Time-resolved transcriptome analysis and lipid pathway reconstruction of the oleaginous green microalga Monoraphidium neglectum reveal a model for triacylglycerol and lipid hyperaccumulation.

Biotechnol Biofuels. 2017;10:197

Authors: Jaeger D, Winkler A, Mussgnug JH, Kalinowski J, Goesmann A, Kruse O

Abstract
BACKGROUND: Oleaginous microalgae are promising production hosts for the sustainable generation of lipid-based bioproducts and as bioenergy carriers such as biodiesel. Transcriptomics of the lipid accumulation phase, triggered efficiently by nitrogen starvation, is a valuable approach for the identification of gene targets for metabolic engineering.
RESULTS: An explorative analysis of the detailed transcriptional response to different stages of nitrogen availability was performed in the oleaginous green alga Monoraphidium neglectum. Transcript data were correlated with metabolic data for cellular contents of starch and of different lipid fractions. A pronounced transcriptional down-regulation of photosynthesis became apparent in response to nitrogen starvation, whereas glucose catabolism was found to be up-regulated. An in-depth reconstruction and analysis of the pathways for glycerolipid, central carbon, and starch metabolism revealed that distinct transcriptional changes were generally found only for specific steps within a metabolic pathway. In addition to pathway analyses, the transcript data were also used to refine the current genome annotation. The transcriptome data were integrated into a database and complemented with data for other microalgae which were also subjected to nitrogen starvation. It is available at https://tdbmn.cebitec.uni-bielefeld.de.
CONCLUSIONS: Based on the transcriptional responses to different stages of nitrogen availability, a model for triacylglycerol and lipid hyperaccumulation is proposed, which involves transcriptional induction of thioesterases, differential regulation of lipases, and a re-routing of the central carbon metabolism. Over-expression of distinct thioesterases was identified to be a potential strategy to increase the oleaginous phenotype of M. neglectum, and furthermore specific lipases were identified as potential targets for future metabolic engineering approaches.

PMID: 28814974 [PubMed]

74 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/08/17

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Performance of objective functions and optimisation procedures for parameter estimation in system biology models.

NPJ Syst Biol Appl. 2017;3:20

Authors: Degasperi A, Fey D, Kholodenko BN

Abstract
Mathematical modelling of signalling pathways aids experimental investigation in system and synthetic biology. Ever increasing data availability prompts the development of large dynamic models with numerous parameters. In this paper, we investigate how the number of unknown parameters affects the convergence of three frequently used optimisation algorithms and four objective functions. We compare objective functions that use data-driven normalisation of the simulations with those that use scaling factors. The data-driven normalisation of the simulation approach implies that simulations are normalised in the same way as the data, making both directly comparable. The scaling factor approach, which is commonly used for parameter estimation in dynamic systems, introduces scaling factors that multiply the simulations to convert them to the scale of the data. Here we show that the scaling factor approach increases, compared to data-driven normalisation of the simulations, the degree of practical non-identifiability, defined as the number of directions in the parameter space, along which parameters are not identifiable. Further, the results indicate that data-driven normalisation of the simulations greatly improve the speed of convergence of all tested algorithms when the overall number of unknown parameters is relatively large (74 parameters in our test problems). Data-driven normalisation of the simulations also markedly improve the performance of the non-gradient-based algorithm tested even when the number of unknown parameters is relatively small (10 parameters in our test problems). As the models and the unknown parameters increase in size, the data-driven normalisation of the simulation approach can be the preferred option, because it does not aggravate non-identifiability and allows for obtaining parameter estimates in a reasonable amount of time.

PMID: 28804640 [PubMed]

41 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/08/15

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Stochastic feeding dynamics arise from the need for information and energy.

Proc Natl Acad Sci U S A. 2017 Aug 11;:

Authors: Scholz M, Dinner AR, Levine E, Biron D

Abstract
Animals regulate their food intake in response to the available level of food. Recent observations of feeding dynamics in small animals showed feeding patterns of bursts and pauses, but their function is unknown. Here, we present a data-driven decision-theoretical model of feeding in Caenorhabditis elegans Our central assumption is that food intake serves a dual purpose: to gather information about the external food level and to ingest food when the conditions are good. The model recapitulates experimentally observed feeding patterns. It naturally implements trade-offs between speed versus accuracy and exploration versus exploitation in responding to a dynamic environment. We find that the model predicts three distinct regimes in responding to a dynamical environment, with a transition region where animals respond stochastically to periodic signals. This stochastic response accounts for previously unexplained experimental data.

PMID: 28802256 [PubMed - as supplied by publisher]

PCAF and SIRT7 modulate PGK1 K323 acetylation in liver cancer cells.

Hepatology. 2017 Aug 12;:

Authors: Hu H, Gao D

PMID: 28802069 [PubMed - as supplied by publisher]

Transcription-Replication Conflict Orientation Modulates R-Loop Levels and Activates Distinct DNA Damage Responses.

Cell. 2017 Aug 10;170(4):774-786.e19

Authors: Hamperl S, Bocek MJ, Saldivar JC, Swigut T, Cimprich KA

Abstract
Conflicts between transcription and replication are a potent source of DNA damage. Co-transcriptional R-loops could aggravate such conflicts by creating an additional barrier to replication fork progression. Here, we use a defined episomal system to investigate how conflict orientation and R-loop formation influence genome stability in human cells. R-loops, but not normal transcription complexes, induce DNA breaks and orientation-specific DNA damage responses during conflicts with replication forks. Unexpectedly, the replisome acts as an orientation-dependent regulator of R-loop levels, reducing R-loops in the co-directional (CD) orientation but promoting their formation in the head-on (HO) orientation. Replication stress and deregulated origin firing increase the number of HO collisions leading to genome-destabilizing R-loops. Our findings connect DNA replication to R-loop homeostasis and suggest a mechanistic basis for genome instability resulting from deregulated DNA replication, observed in cancer and other disease states.

PMID: 28802045 [PubMed - in process]

Recombinant Lactococcus lactis for efficient conversion of cellodextrins into L-lactic acid.

Biotechnol Bioeng. 2017 Aug 12;:

Authors: Gandini C, Tarraran L, Kalemasi D, Pessione E, Mazzoli R

Abstract
Lactic acid bacteria (LAB) are among the most interesting organisms for industrial processes with a long history of application as food starters and biocontrol agents, and an underexploited potential for biorefineries converting biomass into high-value compounds. Lactic acid (LA), their main fermentation product, is among the most requested chemicals owing to its broad range of applications. Notably, LA polymers, i.e., polylactides, have high potential as biodegradable substitutes of fossil-derived plastics. However, LA production by LAB fermentation is currently too expensive for polylactide to be cost-competitive with traditional plastics. LAB have complex nutritional requirements and cannot ferment inexpensive substrates such as cellulose. Metabolic engineering could help reduce such nutritional requirements and enable LAB to directly ferment low-cost polysaccharides. Here, we engineered a Lactococcus lactis strain which constitutively secretes a β-glucosidase and an endoglucanase. The recombinant strain can grow on cellooligosaccharides up to at least cellooctaose and efficiently metabolizes them to L-LA in single-step fermentation. This is the first report of a LAB able to directly metabolize cellooligosaccharides longer that cellohexaose and a significant step towards cost-sustainable consolidated bioprocessing of cellulose into optically pure LA. This article is protected by copyright. All rights reserved.

PMID: 28802003 [PubMed - as supplied by publisher]

Bangladesh Environmental Enteric Dysfunction (BEED) study: protocol for a community-based intervention study to validate non-invasive biomarkers of environmental enteric dysfunction.

BMJ Open. 2017 Aug 11;7(8):e017768

Authors: Mahfuz M, Das S, Mazumder RN, Masudur Rahman M, Haque R, Bhuiyan MMR, Akhter H, Sarker MSA, Mondal D, Muaz SSA, Karim ASMB, Borowitz SM, Moskaluk CA, Barratt MJ, Petri WA, Gordon JI, Ahmed T

Abstract
INTRODUCTION: Environmental enteric dysfunction (EED) is a subacute inflammatory condition of the small intestinal mucosa with unclear aetiology that may account for more than 40% of all cases of stunting. Currently, there are no universally accepted protocols for the diagnosis, treatment and ultimately prevention of EED. The Bangladesh Environmental Enteric Dysfunction (BEED) study is designed to validate non-invasive biomarkers of EED with small intestinal biopsy, better understand disease pathogenesis and identify potential therapeutic targets for interventions designed to control EED and stunting.
METHODS AND ANALYSIS: The BEED study is a community-based intervention where participants are recruited from three cohorts: stunted children aged 12-18 months (length for age Z-score (LAZ) <-2), at risk of stunting children aged 12-18 months (LAZ <-1 to -2) and malnourished adults aged 18-45 years (body mass index <18.5 kg/m(2)). After screening, participants eligible for study provide faecal, urine and plasma specimens to quantify the levels of candidate EED biomarkers before and after receiving a nutritional intervention. Participants who fail to respond to nutritional therapy are considered as the candidates for upper gastrointestinal endoscopy with biopsy. Histopathological scoring for EED will be performed on biopsies obtained from several locations within the proximal small intestine. Candidate EED biomarkers will be correlated with nutritional status, the results of histochemical and immunohistochemical analyses of epithelial and lamina propria cell populations, plus assessments of microbial community structure.
ETHICS AND DISSEMINATION: Ethics approval was obtained in all participating institutes. Results of this study will be submitted for publication in peer-reviewed journals.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT02812615. Registered on 21 June 2016.

PMID: 28801442 [PubMed - in process]

Anti-Inflammatory Chromatinscape Suggests Alternative Mechanisms of Glucocorticoid Receptor Action.

Immunity. 2017 Aug 04;:

Authors: Oh KS, Patel H, Gottschalk RA, Lee WS, Baek S, Fraser IDC, Hager GL, Sung MH

Abstract
Despite the widespread use of glucocorticoids (GCs), their anti-inflammatory effects are not understood mechanistically. Numerous investigations have examined the effects of glucocorticoid receptor (GR) activation prior to inflammatory challenges. However, clinical situations are emulated by a GC intervention initiated in the midst of rampant inflammatory responses. To characterize the effects of a late GC treatment, we profiled macrophage transcriptional and chromatinscapes with Dexamethasone (Dex) treatment before or after stimulation by lipopolysaccharide (LPS). The late activation of GR had a similar gene-expression profile as from GR pre-activation, while ameliorating the disruption of metabolic genes. Chromatin occupancy of GR was not predictive of Dex-regulated gene expression, contradicting the "trans-repression by tethering" model. Rather, GR activation resulted in genome-wide blockade of NF-κB interaction with chromatin and directly induced inhibitors of NF-κB and AP-1. Our investigation using GC treatments with clinically relevant timing highlights mechanisms underlying GR actions for modulating the "inflamed epigenome."

PMID: 28801231 [PubMed - as supplied by publisher]

Molecular signatures of longevity: insights from cross-species comparative studies.

Semin Cell Dev Biol. 2017 Aug 08;:

Authors: Ma S, Gladyshev VN

Abstract
Much of the current research on longevity focuses on the aging process within a single species. Several molecular players (e.g. IGF1 and MTOR), pharmacological compounds (e.g. rapamycin and metformin), and dietary approaches (e.g. calorie restriction and methionine restriction) have been shown to be important in regulating and modestly extending lifespan in model organisms. On the other hand, natural lifespan varies much more significantly across species. Within mammals alone, maximum lifespan differs more than 100 fold, but the underlying regulatory mechanisms remain poorly understood. Recent comparative studies are beginning to shed light on the molecular signatures associated with exceptional longevity. These include genome sequencing of microbats, naked mole rat, blind mole rat, bowhead whale and African turquoise killifish, and comparative analyses of gene expression, metabolites, lipids and ions across multiple mammalian species. Together, they point towards several putative strategies for lifespan regulation and cancer resistance, as well as the pathways and metabolites associated with longevity variation. In particular, longevity may be achieved by both lineage-specific adaptations and common mechanisms that apply across the species. Comparing the resulting cross-species molecular signatures with the within-species lifespan extension strategies will improve our understanding of mechanisms of longevity control and provide a starting point for novel and effective interventions.

PMID: 28800931 [PubMed - as supplied by publisher]

Rattus norvegicus BN/SHR liver and heart left ventricle ribosomal RNA depleted directional RNA sequencing.

BMC Res Notes. 2017 Aug 11;10(1):395

Authors: Wyler E, van Heesch S, Adami E, Hubner N, Landthaler M

Abstract
OBJECTIVE: The spontaneously hypertensive rat strain is a frequently used disease model. In a previous study, we measured translational efficiency from this strain and BN-Lx animals. Here, we describe long RNA sequencing reads from ribosomal RNA depleted samples from the same animals. This data can be used to investigate splicing-related events.
RESULTS: RNA was extracted from rat liver and heart left ventricle from BN-Lx and SHR/Ola rats in biological replicates. Ribosomal RNA was removed and the samples subjected to directional high-throughput RNA-sequencing. Read and alignment statistics indicate high quality of the data. The raw sequencing reads are freely available on the NCBI short read archive and can be used for further research on tissue and strain differences, or analysed together with other published high-throughput data from the same animals.

PMID: 28800773 [PubMed - in process]

An iTRAQ-based proteomic analysis reveals dysregulation of neocortical synaptopodin in Lewy body dementias.

Mol Brain. 2017 Aug 11;10(1):36

Authors: Datta A, Chai YL, Tan JM, Lee JH, Francis PT, Chen CP, Sze SK, Lai MKP

Abstract
Lewy body dementias are the second most common cause of neurodegenerative dementia in the elderly after Alzheimer's disease (AD). The two clinical subgroups of Lewy body dementias, namely, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), are differentiated by the chronology of cognitive symptoms relative to parkinsonism. At present, there remains a debate on whether DLB and PDD are separate disease entities, or fall within the same spectrum of Lewy body dementias. In this study, we compared the detergent-soluble proteome via an 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) analysis of pooled lysates from the prefrontal cortex (BA9) of DLB (n = 19) and PDD (n = 21) patients matched a priori for amyloid (total Aβ42) burden, semi-quantitative scores for Lewy bodies and neurofibrillary tangles together with age-matched control (n = 21) subjects. A total of 1914 proteins were confidently identified by iTRAQ (false discovery rate = 0%). None of the proteins showed a significant yet opposite regulation in between DLB and PDD when compared to aged controls in the proteomic data set as well as following immunoblot analysis of the pooled and individual lysates involving all 61 subjects. The postsynaptic protein, synaptopodin (SYNPO) was significantly down-regulated in both DLB and PDD subgroups, suggesting a defective synaptic transmission in the demented patients. In conclusion, the largely similar proteome of DLB and PDD matched for amyloid burden suggests that variations in concomitant AD-related pathology, abnormal post-translational modifications or protein-protein interactions, defective intracellular trafficking or misfolding of proteins could play a part in driving the clinically observed differences between these two subgroups of Lewy body dementias. This further indicates that amyloid-targeting therapeutic strategies may show different efficacies in DLB versus PDD.

PMID: 28800743 [PubMed - in process]

Proceedings of the ISEV symposium on "HIV, NeuroAIDS, drug abuse & EVs".

J Extracell Vesicles. 2017;6(1):1294360

Authors: Hu G, Witwer KW, Bond VC, Haughey N, Kashanchi F, Pulliam L, Buch S

Abstract
Extracellular vesicles (EVs) are globular, membrane bound nanovesicles (30-100 nm range) that are shed both during normal cellular functioning and under pathological conditions by most cell types. In recent years, there has been significant interest in the study of these vesicles as conduits for the delivery of information between cells from both analogous and disparate tissues. Their ability to carry specialised cargo including signalling mediators, proteins, messenger RNA and miRNAs characterises these vesicles as primary facilitators of cell-to-cell communication and regulation. EVs have also been demonstrated to play important roles in the field of cancer biology and metastasis. However, significant knowledge gaps exist in the role these vesicles play in the context of HIV infection and drug abuse. To foster discussion in this area a satellite symposium on "HIV, NeuroAIDS, Drug Abuse & EVs", was held in conjunction with the annual meeting of the International Society for Extracellular Vesicles (ISEV) in Bethesda, in April 2015. Experts in HIV and drug abuse fields were invited to share their findings on the role of EVs in HIV-1 infection and drug addiction. Additional discussion included current areas of research in EV biology in HIV infection and drug abuse.

PMID: 28800366 [PubMed]

Prescribed Renoprotective Chinese Herbal Medicines Were Associated with a Lower Risk of All-Cause and Disease-Specific Mortality among Patients with Chronic Kidney Disease: A Population-Based Follow-Up Study in Taiwan.

Evid Based Complement Alternat Med. 2017;2017:5632195

Authors: Hsieh CF, Chang HC, Huang SL, Chen CL, Chen WT, Yang CC

Abstract
Chinese herbal medicines (CHMs) containing aristolochic acid (AA) are associated with chronic kidney disease (CKD), but some prescribed CHMs have been shown to possess renoprotective effects. We conducted a nationwide retrospective cohort study to delineate the role of prescribed CHMs on the CKD progression. Renoprotective CHM (RPCHM) was defined if a CHM contained dong chong xia cao (Cordyceps sinensis (Berk.) Sacc.), da huang (Rheum palmatum L), huang qi (Astragalus membranaceus), dan shen (Salvia miltiorrhiza Bge.), and dong quai (Angelica sinensis (Oliv.) Diels) or belonged to specific mixture herbal formulations (Yishen capsule, Saireito, or Wen Pi Tang). Subjects who had ever used AA-containing CHMs, had cancer or HIV prior to CKD diagnosis, or died within the first month of CKD diagnosis were excluded. A total of 11,625 patients were eligible subjects. The adjusted hazard ratio (aHR) for all-cause mortality was 0.6 (p < 0.001) and 0.6 (p = 0.013) among subjects receiving RPCHMs containing Angelica sinensis and those receiving other RPCHMs, respectively. For CKD-related mortality, the aHR among subjects receiving RPCHMs containing Angelica sinensis was 0.6 (p = 0.025). The use of specific RPCHMs, especially those that contained Angelica sinensis, was associated with a lower risk of mortality among CKD patients.

PMID: 28798802 [PubMed]

An Efficient Plant Regeneration and Transformation System of Ma Bamboo (Dendrocalamus latiflorus Munro) Started from Young Shoot as Explant.

Front Plant Sci. 2017;8:1298

Authors: Ye S, Cai C, Ren H, Wang W, Xiang M, Tang X, Zhu C, Yin T, Zhang L, Zhu Q

Abstract
Genetic engineering technology has been successfully used in many plant species, but is limited in woody plants, especially in bamboos. Ma bamboo (Dendrocalamus latiflorus Munro) is one of the most important bamboo species in Asia, and its genetic improvement was largely restricted by the lack of an efficient regeneration and transformation method. Here we reported a plantlet regeneration and Agrobacterium-mediated transformation protocol by using Ma bamboo young shoots as explants. Under our optimized conditions, embryogenic calluses were successfully induced from the excised young shoots on callus induction medium and rapidly grew on callus multiplication medium. Shoots and roots were regenerated on shoot induction medium and root induction medium, respectively, with high efficiency. An Agrobacterium-mediated genetic transformation protocol of Ma bamboo was established, verified by PCR and GUS staining. Furthermore, the maize Lc gene under the control of the ubiquitin promoter was successfully introduced into Ma bamboo genome and generated an anthocyanin over-accumulation phenotype. Our methods established here will facilitate the basic research as well as genetic breeding of this important bamboo species. Key achievements: A stable and high efficiency regeneration and Agrobacterium-mediated transformation protocol for Ma bamboo from vegetative organ is established.

PMID: 28798758 [PubMed]

Draft Genome Sequences of Three β-Lactam-Catabolizing Soil Proteobacteria.

Genome Announc. 2017 Aug 10;5(32):

Authors: Crofts TS, Wang B, Spivak A, Gianoulis TA, Forsberg KJ, Gibson MK, Johnsky LA, Broomall SM, Rosenzweig CN, Skowronski EW, Gibbons HS, Sommer MOA, Dantas G

Abstract
Most antibiotics are derived from the soil, but their catabolism there, which is necessary to close the antibiotic carbon cycle, remains uncharacterized. We report the first draft genome sequences of soil Proteobacteria identified for subsisting solely on β-lactams as their carbon sources. The genomes encode multiple β-lactamases, although their antibiotic catabolic pathways remain enigmatic.

PMID: 28798166 [PubMed]

Complete Genome Sequences of Three Isolates of Xanthomonas fragariae, the Bacterium Responsible for Angular Leaf Spots on Strawberry Plants.

Genome Announc. 2017 Aug 10;5(32):

Authors: Gétaz M, van der Wolf JM, Blom J, Pothier JF

Abstract
Xanthomonas fragariae is a worldwide-spread plant bacterial disease causing angular leaf spots, thus reducing the yield of production for strawberry fruits. Three isolates with various geographic and time origins were sequenced with long-read technology (PacBio) to generate finished genome sequences of virulent strains and observe the variability in their contents.

PMID: 28798165 [PubMed]

Mass spectrometry data of metabolomics analysis of Nepenthes pitchers.

Data Brief. 2017 Oct;14:295-297

Authors: Rosli MAF, Azizan KA, Baharum SN, Goh HH

Abstract
Hybridisation plays a significant role in the evolution and diversification of plants. Hybridisation among Nepenthes species is extensive, either naturally or man-made. To investigate the effects of hybridisation on the chemical compositions, we carried out metabolomics study on pitcher tissue of Nepenthes ampullaria, Nepenthes rafflesiana and their hybrid, Nepenthes × hookeriana. Pitcher samples were harvested and extracted in methanol:chloroform:water via sonication-assisted extraction before analysed using LC-TOF-MS. MS data were analysed using XCMS online version 2.2.5. This is the first MS data report towards the profiling, identification and comprehensive comparison of metabolites present in Nepenthes species.

PMID: 28795107 [PubMed]

Microarray dataset of transgenic rice overexpressing Abp57.

Data Brief. 2017 Oct;14:267-271

Authors: Tan LW, Tan CS, Rahman ZA, Goh HH, Ismail I, Zainal Z

Abstract
The dataset presented in this article describes microarray experiment of Auxin-binding protein 57, Abp57-overexpressing transgenic rice. The gene expression profiles were generated using Affymetrix GeneChip® Rice (Cn) Gene 1.0 ST Arrays. Total RNA from seedlings tissue of transgenic rice and wildtype, which serve as control were used as starting materials for microarray experiment. Detailed experimental methods and data analysis were described here. The raw and normalized microarray data were deposited into Gene Expression Omnibus (GEO) under accession number GSE99055.

PMID: 28795104 [PubMed]