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Metabolic pathways

Héctor Cervera, Silvia Ambrós, Guillermo P Bernet, Guillermo Rodrigo, Santiago F Elena
Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference, is a complex property that captures, in a single figure, differences in performance at every stage of viral infection. To what extent does viral fitness result from specific molecular interactions with host factors and regulatory networks during infection? Can we identify host genes in functional classes whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyvirus (TEV) that differ in fitness...
March 19, 2018: Molecular Biology and Evolution
Evan M Zhao, Yanfei Zhang, Justin Mehl, Helen Park, Makoto A Lalwani, Jared E Toettcher, José L Avalos
The optimization of engineered metabolic pathways requires careful control over the levels and timing of metabolic enzyme expression. Optogenetic tools are ideal for achieving such precise control, as light can be applied and removed instantly without complex media changes. Here we show that light-controlled transcription can be used to enhance the biosynthesis of valuable products in engineered Saccharomyces cerevisiae. We introduce new optogenetic circuits to shift cells from a light-induced growth phase to a darkness-induced production phase, which allows us to control fermentation with only light...
March 21, 2018: Nature
Devram S Ghorpade, Lale Ozcan, Ze Zheng, Sarah M Nicoloro, Yuefei Shen, Emily Chen, Matthias Blüher, Michael P Czech, Ira Tabas
Obesity-induced metabolic disease involves functional integration among several organs via circulating factors, but little is known about crosstalk between liver and visceral adipose tissue (VAT). In obesity, VAT becomes populated with inflammatory adipose tissue macrophages (ATMs). In obese humans, there is a close correlation between adipose tissue inflammation and insulin resistance, and in obese mice, blocking systemic or ATM inflammation improves insulin sensitivity. However, processes that promote pathological adipose tissue inflammation in obesity are incompletely understood...
March 21, 2018: Nature
Jie Meng, Wen-Xiong Wang, Li Li, Guofan Zhang
Lead (Pb) is one of the ubiquitous and toxic elements in aquatic environment. In oysters, gills and digestive glands are the main target organs for Pb-induced toxicity, but there is limited information on the molecular mechanisms underlying its toxicity. The present study investigated the Pb-induced toxicity mechanisms in the Pacific oyster (Crassostrea gigas) based on transcriptome, phenotypic anchoring, and validation of targeted gene expression. Gene ontology and pathway enrichment analyses revealed the differential Pb toxicity mechanisms in the tissues...
March 13, 2018: Aquatic Toxicology
Bridget P Bannerman, Susanne Kramer, Richard G Dorrell, Mark Carrington
The degree of conservation and evolution of cytoplasmic mRNA metabolism pathways across the eukaryotes remains incompletely resolved. In this study, we describe a comprehensive genome and transcriptome-wide analysis of proteins involved in mRNA maturation, translation, and mRNA decay across representative organisms from the six eukaryotic super-groups. We demonstrate that eukaryotes share common pathways for mRNA metabolism that were almost certainly present in the last eukaryotic common ancestor, and show for the first time a correlation between intron density and a selective absence of some Exon Junction Complex (EJC) components in eukaryotes...
2018: PloS One
Germano Guerra, Angela Lucariello, Angelica Perna, Laura Botta, Antonio De Luca, Francesco Moccia
BACKGROUND: Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity (NA) leads to local elevation in cerebral blood flow (CBF) to match the metabolic requirements of firing neurons. Following synaptic activity, an increase in neuronal and/or astrocyte Ca2+ concentration leads to the synthesis of multiple vasoactive messengers. Curiously, the role of endothelial Ca2+ signaling in NVC has been rather neglected, although endothelial cells are known to control the vascular tone in a Ca2+ -dependent manner throughout peripheral vasculature...
March 21, 2018: International Journal of Molecular Sciences
Songzhen He, Xiaoling Tong, Minjin Han, Yanmin Bai, Fangyin Dai
The tyrosine kinases (TKs) are important parts of metazoan signaling pathways and play significant roles in cell growth, development, apoptosis and disease. Genome-wide characterization of TKs has been conducted in many metazoans, however, systematic information about this family in Lepidoptera is still lacking. We retrieved 33 TK-encoding genes in silkworm and classified them into 25 subfamilies by sequence analysis, without members in AXL, FRK, PDGFR, STYK1 and TIE subfamilies. Although domain sequences in each subfamily are conserved, TKs in vertebrates tend to be remarkably conserved and stable...
March 21, 2018: International Journal of Molecular Sciences
Francois Dussart, Ryan Douglas, Elisabet Sjökvist, Peter N Hoebe, Steven H Spoel, Graham R D McGrann
Ramularia collo-cygni (Rcc) causes Ramularia leaf spot (RLS) disease of barley. The fungus develops asymptomatically within its host until late in the growing season when necrotic lesions become visible on upper leaves. Fungal secondary metabolites (SMs) have been proposed as important factors in RLS lesion formation, but the biosynthetic pathways involved remain largely unknown. Mining the Rcc genome revealed the presence of ten polyketide synthases (PKSs), ten non-ribosomal peptide synthetases (NRPSs) and three hybrid PKS-NRPS (HPSs) identified within clusters of genes with predicted functions associated with secondary metabolism...
March 21, 2018: Molecular Plant-microbe Interactions: MPMI
Daniel Joseph Kostyniuk, Brett Matthew Culbert, Jan Alexander Mennigen, Kathleen M Gilmour
Juvenile rainbow trout (Oncorhynchus mykiss) confined in pairs form social hierarchies in which socially subordinate fish display characteristic traits, including reduced growth rates and altered glucose metabolism. These effects are, in part, mediated by chronically elevated cortisol levels and/or reduced feeding. To determine the effects of social status on lipid metabolism, trout were held in pairs for 4 d, following which organismal and liver-specific indices of lipid metabolism were measured. At the organismal level, circulating triglycerides were elevated in dominant trout, whereas subordinate trout exhibited elevated concentrations of circulating free fatty acids (FFA) and lowered plasma total cholesterol levels...
March 21, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Sheila Sharp, Scott J Mitchell, Monique Vallée, Elena Kuzmanova, Michelle Cooper, Delia Belelli, Jeremy J Lambert, Jeffrey T-J Huang
Neurosteroids are brain-derived steroids, capable of rapidly modulating neuronal excitability in a non-genomic manner. Dysregulation of their synthesis, or metabolism has been implicated in many pathological conditions. Here, we describe an isotope dilution based targeted and non-targeted (ID-TNT) profiling of carbonyl neurosteroids/steroids. The method combines stable isotope dilution, hydroxylamine derivatization, high-resolution MS scanning and data dependent MS/MS analysis, allowing absolute quantification of pregnenolone, progesterone, 5α-dihydroprogesterone, 3α,5α-tetrahydroprogesterone and 3β,5α-tetrahydroprogesterone, and relative quantification of other carbonyl containing steroids...
March 21, 2018: Analytical Chemistry
Nicolette Kapp, Xiao X Stander, Barend A Stander
This project investigated the in-vitro effects of a glycolytic inhibitor, 3-bromopyruvate (3-BrP), in combination with and a new in silico-designed inhibitor of the bromodomain-4 (BRD-4) protein, ITH-47, on the U937 acute myeloid leukemia cell line. 3-BrP is an agent that targets the altered metabolism of cancer cells by interfering with glucose metabolism in the glycolytic pathway. ITH-47 is an acetyl-lysine inhibitor that displaces bromdomain 4 proteins from chromatin by competitively binding to the acetyl-lysine recognition pocket of this bromodomain and extraterminal (BET) BRD protein, thereby preventing transcription of cancer-associated genes and further cell growth...
March 20, 2018: Anti-cancer Drugs
Geoffrey D Abrams, David Feldman, Marc R Safran
Vitamin D is known to be important for calcium homeostasis and bone metabolism. It also has important direct effects on skeletal muscle. Unlike authentic vitamins, which cannot be synthesized in the body, vitamin D is produced in the skin using sunlight. Through its nuclear receptor (ie, vitamin D receptor) located throughout the body, including skeletal muscle, vitamin D initiates genomic and nongenomic pathways regulating multiple actions, including myocyte proliferation and growth. In some studies, vitamin D supplementation has been shown to increase muscle strength, particularly in people who are vitamin D deficient...
March 20, 2018: Journal of the American Academy of Orthopaedic Surgeons
Jin Huang, Wan Tang, Shengquan Zhu, Meini Du
Butyric acid (C3 H7 COOH) is an important chemical that is widely used in foodstuffs along with in the chemical and pharmaceutical industries. The bioproduction of butyric acid via large-scale fermentation has the potential to be more economical and efficient than petrochemical synthesis. In this paper, the metabolic pathways involved in the production of butyric acid from Clostridium tyrobutyricum using hexose and pentose as substrates are investigated, and approaches to enhance butyric acid production via genetic modification are discussed...
March 21, 2018: Preparative Biochemistry & Biotechnology
Francesc Font-Clos, Stefano Zapperi, Caterina A M La Porta
OBJECTIVE: Observational studies suggest that obesity might have a Mendelian origin, but it is not clear if gene expression patterns observed in obese subjects are secondary to genetic traits or not. 
 Approach: Here we test a transcriptomic signature of obesity previously identified by our group
 on a large cohort of twin subjects (TwinsUK). 
 Main results: The results show that the signature correlates strongly both with the body mass index (BMI) and fat mass...
March 21, 2018: Physiological Measurement
Vikram Subramanian, Sabine Borchard, Omid Azimzadeh, Wolfgang Sievert, Juliane Merl-Pham, Mariateresa Mancuso, Emanuela Pasquali, Gabriele Multhoff, Bastian Popper, Hans Zischka, Michael J Atkinson, Soile Tapio
High-dose ionizing radiation is known to induce adverse effects such as inflammation and fibrosis in the heart. Transcriptional regulators PPARα and TGFβ are known to be involved in this radiation response. PPARα, an anti-inflammatory transcription factor controlling cardiac energy metabolism, is inactivated by irradiation. The pro-inflammatory and pro-fibrotic TGFβ is activated by irradiation via SMAD-dependent and SMAD-independent pathways. The goal of this study was to investigate how altering the level of PPARα influences the radiation response of these signaling pathways...
March 21, 2018: Journal of Proteome Research
Dong-Uk Yang, Muhammad Hanif Siddiqi, Sungeun Ahn, Sera Kang, Hae-Yong Noh, Deok-Chun Yang
Osteoporosis is a widespread musculoskeletal deformity that affects thousands of older people every year, leading to bone abnormalities and ultimately increasing the risk of bone fractures in both genders. It is considered a lethal disease causing death in thousands of people at the late stage of life. Dendropanax morbifera Leveille is a subtropical broad-leaved prevalent species in Korea. Extracts of the leaves, stems, roots, and seeds of D. morbifera have been used in traditional medicine for the treatment of numerous diseases such as diabetes, atherogenesis, skin disorders, and headaches...
March 20, 2018: In Vitro Cellular & Developmental Biology. Animal
Nicolás De Silva, Mirian Samblas, J Alfredo Martínez, Fermín I Milagro
Obesity is usually associated with low-grade inflammation, which determines the appearance of comorbidities like atherosclerosis and insulin resistance. Infiltrated macrophages in adipose tissue are partly responsible of this inflammatory condition. Numerous studies point to the existence of close intercommunication between macrophages and adipocytes and pay particular attention to the proinflammatory cytokines released by both cell types. However, it has been recently described that in both, circulation and tissue level, there are extracellular vesicles (including microvesicles and exosomes) containing miRNAs, mRNAs, and proteins that can influence the inflammatory response...
March 20, 2018: Journal of Physiology and Biochemistry
Jun Min, Jinpei Wang, Weiwei Chen, Xiaoke Hu
Cupriavidus sp. strain CNP-8 isolated from a pesticide-contaminated soil was able to utilize 2-chloro-4-nitrophenol (2C4NP) as a sole source of carbon, nitrogen and energy, together with the release of nitrite and chloride ions. It could degrade 2C4NP at temperatures from 20 to 40 °C and at pH values from 5 to 10, and degrade 2C4NP as high as 1.6 mM. Kinetics assay showed that biodegradation of 2C4NP followed Haldane substrate inhibition model, with the maximum specific growth rate (μmax ) of 0.148/h, half saturation constant (Ks ) of 0...
March 20, 2018: AMB Express
Shimpei Morimoto, Koji Yahara
Protein expression is regulated by the production and degradation of mRNAs and proteins but the specifics of their relationship are controversial. Although technological advances have enabled genome-wide and time-series surveys of mRNA and protein abundance, recent studies have shown paradoxical results, with most statistical analyses being limited to linear correlation, or analysis of variance applied separately to mRNA and protein datasets. Here, using recently analyzed genome-wide time-series data, we have developed a statistical analysis framework for identifying which types of genes or biological gene groups have significant correlation between mRNA and protein abundance after accounting for potential time delays...
March 2018: Heliyon
Paul P Jung, Zhi Zhang, Nicole Paczia, Christian Jaeger, Tomasz Ignac, Patrick May, Carole L Linster
Aging is a complex trait of broad scientific interest, especially because of its intrinsic link with common human diseases. Pioneering work on aging-related mechanisms has been made in Saccharomyces cerevisiae , mainly through the use of deletion collections isogenic to the S288c reference strain. In this study, using a recently published high-throughput approach, we quantified chronological life span (CLS) within a collection of 58 natural strains across seven different conditions. We observed a broad aging variability suggesting the implication of diverse genetic and environmental factors in chronological aging control...
2018: NPJ Aging and Mechanisms of Disease
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