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mitochondrial engineering

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https://www.readbyqxmd.com/read/29753070/iterative-algorithm-guided-design-of-massive-strain-libraries-applied-to-itaconic-acid-production-in-yeast
#1
Eric M Young, Zheng Zhao, Bianca E M Gielesen, Liang Wu, D Benjamin Gordon, Johannes A Roubos, Christopher A Voigt
Metabolic engineering requires multiple rounds of strain construction to evaluate alternative pathways and enzyme concentrations. Optimizing multigene pathways stepwise or by randomly selecting enzymes and expression levels is inefficient. Here, we apply methods from design of experiments (DOE) to guide the construction of strain libraries from which the maximum information can be extracted without sampling every possible combination. We use Saccharomyces cerevisiae as a host for a novel six-gene pathway to itaconic acid, selected by comparing alternative shunt pathways that bypass the mitochondrial TCA cycle...
May 9, 2018: Metabolic Engineering
https://www.readbyqxmd.com/read/29748134/oxysterol-binding-protein-related-proteins-orps-5-and-8-regulate-calcium-signaling-at-specific-cell-compartments
#2
Ilari Pulli, Taru Lassila, Guoping Pan, Daoguang Yan, Vesa M Olkkonen, Kid Törnquist
Oxysterol-binding protein related-protein 5 and 8 (ORP5/8) localize to the membrane contact sites (MCS) of the endoplasmic reticulum (ER) and the mitochondria, as well as to the ER-plasma membrane (PM) MCS. The MCS are emerging as important regulators of cell signaling events, including calcium (Ca2+ ) signaling. ORP5/8 have been shown to interact with phosphatidylinositol-4,5-bisphosphate (PIP2 ) in the PM, and to modulate mitochondrial respiration and morphology. PIP2 is the direct precursor of inositol trisphosphate (IP3 ), a key second messenger responsible for Ca2+ -release from the intracellular Ca2+ stores...
March 13, 2018: Cell Calcium
https://www.readbyqxmd.com/read/29719092/evaluation-of-the-toxicity-effects-of-silk-fibroin-on-human-lymphocytes-and-monocytes
#3
Parvaneh Naserzadeh, Seyed Alireza Mortazavi, Khadijeh Ashtari, Ahmad Salimi, Mehdi Farokhi, Jalal Pourahmad
Silk fibroin nanoparticles (SFNPs) as a natural polymer have been utilized in biomedical applications such as suture, tissue engineering-based scaffolds, and drug delivery carriers. Since there is little data regarding the toxicity effects on different cells and tissues, we aimed to determine the toxicity mechanisms of SFNPs on human lymphocytes and monocytes based on reliable methods. Our results showed that SFNPs (0.5, 1, and 2 mg/mL) induced oxidative stress via increasing reactive oxygen species production, mitochondrial membrane potential (∆Ψ) collapse, which was correlated to cytochrome c release and Adenosine diphosphate (ADP)/Adenosine tri phosphate (ATP) ratio increase as well as lysosomal as another toxicity mechanism, which led to cytosolic release of lysosomal digestive proteases, phosphor lipases, and apoptosis signaling...
May 2, 2018: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29709692/turning-one-into-five-integrative-taxonomy-uncovers-complex-evolution-of-cryptic-species-in-the-harvester-ant-messor-structor
#4
Florian M Steiner, Sándor Csősz, Bálint Markó, Alexander Gamisch, Lukas Rinnhofer, Clemens Folterbauer, Sarina Hammerle, Christian Stauffer, Wolfgang Arthofer, Birgit C Schlick-Steiner
Seed harvesting ants are ecosystem engineers that shape vegetation, nutrient cycles, and microclimate. Progress in ecological research is, however, slowed down by poor species delimitation. For example, it has not been resolved to date, how many species the European harvester ant Messor "structor" (Latreille, 1798) represents. Since its first description, splitting into additional taxa was often proposed but not accepted later on due to inconsistent support from morphology and ecology. Here, we took an iterative integrative-taxonomy approach - comparing multiple, independent data sets of the same sample - and used traditional morphometrics, Wolbachia symbionts, mitochondrial DNA, amplified fragment length polymorphism, and ecological niche modelling...
April 27, 2018: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/29684791/the-role-of-promyelocytic-leukemia-protein-in-steatosis-associated-hepatic-tumors-related-to-chronic-hepatitis-b-virus-infection
#5
Yih-Lin Chung, Mei-Ling Wu
The persistence of hepatitis B surface antigen (HBsAg) is a risk factor for the development of steatosis-associated tumors in chronic hepatitis B virus (HBV) infection, yet little is known about the metabolic link with this factor. We correlated HBV-related pathogenesis in genetically engineered mice and human carriers with metabolic proteomics and lipogenic gene expression profiles. The immunohistochemistry showed that the promyelocytic leukemia protein (PML, a tumor suppressor involved in genome maintenance and fatty acid oxidation), being inversely influenced by the dynamic HBsAg levels from acute phase to seroclearance, appeared as a lipo-metabolic switch linking HBsAg-induced steatosis (lipogenesis) to HBsAg-lost fat-burning hepatocarcinogenesis (lipolysis)...
April 20, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29656411/study-on-a-65-mer-peptide-mimetic-enzyme-with-gpx-and-sod-dual-function
#6
Juxin Yin, Jianjian Zhuang, Shaowu Lv, Ying Mu
Excessive reactive oxygen species (ROS) levels are harmful to the body. The peroxidase, GPx, and the superoxide dismutase, SOD, are important antioxidant enzymes for preventing ROS-induced damage. Se-CuZn-65P is an enzyme mimetic with dual GPx and SOD antioxidant function. However, currently, its production is mainly based on the cysteine auxotrophic expression technique, which is inefficient, expensive, and time consuming. In this study, we combined protein engineering and the chemical mutation method to synthesize Se-CuZn-65P...
April 15, 2018: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/29651609/the-delta-opioid-peptide-dadle-represses-hypoxia-reperfusion-mimicked-stress-mediated-apoptotic-cell-death-in-human-mesenchymal-stem-cells-in-part-by-downregulating-the-unfolded-protein-response-and-ros-along-with-enhanced-anti-inflammatory-effect
#7
Madhubanti Mullick, Dwaipayan Sen
Hypoxia-reperfusion (H/R) emblems a plethora of pathological conditions which is potent in contributing to the adversities encountered by human mesenchymal stem cells (hMSCs) in post-transplant microenvironment, resulting in transplant failure. D-Alanine 2, Leucine 5 Enkephaline (DADLE)-mediated delta opioid receptor (DOR) activation is well-known for its recuperative properties in different cell types like neuronal and cardiomyocytes. In the current study its effectiveness in assuaging hMSC mortality under H/R-like insult has been delineated...
April 12, 2018: Stem Cell Reviews
https://www.readbyqxmd.com/read/29620538/pharmaceutical-micelles-featured-with-singlet-oxygen-responsive-cargo-release-and-mitochondrial-targeting-for-enhanced-photodynamic-therapy
#8
Xin Zhang, Qi Yan, Di Naer Mulatihan, Jundong Zhu, Aiping Fan, Zheng Wang, Yanjun Zhao
The efficacy of nanoparticulate photodynamic therapy is often compromised by the short life time and limited diffusion radius as well as uncontrolled intracellular distribution of photosensitizer. It was hypothesized that rapid photosensitizer release upon nanoparticle internalization and its preferred accumulation in mitochondria would address the above problems. Hence, the aim of this study was to engineer a multifunctional micellar nanosystem featured with singlet oxygen-responsive cargo release and mitochondria targeting...
April 5, 2018: Nanotechnology
https://www.readbyqxmd.com/read/29618179/non-benzoquinone-geldanamycinanalog-wk-88-1-induces-apoptosis-in-human-breast-cancer-cell-lines
#9
Yu-Ru Zhao, Hong-Mei Li, Meilin Zhu, Jing Li, Tao Ma, Qiang Huo, Young-Soo Hong, Cheng-Zhu Wu
Heat shock protein 90 (Hsp90) is treated as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor, but hepatotoxicity has limited its clinical application. Nevertheless, a new GA analog (WK-88-1) with the non-benzoquinone skeleton, obtained from the genetically engineered Streptomyces hygroscopicus , was found to haveanticancer activity against two human breast cancer cell lines.WK-88-1 produced concentration-dependent inhibition in cell proliferation, cell cycle arrest, and apoptosis inestrogen receptor (ER)-positive MCF-7 andER-negativeMDA-MB-231 cell lines...
April 6, 2018: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29617673/mitochondrial-complex-i-inhibitors-expose-a-vulnerability-for-selective-killing-of-pten-null-cells
#10
Adam Naguib, Grinu Mathew, Colleen R Reczek, Kaitlin Watrud, Alexandra Ambrico, Tali Herzka, Irene Casanova Salas, Matthew F Lee, Nour El-Amine, Wu Zheng, M Emilia Di Francesco, Joseph R Marszalek, Darryl J Pappin, Navdeep S Chandel, Lloyd C Trotman
A hallmark of advanced prostate cancer (PC) is the concomitant loss of PTEN and p53 function. To selectively eliminate such cells, we screened cytotoxic compounds on Pten-/- ;Trp53-/- fibroblasts and their Pten-WT reference. Highly selective killing of Pten-null cells can be achieved by deguelin, a natural insecticide. Deguelin eliminates Pten-deficient cells through inhibition of mitochondrial complex I (CI). Five hundred-fold higher drug doses are needed to obtain the same killing of Pten-WT cells, even though deguelin blocks their electron transport chain equally well...
April 3, 2018: Cell Reports
https://www.readbyqxmd.com/read/29603726/mechanisms-driving-the-lactate-switch-in-chinese-hamster-ovary-cells
#11
REVIEW
Fiona Hartley, Tracy Walker, Vicky Chung, Karl Morten
The metabolism of Chinese Hamster Ovary (CHO) cells in a production environment has been extensively investigated. However, a key metabolic transition, the switch from lactate production to lactate consumption, remains enigmatic. Though commonly observed in CHO cultures, the mechanism(s) by which this metabolic shift is triggered is unknown. Despite this, efforts to control the switch have emerged due to the association of lactate consumption with improved cell growth and productivity. This review aims to consolidate current theories surrounding the lactate switch...
March 31, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29580430/hydroxyethyl-methacrylate-grafted-carboxy-methyl-tamarind-cmt-g-hema-polysaccharide-based-matrix-as-a-suitable-scaffold-for-skin-tissue-engineering
#12
Priyanka Choudhury, Satish Kumar, Abhishek Singh, Ashutosh Kumar, Navneet Kaur, Sridhar Sanyasi, Saurabh Chawla, Chandan Goswami, Luna Goswami
Patho-physiologies related to skin are diverse in nature such as burns, skin ulcers, atopic dermatitis, psoriasis etc. which impose severe bio-medical problems and thus enforce requirement of new and healthy skin prepared through tissues engineering methodologies. However, fully functional and biodegradable matrix for attachment, growth, proliferation and differentiation of the relevant cells is not available. In the present study, we introduce a set of hydrogels synthesized by incorporation of a synthetic monomer (Hydroxyethlmethacryate) with a semi-synthetic polymer backbone (carboxy methyl tamarind, CMT) in different mole ratios...
June 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29570272/a-comprehensive-biochemical-and-biophysical-characterization-of-hemoglobin-based-oxygen-carrier-hboc-therapeutics-all-hbocs-are-not-created-equally
#13
Fantao Meng, Tigist Kassa, Sirsendu Jana, Francine Wood, Xiaoyuan Zhang, Yiping Jia, Felice D'Agnillo, Abdu I Alayash
The development of hemoglobin (Hb)-based oxygen carriers (HBOCs) has been hampered because of safety concerns in humans. Chemical and/or genetic modifications of the Hb introduce varied structural and conformational constraint on the molecule that resulted in proteins with diverse allosteric responses, nitrosative and oxidative side reactions. Here, we present for the first time a comprehensive biochemical and biophysical comparison of human, bovine and genetically engineered HBOCs that have been tested in humans...
March 23, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29562514/amyloid-%C3%AE-and-tau-in-alzheimer-s-disease-novel-pathomechanisms-and-non-pharmacological-treatment-strategies
#14
Rebecca M Nisbet, Jürgen Götz
Accumulation of the peptide amyloid-β (Aβ) and the protein tau in Alzheimer's disease (AD) brains is a gradual process that involves the post-translational modification and assembly of monomeric forms into larger structures that eventually form fibrillar inclusions. This process is thought to both drive and initiate AD. However, why the axonally enriched tau in the course of AD accumulates in the somatodendritic domain is not fully understood. We discuss new data that provide a possible explanation that involves de novo protein synthesis, induced by Aβ and mediated through the kinase Fyn...
March 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29562237/optogenetic-regulation-of-engineered-cellular-metabolism-for-microbial-chemical-production
#15
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
https://www.readbyqxmd.com/read/29511847/characterization-of-novel-roles-of-a-hmg-box-protein-poxhmbb-in-biomass-degrading-enzyme-production-by-penicillium-oxalicum
#16
Ya-Ru Xiong, Shuai Zhao, Li-Hao Fu, Xu-Zhong Liao, Cheng-Xi Li, Yu-Si Yan, Lu-Sheng Liao, Jia-Xun Feng
High-mobility group (HMG)-box proteins are involved in chromatin organization in eukaryotes, especially in sex determination and regulation of mitochondrial DNA compaction. Although a novel HMG-box protein, PoxHmbB, had been initially identified to be required for filter paper cellulase activity by Penicillium oxalicum, the biological roles of HMG-box proteins in biomass-degrading enzyme production have not been systematically explored. The P. oxalicum mutant ∆PoxHmbB lost 34.7-86.5% of cellulase (endoglucanase, p-nitrophenyl-β-cellobiosidase, and p-nitrophenyl-β-glucopyranosidase) activities and 60...
April 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29503093/contractile-work-contributes-to-maturation-of-energy-metabolism-in-hipsc-derived-cardiomyocytes
#17
Bärbel M Ulmer, Andrea Stoehr, Mirja L Schulze, Sajni Patel, Marjan Gucek, Ingra Mannhardt, Sandra Funcke, Elizabeth Murphy, Thomas Eschenhagen, Arne Hansen
Energy metabolism is a key aspect of cardiomyocyte biology. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a promising tool for biomedical application, but they are immature and have not undergone metabolic maturation related to early postnatal development. To assess whether cultivation of hiPSC-CMs in 3D engineered heart tissue format leads to maturation of energy metabolism, we analyzed the mitochondrial and metabolic state of 3D hiPSC-CMs and compared it with 2D culture. 3D hiPSC-CMs showed increased mitochondrial mass, DNA content, and protein abundance (proteome)...
March 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29458125/pluripotent-stem-cells-for-uncovering-the-role-of-mitochondria-in-human-brain-function-and-dysfunction
#18
REVIEW
Annika Zink, Josef Priller, Alessandro Prigione
Mitochondrial dysfunctions are a known pathogenetic mechanism of a number of neurological and psychiatric disorders. At the same time, mutations in genes encoding for components of the mitochondrial respiratory chain cause mitochondrial diseases, which commonly exhibit neurological symptoms. Mitochondria are therefore critical for the functionality of the human nervous system. The importance of mitochondria stems from their key roles in cellular metabolism, calcium handling, redox and protein homeostasis, and overall cellular homeostasis through their dynamic network...
March 30, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29445138/non-toxic-engineered-carbon-nanodiamond-concentrations-induce-oxidative-nitrosative-stress-imbalance-of-energy-metabolism-and-mitochondrial-dysfunction-in-microglial-and-alveolar-basal-epithelial-cells
#19
Claudia G Fresta, Aishik Chakraborty, Manjula B Wijesinghe, Angela M Amorini, Giacomo Lazzarino, Giuseppe Lazzarino, Barbara Tavazzi, Susan M Lunte, Filippo Caraci, Prajnaparamita Dhar, Giuseppe Caruso
Engineered nanoparticles are finding a wide spectrum of biomedical applications, including drug delivery and capacity to trigger cytotoxic phenomena, potentially useful against tumor cells. The full understanding of their biosafety and interactions with cell processes is mandatory. Using microglial (BV-2) and alveolar basal epithelial (A549) cells, in this study we determined the effects of engineered carbon nanodiamonds (ECNs) on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) production, as well as on energy metabolism...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29437373/porous-heat-treated-polyacrylonitrile-scaffolds-for-bone-tissue-engineering
#20
Miroslav Vetrik, Martin Parizek, Daniel Hadraba, Olivia Kukackova, Jiri Brus, Helena Hlidkova, Lucie Komankova, Jiri Hodan, Ondrej Sedlacek, Miroslav Slouf, Lucie Bacakova, Martin Hruby
Heat-treated polyacrylonitrile (HT-PAN), also referred to as black orlon (BO), is a promising carbon-based material used for applications in tissue engineering and regenerative medicine. To the best of our knowledge, no such complex bone morphology-mimicking three-dimensional (3D) BO structure has been reported to date. We report that BO can be easily made into 3D cryogel scaffolds with porous structures, using succinonitrile as a porogen. The cryogels possess a porous morphology, similar to bone tissue. The prepared scaffolds showed strong osteoconductive activity, providing excellent support for the adhesion, proliferation, and mitochondrial activity of human bone-derived cells...
March 14, 2018: ACS Applied Materials & Interfaces
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