

Authors: D. L. Dewi, S. R. Mohapatra, S. Blanco Cabanes, I. Adam, L. F. Somarribas Patterson, B. Berdel, M. Kahloon, L. Thurmann, S. Loth, K. Heilmann, D. Weichenhan, O. Mucke, I. Heiland, P. Wimberger, J. D. Kuhlmann, K. H. Kellner, S. Schott, C. Plass, M. Platten, C. Gerhauser, S. Trump, C. A. Opitz

Date Published: No date defined

Publication Type: Not specified

Morpheus: a user-friendly modeling environment for multiscale and multicellular systems biology.

Abstract (Expand)

Morpheus is a modeling environment for the simulation and integration of cell-based models with ordinary differential equations and reaction-diffusion systems. It allows rapid development of multiscale … models in biological terms and mathematical expressions rather than programming code. Its graphical user interface supports the entire workflow from model construction and simulation to visualization, archiving and batch processing.

Authors: J. Starruss, W. de Back, L. Brusch, A. Deutsch

Date Published: No date defined

Publication Type: Not specified

A Predictive 3D Multi-Scale Model of Biliary Fluid Dynamics in the Liver Lobule.

Abstract (Expand)

Bile, the central metabolic product of the liver, is transported by the bile canaliculi network. The impairment of bile flow in cholestatic liver diseases has urged a demand for insights into its … regulation. Here, we developed a predictive 3D multi-scale model that simulates fluid dynamic properties successively from the subcellular to the tissue level. The model integrates the structure of the bile canalicular network in the mouse liver lobule, as determined by high-resolution confocal and serial block-face scanning electron microscopy, with measurements of bile transport by intravital microscopy. The combined experiment-theory approach revealed spatial heterogeneities of biliary geometry and hepatocyte transport activity. Based on this, our model predicts gradients of bile velocity and pressure in the liver lobule. Validation of the model predictions by pharmacological inhibition of Rho kinase demonstrated a requirement of canaliculi contractility for bile flow in vivo. Our model can be applied to functionally characterize liver diseases and quantitatively estimate biliary transport upon drug-induced liver injury.

Authors: K. Meyer, O. Ostrenko, G. Bourantas, H. Morales-Navarrete, N. Porat-Shliom, F. Segovia-Miranda, H. Nonaka, A. Ghaemi, J. M. Verbavatz, L. Brusch, I. Sbalzarini, Y. Kalaidzidis, R. Weigert, M. Zerial

Date Published: No date defined

Publication Type: Not specified

Phytochrome B regulates resource allocation in Brassica rapa.

Abstract (Expand)

Crop biomass and yield are tightly linked to how the light signaling network translates information about the environment into allocation of resources, including photosynthates. Once activated, the … phytochrome (phy) class of photoreceptors signal and re-deploy carbon resources to alter growth, plant architecture, and reproductive timing. Most of the previous characterization of the light-modulated growth program has been performed in the reference plant Arabidopsis thaliana. Here, we use Brassica rapa as a crop model to test for conservation of the phytochrome-carbon network. In response to elevated levels of CO2, B. rapa seedlings showed increases in hypocotyl length, shoot and root fresh weight, and the number of lateral roots. All of these responses were dependent on nitrogen and polar auxin transport. In addition, we identified putative B. rapa orthologs of PhyB and isolated two nonsense alleles. BrphyB mutants had significantly decreased or absent CO2-stimulated growth responses. Mutant seedlings also showed misregulation of auxin-dependent genes and genes involved in chloroplast development. Adult mutant plants had reduced chlorophyll levels, photosynthetic rate, stomatal index, and seed yield. These findings support a recently proposed holistic role for phytochromes in regulating resource allocation, biomass production, and metabolic state in the developing plant.

Authors: A. A. Arsovski, J. E. Zemke, B. D. Haagen, S. H. Kim, J. L. Nemhauser

Date Published: No date defined

Publication Type: Not specified

Phytochrome, Carbon Sensing, Metabolism, and Plant Growth Plasticity.

Abstract

Not specified

Authors: J. Krahmer, A. Ganpudi, A. Abbas, A. Romanowski, K. J. Halliday

Date Published: No date defined

Publication Type: Not specified

Photosynthate partitioning to starch in Arabidopsis thaliana is insensitive to light intensity but sensitive to photoperiod due to a restriction on growth in the light in short photoperiods.

Abstract (Expand)

Photoperiod duration can be predicted from previous days, but irradiance fluctuates in an unpredictable manner. To investigate how allocation to starch responds to changes in these two environmental … variables, Arabidopsis Col-0 was grown in a 6 h and a 12 h photoperiod at three different irradiances. The absolute rate of starch accumulation increased when photoperiod duration was shortened and when irradiance was increased. The proportion of photosynthate allocated to starch increased strongly when photoperiod duration was decreased but only slightly when irradiance was decreased. There was a small increase in the daytime level of sucrose and twofold increases in glucose, fructose and glucose 6-phosphate at a given irradiance in short photoperiods compared to long photoperiods. The rate of starch accumulation correlated strongly with sucrose and glucose levels in the light, irrespective of whether these sugars were responding to a change in photoperiod or irradiance. Whole plant carbon budget modelling revealed a selective restriction of growth in the light period in short photoperiods. It is proposed that photoperiod sensing, possibly related to the duration of the night, restricts growth in the light period in short photoperiods, increasing allocation to starch and providing more carbon reserves to support metabolism and growth in the long night.

Authors: V. Mengin, E. T. Pyl, T. Alexandre Moraes, R. Sulpice, N. Krohn, B. Encke, M. Stitt

Date Published: No date defined

Publication Type: Not specified

From steady-state to synchronized yeast glycolytic oscillations II: model validation.

Abstract (Expand)

UNLABELLED: In an accompanying paper [du Preez et al., (2012) FEBS J279, 2810-2822], we adapt an existing kinetic model for steady-state yeast glycolysis to simulate limit-cycle oscillations. Here we … validate the model by testing its capacity to simulate a wide range of experiments on dynamics of yeast glycolysis. In addition to its description of the oscillations of glycolytic intermediates in intact cells and the rapid synchronization observed when mixing out-of-phase oscillatory cell populations (see accompanying paper), the model was able to predict the Hopf bifurcation diagram with glucose as the bifurcation parameter (and one of the bifurcation points with cyanide as the bifurcation parameter), the glucose- and acetaldehyde-driven forced oscillations, glucose and acetaldehyde quenching, and cell-free extract oscillations (including complex oscillations and mixed-mode oscillations). Thus, the model was compliant, at least qualitatively, with the majority of available experimental data for glycolytic oscillations in yeast. To our knowledge, this is the first time that a model for yeast glycolysis has been tested against such a wide variety of independent data sets. DATABASE: The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.biochem.sun.ac.za/database/dupreez/index.html.

Authors: F. B. du Preez, D. D. van Niekerk, J. L. Snoep

Date Published: No date defined

Publication Type: Not specified

From steady-state to synchronized yeast glycolytic oscillations I: model construction.

Abstract (Expand)

UNLABELLED: An existing detailed kinetic model for the steady-state behavior of yeast glycolysis was tested for its ability to simulate dynamic behavior. Using a small subset of experimental data, the … original model was adapted by adjusting its parameter values in three optimization steps. Only small adaptations to the original model were required for realistic simulation of experimental data for limit-cycle oscillations. The greatest changes were required for parameter values for the phosphofructokinase reaction. The importance of ATP for the oscillatory mechanism and NAD(H) for inter-and intra-cellular communications and synchronization was evident in the optimization steps and simulation experiments. In an accompanying paper [du Preez F et al. (2012) FEBS J279, 2823-2836], we validate the model for a wide variety of experiments on oscillatory yeast cells. The results are important for re-use of detailed kinetic models in modular modeling approaches and for approaches such as that used in the Silicon Cell initiative. DATABASE: The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.biochem.sun.ac.za/database/dupreez/index.html.

Authors: F. B. du Preez, D. D. van Niekerk, B. Kooi, J. M. Rohwer, J. L. Snoep

Date Published: No date defined

Publication Type: Not specified

Draft genome sequence of the docosahexaenoic acid producing thraustochytrid Aurantiochytrium sp. T66.

Abstract (Expand)

Thraustochytrids are unicellular, marine protists, and there is a growing industrial interest in these organisms, particularly because some species, including strains belonging to the genus Aurantiochytrium, … accumulate high levels of docosahexaenoic acid (DHA). Here, we report the draft genome sequence of Aurantiochytrium sp. T66 (ATCC PRA-276), with a size of 43 Mbp, and 11,683 predicted protein-coding sequences. The data has been deposited at DDBJ/EMBL/Genbank under the accession LNGJ00000000. The genome sequence will contribute new insight into DHA biosynthesis and regulation, providing a basis for metabolic engineering of thraustochytrids.

Authors: B. Liu, H. Ertesvag, I. M. Aasen, O. Vadstein, T. Brautaset, T. M. Heggeset

Date Published: No date defined

Publication Type: Not specified

In situ esterification and extractive fermentation for butyl butyrate production with Clostridium tyrobutyricum.

Abstract (Expand)

Butyl butyrate (BB) is a valuable chemical that can be used as flavor, fragrance, extractant, and so on in various industries. Meanwhile, BB can also be used as a fuel source with excellent compatibility … as gasoline, aviation kerosene, and diesel components. The conventional industrial production of BB is highly energy-consuming and generates various environmental pollutants. Recently, there have been tremendous interests in producing BB from renewable resources through biological routes. In this study, based on the fermentation using the hyper-butyrate producing strain Clostridium tyrobutyricum ATCC 25755, efficient BB production through in situ esterification was achieved by supplementation of lipase and butanol into the fermentation. Three commercially available lipases were assessed and the one from Candida sp. (recombinant, expressed in Aspergillus niger) was identified with highest catalytic activity for BB production. Various conditions that might affect BB production in the fermentation have been further evaluated, including the extractant type, enzyme loading, agitation, pH, and butanol supplementation strategy. Under the optimized conditions (5.0 g L(-1) of enzyme loading, pH at 5.5, butanol kept at 10.0 g L(-1) ), 34.7 g L(-1) BB was obtained with complete consumption of 50 g L(-1) glucose as the starting substrate. To our best knowledge, the BB production achieved in this study is the highest among the ever reported from the batch fermentation process. Our results demonstrated an excellent biological platform for renewable BB production from low-value carbon sources. Biotechnol. Bioeng. 2017;114: 1428-1437. (c) 2017 Wiley Periodicals, Inc.

Authors: Z. T. Zhang, S. Taylor, Y. Wang

Date Published: No date defined

Publication Type: Not specified

Simultaneous Clostridial fermentation, lipase-catalyzed esterification, and ester extraction to enrich diesel with butyl butyrate.

Abstract (Expand)

The recovery of 1-butanol from fermentation broth is energy-intensive since typical concentrations in fermentation broth are below 20 g L(-1). To prevent butanol inhibition and high downstream processing … costs, we aimed at producing butyl esters instead of 1-butanol. It is shown that it is possible to perform simultaneously clostridial fermentation, esterification of the formed butanol to butyl butyrate, and extraction of this ester by hexadecane. The very high partition coefficient of butyl butyrate pulls the esterification towards the product side even at fermentation pH and relatively low butanol concentrations. The hexadecane extractant is a model diesel compound and is nontoxic to the cells. If butyl butyrate enriched diesel can directly be used as car fuel, no product recovery is required. A proof-of-principle experiment for the one-pot bio-ester production from glucose led to 5 g L(-1) butyl butyrate in the hexadecane phase. The principle may be extended to a wide range of esters, especially to longer chain ones.

Authors: C. van den Berg, A. S. Heeres, L. A. van der Wielen, A. J. Straathof

Date Published: No date defined

Publication Type: Not specified

Mechanistic model of temperature influence on flowering through whole-plant accumulation of FT

Abstract

BioRxiv preprint:

Authors: Hannah A Kinmonth-Schultz, Melissa J MacEwen, Daniel D Seaton, Andrew J Millar, Takato Imaizumi, Soo-Hyung Kim

Date Published: No date defined

Publication Type: Not specified

Circadian protein regulation in the green lineage I. A phospho-dawn anticipates light onset before proteins peak in daytime.

Abstract (Expand)

BioRxiv preprint, 4 April 2018. Abstract: Daily light-dark cycles (LD) drive dynamic regulation of plant and algal transcriptomes via photoreceptor pathways and 24-hour, circadian rhythms. Diel regulation … of protein levels and modifications has been less studied. Ostreococcus tauri, the smallest free-living eukaryote, provides a minimal model proteome for the green lineage. Here, we compare transcriptome data under LD to the algal proteome and phosphoproteome, assayed using shotgun mass-spectrometry. Under 10% of 855 quantified proteins were rhythmic but two-thirds of 860 phosphoproteins showed rhythmic modification(s). Most rhythmic proteins peaked in the daytime. Model simulations showed that light-stimulated protein synthesis largely accounts for this distribution of protein peaks. Prompted by apparently dark-stable proteins, we sampled during prolonged dark adaptation, where stable RNAs and very limited change to the proteome suggested a quiescent, cellular “dark state”. In LD, acid-directed and proline-directed protein phosphorylation sites were regulated in antiphase. Strikingly, 39% of rhythmic phospho-sites reached peak levels just before dawn. This anticipatory phosphorylation is distinct from light-responsive translation but consistent with plant phosphoprotein profiles, suggesting that a clock-regulated phospho-dawn prepares green cells for daytime functions.

Authors: Zeenat B. Noordally, Matthew M. Hindle, Sarah F. Martin, Daniel D. Seaton, Ian Simpson, Thierry Le Bihan, Andrew J. Millar

Date Published: No date defined

Publication Type: Not specified

Human iPSC-derived RPE and retinal organoids reveal impaired alternative splicing of genes involved in pre-mRNA splicing in PRPF31 autosomal dominant retinitis pigmentosa

Abstract (Expand)

Mutations in pre-mRNA processing factors (PRPFs) cause 40% of autosomal dominant retinitis pigmentosa (RP), but it is unclear why mutations in ubiquitously expressed PRPFs cause retinal disease. To … understand the molecular basis of this phenotype, we have generated RP type 11 (PRPF31-mutated) patient-specific retinal organoids and retinal pigment epithelium (RPE) from induced pluripotent stem cells (iPSC). Impaired alternative splicing of genes encoding pre-mRNA splicing proteins occurred in patient-specific retinal cells and Prpf31+/− mouse retinae, but not fibroblasts and iPSCs, providing mechanistic insights into retinal-specific phenotypes of PRPFs. RPE was the most affected, characterised by loss of apical-basal polarity, reduced trans-epithelial resistance, phagocytic capacity, microvilli, and cilia length and incidence. Disrupted cilia morphology was observed in patient-derived-photoreceptors that displayed progressive features associated with degeneration and cell stress. In situ gene-editing of a pathogenic mutation rescued key structural and functional phenotypes in RPE and photoreceptors, providing proof-of-concept for future therapeutic strategies. eTOC PRPF31 is a ubiquitously expressed pre-mRNA processing factor that when mutated causes autosomal dominant RP. Using a patient-specific iPSC approach, Buskin and Zhu et al. show that retinal-specific defects result from altered splicing of genes involved in the splicing process itself, leading to impaired splicing, loss of RPE polarity and diminished phagocytic ability as well as reduced cilia incidence and length in both photoreceptors and RPE.

Authors: Adriana Buskin, Lili Zhu, Valeria Chichagova, Basudha Basu, Sina Mozaffari-Jovin, David Dolan, Alastair Droop, Joseph Collin, Revital Bronstein, Sudeep Mehrotra, Michael Farkas, Gerrit Hilgen, Kathryn White, Dean Hallam, Katarzyna Bialas, Git Chung, Carla Mellough, Yuchun Ding, Natalio Krasnogor, Stefan Przyborski, Jumana Al-Aama, Sameer Alharthi, Yaobo Xu, Gabrielle Wheway, Katarzyna Szymanska, Martin McKibbin, Chris F Inglehearn, David J Elliott, Susan Lindsay, Robin R Ali, David H Steel, Lyle Armstrong, Evelyne Sernagor, Eric Pierce, Reinhard Luehrmann, Sushma-Nagaraja Grellscheid, Colin A Johnson, Majlinda Lako

Date Published: No date defined

Publication Type: Not specified

Cultivar-specific transcriptome and pan-transcriptome reconstruction of tetraploid potato

Abstract (Expand)

Background: Although the reference genome of Solanum tuberosum group Phureja double-monoploid (DM) clone is available, knowledge on the genetic diversity of the highly heterozygous tetraploid group … Tuberosum, representing most cultivated varieties, remains largely unexplored. This lack of knowledge hinders further progress in potato research and its subsequent applications in breeding. Results: For the DM genome assembly, two only partially-overlapping gene models exist differing in a unique set of genes and intron/exon structure predictions. First step was to merge and manually curate the merged gene model, creating a union of genes in Phureja scaffold. We next compiled available RNA-Seq datasets (cca. 1.5 billion reads) for three tetraploid potato genotypes (cultivar Désirée, cultivar Rywal, and breeding clone PW363) with diverse breeding pedigrees. Short-read transcriptomes were assembled using CLC, Trinity, Velvet, and rnaSPAdes de novo assemblers using different settings to test for optimal outcome. In addition, for cultivar Rywal, PacBio Iso-Seq full-length transcriptome sequencing was also performed. Revised EvidentialGene redundancy-reducing pipeline was employed to produce accurate and complete cultivar-specific transcriptomes from assemblers output, as well as to attain the pan-transcriptome. Due to being the most diverse dataset in terms of tissues (stem, seedlings and roots) and experimental conditions, cv. Désirée was the most complete transcriptome (95.8% BUSCO completeness). For cv. Rywal and breeding clone PW363 data were available for leaf samples only and the resulting transcriptomes were less complete than cv. Désirée (89.8% and 89.3% BUSCO completeness, respectively). Cross comparison of these cultivar-specific transcriptomes and merged DM gene model suggests that the core potato transcriptome is comprised of 16,339 genes. The pan-transcriptome contains a total of 95,779 transcripts, of which 54,614 transcripts are not present in the Phureja genome. These represent the variants of the novel genes found in the potato pan-genome. Conclusions: Our analysis shows that the available gene model of double-monoploid potato from group Phureja is, to some degree, not complete. The generated transcriptomes and pan-transcriptome represent a valuable resource for potato gene variability exploration, high-throughput -omics analyses, and future breeding programmes.

Authors: Marko Petek, Maja Zagorščak, Živa Ramšak, Sheri Sanders, Elizabeth Tseng, Mohamed Zouine, Anna Coll, Kristina Gruden

Date Published: No date defined

Publication Type: Not specified

Design principles of ROS dynamic networks relevant to precision therapies for age-related diseases

Abstract (Expand)

The eminently complex regulatory network protecting the cell against oxidative stress, surfaces in several disease maps, including that of Parkinson’s disease (PD). How this molecular networking achieves … its various functionalities and how processes operating at the seconds-minutes time scale cause a disease at a time scale of multiple decennia is enigmatic. By computational analysis, we here disentangle the reactive oxygen species (ROS) regulatory network into a hierarchy of subnetworks that each correspond to a different functionality. The detailed dynamic model of ROS management obtained integrates these functionalities and fits in vitro data sets from two different laboratories. The model shows effective ROS-management for a century, followed by a sudden system’s collapse due to the loss of p62 protein. PD related conditions such as lack of DJ-1 protein or increased α-synuclein accelerated the system’s collapse. Various in-silico interventions (e.g. addition of antioxidants or caffeine) slowed down the collapse of the system in silico, suggesting the model may help discover new medicinal and nutritional therapies.

Authors: Alexey Kolodkin, Raju Prasad Sharma, Anna Maria Colangelo, Andrew Ignatenko, Francesca Martorana, Danyel Jennen, Jacco J. Briede, Nathan Brady, Matteo Barberis, Thierry D.G.A. Mondeel, Michele Papa, Vikas Kumar, Bernhard Peters, Alexander Skupin, Lilia Alberghina, Rudi Balling, Hans V. Westerhoff

Date Published: No date defined

Publication Type: Not specified

How scientists are helping plants get the most out of photosynthesis

Abstract

Not specified

Authors: Jonathan Menary, Sebastian Fuller, Stefan Schillberg

Date Published: No date defined

Publication Type: Tech report

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