31,040 results match your criteria novel mitochondrial

In vitro model of ischemic heart failure using human induced pluripotent stem cell-derived cardiomyocytes.

JCI Insight 2021 Apr 20. Epub 2021 Apr 20.

Cardiovascular Regeneration Core Laboratory, University of Michigan, Ann Arbor, United States of America.

Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) have been used extensively to model inherited heart diseases, but hiPSC-CM models of ischemic heart disease are lacking. Here our objective was to generate an hiPSC-CM model of ischemic heart disease. To this end, hiPSCs were differentiated to functional hiPSC-CMs and then purified using either a simulated ischemia media or by using magnetic antibody-based purification targeting the non-myocyte population for depletion from the cell population. Read More

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Mitochondrial Sirt3 contributes to the bone loss caused by aging or estrogen deficiency.

JCI Insight 2021 Apr 20. Epub 2021 Apr 20.

Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, United States of America.

Altered mitochondria activity in osteoblasts and osteoclast has been implicated in the loss of bone mass associated with aging and estrogen deficiency - the two most common causes of osteoporosis. However, the mechanisms that control mitochondrial metabolism in bone cells during health or disease remain unknown. The mitochondrial deacetylase Sirtuin-3 (Sirt3) has been earlier implicated in age-related diseases. Read More

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Inhibiting autophagy targets human leukemic stem cells and hypoxic AML blasts by disrupting mitochondrial homeostasis.

Blood Adv 2021 Apr;5(8):2087-2100

Department of Medicine and.

Leukemia stem cells (LSCs) and therapy-resistant acute myeloid leukemia (AML) blasts contribute to the reinitiation of leukemia after remission, necessitating therapeutic interventions that target these populations. Autophagy is a prosurvival process that allows for cells to adapt to a variety of stressors. Blocking autophagy pharmacologically by using mechanistically distinct inhibitors induced apoptosis and prevented colony formation in primary human AML cells. Read More

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Immunological organ modification during Ex Vivo machine perfusion: The future of organ acceptance.

Transplant Rev (Orlando) 2021 Apr 17;35(2):100586. Epub 2020 Oct 17.

Department of Surgery, Division of Transplantation, University of Wisconsin, Madison, WI, United States of America. Electronic address:

Ex vivo machine perfusion (EVMP) has gained revitalized interest in recent years due to the increasing use of marginal organs which poorly tolerate the standard preservation method static cold storage (SCS). EVMP improves on SCS in a number of ways, most notably by the potential for reconditioning of the donor organ prior to transplantation without the ethical concerns associated with organ modulation before procurement. Immunomodulatory therapies administered during EVMP can influence innate and adaptive immune responses to reduce production of inflammatory molecules and polarize tissue-resident immune cells to a regulatory phenotype. Read More

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A novel and highly effective mitochondrial uncoupling drug in T-cell leukemia.

Blood 2021 Apr 19. Epub 2021 Apr 19.

Rutgers University, New Brunswick, New Jersey, United States.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy. Despite recent advances in treatments with intensified chemotherapy regimens, relapse rates and associated morbidities remain high. In this context, metabolic dependencies have emerged as a druggable opportunity for the treatment of leukemia. Read More

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Metabolic stroke-like episode in a child with FARS2 mutation and SARS-CoV-2 positive cerebrospinal fluid.

Mol Genet Metab Rep 2021 Apr 14:100756. Epub 2021 Apr 14.

Division of Neurology, Children's Hospital Los Angeles, Los Angeles, CA, USA.

The novel SARS-CoV-2 has infected over 48 million persons around the world. Children have been spared with regards to symptoms and sequelae of this highly infectious virus and in those with neurologic issues, the virus has not been present in the cerebrospinal fluid. Here, the authors present the first case of metabolic stroke-like episode with SARS-CoV-2 present in the cerebrospinal fluid in a child with a FARS2 deficiency. Read More

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An expanded set of genome-wide association studies of brain imaging phenotypes in UK Biobank.

Nat Neurosci 2021 Apr 19. Epub 2021 Apr 19.

Department of Statistics and Actuarial Science, Simon Fraser University, Burnaby BC, Canada.

UK Biobank is a major prospective epidemiological study, including multimodal brain imaging, genetics and ongoing health outcomes. Previously, we published genome-wide associations of 3,144 brain imaging-derived phenotypes, with a discovery sample of 8,428 individuals. Here we present a new open resource of genome-wide association study summary statistics, using the 2020 data release, almost tripling the discovery sample size. Read More

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Polyphyllin I promotes cell death via suppressing UPR-mediated CHOP ubiquitination and degradation in non-small cell lung cancer.

Chin J Nat Med 2021 Apr;19(4):255-266

Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address:

Polyphyllin I (PPI) purified from Polyphyllarhizomes displays puissant cytotoxicity in many kinds of cancers. Several researches investigated its anti-cancer activity. But novel mechanisms are still worth investigation. Read More

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Mitophagy pathways and Alzheimer's disease: From pathogenesis to treatment.

Mitochondrion 2021 Apr 16. Epub 2021 Apr 16.

Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, 510006. Electronic address:

Alzheimer's disease (AD) is an age-dependent, incurable mental illness that is associated with the accumulation of aggregates of amyloid-beta (Aβ) and hyperphosphorylated tau fragments (p-tau). Detailed studies on postmortem AD brains, cell lines, and mouse models of AD have shown that numerous cellular alterations, including mitochondrial deficits, synaptic disruption and glial/astrocytic activation, are involved in the disease process. Mitophagy is a cellular process by which damaged/weakened mitochondria are selectively eliminated from the cell. Read More

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Recombinase polymerase amplification with lateral flow strip for detecting Babesia microti infections.

Parasitol Int 2021 Apr 16:102351. Epub 2021 Apr 16.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Key Laboratory of Animal Epidemical Disease and Infectious Zoonoses, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan, Hubei 430070, China. Electronic address:

Babesia microti is one of the most important pathogens causing humans and rodents babesiosis-an emerging tick-borne disease that occurs worldwide. At present, the gold standard for the detection of Babesia is the microscopic examination of blood smears, but this diagnostic test has several limitations. The recombinase polymerase amplification with lateral flow (LF-RPA) assay targeting the mitochondrial cytochrome oxidase subunit I (cox I) gene of B. Read More

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Inhibition of dual leucine zipper kinase prevents chemotherapy-induced peripheral neuropathy and cognitive impairments.

Pain 2021 Apr 15. Epub 2021 Apr 15.

The Neurodegeneration Consortium, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, United States Laboratories of Neuroimmunology, Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, United States Cancer Neuroscience Lab, School of Nursing, Department of Diagnostic Medicine, LIVESTRONG Cancer Institutes, University of Texas at Austin, Austin, TX, United States Institute for Applied Cancer Science, Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, TX, United States Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.

Abstract: Chemotherapy-induced peripheral neuropathy (CIPN) and chemotherapy-induced cognitive impairments (CICI) are common, often severe neurotoxic side effects of cancer treatment that greatly reduce quality of life of cancer patients and survivors. Currently, there are no Food and Drug Administration-approved agents for the prevention or curative treatment of CIPN or CICI. The dual leucine zipper kinase (DLK) is a key mediator of axonal degeneration that is localized to axons and coordinates the neuronal response to injury. Read More

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COVID-19: A Mitochondrial Perspective.

Pankaj Prasun

DNA Cell Biol 2021 Apr 19. Epub 2021 Apr 19.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Coronavirus disease 2019 (COVID-19) is the worst public health crisis of the century. Although we have made tremendous progress in understanding the pathogenesis of this disease, a lot more remains to be learned. Mitochondria appear to be important in COVID-19 pathogenesis because of its role in innate antiviral immunity, as well as inflammation. Read More

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Comparative Analysis of Experimental Methods to Quantify Animal Activity in Caenorhabditis elegans Models of Mitochondrial Disease.

J Vis Exp 2021 Apr 4(170). Epub 2021 Apr 4.

Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine;

Caenorhabditis elegans is widely recognized for its central utility as a translational animal model to efficiently interrogate mechanisms and therapies of diverse human diseases. Worms are particularly well-suited for high-throughput genetic and drug screens to gain deeper insight into therapeutic targets and therapies by exploiting their fast development cycle, large brood size, short lifespan, microscopic transparency, low maintenance costs, robust suite of genomic tools, mutant repositories, and experimental methodologies to interrogate both in vivo and ex vivo physiology. Worm locomotor activity represents a particularly relevant phenotype that is frequently impaired in mitochondrial disease, which is highly heterogeneous in causes and manifestations but collectively shares an impaired capacity to produce cellular energy. Read More

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Iptakalim alleviates synaptic damages via targeting mitochondrial ATP-sensitive potassium channel in depression.

FASEB J 2021 May;35(5):e21581

Neuroprotective Drug Discovery Key Laboratory, Jiangsu Key Laboratory of Neurodegeneration, Center for Global Health, Nanjing Medical University, Nanjing, China.

Synaptic plasticity damages play a crucial role in the onset and development of depression, especially in the hippocampus, which is more susceptible to stress and the most frequently studied brain region in depression. And, mitochondria have a major function in executing the complex processes of neurotransmission and plasticity. We have previously demonstrated that Iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could improve the depressive-like behavior in mice. Read More

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Identification of Mitochondrial-Related Prognostic Biomarkers Associated With Primary Bile Acid Biosynthesis and Tumor Microenvironment of Hepatocellular Carcinoma.

Front Oncol 2021 1;11:587479. Epub 2021 Apr 1.

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hepatocellular carcinoma (HCC) is one of the leading causes of tumor-associated deaths worldwide. Despite great progress in early diagnosis and multidisciplinary tumor management, the long-term prognosis of HCC remains poor. Currently, metabolic reprogramming during tumor development is widely observed to support rapid growth and proliferation of cancer cells, and several metabolic targets that could be used as cancer biomarkers have been identified. Read More

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Metabolic Control of Autoimmunity and Tissue Inflammation in Rheumatoid Arthritis.

Front Immunol 2021 2;12:652771. Epub 2021 Apr 2.

Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States.

Like other autoimmune diseases, rheumatoid arthritis (RA) develops in distinct stages, with each phase of disease linked to immune cell dysfunction. HLA class II genes confer the strongest genetic risk to develop RA. They encode for molecules essential in the activation and differentiation of T cells, placing T cells upstream in the immunopathology. Read More

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Mitochondrial DNA abnormalities provide mechanistic insight and predict reactive oxygen species-stimulating drug efficacy.

BMC Cancer 2021 Apr 17;21(1):427. Epub 2021 Apr 17.

School of Pharmacy and Biomedical Sciences, Institute of Biological and Biomedical Sciences, University of Portsmouth, St Michael's Building, White Swan Road, Portsmouth, PO1 2DT, UK.

Background: Associations between mitochondrial genetic abnormalities (variations and copy number, i.e. mtDNAcn, change) and elevated ROS have been reported in cancer compared to normal cells. Read More

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Mitochondrial Sirtuins in Stem cells and Cancer.

FEBS J 2021 Apr 18. Epub 2021 Apr 18.

Biosciences Institute, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK.

The mammalian sirtuin family consists of seven proteins, three of which (SIRT3, SIRT4, and SIRT5) localise specifically within mitochondria and preserve mitochondrial function and homeostasis. Mitochondrial sirtuins are involved in diverse functions such as deacetylation, ADP-ribosylation, demalonylation and desuccinylation, thus affecting various aspect of cell fate. Intriguingly, mitochondrial sirtuins are able to manage these delicate processes with accuracy mediated by cross-talk between the nucleus and mitochondria. Read More

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Homozygous missense mutation in UQCRC2 associated with severe encephalomyopathy, mitochondrial complex III assembly defect and activation of mitochondrial protein quality control.

Biochim Biophys Acta Mol Basis Dis 2021 Apr 15:166147. Epub 2021 Apr 15.

Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. Electronic address:

The mitochondrial respiratory chain (MRC) complex III (CIII) associates with complexes I and IV (CI and CIV) into supercomplexes. We identified a novel homozygous missense mutation (c.665G>C; p. Read More

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Role of mTORC2 in biphasic regulation of brown fat metabolism in response to mild and severe cold.

J Biol Chem 2021 Apr 15:100632. Epub 2021 Apr 15.

Department of Medicine, Division of Nephrology, University of California at San Francisco, San Francisco, CA, USA,; Cardiovascular Research Institute, University of California at San Francisco, San Francisco, CA, USA,. Electronic address:

Non-shivering thermogenesis is essential for mammals to maintain body temperature. According to the canonical view, temperature is sensed by cutaneous thermoreceptors and nerve impulses transmitted to the hypothalamus, which generates sympathetic signals to ß-adrenergic receptors in brown adipocytes. The energy for heat generation is primarily provided by the oxidation of fatty acids derived from triglyceride hydrolysis and cellular uptake. Read More

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Mitochondria-associated membrane-modulated Ca transfer: A potential treatment target in cardiac ischemia reperfusion injury and heart failure.

Life Sci 2021 Apr 14:119511. Epub 2021 Apr 14.

Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, China. Electronic address:

Effective Ca dependent mitochondrial energy supply is imperative for proper cardiac contractile activity, while disruption of Ca homeostasis participates in the pathogenesis of multiple human diseases. This phenomenon is particularly prominent in cardiac ischemia and reperfusion (I/R) and heart failure, both of which require strict clinical intervention. The interface between endoplasmic reticula (ER) and mitochondria, designated the mitochondria-associated membrane (MAM), is now regarded as a crucial mediator of Ca transportation. Read More

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A novel nonsense variant in MT-CO3 causes MELAS syndrome.

Neuromuscul Disord 2021 Mar 3. Epub 2021 Mar 3.

Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 West Wenhua Road Jinan, Jinan, Shandong 250012 China; Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong 266035 China; Mitochondrial Medicine Laboratory, Qilu Hospital (Qingdao), Shandong University, Qingdao, Shandong 266035 China; Brain Science Research Institute, Shandong University, Jinan, Shandong 250000, China. Electronic address:

Both mitochondrial and nuclear gene mutations can cause cytochrome c oxidase (COX, complex Ⅳ) dysfunction, leading to mitochondrial diseases. Although numerous diseases caused by defects of the COX subunits or COX assembly factors have been documented, clinical cases directly related to mitochondrial cytochrome c oxidase subunit 3 gene (MT-CO3) mutations are relatively rare. Here, we report a 47-year-old female patient presented with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Read More

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IκBα targeting promotes oxidative stress-dependent cell death.

J Exp Clin Cancer Res 2021 Apr 16;40(1):136. Epub 2021 Apr 16.

Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043, Orbassano, Italy.

Background: Oxidative stress is a hallmark of many cancers. The increment in reactive oxygen species (ROS), resulting from an increased mitochondrial respiration, is the major cause of oxidative stress. Cell fate is known to be intricately linked to the amount of ROS produced. Read More

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Loss of coordinated expression between ribosomal and mitochondrial genes revealed by comprehensive characterization of a large family with a rare Mendelian disorder.

Genomics 2021 Apr 13. Epub 2021 Apr 13.

Department of Molecular Biosciences, University of Texas at Austin, Austin, USA. Electronic address:

Non-canonical intronic variants are a poorly characterized yet highly prevalent class of alterations associated with Mendelian disorders. Here, we report the first RNA expression and splicing analysis from a family whose members carry a non-canonical splice variant in an intron of RPL11 (c.396 + 3A > G). Read More

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Stiffness of the extracellular matrix affects apoptosis of nucleus pulposus cells by regulating the cytoskeleton and activating the TRPV2 channel protein.

Cell Signal 2021 Apr 13:110005. Epub 2021 Apr 13.

Department of Orthopaedics, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou, Jiangsu, China. Electronic address:

It is known that nucleus pulposus cells (NPs) play an important role in intervertebral disc degeneration (IVDD), and a previous study indicated that the stiffness of NP tissue changes during the degeneration process. However, the mechanism underlying the cellular response to ECM stiffness is still unclear. To analyze the effects of extracellular matrix (ECM) with different degrees of stiffness on NPs, we prepared polyacrylamide (PA) gels with different elastic moduli, and cells grown under different stiffness conditions were obtained and analyzed. Read More

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Interorganelle communication, aging, and neurodegeneration.

Genes Dev 2021 Apr;35(7-8):449-469

Department of Physiology, University of California at San Francisco, San Francisco, California 94158, USA.

Our cells are comprised of billions of proteins, lipids, and other small molecules packed into their respective subcellular organelles, with the daunting task of maintaining cellular homeostasis over a lifetime. However, it is becoming increasingly evident that organelles do not act as autonomous discrete units but rather as interconnected hubs that engage in extensive communication through membrane contacts. In the last few years, our understanding of how these contacts coordinate organelle function has redefined our view of the cell. Read More

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The structural characterization of a novel water-soluble polysaccharide from edible mushroom Leucopaxillus giganteus and its antitumor activity on H22 tumor-bearing mice.

Chem Biodivers 2021 Apr 16. Epub 2021 Apr 16.

Tianjin university of science and technology, college of food science and engineering, Tianjin 300457, P. R. China, Tianjin, CHINA.

In the present study, a novel cold water-soluble polysaccharide fraction (LGP) with the average molecular weight of 1.78×10 6 Da was extracted and purified from Leucopaxillus giganteus and its primary structure as well as in vivo antitumor activity was evaluated. The monosaccharide composition of LGP was determined by ion chromatography to be galactose, xylose, glucose and fucose in a molar ratio of 2. Read More

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In Silico Identification of Novel Interactions for FABP5 (Fatty Acid-Binding Protein 5) with Nutraceuticals: Possible Repurposing Approach.

Adv Exp Med Biol 2021 ;1308:589-599

Department of Biological Sciences, University of Limerick, Limerick, Ireland.

Fatty Acid Binding-Protein 5 (FABP5) is a cytoplasmic protein, which binds long-chain fatty acids and other hydrophobic ligands. This protein is implicated in several physiological processes including mitochondrial β-oxidation and transport of fatty acids, membrane phospholipid synthesis, lipid metabolism, inflammation and pain. In the present study, we used molecular docking tools to determine the possible interaction of FABP5 with six selected compounds retrieved form Drugbank. Read More

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Activated p53 in the anti-apoptotic milieu of tuberous sclerosis gene mutation induced diseases leads to cell death if thioredoxin reductase is inhibited.

Apoptosis 2021 Apr 16. Epub 2021 Apr 16.

Department of Pharmaceutical Biotechnology, University of Pecs, Pecs, Hungary.

Tuberous sclerosis, angiomyolipoma and lymphangioleiomyomatosis are a group of diseases characterized by mutation in tuberous sclerosis genes (TSC 1-2). TSC mutation leads to continuous activation of the mTOR pathway that requires adaptation to increased ATP requirement. With limited treatment options, there is an increasing demand to identify novel therapeutic targets and to understand the correlations between mTOR pathway activation and the lack of cell death in the presence of TSC mutation. Read More

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Were eukaryotes made by sex?: Sex might have been vital for merging endosymbiont and host genomes giving rise to eukaryotes.

Michael Brandeis

Bioessays 2021 Apr 16:e2000256. Epub 2021 Apr 16.

The Department of Genetics, The Hebrew University of Jerusalem, Jerusalem, Israel.

I hypothesize that the appearance of sex facilitated the merging of the endosymbiont and host genomes during early eukaryote evolution. Eukaryotes were formed by symbiosis between a bacterium that entered an archaeon, eventually giving rise to mitochondria. This entry was followed by the gradual transfer of most bacterial endosymbiont genes into the archaeal host genome. Read More

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