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Frontiers in Bioscience (Landmark Edition)

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https://www.readbyqxmd.com/read/27814661/plant-mitochondrial-dna
#1
Stewart A Morley, Brent L Nielsen
Plants possess mitochondrial genomes that are large and complex compared to animals. Nearly all animal mitochondrial genomes are about 16.5. kbp in length, whereas plant mitochondrial genomes range between 200-2,000 kbp. This is curious if we assume modern mitochondria originated from a common alpha-proteobacterial ancestor. Despite their size, plant mitochondrial genomes do not contain significantly more genes than their animal counterparts. Most of the additional DNA found in plant mitochondrial genomes consists of large introns, repeats and non-coding regions...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814660/clinical-implications-and-pathological-associations-of-circulating-mitochondrial-dna
#2
Eszter Tuboly, Daniel Mcllroy, Gabrielle Briggs, Natalie Lott, Zsolt J Balogh
Mitochondria are membrane-enclosed organelles, the energy-producing centers in almost all eukaryotic cells. The evolutionary emergence of mitochondria is a result of the endocytosis of a-proteobacteria. There are several characteristic features which refer to its prokaryotic ancestors including its independent sets of double-stranded mitochondrial DNA, which is uniquely circular in form and contains a significant amount of unmethylated DNA as CpG islands. Resent research has proven that free mitochondrial DNA found in blood was associated with innate immunomodulation in a broad-range of clinical conditions...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814659/current-strategies-towards-therapeutic-manipulation-of-mtdna-heteroplasmy
#3
Claudia V Pereira, Carlos T Moraes
Mitochondrial disease is a multifactorial disorder involving both nuclear and mitochondrial genomes. Over the past 20 years, great progress was achieved in the field of gene editing which raised the possibility of partial or complete elimination of mutant mtDNA that causes disease phenotypes. Each cell contains thousands of copies of mtDNA which can be either wild-type (WT) or mutant, a condition called heteroplasmy. As there are multiple copies of mtDNA inside a cell, the percentage of mutant mtDNA can vary and a directional shift in the heteroplasmy ratio towards an increase of WT mtDNA copies would have therapeutic value...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814658/third-phase-science-defining-a-novel-model-of-research-into-human-ageing
#4
Marios Kyriazis
While the current paradigm of research into ageing relies heavily upon reductionist premises, and it has clearly not produced any of the dramatic benefits anticipated in our fight against ageing, the majority of scientists are hesitant, unable or unwilling to consider different or alternative models. In this paper I will discuss some of the shortcomings of a reductionist view of research aimed at finding treatments against ageing degeneration, and I will highlight several areas where proposed future treatments for basic age-related degeneration may be vulnerable to severe criticism...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814657/understanding-ligand-receptor-non-covalent-binding-kinetics-using-molecular-modeling
#5
Zhiye Tang, Christopher C Roberts, Chia-En A Chang
Kinetic properties may serve as critical differentiators and predictors of drug efficacy and safety, in addition to the traditionally focused binding affinity. However the quantitative structure-kinetics relationship (QSKR) for modeling and ligand design is still poorly understood. This review provides an introduction to the kinetics of drug binding from a fundamental chemistry perspective. We focus on recent developments of computational tools and their applications to non-covalent binding kinetics.
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814656/alpha-enolase-eno1-a-potential-target-in-novel-immunotherapies
#6
Paola Cappello, Moitza Principe, Sara Bulfamante, Francesco Novelli
Alpha-enolase (ENO1) is a metabolic enzyme involved in the synthesis of pyruvate. It also acts as a plasminogen receptor and mediates the activation of plasmin and extracellular matrix degradation. In tumor cells, ENO1 is up-regulated and supports the Warburg effect; it is expressed at the cell surface, where it promotes cancer invasion, and is subjected to a specific array of post-translational modifications, namely acetylation, methylation and phosphorylation. ENO1 overexpression and post-translational modifications could be of diagnostic and prognostic value in many cancer types...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814655/mitochondrial-dna-repair-and-damage-tolerance
#7
Alexis Stein, Elaine A Sia
The accurate maintenance of mitochondrial DNA (mtDNA) is required in order for eukaryotic cells to assemble a functional electron transport chain. This independently-maintained genome relies on nuclear-encoded proteins that are imported into the mitochondria to carry out replication and repair processes. Decades of research has made clear that mitochondria employ robust and varied mtDNA repair and damage tolerance mechanisms in order to ensure the proper maintenance of the mitochondrial genome. This review focuses on our current understanding of mtDNA repair and damage tolerance pathways including base excision repair, mismatch repair, homologous recombination, non-homologous end joining, translesion synthesis and mtDNA degradation in both yeast and mammalian systems...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814654/a-reciprocal-hla-disease-association-in-rheumatoid-arthritis-and-pemphigus-vulgaris
#8
Vincent Van Drongelen, Joseph Holoshitz
  Human leukocyte antigens (HLA) have been extensively studied as being antigen presenting receptors, but many aspects of their function remain elusive, especially their association with various autoimmune diseases. Here we discuss an illustrative case of the reciprocal relationship between certain HLA-DRB1 alleles and two diseases, rheumatoid arthritis (RA) and pemphigus vulgaris (PV). RA is strongly associated with HLA-DRB1 alleles that encode a five amino acid sequence motif in the 70-74 region of the DR beta chain, called the shared epitope (SE), while PV is associated with the HLA-DRB1*04:02 allele that encodes a different sequence motif in the same region...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814653/mitochondrial-genome-and-epigenome-two-sides-of-the-same-coin
#9
Patrizia D'Aquila, Alberto Montesanto, Francesco Guarasci, Giuseppe Passarino, Dina Bellizzi
The involvement of mitochondrial content, structure and function as well as of the mitochondrial genome (mtDNA) in cell biology, by participating in the main processes occurring in the cells, has been a topic of intense interest for many years. More specifically, the progressive accumulation of variations in mtDNA of post-mitotic tissues represents a major contributing factor to both physiological and pathological phenotypes. Recently, an epigenetic overlay on mtDNA genetics is emerging, as demonstrated by the implication of the mitochondrial genome in the regulation of the intracellular epigenetic landscape being itself object of epigenetic modifications...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814652/mtdna-the-small-workhorse-of-evolutionary-studies
#10
Rob Desalle, Bernd Schierwater, Heike Hadrys
The double-stranded, circular mitochondrial DNA (mtDNA), which is present in all eukaryotic life forms, was initially discovered and characterized in the last century and has been widely used in evolutionary studies. Since then, a large number of studies have taken advantage of the genetic information encoded in this genome. Because of its small size in animals (in general), the technical ease of manipulating mitochondrial genome and the dynamics of its evolutionary change, this genome has been the workhorse of evolutionary studies over the past three decades...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814651/mitochondria-in-the-pathophysiology-of-alzheimer-s-and-parkinson-s-diseases
#11
Isaac G Onyango, Shaharyar M Khan, James P Bennett
Mitochondria are responsible for the majority of energy production in energy-intensive tissues like brain, modulate Ca(+2) signaling and control initiation of cell death. Because of their extensive use of oxygen and lack of protective histone proteins, mitochondria are vulnerable to oxidative stress (ROS)-induced damage to their genome (mtDNA), respiratory chain proteins and ROS repair enzymes. Animal and cell models of PD use toxins that impair mitochondrial complex I activity. Maintenance of mitochondrial mass, mitochondrial biogenesis (mitobiogenesis), particularly in high-energy brain, occurs through complex signaling pathways involving the upstream "master regulator" PGC-1alpha that is transcriptionally and post-translationally regulated...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814650/mitochondrial-transcription-in-mammalian-cells
#12
Inna N Shokolenko, Mikhail F Alexeyev
As a consequence of recent discoveries of intimate involvement of mitochondria with key cellular processes, there has been a resurgence of interest in all aspects of mitochondrial biology, including the intricate mechanisms of mitochondrial DNA maintenance and expression. Despite four decades of research, there remains a lot to be learned about the processes that enable transcription of genetic information from mitochondrial DNA to RNA, as well as their regulation. These processes are vitally important, as evidenced by the lethality of inactivating the central components of mitochondrial transcription machinery...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814649/nitric-oxide-mediated-pathways-and-its-role-in-the-degenerative-diseases
#13
Nan Zhang, Yu Diao, Rongrong Hua, Jun Wang, Song Han, Junfa Li, Yanling Yin
Nitric oxide (NO) is a relatively short-lived inorganic free radical, which can be produced by different types of cells in multi-cellular organisms. This diffusible messenger functions as either an effector or a second messenger in many intercellular communications or intracellular signaling pathways. NO becomes noxious if it is produced in excess. These effects are mainly mediated by the reactivity of NO with various reactive oxygen species, which can be countered by antioxidant enzymes. In addition, NO can directly modify biological molecules via S-nitrosylation and lead to altered signaling responses...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814648/mapping-preserved-real-world-cognition-in-severely-brain-injured-patients
#14
Leah Sinai, Adrian M Owen, Lorina Naci
Decoding the contents of consciousness from brain activity is one of most challenging frontiers of cognitive neuroscience. The ability to interpret mental content without recourse to behavior is most relevant for understanding patients who may be demonstrably conscious, but entirely unable to speak or move willfully in any way, precluding any systematic investigation of their conscious experience. Until recently, patient studies have used structured instructions to elicit willful modulation of brain activity according to command...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814647/role-of-jnk-isoforms-in-the-kainic-acid-experimental-model-of-epilepsy-and-neurodegeneration
#15
Carme Auladell, Luisa de Lemos, Ester Verdaguer, Miren Ettcheto, Oriol Busquets, Alberto Lazarowski, Carlos Beas-Zarate, Jordi Olloquequi, Jaume Folch, Antoni Camins
Chemoconvulsants that induce status epilepticus in rodents have been widely used over the past decades due to their capacity to reproduce with high similarity neuropathological and electroencephalographic features observed in patients with temporal lobe epilepsy (TLE). Kainic acid  is one of the most used chemoconvulsants in experimental models. KA administration mainly induces neuronal loss in the hippocampus. We focused the present review inthe c-Jun N-terminal kinase-signaling pathway (JNK), since it has been shown to play a key role in the process of neuronal death following KA activation...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814646/blockage-of-hemichannels-alters-gene-expression-in-osteocytes-in-a-high-magneto-gravitational-environment
#16
Huiyun Xu, Dandan Ning, Dezhi Zhao, Yunhe Chen, Dongdong Zhao, Sumin Gu, Jean Xin Jiang, Peng Shang
Osteocytes, the most abundant cells in bone, are highly responsive to external environmental changes. We tested how Cx43 hemichannels which mediate the exchange of small molecules between cells and extracellular environment impact genome wide gene expression under conditions of abnormal gravity and magnetic field. To this end, we subjected osteocytic MLO-Y4 cells to a high magneto-gravitational environment and used microarray to examine global gene expression and a specific blocking antibody was used to assess the role of Cx43 hemichannels...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814645/racial-disparities-in-prostate-cancer-a-molecular-perspective
#17
Arun Bhardwaj, Sanjeev K Srivastava, Mohammad Aslam Khan, Vijay K Prajapati, Seema Singh, James E Carter, Ajay P Singh
Prostate cancer incidence and mortality rates are remarkably higher in African-American men as compared to their European-Americans counterparts. Despite these recognitions, precise causes underlying such prevalent racial disparities remain poorly understood. Although socioeconomic factors could account for such differences up to a certain extent, it is now being increasingly realized that such disparity has a molecular basis. Indeed, several differences, including genetic polymorphism, gene mutations, epigenetic modifications, miRNAs alterations, etc...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814644/the-nf-kb-regulates-the-shp-1-expression-in-monocytes-in-congestive-heart-failure
#18
Mirko Pesce, Sara Franceschelli, Alessio Ferrone, Antonia Patruno, Alfredo Grilli, Maria Anna De Lutiis, Francesca R Pluchinotta, Sonia Bergante, Guido Tettamanti, Graziano Riccioni, Mario Felaco, Lorenza Speranza
It has been shown that functional recovery of patients with acute congestive heart failure (ACHF) after treatment with conventional drugs (CD) is mediated by suppression of inflammation in peripheral blood mononuclear cells. Here, we analyzed gene expression profiles of monocytes from symptomatic ACHF patients (NYHA Class III-IV) before and after pharmacological treatment with CD. The treatment was associated with selective down-regulation of "TNFR signaling" and pro-inflammatory mediators CCL5, MIP-1α receptor, CD14, ITGAM, and significant up-regulation of "TNFR signaling" as evidenced by increase in anti-inflammatory factors including NF-kBIA, TNFAIP3 and SHP-1...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814643/cellular-efflux-transporters-and-the-potential-role-of-natural-products-in-combating-efflux-mediated-drug-resistance
#19
Muhammad Ayaz, Fazal Subhan, Abdul Sadiq, Farhat Ullah, Jawad Ahmed, Robert D E Sewell
Efflux mediated multidrug resistance (MDR) is a major problem in the treatment of bacterial, fungal and protozoal infections in addition to cancer chemotherapy. Among other well known mechanisms, efflux pumps are significant contributors to chemo-resistance. Efflux mediated resistance generally occurs through up-regulation of genes responsible for the expression of transporter proteins extruding drugs from the cell to create intracellular sub-therapeutic concentrations leading to resistance. The rapid expansion of MDR pathogens necessitates the discovery of resistance modifying drugs, which in combination with antimicrobial or chemotherapeutic agents would tend to reinstate the action of these drugs and avert the emergence of acquired resistance...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27814642/the-long-story-of-mitochondrial-dna-and-respiratory-complex-i
#20
Mauro Degli Esposti
This article examines the long story of the relationship between mitochondrial DNA (mtDNA) and respiratory complex I, NADH:Ubiquinone Oxidoreductase, from its beginning  in the genome of the bacterial endosymbiont which then evolved into the mitochondria of our cells. The story begins with the evolution of ancient forms of bacterial complex I into the Nuo14 complex I that was present in the alpha proteobacterial ancestor of mitochondria. The story then becomes complicated in the diversity of eukaryotic organisms that are currently recognized...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
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