scholarly journals Rapid selection response to ethanol in S. eubayanus emulates the domestication process under brewing conditions

2020 ◽  
Author(s):  
Wladimir Mardones ◽  
Carlos A. Villarroel ◽  
Valentina Abarca ◽  
Kamila Urbina ◽  
Tomás A. Peña ◽  
...  
Keyword(s):  
Stress Tolerance ◽  
Time Course ◽  
De Novo ◽  
Rapid Evolution ◽  
Selection Response ◽  
Diauxic Shift ◽  
Lager Yeast ◽  
Altered Expression ◽  
Domestication Syndrome ◽  
Domestication Process

ABSTRACTAlthough the typical genomic and phenotypic changes that characterize the evolution of organisms under the human domestication syndrome represent textbook examples of rapid evolution, the molecular processes that underpin such changes are still poorly understood. Domesticated yeasts for brewing, where short generation times and large phenotypic and genomic plasticity were attained in a few generations under selection, are prime examples. To experimentally emulate the lager yeast domestication process, we created a genetically complex (panmictic) artificial population of multiple Saccharomyces eubayanus genotypes, one of the parents of lager yeast. Then we imposed a constant selection regime under a high ethanol concentration in 10 replicated populations during 260 generations (six months) and compared them with evolved controls exposed solely to glucose. Evolved populations exhibited a selection differential of 60% in growth rate in ethanol, mostly explained by the proliferation of a single lineage (CL248.1) that competitively displaced all other clones. Interestingly, the outcome does not require the entire time course of adaptation, as four lineages monopolized the culture at generation 120. Sequencing demonstrated that de novo genetic variants were produced in all evolved lines, including SNPs, aneuploidies, INDELs, and translocations. In addition, the evolved populations showed correlated responses resembling the domestication syndrome: genomic rearrangements, faster fermentation rates, lower production of phenolic-off flavors and lower volatile compound complexity. Expression profiling in beer wort revealed altered expression levels of genes related to methionine metabolism, flocculation, stress tolerance and diauxic shift, likely contributing to higher ethanol and fermentation stress tolerance in the evolved populations. Our study shows that experimental evolution can rebuild the brewing domestication process in “fast motion” in wild yeast, and also provides a powerful tool for studying the genetics of the adaptation process in complex populations.

Arabidopsis 4-COUMAROYL-COA LIGASE 8 contributes to the biosynthesis of the benzenoid ring of coenzyme Q in peroxisomes

2019 ◽  
Vol 476 (22) ◽  
pp. 3521-3532
Author(s):  
Eric Soubeyrand ◽  
Megan Kelly ◽  
Shea A. Keene ◽  
Ann C. Bernert ◽  
Scott Latimer ◽  
...  
Keyword(s):  
Oxidative Metabolism ◽  
Time Course ◽  
Reverse Genetics ◽  
De Novo ◽  
Coenzyme Q ◽  
Control Level ◽  
Wild Type ◽  
Fluorescent Reporters ◽  
Coa Ligase ◽  
Peroxisomal Targeting

Plants have evolved the ability to derive the benzenoid moiety of the respiratory cofactor and antioxidant, ubiquinone (coenzyme Q), either from the β-oxidative metabolism of p-coumarate or from the peroxidative cleavage of kaempferol. Here, isotopic feeding assays, gene co-expression analysis and reverse genetics identified Arabidopsis 4-COUMARATE-COA LIGASE 8 (4-CL8; At5g38120) as a contributor to the β-oxidation of p-coumarate for ubiquinone biosynthesis. The enzyme is part of the same clade (V) of acyl-activating enzymes than At4g19010, a p-coumarate CoA ligase known to play a central role in the conversion of p-coumarate into 4-hydroxybenzoate. A 4-cl8 T-DNA knockout displayed a 20% decrease in ubiquinone content compared with wild-type plants, while 4-CL8 overexpression boosted ubiquinone content up to 150% of the control level. Similarly, the isotopic enrichment of ubiquinone's ring was decreased by 28% in the 4-cl8 knockout as compared with wild-type controls when Phe-[Ring-13C6] was fed to the plants. This metabolic blockage could be bypassed via the exogenous supply of 4-hydroxybenzoate, the product of p-coumarate β-oxidation. Arabidopsis 4-CL8 displays a canonical peroxisomal targeting sequence type 1, and confocal microscopy experiments using fused fluorescent reporters demonstrated that this enzyme is imported into peroxisomes. Time course feeding assays using Phe-[Ring-13C6] in a series of Arabidopsis single and double knockouts blocked in the β-oxidative metabolism of p-coumarate (4-cl8; at4g19010; at4g19010 × 4-cl8), flavonol biosynthesis (flavanone-3-hydroxylase), or both (at4g19010 × flavanone-3-hydroxylase) indicated that continuous high light treatments (500 µE m−2 s−1; 24 h) markedly stimulated the de novo biosynthesis of ubiquinone independently of kaempferol catabolism.

BioMime – A Sirolimus-eluting Coronary Stent System for the Treatment of Patients with De Novo Coronary Lesions – meriT-1 Report

2011 ◽  
Vol 6 (1) ◽  
pp. 39
Author(s):  
Keyword(s):  
Stent Thrombosis ◽  
Time Course ◽  
De Novo ◽  
Drug Eluting Stent ◽  
Cobalt Chromium ◽  
Cardiac Events ◽  
End Points ◽  
Safety And Efficacy ◽  
Binary Restenosis

Background:Since the first reported use of percutaneous transluminal coronary angioplasty, advances in the interventional cardiology arena have been fast paced. Developers and clinicians are adapting from the learning curve awarded by the time-course of drug-eluting stent (DES) evolution. BioMime™ sirolimus-eluting stent (SES) is a step towards biomimicry. The stent is built on a strut of ultra-low thickness (65μm), a cobalt–chromium platform using an intelligent hybrid of closed and open cells allowing for morphology-mediated expansion. It employs a well-known antiproliferative – sirolimus – that elutes from a known biodegradable copolymer formulation within 30 days. The resultant stent demonstrates almost 100% endothelialisation at 30 days in preclinical models.Methods:The meriT-1 was a prospective, single-arm, single-centre trial to evaluate the safety and efficacy of BioMime SES in 30 patients with a single de novo lesion in native coronary arteries. The primary safety and efficacy end-points were major adverse cardiac events (MACE) at 30 days and in-stent late lumen loss at eight months, as measured using quantitative coronary angiographic (QCA) method. Secondary safety and efficacy end-points included MACE at one and two years and angiographic binary restenosis at eight-month angiographic follow-up. Other end-points included the occurrence of stent thrombosis at acute, subacute, late and very late periods and the percentage of diameter stenosis by QCA.Results:No MACE were observed and the median in-stent late luminal loss in 20 (67%) subjects studied by QCA was 0.15mm, with 0% binary restenosis at eight-month follow-up. No stent thrombosis was observed up to one-year follow-up.Conclusions:In comparison to currently available DES, BioMime SES appears to have a considerable scientific basis for prevention of neointimal proliferation, restenosis and associated clinical events.

scholarly journals Lipid Metabolism Is Dysregulated before, during and after Pregnancy in a Mouse Model of Gestational Diabetes

2021 ◽  
Vol 22 (14) ◽  
pp. 7452
Author(s):  
Samuel Furse ◽  
Denise S. Fernandez-Twinn ◽  
Davide Chiarugi ◽  
Albert Koulman ◽  
Susan E. Ozanne
Keyword(s):  
Lipid Metabolism ◽  
Gestational Diabetes ◽  
Glucose Tolerance ◽  
Mouse Model ◽  
Time Course ◽  
De Novo ◽  
Lipid Analysis ◽  
Temporal Distribution ◽  
De Novo Lipogenesis ◽  
Analysis Tool

The aim of the current study was to test the hypothesis that maternal lipid metabolism was modulated during normal pregnancy and that these modulations are altered in gestational diabetes mellitus (GDM). We tested this hypothesis using an established mouse model of diet-induced obesity with pregnancy-associated loss of glucose tolerance and a novel lipid analysis tool, Lipid Traffic Analysis, that uses the temporal distribution of lipids to identify differences in the control of lipid metabolism through a time course. Our results suggest that the start of pregnancy is associated with several changes in lipid metabolism, including fewer variables associated with de novo lipogenesis and fewer PUFA-containing lipids in the circulation. Several of the changes in lipid metabolism in healthy pregnancies were less apparent or occurred later in dams who developed GDM. Some changes in maternal lipid metabolism in the obese-GDM group were so late as to only occur as the control dams’ systems began to switch back towards the non-pregnant state. These results demonstrate that lipid metabolism is modulated in healthy pregnancy and the timing of these changes is altered in GDM pregnancies. These findings raise important questions about how lipid metabolism contributes to changes in metabolism during healthy pregnancies. Furthermore, as alterations in the lipidome are present before the loss of glucose tolerance, they could contribute to the development of GDM mechanistically.

Differential expression of TNF-α, IL-6, and IGF-1 by graded mechanical stress in normal rat myocardium

2002 ◽  
Vol 282 (3) ◽  
pp. H926-H934 ◽  
Author(s):  
Emiliano A. Palmieri ◽  
Giulio Benincasa ◽  
Francesca Di Rella ◽  
Cosma Casaburi ◽  
Maria G. Monti ◽  
...  
Keyword(s):  
Time Course ◽  
De Novo ◽  
Mechanical Stretch ◽  
Progressive Increase ◽  
Compensatory Hypertrophy ◽  
Current Data ◽  
Rat Myocardium ◽  
Tnf Α ◽  
Normal Rat ◽  
Necrosis Factor

An isovolumic normal rat heart Langendorff model was used to examine the effects of moderate (15 mmHg) and severe (35 mmHg) mechanical stretch on the time course (from 0 to 60 min) of myocardial expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and insulin-like growth factor (IGF)-1 and their cognate receptors. After 10 min of moderate stretch, TNF-α was de novo expressed, whereas constitutive IL-6 and IGF-1 levels were slightly upregulated; no further changes occurred up to 60 min. In comparison, severe stretch resulted in a higher and progressive increase in TNF-α, IL-6, and IGF-1 expression up to 20 min. After 20 min, whereas TNF-α expression further increased, IL-6 and IGF-1 levels progressively reduced to values lower than those observed under moderate stretch and in unstretched (5 mmHg) control myocardium (IL-6). Mechanical stretch did not significantly alter the expression of the cognate receptors. Indeed, the TNF-α receptor (p55) tended to be progressively upregulated under severe stretch over time. The current data provide the first demonstration that TNF-α, IL-6, and IGF-1 ligand-receptor systems are differentially expressed within the normal rat myocardium in response to graded mechanical stretch. Such findings may have potential implications with regard to compensatory hypertrophy and failure.

scholarly journals Long-Term Waterlogging as Factor Contributing to Hypoxia Stress Tolerance Enhancement in Cucumber: Comparative Transcriptome Analysis of Waterlogging Sensitive and Tolerant Accessions

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 189
Author(s):  
Kinga Kęska ◽  
Michał Wojciech Szcześniak ◽  
Izabela Makałowska ◽  
Małgorzata Czernicka
Keyword(s):  
Stress Tolerance ◽  
De Novo ◽  
Average Length ◽  
Marker Genes ◽  
Long Term Memory ◽  
Low Oxygen ◽  
Waterlogging Tolerance ◽  
Pre Treatment ◽  
Waterlogging Treatment

Waterlogging (WL), excess water in the soil, is a phenomenon often occurring during plant cultivation causing low oxygen levels (hypoxia) in the soil. The aim of this study was to identify candidate genes involved in long-term waterlogging tolerance in cucumber using RNA sequencing. Here, we also determined how waterlogging pre-treatment (priming) influenced long-term memory in WL tolerant (WL-T) and WL sensitive (WL-S) i.e., DH2 and DH4 accessions, respectively. This work uncovered various differentially expressed genes (DEGs) activated in the long-term recovery in both accessions. De novo assembly generated 36,712 transcripts with an average length of 2236 bp. The results revealed that long-term waterlogging had divergent impacts on gene expression in WL-T DH2 and WL-S DH4 cucumber accessions: after 7 days of waterlogging, more DEGs in comparison to control conditions were identified in WL-S DH4 (8927) than in WL-T DH2 (5957). Additionally, 11,619 and 5007 DEGs were identified after a second waterlogging treatment in the WL-S and WL-T accessions, respectively. We identified genes associated with WL in cucumber that were especially related to enhanced glycolysis, adventitious roots development, and amino acid metabolism. qRT-PCR assay for hypoxia marker genes i.e., alcohol dehydrogenase (adh), 1-aminocyclopropane-1-carboxylate oxidase (aco) and long chain acyl-CoA synthetase 6 (lacs6) confirmed differences in response to waterlogging stress between sensitive and tolerant cucumbers and effectiveness of priming to enhance stress tolerance.

Glucocorticoid-regulated compartmentalization of cell surface-associated glycoproteins in rat hepatoma cells: evidence for an independent response that requires receptor function and de novo RNA synthesis

1987 ◽  
Vol 7 (4) ◽  
pp. 1508-1517
Author(s):  
O K Haffar ◽  
A K Vallerga ◽  
S A Marenda ◽  
H J Witchel ◽  
G L Firestone
Keyword(s):  
Cell Surface ◽  
Time Course ◽  
Rna Synthesis ◽  
De Novo ◽  
Receptor Occupancy ◽  
Receptor Function ◽  
Intracellular Fraction ◽  
Culture Cells ◽  
Viral Glycoproteins ◽  
Rat Hepatoma

The role of glucocorticoid hormones in the compartmentalization of cell surface-associated mouse mammary tumor virus (MMTV) glycoproteins was examined in M1.54, a cloned line of MMTV-infected rat hepatoma tissue culture cells. The expression of cellular [2-3H]mannose-labeled and cell surface 125I-labeled MMTV glycoproteins was examined throughout a time course of exposure to dexamethasone, a synthetic glucocorticoid. Posttranslational localization of cell surface MMTV glycoproteins required 6 h of exposure to hormone and occurred approximately 4 h after their initial production in an intracellular fraction. This regulated localization to the cell surface correlated with glucocorticoid receptor occupancy and was inhibited by exposure to RU 38486, a powerful antagonist of glucocorticoid-mediated responses. Cell surface immunoprecipitation demonstrated that actinomycin D, an inhibitor of de novo RNA synthesis, prevented regulated expression of cell surface viral glycoproteins, suggesting that newly synthesized cellular components mediate this process. The localization of cell surface MMTV glycoproteins appeared normal in a transcriptional variant (CR1) that produces basal levels of MMTV RNA and glycoprotein precursors in the presence of dexamethasone. Thus, regulated compartmentalization of viral glycoproteins is not an obligate consequence of a critical precursor concentration. Taken together, our results suggest that posttranslational trafficking of cell surface-destined MMTV glycoproteins resulted from an independent glucocorticoid hormone response that required receptor function and de novo RNA synthesis.

Expression profiles of organogenesis-related genes over the time course of one-step de novo shoot organogenesis from intact seedlings of kohlrabi

2019 ◽  
Vol 232 ◽  
pp. 257-269 ◽  
Author(s):  
Tatjana Ćosić ◽  
Martin Raspor ◽  
Jelena Savić ◽  
Aleksandar Cingel ◽  
Dragana Matekalo ◽  
...  
Keyword(s):  
Time Course ◽  
De Novo ◽  
Shoot Organogenesis ◽  
Expression Profiles ◽  
One Step

scholarly journals De Novo Transcriptome Assembly, Functional Annotation, and Transcriptome Dynamics Analyses Reveal Stress Tolerance Genes in Mangrove Tree (Bruguiera gymnorhiza)

2021 ◽  
Vol 22 (18) ◽  
pp. 9874
Author(s):  
Matin Miryeganeh ◽  
Hidetoshi Saze
Keyword(s):  
Stress Tolerance ◽  
Molecular Mechanisms ◽  
High Salinity ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Expression Profiles ◽  
Natural Habitats ◽  
Mangrove Species ◽  
Mangrove Tree ◽  
Bruguiera Gymnorhiza

Their high adaptability to difficult coastal conditions makes mangrove trees a valuable resource and an interesting model system for understanding the molecular mechanisms underlying stress tolerance and adaptation of plants to the stressful environmental conditions. In this study, we used RNA sequencing (RNA-Seq) for de novo assembling and characterizing the Bruguiera gymnorhiza (L.) Lamk leaf transcriptome. B. gymnorhiza is one of the most widely distributed mangrove species from the biggest family of mangroves; Rhizophoraceae. The de novo assembly was followed by functional annotations and identification of individual transcripts and gene families that are involved in abiotic stress response. We then compared the genome-wide expression profiles between two populations of B. gymnorhiza, growing under different levels of stress, in their natural habitats. One population living in high salinity environment, in the shore of the Pacific Ocean- Japan, and the other population living about one kilometre farther from the ocean, and next to the estuary of a river; in less saline and more brackish condition. Many genes involved in response to salt and osmotic stress, showed elevated expression levels in trees growing next to the ocean in high salinity condition. Validation of these genes may contribute to future salt-resistance research in mangroves and other woody plants. Furthermore, the sequences and transcriptome data provided in this study are valuable scientific resources for future comparative transcriptome research in plants growing under stressful conditions.

scholarly journals RNA-Seq Transcriptome Analysis of Peripheral Blood From Cattle Infected With Mycobacterium bovis Across an Experimental Time Course

2021 ◽  
Vol 8 ◽  
Author(s):  
Kirsten E. McLoughlin ◽  
Carolina N. Correia ◽  
John A. Browne ◽  
David A. Magee ◽  
Nicolas C. Nalpas ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Mycobacterium Bovis ◽  
Peripheral Blood ◽  
Post Infection ◽  
Time Course ◽  
De Novo ◽  
Differentially Expressed Gene ◽  
Differentially Expressed ◽  
Infection Time ◽  
Time Point

Bovine tuberculosis, caused by infection with members of the Mycobacterium tuberculosis complex, particularly Mycobacterium bovis, is a major endemic disease affecting cattle populations worldwide, despite the implementation of stringent surveillance and control programs in many countries. The development of high-throughput functional genomics technologies, including RNA sequencing, has enabled detailed analysis of the host transcriptome to M. bovis infection, particularly at the macrophage and peripheral blood level. In the present study, we have analysed the transcriptome of bovine whole peripheral blood samples collected at −1 week pre-infection and +1, +2, +6, +10, and +12 weeks post-infection time points. Differentially expressed genes were catalogued and evaluated at each post-infection time point relative to the −1 week pre-infection time point and used for the identification of putative candidate host transcriptional biomarkers for M. bovis infection. Differentially expressed gene sets were also used for examination of cellular pathways associated with the host response to M. bovis infection, construction of de novo gene interaction networks enriched for host differentially expressed genes, and time-series analyses to identify functionally important groups of genes displaying similar patterns of expression across the infection time course. A notable outcome of these analyses was identification of a 19-gene transcriptional biosignature of infection consisting of genes increased in expression across the time course from +1 week to +12 weeks post-infection.

scholarly journals Language impairments in ASD resulting from a failed domestication of the human brain

2016 ◽  
Author(s):  
Antonio Benítez-Burraco ◽  
Wanda Lattanzi ◽  
Elliot Murphy
Keyword(s):  
Human Brain ◽  
Neural Crest ◽  
Language Processing ◽  
Expression Profiles ◽  
Autism Spectrum ◽  
Human Populations ◽  
Altered Expression ◽  
Domestication Syndrome ◽  
High Prevalence ◽  
The Brain

AbstractAutism spectrum disorders (ASD) are pervasive neurodevelopmental disorders entailing social and cognitive deficits, including marked problems with language. Numerous genes have been associated with ASD, but it is unclear how language deficits arise from gene mutation or dysregulation. It is also unclear why ASD shows such high prevalence within human populations. Interestingly, the emergence of a modern faculty of language has been hypothesised to be linked to changes in the human brain/skull, but also to the process of self-domestication of the human species. It is our intention to show that people with ASD exhibit less marked domesticated traits at the morphological, physiological, and behavioural levels. We also discuss many ASD candidates represented among the genes known to be involved in the domestication syndrome (the constellation of traits exhibited by domesticated mammals, which seemingly results from the hypofunction of the neural crest) and among the set of genes involved in language function closely connected to them. Moreover, many of these genes show altered expression profiles in the brain of autists. In addition, some candidates for domestication and language-readiness show the same expression profile in people with ASD and chimps in different brain areas involved in language processing. Similarities regarding the brain oscillatory behaviour of these areas can be expected too. We conclude that ASD may represent an abnormal ontogenetic itinerary for the human faculty of language resulting in part from changes in genes important for the domestication syndrome and, ultimately, from the normal functioning of the neural crest.

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